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Greco V, Lanza V, Tomasello B, Naletova I, Cairns WRL, Sciuto S, Rizzarelli E. Copper Complexes with New Glycyl-l-histidyl-l-lysine-Hyaluronan Conjugates Show Antioxidant Properties and Osteogenic and Angiogenic Synergistic Effects. Bioconjug Chem 2025; 36:662-675. [PMID: 40123442 DOI: 10.1021/acs.bioconjchem.4c00545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/25/2025]
Abstract
In recent years, hyaluronic acid (HA) and the natural tripeptide glycyl-l-histidyl-l-lysine (GHK), especially its copper(II) complex (GHK-Cu), individually have been shown to exert helpful properties for bone protection and regeneration. However, they are not strong enough to handle oxidative stress, hydrolytic attack, or environmental conditions. Being aware that conjugation chemistry has recently emerged as an appealing approach for generating new molecular entities capable of preserving the molecular integrity of their moieties or delaying their degradation, herein we present the synthesis of conjugates of HA with GHK (GHK-HA), at different loadings of the tripeptide. GHK-HA binds copper(II) ions and potentiates the chemical and biological properties of the two components in in vitro assays. The results highlight copper's role in promoting the expression and release of certain trophic, angiogenic, and osteogenic factors, including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), as well as bone morphogenetic protein-2 (BMP-2). The protective and regenerative activities of the metal ion are related to the translocation of its intracellular chaperones Copper Chaperone for Superoxide Dismutase (CCS) and Antioxidant-1 (Atox1) to the nucleus where they act as transcription factors.
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Affiliation(s)
- Valentina Greco
- Department of Chemical Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy
| | - Valeria Lanza
- Institute of Crystallography, National Council of Research (CNR), Via P. Gaifami 18, 95126 Catania, Italy
| | - Barbara Tomasello
- Department of Drug and Health Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy
| | - Irina Naletova
- Institute of Crystallography, National Council of Research (CNR), Via P. Gaifami 18, 95126 Catania, Italy
| | - Warren R L Cairns
- CNR-Institute of Polar Sciences (CNR-ISP), Via Torino 155, 30172 Venice, Italy
| | - Sebastiano Sciuto
- Department of Chemical Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy
| | - Enrico Rizzarelli
- Department of Chemical Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy
- Institute of Crystallography, National Council of Research (CNR), Via P. Gaifami 18, 95126 Catania, Italy
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2
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Castro VIB, Araújo AR, Reis RL, Pashkuleva I, Pires RA. Nanoengineered Self-Assembling Peptides with Increased Proteolytic Stability Promote Wound Healing. ACS APPLIED MATERIALS & INTERFACES 2025; 17:11624-11633. [PMID: 39937124 DOI: 10.1021/acsami.4c18221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2025]
Abstract
The copper complex of the tripeptide glycine-histidine-lysine (GHK) has proven benefits in wound healing and tissue remodeling by promoting blood vessel growth and increasing skin oxygen levels, but its activity is reduced in body fluids due to fast proteolytic cleavage. Herein, we designed several peptides that bear the GHK sequence and can self-assemble into supramolecular nanostructures aiming for enhanced bioactivity. The design involves a phenylalanine (F) backbone known for its ability to form supramolecular assemblies. We tested either coassembly between the structural peptide F4D and the functional sequence GHK or assembly of covalently bound peptides, in which the GHK is bound via the glycine (F4D-GHK) or lysine (F4D-KHG, i.e., inverted GHK sequence). All tested peptides assembled into nanotapes, but their resistance to proteolytic degradation was different: covalently bound peptides generated more stable assemblies. Wound healing assays demonstrated that the supramolecular structures have enhanced bioactivity when compared to GHK alone. Multiplex immunoassay analyses demonstrated the secretion of key regulators of the healing process, such as cytokines, matrix metalloproteinases, and growth factors. Altogether our data show that incorporation of GHK/KHG into supramolecular structures improves its stability, bioactivity, and efficacy in promoting wound healing.
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Affiliation(s)
- Vânia I B Castro
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, 4805-017 Barco, Portugal
- ICVS/3B's-PT Government Associate Laboratory, 4805-017 Braga/Guimarães, Portugal
| | - Ana Rita Araújo
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, 4805-017 Barco, Portugal
- ICVS/3B's-PT Government Associate Laboratory, 4805-017 Braga/Guimarães, Portugal
| | - Rui L Reis
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, 4805-017 Barco, Portugal
- ICVS/3B's-PT Government Associate Laboratory, 4805-017 Braga/Guimarães, Portugal
| | - Iva Pashkuleva
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, 4805-017 Barco, Portugal
- ICVS/3B's-PT Government Associate Laboratory, 4805-017 Braga/Guimarães, Portugal
| | - Ricardo A Pires
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, 4805-017 Barco, Portugal
- ICVS/3B's-PT Government Associate Laboratory, 4805-017 Braga/Guimarães, Portugal
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Resmi R, Parvathy J, Anjali S, Amrita N, Jyothi A, Harikrishnan VS, John A, Joseph R. Platelet-Rich Plasma Loaded Alginate-Based Injectable Hydrogel for Meniscal Tear Repair: In Vivo Evaluation in Lapine Model. J Biomed Mater Res B Appl Biomater 2025; 113:e35541. [PMID: 39891920 DOI: 10.1002/jbm.b.35541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 11/28/2024] [Accepted: 01/20/2025] [Indexed: 02/03/2025]
Abstract
Platelet-rich plasma (PRP) has been employed for orthopedic applications for decades due to the abundance of bioactive cues/growth factors that ameliorate the proliferation and migration of relevant cells involved in tissue repair/regeneration. In this work, PRP was incorporated into injectable compositions of alginate-based hydrogel and evaluated in vitro and in vivo. In vitro tests revealed that PRP addition promoted cell adhesion, cell proliferation, and distribution of seeded fibrochondrocytes on the hydrogel. Further, the DNA quantification and sGAG estimation confirmed the production of fibrocartilage-specific extracellular matrix, predominantly type 1 collagen and sGAG. For in vivo evaluation, tears were created surgically in the rabbit menisci and were filled with injectable hydrogel. Sham and hydrogel without PRP were used as controls. Histopathological evaluation after 3 months of implantation revealed that the healing was partial for sham control, but complete for hydrogel without PRP. The hydrogel served as the scaffold for fibrocartilage tissue regeneration. On the other hand, PRP-incorporated hydrogel showed good healing with low signs of inflammation as evidenced by histology and biochemical content. The healing was complete, and the nature of the regenerated tissues was very close to native tissue indicating that alginate-based hydrogel is a promising candidate for meniscal tissue repair.
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Affiliation(s)
- Rajalekshmi Resmi
- Division of Polymeric Medical Devices, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India
| | - Jayasree Parvathy
- Corporate R&D Center, HLL Life Care Limited, Thiruvananthapuram, Kerala, India
| | - Sudha Anjali
- Department of Biochemistry, University of Kerala, Thiruvananthapuram, Kerala, India
| | - Natarajan Amrita
- Department of Applied Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India
| | - Arun Jyothi
- Department of Orthopaedics, Sree Uthradom Thirunal (SUT) Hospital, Thiruvananthapuram, Kerala, India
| | - V S Harikrishnan
- Division of Laboratory Animal Science, Department of Applied Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India
| | - Annie John
- Department of Biochemistry, University of Kerala, Thiruvananthapuram, Kerala, India
| | - Roy Joseph
- Division of Polymeric Medical Devices, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India
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Trufanova N, Hubenia O, Kot Y, Trufanov O, Kovalenko I, Kot K, Petrenko O. Metabolic Mode of Alginate-Encapsulated Human Mesenchymal Stromal Cells as a Background for Storage at Ambient Temperature. Biopreserv Biobank 2024. [PMID: 39723454 DOI: 10.1089/bio.2024.0103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2024] Open
Abstract
Introduction: Human mesenchymal stromal cells (MSCs) are attractive for both medical practice and biomedical research. Nonfreezing short-term storage may provide safe and simple transportation and promote the practical use of MSCs. Objectives: We aimed to determine the duration of efficient storage at ambient temperature (22°C) of human dermal MSCs in different three-dimensional organization and to investigate the role of cell metabolic mode in the resistance to the ambient storage damaging factors. Methods: MSCs in monolayer, suspension, and encapsulated in alginate microspheres (AMS) were stored in sealed containers at 22°С in culture medium. Viability (fluorescein diacetate /ethidium bromide) and metabolic activity (Alamar Blue assay) were assessed at 0, 3, 7, 10, and 14 days of the storage. Mitochondrial membrane potential (JC-1 test), cell cycle analysis, reactive oxygen species level, and resistance to hydrogen peroxide were analyzed under culture conditions. Results: Alginate encapsulation was shown to maintain viability (about 85%), metabolic activity, and adhesion ability during storage for 7 days. The storage of MSCs in both monolayer and suspension was less efficient. Culture of MSCs in AMS decreased basal metabolic activity, mitochondrial activity, and led to reversible cell cycle arrest compared to standard two-dimensional culture. MSCs in AMS have a lower basal level of reactive oxygen species and higher resistance to hydrogen peroxide compared with those in monolayer culture. Conclusion: Revealed shift into quiescent metabolic mode is essential for alginate-encapsulated MSCs resistance to storage at ambient temperature.
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Affiliation(s)
- Natalia Trufanova
- Institute for Problems of Cryobiology and Cryomedicine of National Academy of Sciences of Ukraine, Kharkiv, Ukraine
| | - Oleksandra Hubenia
- Institute for Problems of Cryobiology and Cryomedicine of National Academy of Sciences of Ukraine, Kharkiv, Ukraine
- Institute for Multiphase Processes, Leibniz University Hannover, Garbsen, Germany
| | - Yurii Kot
- V.N. Karazin Kharkiv National University, Kharkiv, Ukraine
| | - Oleh Trufanov
- Institute for Problems of Cryobiology and Cryomedicine of National Academy of Sciences of Ukraine, Kharkiv, Ukraine
| | - Ihor Kovalenko
- Institute for Problems of Cryobiology and Cryomedicine of National Academy of Sciences of Ukraine, Kharkiv, Ukraine
| | - Kateryna Kot
- V.N. Karazin Kharkiv National University, Kharkiv, Ukraine
| | - Oleksandr Petrenko
- Institute for Problems of Cryobiology and Cryomedicine of National Academy of Sciences of Ukraine, Kharkiv, Ukraine
- V.N. Karazin Kharkiv National University, Kharkiv, Ukraine
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Klontzas ME, Vernardis SI, Batsali A, Papadogiannis F, Panoskaltsis N, Mantalaris A. Machine Learning and Metabolomics Predict Mesenchymal Stem Cell Osteogenic Differentiation in 2D and 3D Cultures. J Funct Biomater 2024; 15:367. [PMID: 39728167 DOI: 10.3390/jfb15120367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 11/27/2024] [Accepted: 12/03/2024] [Indexed: 12/28/2024] Open
Abstract
Stem cells have been widely used to produce artificial bone grafts. Nonetheless, the variability in the degree of stem cell differentiation is an inherent drawback of artificial graft development and requires robust evaluation tools that can certify the quality of stem cell-based products and avoid source-tissue-related and patient-specific variability in outcomes. Omics analyses have been utilised for the evaluation of stem cell attributes in all stages of stem cell biomanufacturing. Herein, metabolomics in combination with machine learning was utilised for the benchmarking of osteogenic differentiation quality in 2D and 3D cultures. Metabolomics analysis was performed with the use of gas chromatography-mass spectrometry (GC-MS). A set of 11 metabolites was used to train an XGboost model which achieved excellent performance in distinguishing between differentiated and undifferentiated umbilical cord blood mesenchymal stem cells (UCB MSCs). The model was benchmarked against samples not present in the training set, being able to efficiently capture osteogenesis in 3D UCB MSC cultures with an area under the curve (AUC) of 82.6%. On the contrary, the model did not capture any differentiation in Wharton's Jelly MSC samples, which are well-known underperformers in osteogenic differentiation (AUC of 56.2%). Mineralisation was significantly correlated with the levels of fumarate, glycerol, and myo-inositol, the four metabolites found most important for model performance (R2 = 0.89, R2 = 0.94, and R2 = 0.96, and p = 0.016, p = 0.0059, and p = 0.0022, respectively). In conclusion, our results indicate that metabolomics in combination with machine learning can be used for the development of reliable potency assays for the evaluation of Advanced Therapy Medicinal Products.
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Affiliation(s)
- Michail E Klontzas
- Artificial Intelligence and Translational Imaging (ATI) Lab, Department of Radiology, School of Medicine, University of Crete, 71003 Heraklion, Greece
- Computational Biomedicine Laboratory, Institute of Computer Science, Foundation for Research and Technology (ICS-FORTH), 70013 Heraklion, Greece
| | | | - Aristea Batsali
- Haemopoiesis Research Laboratory, School of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Fotios Papadogiannis
- Haemopoiesis Research Laboratory, School of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Nicki Panoskaltsis
- BioMedical Systems Engineering Laboratory, Panoz Institute, School of Pharmacy and Pharmaceutical Sciences, Trinity College, D02 PN40 Dublin, Ireland
| | - Athanasios Mantalaris
- BioMedical Systems Engineering Laboratory, Panoz Institute, School of Pharmacy and Pharmaceutical Sciences, Trinity College, D02 PN40 Dublin, Ireland
- National Institute for Bioprocessing Research and Training (NIBRT), Foster Avenue, Mount Merrion, Blackrock, A94 X099 Dublin, Ireland
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Covelli V, Buonocore M, Grimaldi M, Scrima M, Santoro A, Marino C, De Simone V, van Baarle L, Biscu F, Scala MC, Sala M, Matteoli G, D'Ursi AM, Rodriquez M. Peptides as modulators of FPPS enzyme: A multifaceted evaluation from the design to the mechanism of action. Eur J Med Chem 2024; 279:116871. [PMID: 39303514 DOI: 10.1016/j.ejmech.2024.116871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 09/02/2024] [Accepted: 09/10/2024] [Indexed: 09/22/2024]
Abstract
Bone diseases are medical conditions caused by the loss of bone homeostasis consecutive to increased osteoclast activity and diminished osteoblast activity. The mevalonate pathway (MVA) is crucial for maintaining this balance since it drives the post-translational prenylation of small guanosine triphosphatases (GTPases) proteins. Farnesyl pyrophosphate synthase (FPPS) plays a crucial role in the MVA pathway. Consequently, in the treatment of bone-related diseases, FPPS is the target of FDA-approved nitrogen-containing bisphosphonates (N-BPs), which have tropism mainly for bone tissue due to their poor penetration in soft tissues. The development of inhibitors targeting the FPPS enzyme has garnered significant interest in recent decades due to FPPS's role in the biosynthesis of cholesterol and other isoprenoids, which are implicated in cancer, bone diseases, and other conditions. In this study, we describe a multidisciplinary approach to designing novel FPPS inhibitors, combining computational modeling, biochemical assays, and biophysical techniques. A series of peptides and phosphopeptides were designed, synthesized, and evaluated for their ability to inhibit FPPS activity. Molecular docking was employed to predict the binding modes of these compounds to FPPS, while Surface Plasmon Resonance (SPR) and Nuclear Magnetic Resonance (NMR) spectroscopy experiments - based on Saturation Transfer Difference (STD) and an enzymatic NMR assay - were used to measure their binding affinities and kinetics. The biological activity of the most promising compounds was further assessed in cellular assays using murine colorectal cancer (CRC) cells. Additionally, genomics and metabolomics profiling allowed to unravel the possible mechanisms underlying the activity of the peptides, confirming their involvement in the modulation of the MVA pathway. Our findings demonstrate that the designed peptides and phosphopeptides exhibit significant inhibitory activity against FPPS and possess antiproliferative effects on CRC cells, suggesting their potential as therapeutic agents for cancer.
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Affiliation(s)
- Verdiana Covelli
- Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano, 49, 80131, Naples, Italy.
| | - Michela Buonocore
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano, SA, Italy; Department of Chemical Sciences and Research Centre on Bioactive Peptides (CIRPEB), University of Naples Federico II, Strada Comunale Cintia, 80126, Naples, Italy.
| | - Manuela Grimaldi
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano, SA, Italy.
| | - Mario Scrima
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano, SA, Italy.
| | - Angelo Santoro
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano, SA, Italy; Department of Pharmacy, Scuola di Specializzazione in Farmacia Ospedaliera, University of Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano, SA, Italy.
| | - Carmen Marino
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano, SA, Italy.
| | - Veronica De Simone
- Department of Chronic Diseases, Metabolism and Ageing (CHROMETA)-Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Herestraat, 49, 3000, Leuven, Belgium.
| | - Lies van Baarle
- Department of Chronic Diseases, Metabolism and Ageing (CHROMETA)-Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Herestraat, 49, 3000, Leuven, Belgium.
| | - Francesca Biscu
- Department of Chronic Diseases, Metabolism and Ageing (CHROMETA)-Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Herestraat, 49, 3000, Leuven, Belgium.
| | - Maria Carmina Scala
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano, SA, Italy.
| | - Marina Sala
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano, SA, Italy.
| | - Gianluca Matteoli
- Department of Chronic Diseases, Metabolism and Ageing (CHROMETA)-Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Herestraat, 49, 3000, Leuven, Belgium.
| | - Anna Maria D'Ursi
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano, SA, Italy.
| | - Manuela Rodriquez
- Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano, 49, 80131, Naples, Italy.
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Maiti S, Maji B, Badwaik H, Pandey MM, Lakra P, Yadav H. Oxidized ionic polysaccharide hydrogels: Review on derived scaffolds characteristics and tissue engineering applications. Int J Biol Macromol 2024; 280:136089. [PMID: 39357721 DOI: 10.1016/j.ijbiomac.2024.136089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 09/11/2024] [Accepted: 09/25/2024] [Indexed: 10/04/2024]
Abstract
Polysaccharide-based hydrogels have gained prominence due to their non-toxicity, biocompatibility, and structural adaptability for constructing tissue engineering scaffolds. Polysaccharide crosslinking is necessary for hydrogel stability in vivo. The periodate oxidation enables the modification of native polysaccharide characteristics for wound healing and tissue engineering applications. It produces dialdehydes, which are used to crosslink biocompatible amine-containing macromolecules such as chitosan, gelatin, adipic acid dihydrazide, silk fibroin, and peptides via imine/hydrazone linkages. Crosslinked oxidized ionic polysaccharide hydrogels have been studied for wound healing, cardiac and liver tissue engineering, bone, cartilage, corneal tissue regeneration, abdominal wall repair, nucleus pulposus regeneration, and osteoarthritis. Several modified hydrogel systems have been synthesized using antibiotics and inorganic substances to improve porosity, mechanical and viscoelastic properties, desired swelling propensity, and antibacterial efficacy. Thus, the injectable hydrogels provide a host-tissue-mimetic environment with high cell adhesion and viability, making them appropriate for scarless wound healing and tissue engineering applications. This review describes the oxidation procedure for alginate, hyaluronic acid, gellan gum, pectin, xanthan gum and chitosan, as well as the characteristics of the resulting materials. Furthermore, a critical review of scientific advances in wound healing and tissue engineering applications has been provided.
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Affiliation(s)
- Sabyasachi Maiti
- Department of Pharmacy, Indira Gandhi National Tribal University, Amarkantak, Madhya Pradesh, India.
| | - Biswajit Maji
- Department of Chemistry, Indira Gandhi National Tribal University, Amarkantak, Madhya Pradesh, India
| | - Hemant Badwaik
- Department of Pharmaceutical Chemistry, Shri Shankaracharya Institute of Pharmaceutical Sciences and Research, Junwani, Bhilai, Chhattisgarh, India
| | - Murali Monohar Pandey
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan, India
| | - Preeti Lakra
- Department of Pharmacy, Indira Gandhi National Tribal University, Amarkantak, Madhya Pradesh, India
| | - Harsh Yadav
- Department of Pharmacy, Indira Gandhi National Tribal University, Amarkantak, Madhya Pradesh, India
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Wang X, Zheng Z, Zhang Y, Sun J, Liu J, Liu Y, Ding G. Application of hydrogel-loaded dental stem cells in the field of tissue regeneration. Hum Cell 2024; 38:2. [PMID: 39436502 DOI: 10.1007/s13577-024-01134-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Accepted: 10/07/2024] [Indexed: 10/23/2024]
Abstract
Mesenchymal stem cells (MSCs) are highly favored in clinical trials due to their unique characteristics, which have isolated from various human tissues. Derived from dental tissues, dental stem cells (DSCs) are particularly notable for their applications in tissue repair and regenerative medicine, attributed to their readily available sources, absence of ethical controversies, and minimal immunogenicity. Hydrogel-loaded stem cell therapy is widespread across a variety of injuries and diseases, and has good repair capabilities for both soft and hard tissues. This review comprehensively summarizes the regenerative and differentiation potential of various DSCs encapsulated in hydrogels across different tissues. In addition, the existing problems and future direction are also addressed. The application of hydrogel-DSCs composite has gained substantial progress in the field of tissue regeneration and need in-depth study in the future.
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Affiliation(s)
- Xiaolan Wang
- School of Stomatology, Shandong Second Medical University, Baotong West Street No.7166, Weifang, Shandong Province, China
| | - Zejun Zheng
- School of Stomatology, Shandong Second Medical University, Baotong West Street No.7166, Weifang, Shandong Province, China
| | - Ying Zhang
- School of Stomatology, Shandong Second Medical University, Baotong West Street No.7166, Weifang, Shandong Province, China
| | - Jinmeng Sun
- School of Stomatology, Shandong Second Medical University, Baotong West Street No.7166, Weifang, Shandong Province, China
| | - Jian Liu
- School of Stomatology, Shandong Second Medical University, Baotong West Street No.7166, Weifang, Shandong Province, China
| | - Yunxia Liu
- School of Stomatology, Shandong Second Medical University, Baotong West Street No.7166, Weifang, Shandong Province, China.
| | - Gang Ding
- School of Stomatology, Shandong Second Medical University, Baotong West Street No.7166, Weifang, Shandong Province, China.
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9
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Liu J, Pei Y, Huang Y, Jiang H, Tadoh MPT, Huang X, Shen J, Zeng X, Zheng B, Pan J, Yang G, Jiang H, Chen L, Zhou Y. A self-assembling bioactive oligopeptide hydrogel for the treatment of edema following prepuce surgery. J Mater Chem B 2024; 12:9357-9363. [PMID: 39175412 DOI: 10.1039/d4tb01456a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/24/2024]
Abstract
Edema of the prepuce is a common clinical complication following circumcision in urology. Nevertheless, the principal method of gauze wrapping in clinical practice has not yet been demonstrated to be an effective solution to the problem of postoperative edema. It is therefore evident that the development of functional dressings for the treatment of post-circumcision edema has considerable potential for both clinical application and translational significance. The objective of this study was to develop a single-component bioactive oligopeptide hydrogel dressing with favorable anti-inflammatory, pro-angiogenesis properties and biosafety for the treatment of edema following prepuce surgery. A hexapeptide (Ac-FFFGHK-OH) hydrogelator was designed and synthesized through the N-terminal modification of a human-derived glycine-histidine-lysine tripeptide (GHK) with an N-acetylated phenylalanine tripeptide (Ac-FFF). The bioactive Ac-FFFGHK-OH hydrogel can be prepared through a facile self-assembly method. Furthermore, a novel experimental animal model of post-circumcision edema in Sprague-Dawley rats was constructed and the in vivo anti-edema effect of the Ac-FFFGHK-OH hydrogel was confirmed. The mechanism of action in relieving edema was also investigated by in vitro cell experiments. This work may inspire alternative thinking for the development of mono-component bioactive oligopeptide hydrogels for the treatment of edema in various diseases.
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Affiliation(s)
- Jianyong Liu
- Joint Centre of Translational Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
| | - Yu Pei
- School of Ophthalmology and Optometry, Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325000, China
| | - Yingying Huang
- College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Haofei Jiang
- Joint Centre of Translational Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
| | - Mike Pleass Tita Tadoh
- Joint Centre of Translational Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
| | - Xixi Huang
- Joint Centre of Translational Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
| | - Jintao Shen
- Joint Centre of Translational Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
| | - Xiaoxi Zeng
- Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Bin Zheng
- Academy of Medical Engineering and Translational Medicine, Tianjin Key Laboratory of Brain Science and Neural Engineering, Tianjin University, Tianjin 300072, China
| | - Jingye Pan
- Joint Centre of Translational Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
| | - Guoqiang Yang
- Joint Centre of Translational Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
- Joint Centre of Translational Medicine, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China
| | - Haihong Jiang
- Joint Centre of Translational Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
| | - Limin Chen
- Joint Centre of Translational Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
- Joint Centre of Translational Medicine, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China
| | - Yunlong Zhou
- Joint Centre of Translational Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
- Joint Centre of Translational Medicine, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China
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10
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Bian Y, Deng M, Liu J, Li J, Zhang Q, Wang Z, Liao L, Miao J, Li R, Zhou X, Hou G. The glycyl-l-histidyl-l-lysine-Cu 2+ tripeptide complex attenuates lung inflammation and fibrosis in silicosis by targeting peroxiredoxin 6. Redox Biol 2024; 75:103237. [PMID: 38879894 PMCID: PMC11228880 DOI: 10.1016/j.redox.2024.103237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 06/06/2024] [Accepted: 06/09/2024] [Indexed: 06/18/2024] Open
Abstract
Silicosis is the most common type of pneumoconiosis, having a high incidence in workers chronically exposed to crystalline silica (CS). No specific medication exists for this condition. GHK, a tripeptide naturally occurring in human blood and urine, has antioxidant effects. We aimed to investigate the therapeutic effect of GHK-Cu on silicosis and its potential underlying molecular mechanism. An experimental silicosis mouse model was established to observe the effects of GHK-Cu on lung inflammation and fibrosis. Moreover, the effects of GHK-Cu on the alveolar macrophages (AM) were examined using the RAW264.7 cell line. Its molecular target, peroxiredoxin 6 (PRDX6), has been identified, and GHK-Cu can bind to PRDX6, thus attenuating lung inflammation and fibrosis in silicosis mice without significant systemic toxicity. These effects were partly related to the inhibition of the CS-induced oxidative stress in AM induced by GHK-Cu. Thus, our results suggest that GHK-Cu acts as a potential drug by attenuating alveolar macrophage oxidative stress. This, in turn, attenuates the progression of pulmonary inflammation and fibrosis, which provides a reference for the treatment of silicosis.
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Affiliation(s)
- Yiding Bian
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China; China-Japan Friendship Hospital (Institution of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Mingming Deng
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Jia Liu
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Jiaye Li
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Qin Zhang
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Zilin Wang
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China; China-Japan Friendship Hospital (Institution of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Liwei Liao
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Jinrui Miao
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Ruixia Li
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Xiaoming Zhou
- Department of Pulmonary and Critical Care Medicine, Disease, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
| | - Gang Hou
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
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11
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Lin J, Jia S, Cao F, Huang J, Chen J, Wang J, Liu P, Zeng H, Zhang X, Cui W. Research Progress on Injectable Microspheres as New Strategies for the Treatment of Osteoarthritis Through Promotion of Cartilage Repair. ADVANCED FUNCTIONAL MATERIALS 2024; 34. [DOI: 10.1002/adfm.202400585] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Indexed: 07/07/2024]
Abstract
AbstractOsteoarthritis (OA) is a degenerative disease caused by a variety of factors with joint pain as the main symptom, including fibrosis, chapping, ulcers, and loss of cartilage. Traditional treatment can only delay the progression of OA, and classical delivery system have many side effects. In recent years, microspheres have shown great application prospects in the field of OA treatment. Microspheres can support cells, reproduce the natural tissue microenvironment in vitro and in vivo, and are an efficient delivery system for the release of drugs or biological agents, which can promote cell proliferation, migration, and differentiation. Thus, they have been widely used in cartilage repair and regeneration. In this review, preparation processes, basic materials, and functional characteristics of various microspheres commonly used in OA treatment are systematically reviewed. Then it is introduced surface modification strategies that can improve the biological properties of microspheres and discussed a series of applications of microsphere functionalized scaffolds in OA treatment. Finally, based on bibliometrics research, the research development, future potential, and possible research hotspots of microspheres in the field of OA therapy is systematically and dynamically evaluated. The comprehensive and systematic review will bring new understanding to the field of microsphere treatment of OA.
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Affiliation(s)
- Jianjing Lin
- Department of Sports Medicine and Rehabilitation Peking University Shenzhen Hospital Shenzhen Guangdong 518036 P. R. China
| | - Shicheng Jia
- Department of Sports Medicine and Rehabilitation Peking University Shenzhen Hospital Shenzhen Guangdong 518036 P. R. China
- Shantou University Medical College Shantou Guangdong 515041 P. R. China
| | - Fuyang Cao
- Department of Orthopedics Second Hospital of Shanxi Medical University Taiyuan Shanxi 030001 P. R. China
| | - Jingtao Huang
- Shantou University Medical College Shantou Guangdong 515041 P. R. China
| | - Jiayou Chen
- Department of Sports Medicine and Rehabilitation Peking University Shenzhen Hospital Shenzhen Guangdong 518036 P. R. China
- Shantou University Medical College Shantou Guangdong 515041 P. R. China
| | - Juan Wang
- Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 P. R. China
| | - Peng Liu
- National & Local Joint Engineering Research Center of Orthopaedic Biomaterials Peking University Shenzhen Hospital Shenzhen Guangdong 518036 P. R. China
| | - Hui Zeng
- Shenzhen Second People's Hospital (First Affiliated Hospital of Shenzhen University) Shenzhen Guangdong 518035 China
| | - Xintao Zhang
- Department of Sports Medicine and Rehabilitation Peking University Shenzhen Hospital Shenzhen Guangdong 518036 P. R. China
| | - Wenguo Cui
- Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 P. R. China
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12
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Luo Y, Gao Y. Potential Role of Hydrogels in Stem Cell Culture and Hepatocyte Differentiation. NANO BIOMEDICINE AND ENGINEERING 2024; 16:188-202. [DOI: 10.26599/nbe.2024.9290055] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2025]
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13
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Ma X, Zhao Y, Jiang X, Fan M, He C, Qi H, Wang Y, Wang D, Ke Y, Xu H, Chen C, Wang J. Controlled Assembly and Disassembly of Higher-Order Peptide Nanotubes. ACS APPLIED MATERIALS & INTERFACES 2024; 16:9787-9798. [PMID: 38350068 DOI: 10.1021/acsami.3c17509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/15/2024]
Abstract
The controlled peptide self-assembly and disassembly are not only implicated in many cellular processes but also possess huge application potential in a wide range of biotechnology and biomedicine. β-sheet peptide assemblies possess high kinetic stability, so it is usually hard to disassemble them rapidly. Here, we reported that both the self-assembly and disassembly of a designed short β-sheet peptide IIIGGHK could be well harnessed through the variations of concentration, pH, and mechanical stirring. Microscopic imaging, neutron scattering, and infrared spectroscopy were used to track the assembly and disassembly processes upon these stimuli, especially the interconversion between thin, left-handed protofibrils and higher-order nanotubes with superstructural right-handedness. The underlying rationale for these controlled disassembly processes mainly lies in the fact that the specific His-His interactions between protofibrils were responsive to these stimuli. By taking advantage of the peptide self-assembly and disassembly, the encapsulation of the hydrophobic drug curcumin and its rapid release upon stimuli were achieved. Additionally, the peptide hydrogels facilitated the differentiation of neural cells while maintaining low cell cytotoxicity. We believe that such dynamic and reversible structural transformation in this work provides a distinctive paradigm for controlling the peptide self-assembly and disassembly, thus laying a foundation for practical applications of peptide assemblies.
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Affiliation(s)
- Xiaoyue Ma
- State Key Laboratory of Heavy Oil Processing and Department of Biological and Energy Chemical Engineering, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China
| | - Yurong Zhao
- State Key Laboratory of Heavy Oil Processing and Department of Biological and Energy Chemical Engineering, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China
| | - Xiaofang Jiang
- State Key Laboratory of Heavy Oil Processing and Department of Biological and Energy Chemical Engineering, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China
| | - Mengchen Fan
- State Key Laboratory of Heavy Oil Processing and Department of Biological and Energy Chemical Engineering, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China
| | - Chunyong He
- Dongguan Neutron Source Science Center, Dalang, Dongguan 523803, China
- Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, China
| | - Hao Qi
- State Key Laboratory of Heavy Oil Processing and Department of Biological and Energy Chemical Engineering, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China
| | - Yan Wang
- State Key Laboratory of Heavy Oil Processing and Department of Biological and Energy Chemical Engineering, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China
| | - Dong Wang
- State Key Laboratory of Heavy Oil Processing and Department of Biological and Energy Chemical Engineering, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China
| | - Yubin Ke
- Dongguan Neutron Source Science Center, Dalang, Dongguan 523803, China
- Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, China
| | - Hai Xu
- State Key Laboratory of Heavy Oil Processing and Department of Biological and Energy Chemical Engineering, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China
| | - Cuixia Chen
- State Key Laboratory of Heavy Oil Processing and Department of Biological and Energy Chemical Engineering, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China
| | - Jiqian Wang
- State Key Laboratory of Heavy Oil Processing and Department of Biological and Energy Chemical Engineering, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China
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14
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Lee S, Lee SM, Lee SH, Choi WK, Park SJ, Kim DY, Oh SW, Oh J, Cho JY, Lee J, Chien PN, Nam SY, Heo CY, Lee YS, Kwak EA, Chung WJ. In situ photo-crosslinkable hyaluronic acid-based hydrogel embedded with GHK peptide nanofibers for bioactive wound healing. Acta Biomater 2023; 172:159-174. [PMID: 37832839 DOI: 10.1016/j.actbio.2023.10.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 09/18/2023] [Accepted: 10/06/2023] [Indexed: 10/15/2023]
Abstract
A versatile hydrogel was developed for enhancing bioactive wound healing by introducing the amphiphilic GHK peptide (GHK-C16) into a photo-crosslinkable tyramine-modified hyaluronic acid (HA-Ty). GHK-C16 self-assembled into GHK nanofibers (GHK NF) in HA-Ty solution, which underwent in situ gelation after the wound area was filled with precursor solution. Blue light irradiation (460-490 nm), with riboflavin phosphate as a photoinitiator, was used to trigger crosslinking, which enhanced the stability of the highly degradable hyaluronic acid and enabled sustained release of the nanostructured GHK derivatives. The hydrogels provided a microenvironment that promoted the proliferation of dermal fibroblasts and the activation of cytokines, leading to reduced inflammation and increased collagen expression during wound healing. The complexation of Cu2+ into GHK nanofibers resulted in superior wound healing capabilities compared with non-lipidated GHK peptide with a comparable level of growth factor (EGF). Additionally, nanostructured Cu-GHK improved angiogenesis through vascular endothelial growth factor (VEGF) activation, which exerted a synergistic therapeutic effect. Furthermore, in vivo wound healing experiments revealed that the Cu-GHK NF/HA-Ty hydrogel accelerated wound healing through densely packed remodeled collagen in the dermis and promoting the growth of denser fibroblasts. HA-Ty hydrogels incorporating GHK NF also possessed improved mechanical properties and a faster wound healing rate, making them suitable for advanced bioactive wound healing applications. STATEMENT OF SIGNIFICANCE: By combining photo-crosslinkable tyramine-modified hyaluronic acid with self-assembled Cu-GHK-C16 peptide nanofibers (Cu-GHK NF), the Cu-GHK NF/HA-Ty hydrogel offers remarkable advantages over conventional non-structured Cu-GHK for wound healing. It enhances cell proliferation, migration, and collagen remodeling-critical factors in tissue regeneration. The incorporation of GHK nanofibers complexed with copper ions imparts potent anti-inflammatory effects, promoting cytokine activation and angiogenesis during wound healing. The Cu-GHK NF/hydrogel's unique properties, including in situ photo-crosslinking, ensure high customization and potency in tissue regeneration, providing a cost-effective alternative to growth factors. In vivo experiments further validate its efficacy, demonstrating significant wound closure, collagen remodeling, and increased fibroblast density. Overall, the Cu-GHK NF/HA-Ty hydrogel represents an advanced therapeutic option for wound healing applications.
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Affiliation(s)
- Seohui Lee
- Department of Integrative Biotechnology, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea
| | - Sang Min Lee
- Department of Integrative Biotechnology, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea
| | - Sang Hyun Lee
- Department of Integrative Biotechnology, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea
| | - Woong-Ku Choi
- Department of Integrative Biotechnology, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea
| | - Sung-Jun Park
- School of Chemical and Biological Engineering, Seoul National University, 151-744, Seoul, Republic of Korea
| | - Do Yeon Kim
- Department of Integrative Biotechnology, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea
| | - Sae Woong Oh
- Department of Integrative Biotechnology, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea
| | - Jieun Oh
- Department of Integrative Biotechnology, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea
| | - Jae Youl Cho
- Department of Integrative Biotechnology, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea
| | - Jongsung Lee
- Department of Integrative Biotechnology, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea
| | - Pham Ngoc Chien
- Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Sun Young Nam
- Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Chan Yeong Heo
- Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; Department of Medical Device Development, College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Yoon-Sik Lee
- School of Chemical and Biological Engineering, Seoul National University, 151-744, Seoul, Republic of Korea
| | - Eun-A Kwak
- Research Institute of Biomolecule Control, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea.
| | - Woo-Jae Chung
- Department of Integrative Biotechnology, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea; Research Institute of Biomolecule Control, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea; Center for Biologics, Sungkyunkwan University, Suwon 16419, Republic of Korea.
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15
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Wang J, Liu S, Huang J, Ren K, Zhu Y, Yang S. Alginate: Microbial production, functionalization, and biomedical applications. Int J Biol Macromol 2023; 242:125048. [PMID: 37236570 DOI: 10.1016/j.ijbiomac.2023.125048] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 04/21/2023] [Accepted: 05/22/2023] [Indexed: 05/28/2023]
Abstract
Alginates are natural polysaccharides widely participating in food, pharmaceutical, and environmental applications due to their excellent gelling capacity. Their excellent biocompatibility and biodegradability further extend their application to biomedical fields. The low consistency in molecular weight and composition of algae-based alginates may limit their performance in advanced biomedical applications. It makes microbial alginate production more attractive due to its potential for customizing alginate molecules with stable characteristics. Production costs remain the primary factor limiting the commercialization of microbial alginates. However, carbon-rich wastes from sugar, dairy, and biodiesel industries may serve as potential substitutes for pure sugars for microbial alginate production to reduce substrate costs. Fermentation parameter control and genetic engineering strategies may further improve the production efficiency and customize the molecular composition of microbial alginates. To meet the specific needs of biomedical applications, alginates may need functionalization, such as functional group modifications and crosslinking treatments, to achieve enhanced mechanical properties and biochemical activities. The development of alginate-based composites incorporated with other polysaccharides, gelatin, and bioactive factors can integrate the advantages of each component to meet multiple requirements in wound healing, drug delivery, and tissue engineering applications. This review provided a comprehensive insight into the sustainable production of high-value microbial alginates. It also discussed recent advances in alginate modification strategies and alginate-based composites for representative biomedical applications.
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Affiliation(s)
- Jianfei Wang
- Department of Chemical Engineering, SUNY College of Environmental Science and Forestry, Syracuse, NY 13210, United States
| | - Shijie Liu
- Department of Chemical Engineering, SUNY College of Environmental Science and Forestry, Syracuse, NY 13210, United States.
| | - Jiaqi Huang
- Department of Chemical Engineering, SUNY College of Environmental Science and Forestry, Syracuse, NY 13210, United States; The Center for Biotechnology & Interdisciplinary Studies (CBIS) at Rensselaer Polytechnic Institute, Troy, NY 12180, United States
| | - Kexin Ren
- Department of Chemical Engineering, SUNY College of Environmental Science and Forestry, Syracuse, NY 13210, United States
| | - Yan Zhu
- Department of Chemical Engineering, SUNY College of Environmental Science and Forestry, Syracuse, NY 13210, United States
| | - Siying Yang
- Department of Chemical Engineering, SUNY College of Environmental Science and Forestry, Syracuse, NY 13210, United States
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16
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Zhang Q, Liu J, Deng MM, Tong R, Hou G. Relief of ovalbumin-induced airway remodeling by the glycyl-l-histidyl-l-lysine-Cu 2+ tripeptide complex via activation of SIRT1 in airway epithelial cells. Biomed Pharmacother 2023; 164:114936. [PMID: 37257226 DOI: 10.1016/j.biopha.2023.114936] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 05/13/2023] [Accepted: 05/22/2023] [Indexed: 06/02/2023] Open
Abstract
Fixed airflow limitation (FAO), prevalent in patients with severe or difficult-to-treat asthma, is mainly caused by airway remodeling. Airway remodeling is initiated by inflammation and involves subsequent pathological changes. Glycyl-l-histidyl-l-lysine (GHK) is a matrikine with anti-inflammatory and antioxidant effects, naturally existing in human tissue. At present, the GHK level in human plasma and whether it is related to airway remodeling of asthma remain unclear. This study was conducted to determine how GHK is involved in airway remodeling in asthma. Our result showed that the plasma GHK levels of patients with asthma were significantly lower than those of age-matched healthy controls. In asthma patients, plasma GHK levels display a moderate correlation with FEF25-75%, and patients with FAO had significantly lower GHK levels. Ovalbumin-induced mice of asthma model treated with PBS or GHK-Cu (a form of GHK with higher bioavailability) were used to evaluate the effect of exogenous GHK supplement on airway remodeling. GHK-Cu administration alleviated airway remodeling, as reflected by decreased peribronchial collagen deposition and airway mucus secretion, and suppressed epithelial-mesenchymal transition. The therapeutical effect related to decreased TGF-β1 level. Successively, network pharmacology and the validation data of experiments in vivo and vitro demonstrated that GHK-Cu decreased TGF-β1 level by increasing SIRT1 expression and activating SIRT1 deacetylation in airway epithelial cells, thereby alleviating airway remodeling. Collectively, decreased plasma GHK levels were related to FAO in asthma patients. Through the direct binding and activation of SIRT1, exogenous GHK-Cu administration alleviated airway remodeling in asthmatic mice.
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Affiliation(s)
- Qin Zhang
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, Beijing 100029, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing 100029, China; National Clinical Research Center for Respiratory Diseases, Beijing 100029, China; National Center for Respiratory Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, Beijing 100029, China; Institute of Respiratory Disease, the First Hospital of China Medical University, No. 155, Nanjing Street, Heping District, 110000 Shenyang, China
| | - Jia Liu
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 555, Zuchongzhi Road, Pudong District, Shanghai 201203, China
| | - Ming-Ming Deng
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, Beijing 100029, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing 100029, China; National Clinical Research Center for Respiratory Diseases, Beijing 100029, China; National Center for Respiratory Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, Beijing 100029, China
| | - Run Tong
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, Beijing 100029, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing 100029, China; National Clinical Research Center for Respiratory Diseases, Beijing 100029, China; National Center for Respiratory Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, Beijing 100029, China
| | - Gang Hou
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, Beijing 100029, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing 100029, China; National Clinical Research Center for Respiratory Diseases, Beijing 100029, China; National Center for Respiratory Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, Beijing 100029, China.
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17
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Zhou Y, Ping X, Guo Y, Heng BC, Wang Y, Meng Y, Jiang S, Wei Y, Lai B, Zhang X, Deng X. Assessing Biomaterial-Induced Stem Cell Lineage Fate by Machine Learning-Based Artificial Intelligence. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2023; 35:e2210637. [PMID: 36756993 DOI: 10.1002/adma.202210637] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 02/02/2023] [Indexed: 05/12/2023]
Abstract
Current functional assessment of biomaterial-induced stem cell lineage fate in vitro mainly relies on biomarker-dependent methods with limited accuracy and efficiency. Here a "Mesenchymal stem cell Differentiation Prediction (MeD-P)" framework for biomaterial-induced cell lineage fate prediction is reported. MeD-P contains a cell-type-specific gene expression profile as a reference by integrating public RNA-seq data related to tri-lineage differentiation (osteogenesis, chondrogenesis, and adipogenesis) of human mesenchymal stem cells (hMSCs) and a predictive model for classifying hMSCs differentiation lineages using the k-nearest neighbors (kNN) strategy. It is shown that MeD-P exhibits an overall accuracy of 90.63% on testing datasets, which is significantly higher than the model constructed based on canonical marker genes (80.21%). Moreover, evaluations of multiple biomaterials show that MeD-P provides accurate prediction of lineage fate on different types of biomaterials as early as the first week of hMSCs culture. In summary, it is demonstrated that MeD-P is an efficient and accurate strategy for stem cell lineage fate prediction and preliminary biomaterial functional evaluation.
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Affiliation(s)
- Yingying Zhou
- Department of Dental Materials and Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Xianfeng Ping
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
- Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Yusi Guo
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Boon Chin Heng
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
- Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Yijun Wang
- Department of Dental Materials and Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Yanze Meng
- Department of Dental Materials and Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Shengjie Jiang
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Yan Wei
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Binbin Lai
- Biomedical Engineering Department, Peking University, Beijing, 100191, P. R. China
- Department of Dermatology and Venereology, Peking University First Hospital, Beijing, 100034, P. R. China
| | - Xuehui Zhang
- Department of Dental Materials and Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Xuliang Deng
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
- Biomedical Engineering Department, Peking University, Beijing, 100191, P. R. China
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18
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Sugimoto K, Zhou Y, Galindo TGP, Kimura R, Tagaya M. Investigation of Surface Layers on Biological and Synthetic Hydroxyapatites Based on Bone Mineralization Process. Biomimetics (Basel) 2023; 8:biomimetics8020184. [PMID: 37218770 DOI: 10.3390/biomimetics8020184] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 04/21/2023] [Accepted: 04/25/2023] [Indexed: 05/24/2023] Open
Abstract
In this review, the current status of the influence of added ions (i.e., SiO44-, CO32-, etc.) and surface states (i.e., hydrated and non-apatite layers) on the biocompatibility nature of hydroxyapatite (HA, Ca10(PO4)6(OH)2) is discussed. It is well known that HA is a type of calcium phosphate with high biocompatibility that is present in biological hard tissues such as bones and enamel. This biomedical material has been extensively studied due to its osteogenic properties. The chemical composition and crystalline structure of HA change depending on the synthetic method and the addition of other ions, thereby affecting the surface properties related to biocompatibility. This review illustrates the structural and surface properties of HA substituted with ions such as silicate, carbonate, and other elemental ions. The importance of the surface characteristics of HA and its components, the hydration layers, and the non-apatite layers for the effective control of biomedical function, as well as their relationship at the interface to improve biocompatibility, has been highlighted. Since the interfacial properties will affect protein adsorption and cell adhesion, the analysis of their properties may provide ideas for effective bone formation and regeneration mechanisms.
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Affiliation(s)
- Kazuto Sugimoto
- Department of Materials Science and Technology, Nagaoka University of Technology, Kamitomioka 1603-1, Nagaoka, Niigata 940-2188, Japan
| | - Yanni Zhou
- Department of Materials Science and Bioengineering, Nagaoka University of Technology, Kamitomioka 1603-1, Nagaoka, Niigata 940-2188, Japan
| | | | - Reo Kimura
- Department of Materials Science and Bioengineering, Nagaoka University of Technology, Kamitomioka 1603-1, Nagaoka, Niigata 940-2188, Japan
| | - Motohiro Tagaya
- Department of Materials Science and Bioengineering, Nagaoka University of Technology, Kamitomioka 1603-1, Nagaoka, Niigata 940-2188, Japan
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19
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Qian W, Gong G, Su H, Zhao Y, Fu W, Wang Y, Ji W, Sun X, Zhang B, Ma L, Li J, Zhang X, Li S, Sheng E, Lu Y, Zhu D. Hepar-on-a-sensor-platform with hybridization chain reaction amplification strategy to intuitively monitor the hepatoxicity of natural compounds. Acta Biomater 2023; 160:73-86. [PMID: 36804823 DOI: 10.1016/j.actbio.2023.02.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 02/09/2023] [Accepted: 02/09/2023] [Indexed: 02/17/2023]
Abstract
The irrational use of natural compounds in the treatment of diseases can lead to serious side effects, especially hepatoxicity, and its toxic effects are usually cumulative and imperceptible. Therefore, an accurate sensing platform is urgently needed to monitor the hepatotoxicity of natural compounds. Here, we deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and a thorough validation was adopted to evaluate the bioprinted hepatic constructs. The engineered hepar-platform was then employed to access its biological response toward Emodin (EM) and Triptolide (TP), two typical hepatotoxic natural compounds. Subsequently, we integrated it with a robust fluorescent sensor based on hybridization chain reaction amplification strategy (HCR) to monitor the early hepatotoxic biomarker - glutathione-S-transferase-alpha (GST-α) secreted by this 3D constructs. Our study was the first attempt to construct an accurate hepar-on-a-sensor platform that could effectively detect GST-α for monitoring the hepatoxic effects of natural compounds. The limit of detection of the platform was 0.3 ng ml-1 and the accuracy of this platform was verified by enzyme linked immunosorbent assay. Furthermore, the variation of GST-α induced by EM and TP was consistent with hepatotoxicity studies, thus providing an important application value for evaluating the hepatotoxicity of natural compounds. STATEMENT OF SIGNIFICANCE: 1. We deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and elucidated the essential reasons why hybrid bioinks more suitable for 3D extrusion from biomaterials itself. Also, a thorough validation associated with a series of important proteins and genes involved in liver cell metabolism was adopted to evaluate the bioprinted hepatic constructs accurately 2. Glutathione-S-transferase-alpha is a soluble trace biomarker for acute hepatotoxic injury, the hepatotoxic effects of natural compounds on the secretion of GST-α has not been reported to date. We integrated our 3D hepar-platform with recognition molecules-aptamers and HCR amplification strategy to monitor the variation of GST-α, aiming at developing a robust and stable fluorescent biosensing platform to monitor the hepatoxicity of natural compounds.
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Affiliation(s)
- Wenhui Qian
- School of Pharmacy, Nanjing University of Chinese Medicine,Nanjing, Jiangsu 210023, PR China; Department of Pharmacy, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, PR China
| | - Guangming Gong
- Department of Pharmacy, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, PR China
| | - Hua Su
- Department of Pharmacy, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, PR China
| | - Yang Zhao
- Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China
| | - Wenjuan Fu
- School of Pharmacy, Nanjing University of Chinese Medicine,Nanjing, Jiangsu 210023, PR China
| | - Yuting Wang
- School of Pharmacy, Nanjing University of Chinese Medicine,Nanjing, Jiangsu 210023, PR China
| | - Wenwen Ji
- School of Pharmacy, Nanjing University of Chinese Medicine,Nanjing, Jiangsu 210023, PR China
| | - Xuetong Sun
- School of Pharmacy, Nanjing University of Chinese Medicine,Nanjing, Jiangsu 210023, PR China
| | - Bei Zhang
- School of Pharmacy, Nanjing University of Chinese Medicine,Nanjing, Jiangsu 210023, PR China
| | - Lijuan Ma
- School of Pharmacy, Nanjing University of Chinese Medicine,Nanjing, Jiangsu 210023, PR China
| | - Jianting Li
- School of Pharmacy, Nanjing University of Chinese Medicine,Nanjing, Jiangsu 210023, PR China
| | - Xiangying Zhang
- School of Pharmacy, Nanjing University of Chinese Medicine,Nanjing, Jiangsu 210023, PR China
| | - Su Li
- School of Pharmacy, Nanjing University of Chinese Medicine,Nanjing, Jiangsu 210023, PR China
| | - Enze Sheng
- School of Pharmacy, Nanjing University of Chinese Medicine,Nanjing, Jiangsu 210023, PR China
| | - Yin Lu
- School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
| | - Dong Zhu
- School of Pharmacy, Nanjing University of Chinese Medicine,Nanjing, Jiangsu 210023, PR China.
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20
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Abdal Dayem A, Lee SB, Lim KM, Kim A, Shin HJ, Vellingiri B, Kim YB, Cho SG. Bioactive peptides for boosting stem cell culture platform: Methods and applications. Biomed Pharmacother 2023; 160:114376. [PMID: 36764131 DOI: 10.1016/j.biopha.2023.114376] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Revised: 02/02/2023] [Accepted: 02/03/2023] [Indexed: 02/10/2023] Open
Abstract
Peptides, short protein fragments, can emulate the functions of their full-length native counterparts. Peptides are considered potent recombinant protein alternatives due to their specificity, high stability, low production cost, and ability to be easily tailored and immobilized. Stem cell proliferation and differentiation processes are orchestrated by an intricate interaction between numerous growth factors and proteins and their target receptors and ligands. Various growth factors, functional proteins, and cellular matrix-derived peptides efficiently enhance stem cell adhesion, proliferation, and directed differentiation. For that, peptides can be immobilized on a culture plate or conjugated to scaffolds, such as hydrogels or synthetic matrices. In this review, we assess the applications of a variety of peptides in stem cell adhesion, culture, organoid assembly, proliferation, and differentiation, describing the shortcomings of recombinant proteins and their full-length counterparts. Furthermore, we discuss the challenges of peptide applications in stem cell culture and materials design, as well as provide a brief outlook on future directions to advance peptide applications in boosting stem cell quality and scalability for clinical applications in tissue regeneration.
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Affiliation(s)
- Ahmed Abdal Dayem
- Department of Stem Cell and Regenerative Biotechnology, KU Convergence Science and Technology Institute, Konkuk University, Seoul 05029, Republic of Korea
| | - Soo Bin Lee
- Department of Stem Cell and Regenerative Biotechnology, KU Convergence Science and Technology Institute, Konkuk University, Seoul 05029, Republic of Korea
| | - Kyung Min Lim
- Department of Stem Cell and Regenerative Biotechnology, KU Convergence Science and Technology Institute, Konkuk University, Seoul 05029, Republic of Korea; R&D Team, StemExOne co., ltd. 303, Life Science Bldg, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Aram Kim
- Department of Urology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05029, Republic of Korea; R&D Team, StemExOne co., ltd. 303, Life Science Bldg, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Hyun Jin Shin
- Department of Ophthalmology, Research Institute of Medical Science, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05029, Republic of Korea; R&D Team, StemExOne co., ltd. 303, Life Science Bldg, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Balachandar Vellingiri
- Stem cell and Regenerative Medicine/Translational Research, Department of Zoology, School of Basic Sciences, Central University of Punjab (CUPB), Bathinda 151401, Punjab, India
| | - Young Bong Kim
- Department of Biomedical Science & Engineering, KU Convergence Science and Technology Institute, Konkuk University, Seoul 05029, Republic of Korea
| | - Ssang-Goo Cho
- Department of Stem Cell and Regenerative Biotechnology, KU Convergence Science and Technology Institute, Konkuk University, Seoul 05029, Republic of Korea; R&D Team, StemExOne co., ltd. 303, Life Science Bldg, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea.
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21
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Sung TC, Wang T, Liu Q, Ling QD, Subbiah SK, Renuka RR, Hsu ST, Umezawa A, Higuchi A. Cell-binding peptides on the material surface guide stem cell fate of adhesion, proliferation and differentiation. J Mater Chem B 2023; 11:1389-1415. [PMID: 36727243 DOI: 10.1039/d2tb02601e] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Human cells, especially stem cells, need to communicate and interact with extracellular matrix (ECM) proteins, which not only serve as structural components but also guide and support cell fate and properties such as cell adhesion, proliferation, survival and differentiation. The binding of the cells with ECM proteins or ECM-derived peptides via cell adhesion receptors such as integrins activates several signaling pathways that determine the cell fate, morphological change, proliferation and differentiation. The development of synthetic ECM protein-derived peptides that mimic the biological and biochemical functions of natural ECM proteins will benefit academic and clinical application. Peptides derived from or inspired by specific ECM proteins can act as agonists of each ECM protein receptor. Given that most ECM proteins function in cell adhesion via integrin receptors, many peptides have been developed that bind to specific integrin receptors. In this review, we discuss the peptide sequence, immobilization design, reaction method, and functions of several ECM protein-derived peptides. Various peptide sequences derived from mainly ECM proteins, which are used for coating or grafting on dishes, scaffolds, hydrogels, implants or nanofibers, have been developed to improve the adhesion, proliferation or differentiation of stem cells and to culture differentiated cells. This review article will help to inform the optimal choice of ECM protein-derived peptides for the development of scaffolds, implants, hydrogels, nanofibers and 2D cell culture dishes to regulate the proliferation and direct the differentiation of stem cells into specific lineages.
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Affiliation(s)
- Tzu-Cheng Sung
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, No. 270, Xueyuan Road, Wenzhou, Zhejiang, 325027, China.
| | - Ting Wang
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, No. 270, Xueyuan Road, Wenzhou, Zhejiang, 325027, China.
| | - Qian Liu
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, No. 270, Xueyuan Road, Wenzhou, Zhejiang, 325027, China.
| | - Qing-Dong Ling
- Cathay Medical Research Institute, Cathay General Hospital, No. 32, Ln 160, Jian-Cheng Road, Hsi-Chi City, Taipei 221, Taiwan
| | - Suresh Kumar Subbiah
- Centre for Materials Engineering and Regenerative Medicine, Bharath Institute of Higher Education and Research, 173, Agaram Road, Tambaram East, Chennai-73, 600078, India
| | - Remya Rajan Renuka
- Centre for Materials Engineering and Regenerative Medicine, Bharath Institute of Higher Education and Research, 173, Agaram Road, Tambaram East, Chennai-73, 600078, India
| | - Shih-Tien Hsu
- Department of Internal Medicine, Taiwan Landseed Hospital, 77 Kuangtai Road, Pingjen City, Tao-Yuan County 32405, Taiwan
| | - Akihiro Umezawa
- Department of Reproduction, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan
| | - Akon Higuchi
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, No. 270, Xueyuan Road, Wenzhou, Zhejiang, 325027, China. .,Department of Chemical and Materials Engineering, National Central University, No. 300, Jhongda RD., Jhongli, Taoyuan, 32001, Taiwan. .,R & D Center for Membrane Technology, Chung Yuan Christian University, 200 Chung-Bei Rd., Jhongli, Taoyuan 320, Taiwan
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22
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Qiu G, Huang M, Liu J, Ma T, Schneider A, Oates TW, Lynch CD, Weir MD, Zhang K, Zhao L, Xu HHK. Human periodontal ligament stem cell encapsulation in alginate-fibrin-platelet lysate microbeads for dental and craniofacial regeneration. J Dent 2022; 124:104219. [PMID: 35817226 DOI: 10.1016/j.jdent.2022.104219] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 05/20/2022] [Accepted: 05/25/2022] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVE Tissue engineering is promising for dental and craniofacial regeneration. The objectives of this study were to develop a novel xeno-free alginate-fibrin-platelet lysate hydrogel with human periodontal ligament stem cells (hPDLSCs) for dental regeneration, and to investigate the proliferation and osteogenic differentiation of hPDLSCs using hPL as a cell culture nutrient supplement. METHODS hPDLSCs were cultured with Dulbecco's modified eagle medium (DMEM), DMEM + 10% fetal bovine serum (FBS), and DMEM + hPL (1%, 2.5%, and 5%). hPDLSCs were encapsulated in alginate-fibrin microbeads (Alg+Fib), alginate-hPL microbeads (Alg+hPL), or alginate-fibrin-hPL microbeads (Alg+Fib+hPL). hPDLSCs encapsulated in alginate microbeads were induced with an osteogenic medium containing hPL or FBS. Quantitative real-time polymerase chain reaction (qRT-PCR), alkaline phosphatase (ALP) activity, ALP staining, and alizarin red (ARS) staining was investigated. RESULTS hPDLSCs were released faster from Alg+Fib+hPL than from Alg+hPL. At 14 days, ALP activity was 44.1 ± 7.61 mU/mg for Alg+Fib+hPL group, higher than 28.07 ± 5.15 mU/mg of Alg+Fib (p<0.05) and 0.95 ± 0.2 mU/mg of control (p<0.01). At 7 days, osteogenic genes (ALP, RUNX2, COL1, and OPN) in Alg+Fib+hPL and Alg+Fib were 3-10 folds those of control. At 21 days, the hPDLSC-synthesized bone mineral amount in Alg+Fib+hPL and Alg+Fib was 7.5 folds and 4.3 folds that of control group, respectively. CONCLUSIONS The 2.5% hPL was determined to be optimal for hPDLSCs. Adding hPL into alginate hydrogel improved the viability of the hPDLSCs encapsulated in the microbeads. The hPL-based medium enhanced the osteogenic differentiation of hPDLSCs in Alg+Fib+hPL construct, showing a promising xeno-free approach for delivering hPDLSCs to enhance dental, craniofacial and orthopedic regenerations.
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Affiliation(s)
- Gengtao Qiu
- Department of Trauma and Joint Surgery, Shunde Hospital, Southern Medical University, Foshan, Guangdong, China; Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, United States of America; Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Mingguang Huang
- Department of Trauma and Joint Surgery, Shunde Hospital, Southern Medical University, Foshan, Guangdong, China
| | - Jin Liu
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, United States of America; Key Laboratory of Shannxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shannxi, China
| | - Tao Ma
- Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, United States of America
| | - Abraham Schneider
- Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, United States of America; Member, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, United States of America
| | - Thomas W Oates
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, United States of America
| | - Christopher D Lynch
- Restorative Dentistry, University Dental School and Hospital, University College Cork, Wilton, Cork, Ireland
| | - Michael D Weir
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, United States of America.
| | - Ke Zhang
- Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China.
| | - Liang Zhao
- Department of Trauma and Joint Surgery, Shunde Hospital, Southern Medical University, Foshan, Guangdong, China; Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
| | - Hockin H K Xu
- Department of Trauma and Joint Surgery, Shunde Hospital, Southern Medical University, Foshan, Guangdong, China; Member, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, United States of America; Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, United States of America
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23
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Endo- and Exometabolome Crosstalk in Mesenchymal Stem Cells Undergoing Osteogenic Differentiation. Cells 2022; 11:cells11081257. [PMID: 35455937 PMCID: PMC9024772 DOI: 10.3390/cells11081257] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 04/03/2022] [Accepted: 04/05/2022] [Indexed: 02/04/2023] Open
Abstract
This paper describes, for the first time to our knowledge, a lipidome and exometabolome characterization of osteogenic differentiation for human adipose tissue stem cells (hAMSCs) using nuclear magnetic resonance (NMR) spectroscopy. The holistic nature of NMR enabled the time-course evolution of cholesterol, mono- and polyunsaturated fatty acids (including ω-6 and ω-3 fatty acids), several phospholipids (phosphatidylcholine, phosphatidylethanolamine, sphingomyelins, and plasmalogens), and mono- and triglycerides to be followed. Lipid changes occurred almost exclusively between days 1 and 7, followed by a tendency for lipidome stabilization after day 7. On average, phospholipids and longer and more unsaturated fatty acids increased up to day 7, probably related to plasma membrane fluidity. Articulation of lipidome changes with previously reported polar endometabolome profiling and with exometabolome changes reported here in the same cells, enabled important correlations to be established during hAMSC osteogenic differentiation. Our results supported hypotheses related to the dynamics of membrane remodelling, anti-oxidative mechanisms, protein synthesis, and energy metabolism. Importantly, the observation of specific up-taken or excreted metabolites paves the way for the identification of potential osteoinductive metabolites useful for optimized osteogenic protocols.
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24
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Bispo DC, Jesus CSH, Correia M, Ferreira F, Bonifazio G, Goodfellow BJ, Oliveira MB, Mano JF, Gil AM. NMR Metabolomics Assessment of Osteogenic Differentiation of Adipose-Tissue-Derived Mesenchymal Stem Cells. J Proteome Res 2022; 21:654-670. [PMID: 35061379 PMCID: PMC9776527 DOI: 10.1021/acs.jproteome.1c00832] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
This Article presents, for the first time to our knowledge, an untargeted nuclear magnetic resonance (NMR) metabolomic characterization of the polar intracellular metabolic adaptations of human adipose-derived mesenchymal stem cells during osteogenic differentiation. The use of mesenchymal stem cells (MSCs) for bone regeneration is a promising alternative to conventional bone grafts, and untargeted metabolomics may unveil novel metabolic information on the osteogenic differentiation of MSCs, allowing their behavior to be understood and monitored/guided toward effective therapies. Our results unveiled statistically relevant changes in the levels of just over 30 identified metabolites, illustrating a highly dynamic process with significant variations throughout the whole 21-day period of osteogenic differentiation, mainly involving amino acid metabolism and protein synthesis; energy metabolism and the roles of glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation; cell membrane metabolism; nucleotide metabolism (including the specific involvement of O-glycosylation intermediates and NAD+); and metabolic players in protective antioxidative mechanisms (such as glutathione and specific amino acids). Different metabolic stages are proposed and are supported by putative biochemical explanations for the metabolite changes observed. This work lays the groundwork for the use of untargeted NMR metabolomics to find potential metabolic markers of osteogenic differentiation efficacy.
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Affiliation(s)
- Daniela
S. C. Bispo
- Department
of Chemistry, CICECO - Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro, Portugal
| | - Catarina S. H. Jesus
- Department
of Chemistry, CICECO - Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro, Portugal
| | - Marlene Correia
- Department
of Chemistry, CICECO - Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro, Portugal
| | - Filipa Ferreira
- Department
of Chemistry, CICECO - Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro, Portugal
| | - Giulia Bonifazio
- Department
of Chemistry, CICECO - Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro, Portugal,Department
of Biotechnology Lazzaro Spallanzani, University
of Pavia, Corso Str.
Nuova, 65, 27100 Pavia PV, Italy
| | - Brian J. Goodfellow
- Department
of Chemistry, CICECO - Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro, Portugal
| | - Mariana B. Oliveira
- Department
of Chemistry, CICECO - Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro, Portugal
| | - João F. Mano
- Department
of Chemistry, CICECO - Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro, Portugal
| | - Ana M. Gil
- Department
of Chemistry, CICECO - Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro, Portugal,
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25
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Bone Regeneration and Oxidative Stress: An Updated Overview. Antioxidants (Basel) 2022; 11:antiox11020318. [PMID: 35204201 PMCID: PMC8868092 DOI: 10.3390/antiox11020318] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 01/27/2022] [Accepted: 02/02/2022] [Indexed: 11/17/2022] Open
Abstract
Bone tissue engineering is a complex domain that requires further investigation and benefits from data obtained over past decades. The models are increasing in complexity as they reveal new data from co-culturing and microfluidics applications. The in vitro models now focus on the 3D medium co-culturing of osteoblasts, osteoclasts, and osteocytes utilizing collagen for separation; this type of research allows for controlled medium and in-depth data analysis. Oxidative stress takes a toll on the domain, being beneficial as well as destructive. Reactive oxygen species (ROS) are molecules that influence the differentiation of osteoclasts, but over time their increasing presence can affect patients and aid the appearance of diseases such as osteoporosis. Oxidative stress can be limited by using antioxidants such as vitamin K and N-acetyl cysteine (NAC). Scaffolds and biocompatible coatings such as hydroxyapatite and bioactive glass are required to isolate the implant, protect the zone from the metallic, ionic exchange, and enhance the bone regeneration by mimicking the composition and structure of the body, thus enhancing cell proliferation. The materials can be further functionalized with growth factors that create a better response and higher chances of success for clinical use. This review highlights the vast majority of newly obtained information regarding bone tissue engineering, such as new co-culturing models, implant coatings, scaffolds, biomolecules, and the techniques utilized to obtain them.
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26
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Sari B, Isik M, Eylem CC, Kilic C, Okesola BO, Karakaya E, Emregul E, Nemutlu E, Derkus B. Omics Technologies for High-Throughput-Screening of Cell-Biomaterial Interactions. Mol Omics 2022; 18:591-615. [DOI: 10.1039/d2mo00060a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Recent research effort in biomaterial development has largely focused on engineering bio-instructive materials to stimulate specific cell signaling. Assessing the biological performance of these materials using time-consuming and trial-and-error traditional...
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Rosiak P, Latanska I, Paul P, Sujka W, Kolesinska B. Modification of Alginates to Modulate Their Physic-Chemical Properties and Obtain Biomaterials with Different Functional Properties. Molecules 2021; 26:7264. [PMID: 34885846 PMCID: PMC8659150 DOI: 10.3390/molecules26237264] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 11/27/2021] [Accepted: 11/28/2021] [Indexed: 01/02/2023] Open
Abstract
Modified alginates have a wide range of applications, including in the manufacture of dressings and scaffolds used for regenerative medicine, in systems for selective drug delivery, and as hydrogel materials. This literature review discusses the methods used to modify alginates and obtain materials with new or improved functional properties. It discusses the diverse biological and functional activity of alginates. It presents methods of modification that utilize both natural and synthetic peptides, and describes their influence on the biological properties of the alginates. The success of functionalization depends on the reaction conditions being sufficient to guarantee the desired transformations and provide modified alginates with new desirable properties, but mild enough to prevent degradation of the alginates. This review is a literature description of efficient methods of alginate functionalization using biologically active ligands. Particular attention was paid to methods of alginate functionalization with peptides, because the combination of the properties of alginates and peptides leads to the obtaining of conjugates with properties resulting from both components as well as a completely new, different functionality.
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Affiliation(s)
- Piotr Rosiak
- Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland; (P.R.); (P.P.)
| | - Ilona Latanska
- Tricomed S.A., Swietojanska 5/9, 93-493 Lodz, Poland; (I.L.); (W.S.)
| | - Paulina Paul
- Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland; (P.R.); (P.P.)
| | - Witold Sujka
- Tricomed S.A., Swietojanska 5/9, 93-493 Lodz, Poland; (I.L.); (W.S.)
| | - Beata Kolesinska
- Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland; (P.R.); (P.P.)
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Maity C, Das N. Alginate-Based Smart Materials and Their Application: Recent Advances and Perspectives. Top Curr Chem (Cham) 2021; 380:3. [PMID: 34812965 DOI: 10.1007/s41061-021-00360-8] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 11/03/2021] [Indexed: 12/14/2022]
Abstract
Nature produces materials using available molecular building blocks following a bottom-up approach. These materials are formed with great precision and flexibility in a controlled manner. This approach offers the inspiration for manufacturing new artificial materials and devices. Synthetic artificial materials can find many important applications ranging from personalized therapeutics to solutions for environmental problems. Among these materials, responsive synthetic materials are capable of changing their structure and/or properties in response to external stimuli, and hence are termed "smart" materials. Herein, this review focuses on alginate-based smart materials and their stimuli-responsive preparation, fragmentation, and applications in diverse fields from drug delivery and tissue engineering to water purification and environmental remediation. In the first part of this report, we review stimuli-induced preparation of alginate-based materials. Stimuli-triggered decomposition of alginate materials in a controlled fashion is documented in the second part, followed by the application of smart alginate materials in diverse fields. Because of their biocompatibility, easy accessibility, and simple techniques of material formation, alginates can provide solutions for several present and future problems of humankind. However, new research is needed for novel alginate-based materials with new functionalities and well-defined properties for targeted applications.
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Affiliation(s)
- Chandan Maity
- Department of Chemistry, School of Advanced Science (SAS), Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India.
| | - Nikita Das
- Department of Chemistry, School of Advanced Science (SAS), Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India
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29
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Klontzas ME, Protonotarios A. High-Resolution Imaging for the Analysis and Reconstruction of 3D Microenvironments for Regenerative Medicine: An Application-Focused Review. Bioengineering (Basel) 2021; 8:182. [PMID: 34821748 PMCID: PMC8614770 DOI: 10.3390/bioengineering8110182] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 11/07/2021] [Accepted: 11/08/2021] [Indexed: 11/29/2022] Open
Abstract
The rapid evolution of regenerative medicine and its associated scientific fields, such as tissue engineering, has provided great promise for multiple applications where replacement and regeneration of damaged or lost tissue is required. In order to evaluate and optimise the tissue engineering techniques, visualisation of the material of interest is crucial. This includes monitoring of the cellular behaviour, extracellular matrix composition, scaffold structure, and other crucial elements of biomaterials. Non-invasive visualisation of artificial tissues is important at all stages of development and clinical translation. A variety of preclinical and clinical imaging methods-including confocal multiphoton microscopy, optical coherence tomography, magnetic resonance imaging (MRI), and computed tomography (CT)-have been used for the evaluation of artificial tissues. This review attempts to present the imaging methods available to assess the composition and quality of 3D microenvironments, as well as their integration with human tissues once implanted in the human body. The review provides tissue-specific application examples to demonstrate the applicability of such methods on cardiovascular, musculoskeletal, and neural tissue engineering.
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Affiliation(s)
- Michail E. Klontzas
- Department of Medical Imaging, University Hospital of Heraklion, 71110, Heraklion, Crete, Greece
- Computational Biomedicine Laboratory, Institute of Computer Science, Foundation for Research and Technology (FORTH), 70013 Heraklion, Crete, Greece
- Department of Radiology, School of Medicine, Voutes Campus, University of Crete, 71003 Heraklion, Crete, Greece
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30
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Passanha FR, Gomes DB, Piotrowska J, Moroni L, Baker MB, LaPointe VLS. A comparative study of mesenchymal stem cells cultured as cell-only aggregates and in encapsulated hydrogels. J Tissue Eng Regen Med 2021; 16:14-25. [PMID: 34655456 PMCID: PMC9297862 DOI: 10.1002/term.3257] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 09/27/2021] [Accepted: 10/07/2021] [Indexed: 01/01/2023]
Abstract
There is increasing evidence that cells cultured in three‐dimensional (3D) settings have superior performance compared to their traditional counterparts in monolayers. This has been attributed to cell–cell and cell–extracellular matrix interactions that more closely resemble the in vivo tissue architecture. The rapid adoption of 3D cell culture systems as experimental tools for diverse applications has not always been matched by an improved understanding of cell behavior in different 3D environments. Here, we studied human mesenchymal stem/stromal cells (hMSCs) as scaffold‐free self‐assembled aggregates of low and high cell number and compared them to cell‐laden alginate hydrogels with and without arginine‐glycine‐aspartic acid peptides. We observed a significant decrease in the size of cell‐only aggregates over 14 days in culture compared to the cells encapsulated in alginate hydrogels. Alginate hydrogels had persistently more living cells for a longer period (14 days) in culture as measured by total DNA content. Proliferation studies revealed that a weeklong culture of hMSCs in 3D culture, whether as aggregates or cell‐laden alginate hydrogels, reduced their proliferation over time. Cell cycle analysis found no significant differences between days 1 and 7 for the different culture systems. The findings of this study improve our understanding of how aggregate cultures differ with or without a hydrogel carrier, and whether aggregation itself is important when it comes to the 3D culture of hMSCs.
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Affiliation(s)
- Fiona R Passanha
- Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology- Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands
| | - David B Gomes
- Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands
| | - Justyna Piotrowska
- Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology- Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands
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- Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology- Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands.,Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands.,University College Maastricht, Maastricht University, Maastricht, The Netherlands
| | - Lorenzo Moroni
- Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands
| | - Matthew B Baker
- Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands
| | - Vanessa L S LaPointe
- Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology- Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands
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31
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Metabolomics in Bone Research. Metabolites 2021; 11:metabo11070434. [PMID: 34357328 PMCID: PMC8303949 DOI: 10.3390/metabo11070434] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/18/2021] [Accepted: 06/28/2021] [Indexed: 12/12/2022] Open
Abstract
Identifying the changes in endogenous metabolites in response to intrinsic and extrinsic factors has excellent potential to obtain an understanding of cells, biofluids, tissues, or organisms' functions and interactions with the environment. The advantages provided by the metabolomics strategy have promoted studies in bone research fields, including an understanding of bone cell behaviors, diagnosis and prognosis of diseases, and the development of treatment methods such as implanted biomaterials. This review article summarizes the metabolism changes during osteogenesis, osteoclastogenesis, and immunoregulation in hard tissue. The second section of this review is dedicated to describing and discussing metabolite changes in the most relevant bone diseases: osteoporosis, bone injuries, rheumatoid arthritis, and osteosarcoma. We consolidated the most recent finding of the metabolites and metabolite pathways affected by various bone disorders. This collection can serve as a basis for future metabolomics-driven bone research studies to select the most relevant metabolites and metabolic pathways. Additionally, we summarize recent metabolic studies on metabolomics for the development of bone disease treatment including biomaterials for bone engineering. With this article, we aim to provide a comprehensive summary of metabolomics in bone research, which can be helpful for interdisciplinary researchers, including material engineers, biologists, and clinicians.
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Guo JL, Kim YS, Koons GL, Lam J, Navara AM, Barrios S, Xie VY, Watson E, Smith BT, Pearce HA, Orchard EA, van den Beucken JJJP, Jansen JA, Wong ME, Mikos AG. Bilayered, peptide-biofunctionalized hydrogels for in vivo osteochondral tissue repair. Acta Biomater 2021; 128:120-129. [PMID: 33930575 PMCID: PMC8222183 DOI: 10.1016/j.actbio.2021.04.038] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 04/01/2021] [Accepted: 04/19/2021] [Indexed: 10/21/2022]
Abstract
Osteochondral defects present a unique clinical challenge due to their combination of phenotypically distinct cartilage and bone, which require specific, stratified biochemical cues for tissue regeneration. Furthermore, the articular cartilage exhibits significantly worse regeneration than bone due to its largely acellular and avascular nature, prompting significant demand for regenerative therapies. To address these clinical challenges, we have developed a bilayered, modular hydrogel system that enables the click functionalization of cartilage- and bone-specific biochemical cues to each layer. In this system, the crosslinker poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol) (PdBT) was click conjugated with either a cartilage- or bone-specific peptide sequence of interest, and then mixed with a suspension of thermoresponsive polymer and mesenchymal stem cells (MSCs) to generate tissue-specific, cell-encapsulated hydrogel layers targeting the cartilage or bone. We implanted bilayered hydrogels in rabbit femoral condyle defects and investigated the effects of tissue-specific peptide presentation and cell encapsulation on osteochondral tissue repair. After 12 weeks implantation, hydrogels with a chondrogenic peptide sequence produced higher histological measures of overall defect filling, cartilage surface regularity, glycosaminoglycan (GAG)/cell content of neocartilage and adjacent cartilage, and bone filling and bonding compared to non-chondrogenic hydrogels. Furthermore, MSC encapsulation promoted greater histological measures of overall defect filling, cartilage thickness, GAG/cell content of neocartilage, and bone filling. Our results establish the utility of this click functionalized hydrogel system for in vivo repair of the osteochondral unit. STATEMENT OF SIGNIFICANCE: Osteochondral repair requires mimicry of both cartilage- and bone-specific biochemical cues, which are highly distinct. While traditional constructs for osteochondral repair have mimicked gross compositional differences between the cartilage and bone in mineral content, mechanical properties, proteins, or cell types, few constructs have recapitulated the specific biochemical cues responsible for the differential development of cartilage and bone. In this study, click biofunctionalized, bilayered hydrogels produced stratified presentation of developmentally inspired peptide sequences for chondrogenesis and osteogenesis. This work represents, to the authors' knowledge, the first application of bioconjugation chemistry for the simultaneous repair of bone and cartilage tissue. The conjugation of tissue-specific peptide sequences successfully promoted development of both cartilage and bone tissues in vivo.
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Affiliation(s)
- Jason L Guo
- Department of Bioengineering, Rice University, Houston, TX, USA.
| | - Yu Seon Kim
- Department of Bioengineering, Rice University, Houston, TX, USA.
| | - Gerry L Koons
- Department of Bioengineering, Rice University, Houston, TX, USA.
| | - Johnny Lam
- Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
| | - Adam M Navara
- Department of Bioengineering, Rice University, Houston, TX, USA.
| | - Sergio Barrios
- Department of Bioengineering, Rice University, Houston, TX, USA.
| | - Virginia Y Xie
- Department of Bioengineering, Rice University, Houston, TX, USA.
| | - Emma Watson
- Department of Bioengineering, Rice University, Houston, TX, USA.
| | - Brandon T Smith
- Department of Bioengineering, Rice University, Houston, TX, USA.
| | - Hannah A Pearce
- Department of Bioengineering, Rice University, Houston, TX, USA.
| | | | | | - John A Jansen
- Department of Dentistry - Biomaterials, Radboud University Medical Center, Nijmegen, The Netherlands.
| | - Mark E Wong
- Department of Surgery, Division of Maxillofacial Surgery, The University of Texas School of Dentistry, Houston, TX, USA.
| | - Antonios G Mikos
- Department of Bioengineering, Rice University, Houston, TX, USA.
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33
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Bispo DSC, Jesus CSH, Marques IMC, Romek KM, Oliveira MB, Mano JF, Gil AM. Metabolomic Applications in Stem Cell Research: a Review. Stem Cell Rev Rep 2021; 17:2003-2024. [PMID: 34131883 DOI: 10.1007/s12015-021-10193-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/24/2021] [Indexed: 12/17/2022]
Abstract
This review describes the use of metabolomics to study stem cell (SC) characteristics and function, excluding SCs in cancer research, suited to a fully dedicated text. The interest in employing metabolomics in SC research has consistently grown and emphasis is, here, given to developments reported in the past five years. This text informs on the existing methodologies and their complementarity regarding the information provided, comprising untargeted/targeted approaches, which couple mass spectrometry or nuclear magnetic resonance spectroscopy with multivariate analysis (and, in some cases, pathway analysis and integration with other omics), and more specific analytical approaches, namely isotope tracing to highlight particular metabolic pathways, or in tandem microscopic strategies to pinpoint characteristics within a single cell. The bulk of this review covers the existing applications in various aspects of mesenchymal SC behavior, followed by pluripotent and neural SCs, with a few reports addressing other SC types. Some of the central ideas investigated comprise the metabolic/biological impacts of different tissue/donor sources and differentiation conditions, including the importance of considering 3D culture environments, mechanical cues and/or media enrichment to guide differentiation into specific lineages. Metabolomic analysis has considered cell endometabolomes and exometabolomes (fingerprinting and footprinting, respectively), having measured both lipid species and polar metabolites involved in a variety of metabolic pathways. This review clearly demonstrates the current enticing promise of metabolomics in significantly contributing towards a deeper knowledge on SC behavior, and the discovery of new biomarkers of SC function with potential translation to in vivo clinical practice.
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Affiliation(s)
- Daniela S C Bispo
- Department of Chemistry, CICECO - Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitario de Santiago, 3810-193, Aveiro, Portugal
| | - Catarina S H Jesus
- Department of Chemistry, CICECO - Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitario de Santiago, 3810-193, Aveiro, Portugal
| | - Inês M C Marques
- Department of Chemistry, CICECO - Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitario de Santiago, 3810-193, Aveiro, Portugal
| | - Katarzyna M Romek
- Department of Chemistry, CICECO - Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitario de Santiago, 3810-193, Aveiro, Portugal
| | - Mariana B Oliveira
- Department of Chemistry, CICECO - Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitario de Santiago, 3810-193, Aveiro, Portugal
| | - João F Mano
- Department of Chemistry, CICECO - Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitario de Santiago, 3810-193, Aveiro, Portugal
| | - Ana M Gil
- Department of Chemistry, CICECO - Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitario de Santiago, 3810-193, Aveiro, Portugal.
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34
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Carvalho MS, Cabral JMS, da Silva CL, Vashishth D. Bone Matrix Non-Collagenous Proteins in Tissue Engineering: Creating New Bone by Mimicking the Extracellular Matrix. Polymers (Basel) 2021; 13:polym13071095. [PMID: 33808184 PMCID: PMC8036283 DOI: 10.3390/polym13071095] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/18/2021] [Accepted: 03/20/2021] [Indexed: 02/06/2023] Open
Abstract
Engineering biomaterials that mimic the extracellular matrix (ECM) of bone is of significant importance since most of the outstanding properties of the bone are due to matrix constitution. Bone ECM is composed of a mineral part comprising hydroxyapatite and of an organic part of primarily collagen with the rest consisting on non-collagenous proteins. Collagen has already been described as critical for bone tissue regeneration; however, little is known about the potential effect of non-collagenous proteins on osteogenic differentiation, even though these proteins were identified some decades ago. Aiming to engineer new bone tissue, peptide-incorporated biomimetic materials have been developed, presenting improved biomaterial performance. These promising results led to ongoing research focused on incorporating non-collagenous proteins from bone matrix to enhance the properties of the scaffolds namely in what concerns cell migration, proliferation, and differentiation, with the ultimate goal of designing novel strategies that mimic the native bone ECM for bone tissue engineering applications. Overall, this review will provide an overview of the several non-collagenous proteins present in bone ECM, their functionality and their recent applications in the bone tissue (including dental) engineering field.
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Affiliation(s)
- Marta S. Carvalho
- Center for Biotechnology and Interdisciplinary Studies, Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
- Department of Bioengineering and iBB—Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal; (J.M.S.C.); (C.L.d.S.)
- Associate Laboratory i4HB—Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal
- Correspondence: (M.S.C.); (D.V.)
| | - Joaquim M. S. Cabral
- Department of Bioengineering and iBB—Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal; (J.M.S.C.); (C.L.d.S.)
- Associate Laboratory i4HB—Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal
| | - Cláudia L. da Silva
- Department of Bioengineering and iBB—Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal; (J.M.S.C.); (C.L.d.S.)
- Associate Laboratory i4HB—Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal
| | - Deepak Vashishth
- Center for Biotechnology and Interdisciplinary Studies, Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
- Correspondence: (M.S.C.); (D.V.)
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35
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Kong X, Chen L, Li B, Quan C, Wu J. Applications of oxidized alginate in regenerative medicine. J Mater Chem B 2021; 9:2785-2801. [PMID: 33683259 DOI: 10.1039/d0tb02691c] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Because of its ideal degradation rate and features, oxidized alginate (OA) is selected as an appropriate substitute and has been introduced into hydrogels, microspheres, 3D-printed/composite scaffolds, membranes, and electrospinning and coating materials. By taking advantage of OA, the OA-based materials can be easily functionalized and deliver drugs or growth factors to promote tissue regeneration. In 1928, it was first found that alginate could be oxidized using periodate, yielding OA. Since then, considerable progress has been made in the research on the modification and application of alginate after oxidation. In this article, we summarize the key properties and existing applications of OA and various OA-based materials and discuss their prospects in regenerative medicine.
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Affiliation(s)
- Xiaoli Kong
- Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering, Sun Yat-sen University, Guangzhou 510006, P. R. China.
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Guo JL, Diaz-Gomez L, Xie VY, Bittner SM, Jiang EY, Wang B, Mikos AG. Three-Dimensional Printing of Click Functionalized, Peptide Patterned Scaffolds for Osteochondral Tissue Engineering. ACTA ACUST UNITED AC 2021; 22. [PMID: 33997430 DOI: 10.1016/j.bprint.2021.e00136] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Osteochondral repair remains a significant clinical challenge due to the multiple tissue phenotypes and complex biochemical milieu in the osteochondral unit. To repair osteochondral defects, it is necessary to mimic the gradation between bone and cartilage, which requires spatial patterning of multiple tissue-specific cues. To address this need, we have developed a facile system for the conjugation and patterning of tissue-specific peptides by melt extrusion of peptide-functionalized poly(ε-caprolactone) (PCL). In this study, alkyne-terminated PCL was conjugated to tissue-specific peptides via a mild, aqueous, and Ru(II)-catalyzed click reaction. The PCL-peptide composites were then 3D printed by multimaterial segmented printing to generate user-defined patterning of tissue-specific peptides. To confirm the bioactivity of 3D printed PCL-peptide composites, bone- and cartilage-specific scaffolds were seeded with mesenchymal stem cells and assessed for deposition of tissue-specific extracellular matrix in vitro. PCL-peptide scaffolds successfully promoted osteogenic and chondrogenic matrix deposition, with effects dependent on the identity of conjugated peptide.
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Affiliation(s)
- Jason L Guo
- Department of Bioengineering, Rice University, Houston, TX
| | | | - Virginia Y Xie
- Department of Bioengineering, Rice University, Houston, TX
| | - Sean M Bittner
- Department of Bioengineering, Rice University, Houston, TX
| | - Emily Y Jiang
- Department of Bioengineering, Rice University, Houston, TX
| | - Bonnie Wang
- Department of Bioengineering, Rice University, Houston, TX
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Scott RA, Kiick KL, Akins RE. Substrate stiffness directs the phenotype and polarization state of cord blood derived macrophages. Acta Biomater 2021; 122:220-235. [PMID: 33359292 DOI: 10.1016/j.actbio.2020.12.040] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 12/01/2020] [Accepted: 12/17/2020] [Indexed: 01/05/2023]
Abstract
Cord blood (CB) mononuclear cell populations have demonstrated significant promise in biomaterials-based regenerative therapies; however, the contributions of monocyte and macrophage subpopulations towards proper tissue healing and regeneration are not well understood, and the phenotypic responses of macrophage to microenvironmental cues have not been well-studied. In this work, we evaluated the effects of cytokine stimulation and altered substrate stiffness. Macrophage derived from CB CD14+ monocytes adopted distinct inflammatory (M1) and anti-inflammatory (M2a and M2c) phenotypes in response to cytokine stimulation (M1: lipopolysaccharide (LPS) and interferon (IFN-γ); M2a: interleukin (IL)-4 and IL-13; M2c: IL-10) as determined through expression of relevant cell surface markers and growth factors. Cytokine-induced macrophage readily altered their phenotypes upon sequential administration of different cytokine cocktails. The impact of substrate stiffness on macrophage phenotype was evaluated by seeding CB-derived macrophage on 3wt%, 6wt%, and 14wt% poly(ethylene glycol)-based hydrogels, which exhibited swollen shear moduli of 0.1, 3.4, and 10.3 kPa, respectively. Surface marker expression and cytokine production varied depending on modulus, with anti-inflammatory phenotypes increasing with elevated substrate stiffness. Integration of specific hydrogel moduli and cytokine cocktail treatments resulted in the differential regulation of macrophage phenotypic biomarkers. These data suggest that CB-derived macrophages exhibit predictable behaviors that can be directed and finely tuned by combinatorial modulation of substrate physical properties and cytokine profiles.
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Mazziotta C, Lanzillotti C, Iaquinta MR, Taraballi F, Torreggiani E, Rotondo JC, Otòn-Gonzalez L, Mazzoni E, Frontini F, Bononi I, De Mattei M, Tognon M, Martini F. MicroRNAs Modulate Signaling Pathways in Osteogenic Differentiation of Mesenchymal Stem Cells. Int J Mol Sci 2021; 22:2362. [PMID: 33673409 PMCID: PMC7956574 DOI: 10.3390/ijms22052362] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/18/2021] [Accepted: 02/24/2021] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cells (MSCs) have been identified in many adult tissues and they have been closely studied in recent years, especially in view of their potential use for treating diseases and damaged tissues and organs. MSCs are capable of self-replication and differentiation into osteoblasts and are considered an important source of cells in tissue engineering for bone regeneration. Several epigenetic factors are believed to play a role in the osteogenic differentiation of MSCs, including microRNAs (miRNAs). MiRNAs are small, single-stranded, non-coding RNAs of approximately 22 nucleotides that are able to regulate cell proliferation, differentiation and apoptosis by binding the 3' untranslated region (3'-UTR) of target mRNAs, which can be subsequently degraded or translationally silenced. MiRNAs control gene expression in osteogenic differentiation by regulating two crucial signaling cascades in osteogenesis: the transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP) and the Wingless/Int-1(Wnt)/β-catenin signaling pathways. This review provides an overview of the miRNAs involved in osteogenic differentiation and how these miRNAs could regulate the expression of target genes.
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Affiliation(s)
- Chiara Mazziotta
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Carmen Lanzillotti
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Maria Rosa Iaquinta
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Francesca Taraballi
- Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX 77030, USA;
- Orthopedics and Sports Medicine, Houston Methodist Hospital, 6565 Fannin Street, Houston, TX 77030, USA
| | - Elena Torreggiani
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - John Charles Rotondo
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Lucia Otòn-Gonzalez
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Elisa Mazzoni
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Francesca Frontini
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Ilaria Bononi
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Monica De Mattei
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Mauro Tognon
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Fernanda Martini
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
- Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 70, Eliporto Street, 44121 Ferrara, Italy
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Klontzas ME, Kakkos GA, Papadakis GZ, Marias K, Karantanas AH. Advanced clinical imaging for the evaluation of stem cell based therapies. Expert Opin Biol Ther 2021; 21:1253-1264. [PMID: 33576278 DOI: 10.1080/14712598.2021.1890711] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Introduction: As stem cell treatments reach closer to the clinic, the need for appropriate noninvasive imaging for accurate disease diagnosis, treatment planning, follow-up, and early detection of complications, is constantly rising. Clinical radiology affords an extensive arsenal of advanced imaging techniques, to provide anatomical and functional information on the whole spectrum of stem cell treatments from diagnosis to follow-up.Areas covered: This manuscript aims at providing a critical review of major published studies on the utilization of advanced imaging for stem cell treatments. Uses of magnetic resonance imaging (MRI), computed tomography (CT), ultrasound, and positron emission tomography (PET) are reviewed and interrogated for their applicability to stem cell imaging.Expert opinion: A wide spectrum of imaging methods have been utilized for the evaluation of stem cell therapies. The majority of published techniques are not clinically applicable, using methods exclusively applicable to animals or technology irrelevant to current clinical practice. Harmonization of preclinical methods with clinical reality is necessary for the timely translation of stem cell therapies to the clinic. Methods such as diffusion weighted MRI, hybrid imaging, and contrast-enhanced ultrasound hold great promise and should be routinely incorporated in the evaluation of patients receiving stem cell treatments.
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Affiliation(s)
- Michail E Klontzas
- Department of Medical Imaging, University Hospital of Heraklion, Crete, Greece.,Advanced Hybrid Imaging Systems, Institute of Computer Science, Foundation for Research and Technology (FORTH), Heraklion, Crete, Greece
| | - George A Kakkos
- Department of Medical Imaging, University Hospital of Heraklion, Crete, Greece
| | - Georgios Z Papadakis
- Advanced Hybrid Imaging Systems, Institute of Computer Science, Foundation for Research and Technology (FORTH), Heraklion, Crete, Greece.,Computational Biomedicine Laboratory (CBML), Foundation for Research and Technology Hellas (FORTH), Heraklion, Crete, Greece.,Department of Radiology, School of Medicine, University of Crete, Heraklion, Crete, Greece
| | - Kostas Marias
- Computational Biomedicine Laboratory (CBML), Foundation for Research and Technology Hellas (FORTH), Heraklion, Crete, Greece.,Department of Electrical and Computer Engineering, Hellenic Mediterranean University, Heraklion, Crete, Greece
| | - Apostolos H Karantanas
- Department of Medical Imaging, University Hospital of Heraklion, Crete, Greece.,Advanced Hybrid Imaging Systems, Institute of Computer Science, Foundation for Research and Technology (FORTH), Heraklion, Crete, Greece.,Computational Biomedicine Laboratory (CBML), Foundation for Research and Technology Hellas (FORTH), Heraklion, Crete, Greece.,Department of Radiology, School of Medicine, University of Crete, Heraklion, Crete, Greece
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40
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Wang J, Wang C, Zhang H, Liu Y, Shi T. Mass spectral and theoretical investigations of the transient proton-bound dimers on the cleavage processes of the peptide GHK and its analogues. RSC Adv 2021; 11:4077-4086. [PMID: 35424374 PMCID: PMC8694339 DOI: 10.1039/d0ra07600g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 01/14/2021] [Indexed: 11/21/2022] Open
Abstract
Fragmentation mechanisms of the singly protonated peptides GHK, GHKH and HGHK have been investigated by mass spectrometry and theoretical calculations. Fragmentation behavior of the protonated H-K amide bond in GHK was changed completely when a histidinyl residue was introduced into the C-terminus of GHK. The H-K amide bond breaking was a predominant pathway in the case of GHK and GHKH. For HGHK, the histidinyl residue at the N-terminus hampered significantly breaking of the H-K amide bond resulting in a high potential energy barrier; calculations indicated that this histidinyl effect played a vital role for the H-K amide bond fragmentation. Subsequent analysis of the fragmentation mechanism revealed that recombination processes of the hydrogen bonding for the intermediate products were all exergonic. Formation of a proton-bound dimer (PBD) lowering the energy barriers from a thermodynamic perspective for all the designed fragmentation pathways was demonstrated to be feasible by our systematic calculations. Moreover, the involvement of different PBDs was further confirmed by analyses of the reduced density gradient (RDG) isosurfaces and scatter maps. A dynamically favored pathway was likely via six-membered ring or nine-membered ring structures generated by the diketopiperazine as revealed by atom-in-molecules (AIM) analyses, since the steric interaction energies in the newly formed ring were estimated to be relatively small when compared to the products generated from a lactam and/or an oxazolone pathway. This is the first feasibility investigation from a dynamic viewpoint for formation of different rings involved in the lactam, oxazolone or diketopiperazine pathways in the fragmentation mechanisms proposed.
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Affiliation(s)
- Jinhu Wang
- College of Chemistry, Chemical Engineering and Materials Science, Zaozhuang University Zaozhuang 277160 Shandong Province P. R. China
| | - Cheng Wang
- Department of Traditional Chinese Medicine, Zaozhuang Municipal Hospital Zaozhuang 277102 Shandong Province P. R. China
| | - Han Zhang
- College of Chemistry, Chemical Engineering and Materials Science, Zaozhuang University Zaozhuang 277160 Shandong Province P. R. China
| | - Yang Liu
- College of Chemistry, Chemical Engineering and Materials Science, Zaozhuang University Zaozhuang 277160 Shandong Province P. R. China
| | - Tiesheng Shi
- College of Chemistry, Chemical Engineering and Materials Science, Zaozhuang University Zaozhuang 277160 Shandong Province P. R. China
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Um S, Ha J, Choi SJ, Oh W, Jin HJ. Prospects for the therapeutic development of umbilical cord blood-derived mesenchymal stem cells. World J Stem Cells 2020; 12:1511-1528. [PMID: 33505598 PMCID: PMC7789129 DOI: 10.4252/wjsc.v12.i12.1511] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 10/23/2020] [Accepted: 11/12/2020] [Indexed: 02/06/2023] Open
Abstract
Umbilical cord blood (UCB) is a primitive and abundant source of mesenchymal stem cells (MSCs). UCB-derived MSCs have a broad and efficient therapeutic capacity to treat various diseases and disorders. Despite the high latent self-renewal and differentiation capacity of these cells, the safety, efficacy, and yield of MSCs expanded for ex vivo clinical applications remains a concern. However, immunomodulatory effects have emerged in various disease models, exhibiting specific mechanisms of action, such as cell migration and homing, angiogenesis, anti-apoptosis, proliferation, anti-cancer, anti-fibrosis, anti-inflammation and tissue regeneration. Herein, we review the current literature pertaining to the UCB-derived MSC application as potential treatment strategies, and discuss the concerns regarding the safety and mass production issues in future applications.
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Affiliation(s)
- Soyoun Um
- Research Team for Immune Cell Therapy, Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
| | - Jueun Ha
- Research Team for Osteoarthritis, Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
| | - Soo Jin Choi
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
| | - Wonil Oh
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
| | - Hye Jin Jin
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
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Li Y, Bouza M, Wu C, Guo H, Huang D, Doron G, Temenoff JS, Stecenko AA, Wang ZL, Fernández FM. Sub-nanoliter metabolomics via mass spectrometry to characterize volume-limited samples. Nat Commun 2020; 11:5625. [PMID: 33159052 PMCID: PMC7648103 DOI: 10.1038/s41467-020-19444-y] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 09/28/2020] [Indexed: 01/18/2023] Open
Abstract
The human metabolome provides a window into the mechanisms and biomarkers of various diseases. However, because of limited availability, many sample types are still difficult to study by metabolomic analyses. Here, we present a mass spectrometry (MS)-based metabolomics strategy that only consumes sub-nanoliter sample volumes. The approach consists of combining a customized metabolomics workflow with a pulsed MS ion generation method, known as triboelectric nanogenerator inductive nanoelectrospray ionization (TENGi nanoESI) MS. Samples tested with this approach include exhaled breath condensate collected from cystic fibrosis patients as well as in vitro-cultured human mesenchymal stromal cells. Both test samples are only available in minimum amounts. Experiments show that picoliter-volume spray pulses suffice to generate high-quality spectral fingerprints, which increase the information density produced per unit sample volume. This TENGi nanoESI strategy has the potential to fill in the gap in metabolomics where liquid chromatography-MS-based analyses cannot be applied. Our method opens up avenues for future investigations into understanding metabolic changes caused by diseases or external stimuli.
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Affiliation(s)
- Yafeng Li
- School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA
| | - Marcos Bouza
- School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA
| | - Changsheng Wu
- School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA
| | - Hengyu Guo
- School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA
| | - Danning Huang
- School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA
| | - Gilad Doron
- W.H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA
| | - Johnna S Temenoff
- W.H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA.,Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA
| | - Arlene A Stecenko
- Emory + Children's Center for Cystic Fibrosis and Airways Disease Research and Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, 30322, USA
| | - Zhong Lin Wang
- School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.,Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 100083, China
| | - Facundo M Fernández
- School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA. .,Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
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Zoughaib M, Luong D, Garifullin R, Gatina DZ, Fedosimova SV, Abdullin TI. Enhanced angiogenic effects of RGD, GHK peptides and copper (II) compositions in synthetic cryogel ECM model. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 120:111660. [PMID: 33545827 DOI: 10.1016/j.msec.2020.111660] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 09/24/2020] [Accepted: 10/18/2020] [Indexed: 02/07/2023]
Abstract
Synthetic oligopeptides are a promising alternative to natural full-length growth factors and extracellular matrix (ECM) proteins in tissue regeneration and therapeutic angiogenesis applications. In this work, angiogenic properties of dual and triple compositions containing RGD, GHK peptides and copper (II) ions (Cu2+) were for the first time studied. To reveal specific in vitro effects of these compositions in three-dimensional scaffold, adamantyl group bearing peptides, namely Ada-Ahx-GGRGD (1) and Ada-Ahx-GGGHK (2), were effectively immobilized in bioinert pHEMA macroporous cryogel via host-guest β-cyclodextrin-adamantane interaction. The cryogels were additionally functionalized with Cu2+ via the formation of GHK-Cu complex. Angiogenic responses of HUVECs grown within the cryogel ECM model were analyzed. The results demonstrate that the combination of RGD with GHK and further with Cu2+ dramatically increases cell proliferation, differentiation, and production of a series of angiogenesis related cytokines and growth factors. Furthermore, the level of glutathione, a key cellular antioxidant and redox regulator, was altered in relation to the angiogenic effects. These results are of particular interest for establishing the role of multiple peptide signals on regeneration related processes and for developing improved tissue engineering materials.
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Affiliation(s)
- Mohamed Zoughaib
- Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia
| | - Duong Luong
- Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia
| | - Ruslan Garifullin
- Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia; Institute of Materials Science and Nanotechnology, Bilkent University, 06800 Ankara, Turkey
| | - Dilara Z Gatina
- Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia
| | - Svetlana V Fedosimova
- Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia
| | - Timur I Abdullin
- Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
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Bai R, Peng L, Sun Q, Zhang Y, Zhang L, Wei Y, Han B. Metallic Antibacterial Surface Treatments of Dental and Orthopedic Materials. MATERIALS (BASEL, SWITZERLAND) 2020; 13:4594. [PMID: 33076495 PMCID: PMC7658793 DOI: 10.3390/ma13204594] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 10/05/2020] [Accepted: 10/13/2020] [Indexed: 12/12/2022]
Abstract
The oral cavity harbors complex microbial communities, which leads to biomaterial-associated infections (BAI) during dental and orthopedic treatments. Conventional antibiotic treatments have met great challenges recently due to the increasing emergency of drug-resistant bacteria. To tackle this clinical issue, antibacterial surface treatments, containing surface modification and coatings, of dental and orthopedic materials have become an area of intensive interest now. Among various antibacterial agents used in surface treatments, metallic agents possess unique properties, mainly including broad-spectrum antibacterial properties, low potential to develop bacterial resistance, relative biocompatibility, and chemical stability. Therefore, this review mainly focuses on underlying antibacterial applications and the mechanisms of metallic agents in dentistry and orthopedics. An overview of the present review indicates that much work remains to be done to deepen the understanding of antibacterial mechanisms and potential side-effects of metallic agents.
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Affiliation(s)
- Rushui Bai
- Department of Orthodontics, Peking University School and Hospital of Stomatology & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China; (R.B.); (L.P.); (Q.S.); (Y.Z.); (L.Z.)
| | - Liying Peng
- Department of Orthodontics, Peking University School and Hospital of Stomatology & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China; (R.B.); (L.P.); (Q.S.); (Y.Z.); (L.Z.)
| | - Qiannan Sun
- Department of Orthodontics, Peking University School and Hospital of Stomatology & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China; (R.B.); (L.P.); (Q.S.); (Y.Z.); (L.Z.)
| | - Yunfan Zhang
- Department of Orthodontics, Peking University School and Hospital of Stomatology & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China; (R.B.); (L.P.); (Q.S.); (Y.Z.); (L.Z.)
| | - Lingyun Zhang
- Department of Orthodontics, Peking University School and Hospital of Stomatology & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China; (R.B.); (L.P.); (Q.S.); (Y.Z.); (L.Z.)
| | - Yan Wei
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China
| | - Bing Han
- Department of Orthodontics, Peking University School and Hospital of Stomatology & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China; (R.B.); (L.P.); (Q.S.); (Y.Z.); (L.Z.)
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Papadogiannis F, Batsali A, Klontzas ME, Karabela M, Georgopoulou A, Mantalaris A, Zafeiropoulos NE, Chatzinikolaidou M, Pontikoglou C. Osteogenic differentiation of bone marrow mesenchymal stem cells on chitosan/gelatin scaffolds: gene expression profile and mechanical analysis. ACTA ACUST UNITED AC 2020; 15:064101. [PMID: 32629436 DOI: 10.1088/1748-605x/aba325] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
In the present study we explore the extracellular matrix (ECM) produced by human bone marrow mesenchymal stem/stromal cells (BM-MSCs) induced to undergo osteogenic differentiation within porous chitosan/gelatin (CS:Gel) scaffolds by investigating their multiple gene expression profile and mechanical behavior. Initially, the efficiency of the BM-MSCs osteogenic differentiation within the constructs was confirmed by the significant rise in the expression of the osteogenesis associated genes DLX5, RUNX2, ALP and OSC. In line with these findings, OSC and Col1A1 protein expression was also detected in BM-MSCs on the CS:Gel scaffolds at day 14 of osteogenic differentiation. We then profiled, for the first time, the expression of 84 cell adhesion and ECM molecules using PCR arrays. The arrays, which were conducted at day 14 of osteogenic differentiation, demonstrated that 49 genes including collagens, integrins, laminins, ECM proteases, catenins, thrombospondins, ECM protease inhibitors and cell-cell adhesion molecules were differentially expressed in BM-MSCs seeded on scaffolds compared to tissue culture polystyrene control. Moreover, we performed dynamic mechanical analysis of the cell-loaded scaffolds on days 0, 7 and 14 to investigate the correlation between the biological results and the mechanical behavior of the constructs. Our data demonstrate a significant increase in the stiffness of the constructs with storage modulus values of 2 MPa on day 7, compared to 0.5 MPa on day 0, following a drop of the stiffness at 0.8 MPa on day 14, that may be attributed to the significant increase of specific ECM protease gene expression such as MMP1, MMP9, MMP11 and MMP16 at this time period.
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Affiliation(s)
- Fotios Papadogiannis
- Hemopoiesis Research Laboratory, School of Medicine, University of Crete, Heraklion, Greece. Department of Materials Science and Technology, University of Crete, Heraklion, Greece. All authors contributed equally to this work
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Lohberger B, Eck N, Glaenzer D, Lichtenegger H, Ploszczanski L, Leithner A. Cobalt Chromium Molybdenum Surface Modifications Alter the Osteogenic Differentiation Potential of Human Mesenchymal Stem Cells. MATERIALS 2020; 13:ma13194292. [PMID: 32992906 PMCID: PMC7579014 DOI: 10.3390/ma13194292] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 09/14/2020] [Accepted: 09/22/2020] [Indexed: 12/29/2022]
Abstract
Surface roughness on orthopedic implant materials has been shown to be highly influential on the behavior of osteogenic cells. Mesenchymal stem and progenitor cells (MSPCs) migrate to the interface, adhere, proliferate, and differentiate into osteoblasts, which subsequently form bone matrix. Modifications of the implant surfaces should accelerate this process and improve biocompatibility. In this study, five surface topographies on cobalt chromium molybdenum (CoCrMo) were engineered to examine the influence on MSPCs. Scanning electron microscopy revealed significant differences in the morphology of untreated CoCrMo discs in comparison with CoCrMo with a titanium nitride (TiN) coating, polished and porous coated CoCrMo surfaces, and CoCrMo with a pure titanium (cpTi) coating. Elemental analysis was performed using energy-dispersive X-ray spectroscopy (EDX). Human primary MSPCs were expanded from tissue samples of spongiosa bone and characterized according to the criteria of the International Society for Cellular Therapy. The characteristic phenotype of MSPC was confirmed by flow cytometry and multilineage differentiation. Alcaline phosphatase and osteopontin expression increased significantly in all groups about 5-fold and 10-fold, respectively, in comparison to the undifferentiated controls. The porous coated surface showed a reduced expression of osteogenic markers. Due to the osteogenic differentiation, the expression of integrin α5β1, which is particularly important for cell-material contact, increased 4–7-fold. In the dynamic process of bone biology, MSPCs cultured and differentiated on cpTi, showed significant upregulation of IL6 and leptin.
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Affiliation(s)
- Birgit Lohberger
- Department of Orthopedics and Trauma, Medical University Graz, 8036 Graz, Austria; (N.E.); (D.G.); (A.L.)
- Correspondence: ; Tel.: +43-316-385-81640; Fax: +43-316 385-14806
| | - Nicole Eck
- Department of Orthopedics and Trauma, Medical University Graz, 8036 Graz, Austria; (N.E.); (D.G.); (A.L.)
| | - Dietmar Glaenzer
- Department of Orthopedics and Trauma, Medical University Graz, 8036 Graz, Austria; (N.E.); (D.G.); (A.L.)
| | - Helga Lichtenegger
- Department of Material Sciences and Process Engineering, Institute of Physics and Materials Science, University of Natural Resources and Life Sciences, 1160 Vienna, Austria; (H.L.); (L.P.)
| | - Leon Ploszczanski
- Department of Material Sciences and Process Engineering, Institute of Physics and Materials Science, University of Natural Resources and Life Sciences, 1160 Vienna, Austria; (H.L.); (L.P.)
| | - Andreas Leithner
- Department of Orthopedics and Trauma, Medical University Graz, 8036 Graz, Austria; (N.E.); (D.G.); (A.L.)
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Jang HY, Shin JY, Oh SH, Byun JH, Lee JH. PCL/HA Hybrid Microspheres for Effective Osteogenic Differentiation and Bone Regeneration. ACS Biomater Sci Eng 2020; 6:5172-5180. [PMID: 33455267 DOI: 10.1021/acsbiomaterials.0c00550] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
The purpose of this study is to develop a bioactive bone graft based on polycaprolactone (PCL, synthetic polymer; used in clinical practices as a grafting material for craniofacial bone defects) and hyaluronic acid (HA, bioactive natural polymer; known as a promoting substance for bone regeneration) that would be fabricated by clinically available procedures (mild condition without toxic chemicals) and provide bioactivity for sufficient period, and thus effectively induce bone reconstruction. For this, PCL/HA hybrid microspheres were produced by a spray-precipitation technique using clinically adapted solvents. The HA was stably and evenly entrapped in the PCL/HA hybrid microspheres. It was demonstrated that the PCL/HA hybrid microspheres provide an appropriate environment for proliferation and osteogenic differentiation of human periosteum-derived cells (hPDCs) (in vitro) and allow significantly enhanced bone regeneration (in vivo) compared with PCL microspheres without HA. The PCL/HA hybrid microspheres can be a simple but clinically applicable bioactive bone graft for large-sized bone defects.
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Affiliation(s)
- Hee Yun Jang
- Department of Advanced Materials, Hannam University, Daejeon 34054, Republic of Korea
| | - Jun Yung Shin
- Department of Advanced Materials, Hannam University, Daejeon 34054, Republic of Korea
| | - Se Heang Oh
- Department of Nanobiomedical Science, Dankook University, Cheonan 31116, Republic of Korea.,Center for Bio-Medical Engineering Core Facility, Dankook University, Cheonan 31116, Republic of Korea
| | - June-Ho Byun
- Department of Oral and Maxillofacial Surgery, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Republic of Korea
| | - Jin Ho Lee
- Department of Advanced Materials, Hannam University, Daejeon 34054, Republic of Korea
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In Vitro Production of Calcified Bone Matrix onto Wool Keratin Scaffolds via Osteogenic Factors and Electromagnetic Stimulus. MATERIALS 2020; 13:ma13143052. [PMID: 32650489 PMCID: PMC7411850 DOI: 10.3390/ma13143052] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 07/03/2020] [Accepted: 07/04/2020] [Indexed: 12/15/2022]
Abstract
Pulsed electromagnetic field (PEMF) has drawn attention as a potential tool to improve the ability of bone biomaterials to integrate into the surrounding tissue. We investigated the effects of PEMF (frequency, 75 Hz; magnetic induction amplitude, 2 mT; pulse duration, 1.3 ms) on human osteoblast-like cells (SAOS-2) seeded onto wool keratin scaffolds in terms of proliferation, differentiation, and production of the calcified bone extracellular matrix. The wool keratin scaffold offered a 3D porous architecture for cell guesting and nutrient diffusion, suggesting its possible use as a filler to repair bone defects. Here, the combined approach of applying a daily PEMF exposure with additional osteogenic factors stimulated the cells to increase both the deposition of bone-related proteins and calcified matrix onto the wool keratin scaffolds. Also, the presence of SAOS-2 cells, or PEMF, or osteogenic factors did not influence the compression behavior or the resilience of keratin scaffolds in wet conditions. Besides, ageing tests revealed that wool keratin scaffolds were very stable and showed a lower degradation rate compared to commercial collagen sponges. It is for these reasons that this tissue engineering strategy, which improves the osteointegration properties of the wool keratin scaffold, may have a promising application for long term support of bone formation in vivo.
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Neves MI, Moroni L, Barrias CC. Modulating Alginate Hydrogels for Improved Biological Performance as Cellular 3D Microenvironments. Front Bioeng Biotechnol 2020; 8:665. [PMID: 32695759 PMCID: PMC7338591 DOI: 10.3389/fbioe.2020.00665] [Citation(s) in RCA: 108] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Accepted: 05/28/2020] [Indexed: 01/09/2023] Open
Abstract
The rational choice and design of biomaterials for biomedical applications is crucial for successful in vitro and in vivo strategies, ultimately dictating their performance and potential clinical applications. Alginate, a marine-derived polysaccharide obtained from seaweeds, is one of the most widely used polymers in the biomedical field, particularly to build three dimensional (3D) systems for in vitro culture and in vivo delivery of cells. Despite their biocompatibility, alginate hydrogels often require modifications to improve their biological activity, namely via inclusion of mammalian cell-interactive domains and fine-tuning of mechanical properties. These modifications enable the addition of new features for greater versatility and control over alginate-based systems, extending the plethora of applications and procedures where they can be used. Additionally, hybrid systems based on alginate combination with other components can also be explored to improve the mimicry of extracellular microenvironments and their dynamics. This review provides an overview on alginate properties and current clinical applications, along with different strategies that have been reported to improve alginate hydrogels performance as 3D matrices and 4D dynamic systems.
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Affiliation(s)
- Mariana Isabel Neves
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.,INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.,FEUP - Faculdade de Engenharia da Universidade do Porto, Porto, Portugal
| | - Lorenzo Moroni
- MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands.,CNR NANOTEC - Institute of Nanotechnology, Università del Salento, Lecce, Italy
| | - Cristina Carvalho Barrias
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.,INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.,ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
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Balitaan JNI, Hsiao CD, Yeh JM, Santiago KS. Innovation inspired by nature: Biocompatible self-healing injectable hydrogels based on modified-β-chitin for wound healing. Int J Biol Macromol 2020; 162:723-736. [PMID: 32553972 DOI: 10.1016/j.ijbiomac.2020.06.129] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 06/10/2020] [Accepted: 06/12/2020] [Indexed: 12/24/2022]
Abstract
Remarkable properties of hydrogels are compromised by failure to recover from damage, bringing their intended functions to an end. To address this, hydrogels can be functionalized with self-healing property to enable them to restore themselves after damage, thus, extending their lifetime. Herein, hydrogels were prepared by cross-linking acrylamide-modified β-chitin (Am-β-Chn) with alginate dialdehyde (ADA) to form Schiff base, showing IR characteristic peak at 1650 cm-1, attributed to the stretching vibration of CN. The dynamic Schiff base and H-bond rendered the double crosslinked hydrogels self-healing as demonstrated by continuous step strain rheology. Characterization of the hydrogels revealed excellent biocompatibility, biodegradability, injectability and self-healing properties. Furthermore, the wound healing property of the hydrogels was investigated in vivo using zebrafish as a model system. Indirect application of Am-β-Chn/ADA hydrogel remarkably led to ~87% wound healing as compared to control which gave ~50%, suggesting that hydrogels are effective in accelerating wound healing. However, a clear understanding of the exact mechanism of its wound healing property remains to be investigated. To the best of our knowledge, this is the first innovation of developing novel double crosslinked Am-β-Chn/ADA hydrogels with both self-healing and accelerated wound healing properties, directly from marine-food wastes.
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Affiliation(s)
- Jolleen Natalie I Balitaan
- The Graduate School, University of Santo Tomas, España Boulevard, Manila 1008, Philippines; Department of Chemistry, College of Science, España Boulevard, Manila 1008, Philippines
| | - Chung-Der Hsiao
- Department of Bioscience Technology, Chung Yuan Christian University, Chung Li 32023, Taiwan, ROC
| | - Jui-Ming Yeh
- Department of Chemistry, Chung Yuan Christian University, Chung Li 32023, Taiwan, ROC; Center for Nanotechnology, Chung Yuan Christian University, Chung Li 32023, Taiwan, ROC; R&D Center for Membrane Technology, Chung Yuan Christian University, Chung Li 32023, Taiwan, ROC
| | - Karen S Santiago
- The Graduate School, University of Santo Tomas, España Boulevard, Manila 1008, Philippines; Department of Chemistry, College of Science, España Boulevard, Manila 1008, Philippines; Research Center for Natural and Applied Sciences, University of Santo Tomas, España Boulevard, Manila 1008, Philippines.
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