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Arias-Mainer C, Romero-Gavilán F, Cerqueira A, Peñarocha-Oltra D, García-Arnáez I, Amorrotu O, Azkargorta M, Elortza F, Gurruchaga M, Goñi I, Suay J. Quercetin-doped sol-gel coatings on titanium implants: a promising approach for enhanced immune response and cell adhesion. J Mater Chem B 2025. [PMID: 40371955 DOI: 10.1039/d4tb02821j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2025]
Abstract
Quercetin (QUE), a natural flavonoid found in various fruits and vegetables, has diverse biological functions, including anti-inflammatory effects, regulation of cell adhesion and oxidative stress mitigation. In this study, sol-gel materials with increasing concentrations of quercetin (0.5, 1 and 2 wt%) were synthesised and applied onto titanium (Ti) surfaces as coatings. The materials were characterised physiochemically, and in vitro responses were examined using HOb osteoblastic cells and THP-1 macrophages. Human serum protein adsorption was evaluated using nLC-MS/MS. The incorporation of quercetin did not affect the sol-gel network cross-linking, and a controlled release of quercetin was achieved. The materials exhibited no cytotoxicity at any concentration. The HOb cells cultured on quercetin-doped materials were more elongated than those grown on QUE-free coatings, with protruding lamellipodia and increased cell surface. QUE-doped surfaces enhanced the expression of BMP-2, RANKL, and cell adhesion-related genes CTNNB1 and β-actin. In the THP-1 cells, pro-inflammatory gene expression (IL-1β, MCP-1 and iNOS) was down-regulated on 0.5QUE material, while it increased on 2QUE, as did the cytokine liberation. These changes correlated with altered protein adsorption patterns. The 2QUE coatings enhanced the adsorption of acute-phase proteins (SAA1, SAA2 and SAA4), indicating an inflammatory response; this behaviour was not seen on 0.5QUE. Moreover, cell adhesion (COF1, PROF1) and oxidative stress proteins (GPX3, SEPP1, AMBP) were preferentially adsorbed onto QUE-doped coatings. These results highlight the significance of optimising quercetin concentration in sol-gel coatings to modulate the immune response and enhance cell adhesion effectively.
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Affiliation(s)
- C Arias-Mainer
- Department of Industrial Systems Engineering and Design, Universitat Jaume I, Castellon de la Plana, Spain.
| | - F Romero-Gavilán
- Department of Industrial Systems Engineering and Design, Universitat Jaume I, Castellon de la Plana, Spain.
| | - A Cerqueira
- Department of Industrial Systems Engineering and Design, Universitat Jaume I, Castellon de la Plana, Spain.
| | - D Peñarocha-Oltra
- Department of Stomatology, Valencia University Medical and Dental School, Valencia, Spain
| | - I García-Arnáez
- Department of Polymers and Advanced Materials: Physics, Chemistry and Technology, Universidad del País Vasco, San Sebastián, Spain
| | - O Amorrotu
- Department of Polymers and Advanced Materials: Physics, Chemistry and Technology, Universidad del País Vasco, San Sebastián, Spain
| | - M Azkargorta
- Proteomics Platform, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), CIBERehd, ProteoRed-ISCIII, Bizkaia Science and Technology Park, Derio, Spain
| | - F Elortza
- Proteomics Platform, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), CIBERehd, ProteoRed-ISCIII, Bizkaia Science and Technology Park, Derio, Spain
| | - M Gurruchaga
- Department of Polymers and Advanced Materials: Physics, Chemistry and Technology, Universidad del País Vasco, San Sebastián, Spain
| | - I Goñi
- Department of Polymers and Advanced Materials: Physics, Chemistry and Technology, Universidad del País Vasco, San Sebastián, Spain
| | - J Suay
- Department of Industrial Systems Engineering and Design, Universitat Jaume I, Castellon de la Plana, Spain.
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Shao M, Rahmdel M, Shayan SK, Hassannia E, Khedmatgozar M, Yousefi K, Ali-Khiavi P, Hjazi A, Al-Aouadi RFA, Sarvestani PA, Fard MRG, Nourizadeh M, Khiabani SS, Suliman M, Nataj PG, Hamzehzadeh S. Advancements in Biomaterials for Stem Cell Differentiation. Stem Cell Rev Rep 2025:10.1007/s12015-025-10879-8. [PMID: 40257542 DOI: 10.1007/s12015-025-10879-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/04/2025] [Indexed: 04/22/2025]
Abstract
The field of regenerative medicine has witnessed significant advancements in recent years, particularly in the application of biomaterials to enhance stem cell differentiation. Biomaterials serve as scaffolds that can support cellular functions and influence the fate of stem cells through biochemical and physical cues. This paper reviews recent advancements in biomaterials designed for stem cell differentiation, focusing on their composition, properties, and applications in tissue engineering. We explore various types of biomaterials, including natural polymers, synthetic polymers, hydrogels, and nanomaterials, and discuss how they can be tailored to create microenvironments that promote specific differentiation pathways. Additionally, we highlight the challenges and future directions in this rapidly evolving field.
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Affiliation(s)
- Mingchen Shao
- Department of Cardiovascular Surgery, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991, Moscow, Russian Federation
| | - Mohamad Rahmdel
- Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Sepideh Karkon Shayan
- Clinical Research Development Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elham Hassannia
- Student Research Commitee, School of Medicine, Kerman University of Medical Ssciences, Kerman, Iran
| | | | - Khadije Yousefi
- Department of Materials Science and Engineering, School of Engineering, Yasouj University, Yasouj, Iran
| | - Payam Ali-Khiavi
- Student Research Commitee, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ahmed Hjazi
- Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, 11942, Al-Kharj, Saudi Arabia
| | | | - Paria Arjmandi Sarvestani
- Department of Biomedical Engineering, Faculty of Engineering, Zand Institute of Higher Education, Shiraz, Iran
| | | | - Mehrdad Nourizadeh
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Muath Suliman
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, 61413, Abha, Saudi Arabia
| | | | - Sina Hamzehzadeh
- Clinical Research Development Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Kary AD, Noelle H, Magin CM. Tissue-Informed Biomaterial Innovations Advance Pulmonary Regenerative Engineering. ACS Macro Lett 2025; 14:434-447. [PMID: 40102038 DOI: 10.1021/acsmacrolett.5c00075] [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: 03/20/2025]
Abstract
Irreversible progressive pulmonary diseases drastically reduce the patient quality of life, while transplantation remains the only definitive cure. Research into lung regeneration pathways holds significant potential to expand and promote the discovery of new treatment options. Polymeric biomaterials designed to replicate key tissue characteristics (i.e., biochemical composition and mechanical cues) show promise for creating environments in which to study chronic lung diseases and initiate lung tissue regeneration. In this Viewpoint, we explore how naturally derived materials can be employed alone or combined with engineered polymer systems to create advanced tissue culture platforms. Pulmonary tissue models have historically leveraged natural materials, including basement membrane extracts and a decellularized extracellular matrix, as platforms for lung regeneration studies. Here, we provide an overview of the progression of pulmonary regenerative engineering, exploring how innovations in the growing field of tissue-informed biomaterials have the potential to advance lung regeneration research by bridging the gap between biological relevance and mechanical precision.
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Affiliation(s)
- Anton D Kary
- Department of Bioengineering, University of Colorado, Denver | Anschutz Medical Campus, Aurora, Colorado 80045, United States
| | - Haley Noelle
- Department of Bioengineering, University of Colorado, Denver | Anschutz Medical Campus, Aurora, Colorado 80045, United States
| | - Chelsea M Magin
- Department of Bioengineering, University of Colorado, Denver | Anschutz Medical Campus, Aurora, Colorado 80045, United States
- Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, United States
- Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, United States
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4
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Sharun K, El-Husseiny HM, Muthu S. Editorial: Advances in veterinary tissue engineering: unlocking potential with cell-free and cell-based methods. Front Vet Sci 2025; 12:1591272. [PMID: 40206259 PMCID: PMC11980686 DOI: 10.3389/fvets.2025.1591272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Accepted: 03/13/2025] [Indexed: 04/11/2025] Open
Affiliation(s)
- Khan Sharun
- Center for Regenerative Nanomedicine, Northwestern University, Chicago, IL, United States
- Graduate Institute of Medicine, Yuan Ze University, Taoyuan, Taiwan
| | - Hussein M. El-Husseiny
- Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, Fuchu, Japan
- Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Benha University, Toukh, Egypt
- Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, Tokyo, Japan
| | - Sathish Muthu
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore, Tamil Nadu, India
- Central Research Laboratory, Meenakshi Medical College Hospital and Research Institute, Meenakshi Academy of Higher Education and Research, Chennai, India
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An J, Ma T, Wang Q, Zhang J, Santerre JP, Wang W, Ma P, Zhang X. Defining optimal electrospun membranes to enhance biological activities of human endometrial MSCs. Front Bioeng Biotechnol 2025; 13:1551791. [PMID: 40078795 PMCID: PMC11896994 DOI: 10.3389/fbioe.2025.1551791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Accepted: 02/03/2025] [Indexed: 03/14/2025] Open
Abstract
Introduction Human endometrial mesenchymal stem cells (H-EMSCs) can inhibit endometrial fibrosis and repair damaged endometrium. However, direct cell injection into dam-aged endometrium shows limited cell survival. Cell seeding onto biomaterial-based electrospun membranes could improve H-EMSCs' survival and prolong their stay at the damaged endometrium. Polycaprolactone (PCL), silk fibroin (SF) and hyaluronic acid (HA) are synthetic or natural biomaterials used by the biomedicine field, however, their effects on the biological activities of H-EMSCs remain unclear. Methods In this study, CD90+CD73+CD45- H-EMSCs were extracted from human endometrium and H-EMSCs showed enhanced adhesion, proliferation on PCL-HA vs. PCL, PCL-SF, establishing the potential of the composite to address cell survival issues. Results H-EMSCs cultured on PCL-HA showed decreased IL-6 gene expression and increased IL-10, VEGFA, TGF-β gene expression vs. PCL-SF, establishing the potential to create a favorable micro-environment for generating vascularized endometrial tissues. PCL, PCL-SF, PCL-HA all supported CD90 and Meflin expression of the seeded H-EMSCs, establishing PCL as a platform to form enhanced biomaterial composites for endometrial repair in the future. Discussion This study provided significant evidence sup-porting the potential of appropriately tailored composites of PCL and HA to moder-ate inflammation and wound-healing, which can be applied for endometrial tissue repair and regeneration.
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Affiliation(s)
- Jiangru An
- International Joint Laboratory of Biomaterials and Tissue Regeneration, School of Basic Medicine, Binzhou Medical University, Yantai, Shandong, China
| | - Tianyi Ma
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
| | - Qiuhua Wang
- International Joint Laboratory of Biomaterials and Tissue Regeneration, School of Basic Medicine, Binzhou Medical University, Yantai, Shandong, China
| | - Jinyi Zhang
- International Joint Laboratory of Biomaterials and Tissue Regeneration, School of Basic Medicine, Binzhou Medical University, Yantai, Shandong, China
| | - J. Paul Santerre
- International Joint Laboratory of Biomaterials and Tissue Regeneration, School of Basic Medicine, Binzhou Medical University, Yantai, Shandong, China
- Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada
| | - Wenshuang Wang
- Department of Gynecology, Yuhuangding Hospital, Yantai, Shandong, China
| | - Peng Ma
- International Joint Laboratory of Biomaterials and Tissue Regeneration, School of Basic Medicine, Binzhou Medical University, Yantai, Shandong, China
| | - Xiaoqing Zhang
- International Joint Laboratory of Biomaterials and Tissue Regeneration, School of Basic Medicine, Binzhou Medical University, Yantai, Shandong, China
- Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada
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Kim D, Kim SG. Cell Homing Strategies in Regenerative Endodontic Therapy. Cells 2025; 14:201. [PMID: 39936992 PMCID: PMC11817319 DOI: 10.3390/cells14030201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 01/24/2025] [Accepted: 01/28/2025] [Indexed: 02/13/2025] Open
Abstract
Cell homing, a process that leverages the body's natural ability to recruit cells and repair damaged tissues, presents a promising alternative to cell transplantation methods. Central to this approach is the recruitment of endogenous stem/progenitor cells-such as those from the apical papilla, bone marrow, and periapical tissues-facilitated by chemotactic biological cues. Moreover, biomaterial scaffolds embedded with signaling molecules create supportive environments, promoting cell migration, adhesion, and differentiation for the regeneration of the pulp-dentin complex. By analyzing in vivo animal studies using cell homing strategies, this review explores how biomolecules and scaffold materials enhance the recruitment of endogenous stem cells to the site of damaged dental pulp tissue, thereby promoting repair and regeneration. It also examines the key principles, recent advancements, and current limitations linked to cell homing-based regenerative endodontic therapy, highlighting the interplay of biomaterials, signaling molecules, and their broader clinical implications.
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Affiliation(s)
- David Kim
- Center for Dental and Craniofacial Research, Columbia University College of Dental Medicine, New York, NY 10032, USA;
| | - Sahng G. Kim
- Division of Endodontics, Columbia University College of Dental Medicine, New York, NY 10032, USA
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7
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Salehi Abar E, Vandghanooni S, Torab A, Jaymand M, Eskandani M. A comprehensive review on nanocomposite biomaterials based on gelatin for bone tissue engineering. Int J Biol Macromol 2024; 254:127556. [PMID: 37884249 DOI: 10.1016/j.ijbiomac.2023.127556] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 10/09/2023] [Accepted: 10/18/2023] [Indexed: 10/28/2023]
Abstract
The creation of a suitable scaffold is a crucial step in the process of bone tissue engineering (BTE). The scaffold, acting as an artificial extracellular matrix, plays a significant role in determining the fate of cells by affecting their proliferation and differentiation in BTE. Therefore, careful consideration should be given to the fabrication approach and materials used for scaffold preparation. Natural polypeptides such as gelatin and collagen have been widely used for this purpose. The unique properties of nanoparticles, which vary depending on their size, charge, and physicochemical properties, have demonstrated potential in solving various challenges encountered in BTE. Therefore, nanocomposite biomaterials consisting of polymers and nanoparticles have been extensively used for BTE. Gelatin has also been utilized in combination with other nanomaterials to apply for this purpose. Composites of gelatin with various types of nanoparticles are particularly promising for creating scaffolds with superior biological and physicochemical properties. This review explores the use of nanocomposite biomaterials based on gelatin and various types of nanoparticles together for applications in bone tissue engineering.
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Affiliation(s)
- Elaheh Salehi Abar
- Department of Prosthodontics, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran; Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Somayeh Vandghanooni
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Torab
- Department of Prosthodontics, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Jaymand
- Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Morteza Eskandani
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
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8
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Lee CS, Lee M, Na K, Hwang HS. Stem Cell-Derived Extracellular Vesicles for Cancer Therapy and Tissue Engineering Applications. Mol Pharm 2023; 20:5278-5311. [PMID: 37867343 DOI: 10.1021/acs.molpharmaceut.3c00376] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2023]
Abstract
Recently, stem cells and their secretomes have attracted great attention in biomedical applications, particularly extracellular vesicles (EVs). EVs are secretomes of cells for cell-to-cell communication. They play a role as intercellular messengers as they carry proteins, nucleic acids, lipids, and therapeutic agents. They have also been utilized as drug-delivery vehicles due to their biocompatibility, low immunogenicity, stability, targetability, and engineerable properties. The therapeutic potential of EVs can be further enhanced by surface engineering and modification using functional molecules such as aptamers, peptides, and antibodies. As a consequence, EVs hold great promise as effective delivery vehicles for enhancing treatment efficacy while avoiding side effects. Among various cell types that secrete EVs, stem cells are ideal sources of EVs because stem cells have unique properties such as self-renewal and regenerative potential for transplantation into damaged tissues that can facilitate their regeneration. However, challenges such as immune rejection and ethical considerations remain significant hurdles. Stem cell-derived EVs have been extensively explored as a cell-free approach that bypasses many challenges associated with cell-based therapy in cancer therapy and tissue regeneration. In this review, we summarize and discuss the current knowledge of various types of stem cells as a source of EVs, their engineering, and applications of EVs, focusing on cancer therapy and tissue engineering.
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Affiliation(s)
- Chung-Sung Lee
- Department of Pharmaceutical Engineering, Soonchunhyang University, Asan 31538, Republic of Korea
| | - Min Lee
- Division of Advanced Prosthodontics, University of California, Los Angeles, California 90095, United States
- Department of Bioengineering, University of California, Los Angeles, California 90095, United States
| | - Kun Na
- Department of BioMedical-Chemical Engineering, The Catholic University of Korea, Bucheon 14662, Republic of Korea
- Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Republic of Korea
| | - Hee Sook Hwang
- Department of Pharmaceutical Engineering, Dankook University, Cheonan 31116, Republic of Korea
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9
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Markowska A, Koziorowski D, Szlufik S. Microglia and Stem Cells for Ischemic Stroke Treatment-Mechanisms, Current Status, and Therapeutic Challenges. FRONT BIOSCI-LANDMRK 2023; 28:269. [PMID: 37919085 DOI: 10.31083/j.fbl2810269] [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: 07/28/2023] [Revised: 09/07/2023] [Accepted: 09/12/2023] [Indexed: 11/04/2023]
Abstract
Ischemic stroke is one of the major causes of death and disability. Since the currently used treatment option of reperfusion therapy has several limitations, ongoing research is focusing on the neuroprotective effects of microglia and stem cells. By exerting the bystander effect, secreting exosomes and forming biobridges, mesenchymal stem cells (MSCs), neural stem cells (NSCs), induced pluripotent stem cells (iPSCs), and multilineage-differentiating stress-enduring cells (Muse cells) have been shown to stimulate neurogenesis, angiogenesis, cell migration, and reduce neuroinflammation. Exosome-based therapy is now being extensively researched due to its many advantageous properties over cell therapy, such as lower immunogenicity, no risk of blood vessel occlusion, and ease of storage and modification. However, although preclinical studies have shown promising therapeutic outcomes, clinical trials have been associated with several translational challenges. This review explores the therapeutic effects of preconditioned microglia as well as various factors secreted in stem cell-derived extracellular vesicles with their mechanisms of action explained. Furthermore, an overview of preclinical and clinical studies is presented, explaining the main challenges of microglia and stem cell therapies, and providing potential solutions. In particular, a highlight is the use of novel stem cell therapy of Muse cells, which bypasses many of the conventional stem cell limitations. The paper concludes with suggestions for directions in future neuroprotective research.
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Affiliation(s)
- Aleksandra Markowska
- Department of Neurology, Faculty of Health Sciences, Medical University of Warsaw, 03-242 Warsaw, Poland
| | - Dariusz Koziorowski
- Department of Neurology, Faculty of Health Sciences, Medical University of Warsaw, 03-242 Warsaw, Poland
| | - Stanisław Szlufik
- Department of Neurology, Faculty of Health Sciences, Medical University of Warsaw, 03-242 Warsaw, Poland
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Tavakoli S, Evans A, Oommen OP, Creemers L, Nandi JB, Hilborn J, Varghese OP. Unveiling extracellular matrix assembly: Insights and approaches through bioorthogonal chemistry. Mater Today Bio 2023; 22:100768. [PMID: 37600348 PMCID: PMC10432810 DOI: 10.1016/j.mtbio.2023.100768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 08/05/2023] [Accepted: 08/06/2023] [Indexed: 08/22/2023] Open
Abstract
Visualizing cells, tissues, and their components specifically without interference with cellular functions, such as biochemical reactions, and cellular viability remains important for biomedical researchers worldwide. For an improved understanding of disease progression, tissue formation during development, and tissue regeneration, labeling extracellular matrix (ECM) components secreted by cells persists is required. Bioorthogonal chemistry approaches offer solutions to visualizing and labeling ECM constituents without interfering with other chemical or biological events. Although biorthogonal chemistry has been studied extensively for several applications, this review summarizes the recent advancements in using biorthogonal chemistry specifically for metabolic labeling and visualization of ECM proteins and glycosaminoglycans that are secreted by cells and living tissues. Challenges, limitations, and future directions surrounding biorthogonal chemistry involved in the labeling of ECM components are discussed. Finally, potential solutions for improvements to biorthogonal chemical approaches are suggested. This would provide theoretical guidance for labeling and visualization of de novo proteins and polysaccharides present in ECM that are cell-secreted for example during tissue remodeling or in vitro differentiation of stem cells.
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Affiliation(s)
- Shima Tavakoli
- Macromolecular Chemistry Division, Department of Chemistry–Ångström Laboratory, Uppsala University, 751 21, Uppsala, Sweden
| | - Austin Evans
- Bioengineering and Nanomedicine Group, Faculty of Medicine and Health Technologies, Tampere University, 33720, Tampere, Finland
| | - Oommen P. Oommen
- Bioengineering and Nanomedicine Group, Faculty of Medicine and Health Technologies, Tampere University, 33720, Tampere, Finland
| | - Laura Creemers
- Department of Orthopedics, University Medical Center Utrecht, 3584, CX, Utrecht, the Netherlands
| | - Jharna Barman Nandi
- Department of Chemistry, Sarojini Naidu College for Women, 30 Jessore Road, Kolkata, 700028, India
| | - Jöns Hilborn
- Macromolecular Chemistry Division, Department of Chemistry–Ångström Laboratory, Uppsala University, 751 21, Uppsala, Sweden
| | - Oommen P. Varghese
- Macromolecular Chemistry Division, Department of Chemistry–Ångström Laboratory, Uppsala University, 751 21, Uppsala, Sweden
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11
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Sanyal A, Ghosh A, Roy C, Mazumder I, Marrazzo P. Revolutionizing the Use of Honeybee Products in Healthcare: A Focused Review on Using Bee Pollen as a Potential Adjunct Material for Biomaterial Functionalization. J Funct Biomater 2023; 14:352. [PMID: 37504847 PMCID: PMC10381877 DOI: 10.3390/jfb14070352] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 06/23/2023] [Accepted: 07/02/2023] [Indexed: 07/29/2023] Open
Abstract
The field of biomedical engineering highly demands technological improvements to allow the successful engraftment of biomaterials requested for healing damaged host tissues, tissue regeneration, and drug delivery. Polymeric materials, particularly natural polymers, are one of the primary suitable materials employed and functionalized to enhance their biocompatibility and thus confer advantageous features after graft implantation. Incorporating bioactive substances from nature is a good technique for expanding or increasing the functionality of biomaterial scaffolds, which may additionally encourage tissue healing. Our ecosystem provides natural resources, like honeybee products, comprising a rich blend of phytochemicals with interesting bioactive properties, which, when functionally coupled with biomedical biomaterials, result in the biomaterial exhibiting anti-inflammatory, antimicrobial, and antioxidant effects. Bee pollen is a sustainable product recently discovered as a new functionalizing agent for biomaterials. This review aims to articulate the general idea of using honeybee products for biomaterial engineering, mainly focusing on describing recent literature on experimental studies on biomaterials functionalized with bee pollen. We have also described the underlying mechanism of the bioactive attributes of bee pollen and shared our perspective on how future biomedical research will benefit from the fabrication of such functionalized biomaterials.
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Affiliation(s)
- Arka Sanyal
- School of Biotechnology, KIIT Deemed University, Bhubaneswar 751024, India
| | - Anushikha Ghosh
- School of Biotechnology, KIIT Deemed University, Bhubaneswar 751024, India
| | - Chandrashish Roy
- School of Biotechnology, KIIT Deemed University, Bhubaneswar 751024, India
| | - Ishanee Mazumder
- School of Biotechnology, KIIT Deemed University, Bhubaneswar 751024, India
| | - Pasquale Marrazzo
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy
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12
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Oliver-Cervelló L, Martin-Gómez H, Gonzalez-Garcia C, Salmeron-Sanchez M, Ginebra MP, Mas-Moruno C. Protease-degradable hydrogels with multifunctional biomimetic peptides for bone tissue engineering. Front Bioeng Biotechnol 2023; 11:1192436. [PMID: 37324414 PMCID: PMC10267393 DOI: 10.3389/fbioe.2023.1192436] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 05/23/2023] [Indexed: 06/17/2023] Open
Abstract
Mimicking bone extracellular matrix (ECM) is paramount to develop novel biomaterials for bone tissue engineering. In this regard, the combination of integrin-binding ligands together with osteogenic peptides represents a powerful approach to recapitulate the healing microenvironment of bone. In the present work, we designed polyethylene glycol (PEG)-based hydrogels functionalized with cell instructive multifunctional biomimetic peptides (either with cyclic RGD-DWIVA or cyclic RGD-cyclic DWIVA) and cross-linked with matrix metalloproteinases (MMPs)-degradable sequences to enable dynamic enzymatic biodegradation and cell spreading and differentiation. The analysis of the intrinsic properties of the hydrogel revealed relevant mechanical properties, porosity, swelling and degradability to engineer hydrogels for bone tissue engineering. Moreover, the engineered hydrogels were able to promote human mesenchymal stem cells (MSCs) spreading and significantly improve their osteogenic differentiation. Thus, these novel hydrogels could be a promising candidate for applications in bone tissue engineering, such as acellular systems to be implanted and regenerate bone or in stem cells therapy.
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Affiliation(s)
- Lluís Oliver-Cervelló
- Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya (UPC), Barcelona, Spain
- Barcelona Research Center in Multiscale Science and Engineering, UPC, Barcelona, Spain
| | - Helena Martin-Gómez
- Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya (UPC), Barcelona, Spain
- Barcelona Research Center in Multiscale Science and Engineering, UPC, Barcelona, Spain
| | - Cristina Gonzalez-Garcia
- Centre for the Cellular Microenvironment, Advanced Research Centre, University of Glasgow, Glasgow, United Kingdom
| | - Manuel Salmeron-Sanchez
- Centre for the Cellular Microenvironment, Advanced Research Centre, University of Glasgow, Glasgow, United Kingdom
| | - Maria-Pau Ginebra
- Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya (UPC), Barcelona, Spain
- Barcelona Research Center in Multiscale Science and Engineering, UPC, Barcelona, Spain
- Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
| | - Carlos Mas-Moruno
- Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya (UPC), Barcelona, Spain
- Barcelona Research Center in Multiscale Science and Engineering, UPC, Barcelona, Spain
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Alcalá-Alcalá S, Casarrubias-Anacleto JE, Mondragón-Guillén M, Tavira-Montalvan CA, Bonilla-Hernández M, Gómez-Galicia DL, Gosset G, Meneses-Acosta A. Melanin Nanoparticles Obtained from Preformed Recombinant Melanin by Bottom- Up and Top- Down Approaches. Polymers (Basel) 2023; 15:polym15102381. [PMID: 37242955 DOI: 10.3390/polym15102381] [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: 03/17/2023] [Revised: 05/15/2023] [Accepted: 05/16/2023] [Indexed: 05/28/2023] Open
Abstract
Melanin is an insoluble, amorphous polymer that forms planar sheets that aggregate naturally to create colloidal particles with several biological functions. Based on this, here, a preformed recombinant melanin (PRM) was utilized as the polymeric raw material to generate recombinant melanin nanoparticles (RMNPs). These nanoparticles were prepared using bottom-up (nanocrystallization-NC, and double emulsion-solvent evaporation-DE) and top-down (high-pressure homogenization-HP) manufacturing approaches. The particle size, Z-potential, identity, stability, morphology, and solid-state properties were evaluated. RMNP biocompatibility was determined in human embryogenic kidney (HEK293) and human epidermal keratinocyte (HEKn) cell lines. RMNPs prepared by NC reached a particle size of 245.9 ± 31.5 nm and a Z-potential of -20.2 ± 1.56 mV; 253.1 ± 30.6 nm and -39.2 ± 0.56 mV compared to that obtained by DE, as well as RMNPs of 302.2 ± 69.9 nm and -38.6 ± 2.25 mV using HP. Spherical and solid nanostructures in the bottom-up approaches were observed; however, they were an irregular shape with a wide size distribution when the HP method was applied. Infrared (IR) spectra showed no changes in the chemical structure of the melanin after the manufacturing process but did exhibit an amorphous crystal rearrangement according to calorimetric and PXRD analysis. All RMNPs presented long stability in an aqueous suspension and resistance to being sterilized by wet steam and ultraviolet (UV) radiation. Finally, cytotoxicity assays showed that RMNPs are safe up to 100 μg/mL. These findings open new possibilities for obtaining melanin nanoparticles with potential applications in drug delivery, tissue engineering, diagnosis, and sun protection, among others.
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Affiliation(s)
- Sergio Alcalá-Alcalá
- Laboratorio de Investigación en Tecnología Farmacéutica, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, Mexico
| | - José Eduardo Casarrubias-Anacleto
- Laboratorio de Investigación en Tecnología Farmacéutica, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, Mexico
| | - Maximiliano Mondragón-Guillén
- Laboratorio de Biotecnología Farmacéutica, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, Mexico
| | - Carlos Alberto Tavira-Montalvan
- Laboratorio de Biotecnología Farmacéutica, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, Mexico
| | - Marcos Bonilla-Hernández
- Laboratorio de Investigación en Tecnología Farmacéutica, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, Mexico
| | - Diana Lizbeth Gómez-Galicia
- Farmacia Hospitalaria, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, Mexico
| | - Guillermo Gosset
- Departamento de Ingeniería Celular y Biocatálisis, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca 62209, Morelos, Mexico
| | - Angélica Meneses-Acosta
- Laboratorio de Biotecnología Farmacéutica, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, Mexico
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Tamo AK, Tran TA, Doench I, Jahangir S, Lall A, David L, Peniche-Covas C, Walther A, Osorio-Madrazo A. 3D Printing of Cellulase-Laden Cellulose Nanofiber/Chitosan Hydrogel Composites: Towards Tissue Engineering Functional Biomaterials with Enzyme-Mediated Biodegradation. MATERIALS (BASEL, SWITZERLAND) 2022; 15:6039. [PMID: 36079419 PMCID: PMC9456765 DOI: 10.3390/ma15176039] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 08/23/2022] [Accepted: 08/23/2022] [Indexed: 05/18/2023]
Abstract
The 3D printing of a multifunctional hydrogel biomaterial with bioactivity for tissue engineering, good mechanical properties and a biodegradability mediated by free and encapsulated cellulase was proposed. Bioinks of cellulase-laden and cellulose nanofiber filled chitosan viscous suspensions were used to 3D print enzymatic biodegradable and biocompatible cellulose nanofiber (CNF) reinforced chitosan (CHI) hydrogels. The study of the kinetics of CNF enzymatic degradation was studied in situ in fibroblast cell culture. To preserve enzyme stability as well as to guarantee its sustained release, the cellulase was preliminarily encapsulated in chitosan-caseinate nanoparticles, which were further incorporated in the CNF/CHI viscous suspension before the 3D printing of the ink. The incorporation of the enzyme within the CHI/CNF hydrogel contributed to control the decrease of the CNF mechanical reinforcement in the long term while keeping the cell growth-promoting property of chitosan. The hydrolysis kinetics of cellulose in the 3D printed scaffolds showed a slow but sustained degradation of the CNFs with enzyme, with approximately 65% and 55% relative activities still obtained after 14 days of incubation for the encapsulated and free enzyme, respectively. The 3D printed composite hydrogels showed excellent cytocompatibility supporting fibroblast cell attachment, proliferation and growth. Ultimately, the concomitant cell growth and biodegradation of CNFs within the 3D printed CHI/CNF scaffolds highlights the remarkable potential of CHI/CNF composites in the design of tissue models for the development of 3D constructs with tailored in vitro/in vivo degradability for biomedical applications.
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Affiliation(s)
- Arnaud Kamdem Tamo
- Laboratory for Bioinspired Materials BMBT, Institute of Microsystems Engineering IMTEK, University of Freiburg, 79110 Freiburg, Germany or
- Freiburg Center for Interactive Materials and Bioinspired Technologies FIT, University of Freiburg, 79110 Freiburg, Germany
- Freiburg Materials Research Center FMF, University of Freiburg, 79104 Freiburg, Germany
| | - Tuan Anh Tran
- Laboratory for Bioinspired Materials BMBT, Institute of Microsystems Engineering IMTEK, University of Freiburg, 79110 Freiburg, Germany or
- Freiburg Center for Interactive Materials and Bioinspired Technologies FIT, University of Freiburg, 79110 Freiburg, Germany
- Freiburg Materials Research Center FMF, University of Freiburg, 79104 Freiburg, Germany
| | - Ingo Doench
- Laboratory for Bioinspired Materials BMBT, Institute of Microsystems Engineering IMTEK, University of Freiburg, 79110 Freiburg, Germany or
- Freiburg Center for Interactive Materials and Bioinspired Technologies FIT, University of Freiburg, 79110 Freiburg, Germany
- Freiburg Materials Research Center FMF, University of Freiburg, 79104 Freiburg, Germany
| | - Shaghayegh Jahangir
- Laboratory for Bioinspired Materials BMBT, Institute of Microsystems Engineering IMTEK, University of Freiburg, 79110 Freiburg, Germany or
- Freiburg Center for Interactive Materials and Bioinspired Technologies FIT, University of Freiburg, 79110 Freiburg, Germany
- Freiburg Materials Research Center FMF, University of Freiburg, 79104 Freiburg, Germany
| | - Aastha Lall
- Laboratory for Bioinspired Materials BMBT, Institute of Microsystems Engineering IMTEK, University of Freiburg, 79110 Freiburg, Germany or
- Freiburg Center for Interactive Materials and Bioinspired Technologies FIT, University of Freiburg, 79110 Freiburg, Germany
- Freiburg Materials Research Center FMF, University of Freiburg, 79104 Freiburg, Germany
| | - Laurent David
- Polymer Materials Engineering IMP CNRS UMR 5223, Université Lyon, Université Claude Bernard Lyon 1, Université Jean Monnet St Etienne, INSA de Lyon, CNRS, 69622 Villeurbanne, France
| | - Carlos Peniche-Covas
- Center of Biomaterials, Faculty of Chemistry, University of Havana, Havana 10400, Cuba
| | - Andreas Walther
- ABMS Lab, Active, Adaptive and Autonomous Bioinspired Materials, Department of Chemistry, University of Mainz, 55128 Mainz, Germany
| | - Anayancy Osorio-Madrazo
- Laboratory for Bioinspired Materials BMBT, Institute of Microsystems Engineering IMTEK, University of Freiburg, 79110 Freiburg, Germany or
- Freiburg Center for Interactive Materials and Bioinspired Technologies FIT, University of Freiburg, 79110 Freiburg, Germany
- Freiburg Materials Research Center FMF, University of Freiburg, 79104 Freiburg, Germany
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Pan Y, Luo Y, Hong J, He H, Dai L, Zhu H, Wu J. Advances for the treatment of lower extremity arterial disease associated with diabetes mellitus. Front Mol Biosci 2022; 9:929718. [PMID: 36060247 PMCID: PMC9429832 DOI: 10.3389/fmolb.2022.929718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 07/19/2022] [Indexed: 11/13/2022] Open
Abstract
Lower extremity arterial disease (LEAD) is a major vascular complication of diabetes. Vascular endothelial cells dysfunction can exacerbate local ischemia, leading to a significant increase in amputation, disability, and even mortality in patients with diabetes combined with LEAD. Therefore, it is of great clinical importance to explore proper and effective treatments. Conventional treatments of diabetic LEAD include lifestyle management, medication, open surgery, endovascular treatment, and amputation. As interdisciplinary research emerges, regenerative medicine strategies have provided new insights to treat chronic limb threatening ischemia (CLTI). Therapeutic angiogenesis strategies, such as delivering growth factors, stem cells, drugs to ischemic tissues, have also been proposed to treat LEAD by fundamentally stimulating multidimensional vascular regeneration. Recent years have seen the rapid growth of tissue engineering technology; tissue-engineered biomaterials have been used to study the treatment of LEAD, such as encapsulation of growth factors and drugs in hydrogel to facilitate the restoration of blood perfusion in ischemic tissues of animals. The primary purpose of this review is to introduce treatments and novel biomaterials development in LEAD. Firstly, the pathogenesis of LEAD is briefly described. Secondly, conventional therapies and therapeutic angiogenesis strategies of LEAD are discussed. Finally, recent research advances and future perspectives on biomaterials in LEAD are proposed.
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Affiliation(s)
- Yang Pan
- Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yuting Luo
- Key Laboratory of Biotechnology and Pharmaceutical Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jing Hong
- Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Huacheng He
- College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang, China
- *Correspondence: Huacheng He, ; Hong Zhu,
| | - Lu Dai
- The Fourth Outpatient Department, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Hong Zhu
- Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- *Correspondence: Huacheng He, ; Hong Zhu,
| | - Jiang Wu
- Key Laboratory of Biotechnology and Pharmaceutical Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
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Abstract
The successful transplantation of stem cells has the potential to transform regenerative medicine approaches and open promising avenues to repair, replace, and regenerate diseased, damaged, or aged tissues. However, pre-/post-transplantation issues of poor cell survival, retention, cell fate regulation, and insufficient integration with host tissues constitute significant challenges. The success of stem cell transplantation depends upon the coordinated sequence of stem cell renewal, specific lineage differentiation, assembly, and maintenance of long-term function. Advances in biomaterials can improve pre-/post-transplantation outcomes by integrating biophysiochemical cues and emulating tissue microenvironments. This review highlights leading biomaterials-based approaches for enhancing stem cell transplantation.
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Affiliation(s)
- Bhushan N Kharbikar
- Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA
| | - Priya Mohindra
- UC Berkeley-UCSF Graduate Program in Bioengineering, San Francisco, CA 94158, USA
| | - Tejal A Desai
- Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA; UC Berkeley-UCSF Graduate Program in Bioengineering, San Francisco, CA 94158, USA; Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA; School of Engineering, Brown University, Providence, RI, 02912, USA.
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17
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Bacterial Cellulose-A Remarkable Polymer as a Source for Biomaterials Tailoring. MATERIALS 2022; 15:ma15031054. [PMID: 35160997 PMCID: PMC8839122 DOI: 10.3390/ma15031054] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 01/19/2022] [Accepted: 01/27/2022] [Indexed: 12/11/2022]
Abstract
Nowadays, the development of new eco-friendly and biocompatible materials using ‘green’ technologies represents a significant challenge for the biomedical and pharmaceutical fields to reduce the destructive actions of scientific research on the human body and the environment. Thus, bacterial cellulose (BC) has a central place among these novel tailored biomaterials. BC is a non-pathogenic bacteria-produced polysaccharide with a 3D nanofibrous structure, chemically identical to plant cellulose, but exhibiting greater purity and crystallinity. Bacterial cellulose possesses excellent physicochemical and mechanical properties, adequate capacity to absorb a large quantity of water, non-toxicity, chemical inertness, biocompatibility, biodegradability, proper capacity to form films and to stabilize emulsions, high porosity, and a large surface area. Due to its suitable characteristics, this ecological material can combine with multiple polymers and diverse bioactive agents to develop new materials and composites. Bacterial cellulose alone, and with its mixtures, exhibits numerous applications, including in the food and electronic industries and in the biotechnological and biomedical areas (such as in wound dressing, tissue engineering, dental implants, drug delivery systems, and cell culture). This review presents an overview of the main properties and uses of bacterial cellulose and the latest promising future applications, such as in biological diagnosis, biosensors, personalized regenerative medicine, and nerve and ocular tissue engineering.
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Kang HT, Jang K, Jun DW, Yoon EL, Lee SM, Saeed WK, Lee JH. Macro-encapsulation of mesenchymal stem cells in acute and chronic liver injury animal models. J Gastroenterol Hepatol 2021; 36:1997-2007. [PMID: 33554346 DOI: 10.1111/jgh.15434] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Revised: 12/19/2020] [Accepted: 02/02/2021] [Indexed: 01/10/2023]
Abstract
BACKGROUND AND AIM Stem cell treatments using scaffolds for liver disease have been well studied. However, macro-encapsulation of mesenchymal stem cells (MSCs) to minimize or inhibit stem cell homing has not been evaluated. Here, we conducted a proof-of-concept study using MSCs macro-encapsulated in poly lactic-co-glycolic acid in liver disease models. METHODS Poly lactic-co-glycolic acid semipermeable membranes (surface pore size up to 40 μm) were used as the macro-encapsulation system. Macro-encapsulated pouches were loaded with MSCs and sealed. Each pouch was implanted in the subcutaneous region of the dorsum or interlobular space of the liver. Acute liver injury was induced using thioacetamide intraperitoneal injection thrice a week. For the chronic liver fibrosis model, thioacetamide dose was gradually increased, starting from 100 to 400 mg/kg over 16 weeks (thrice a week). RESULTS In the acute liver injury model, the treated groups showed decreased liver inflammation and necrosis compared with the control. Hepatic fibrosis decreased in the treated group in the chronic liver fibrosis model compared with that in the control group. Encapsulated MSCs exhibited changed cell morphology and characteristics after implantation, showing increased periodic acid-Schiff staining and CYP2E1 expression. Migration and homing of MSCs into the liver was not observed. Under hypoxic conditions, macro-encapsulated MSCs secreted more growth hormones, including vascular endothelial growth factor, platelet-derived growth factor, angiopoietin-2, and placental growth factor, than monolayered MSCs in vitro. CONCLUSIONS Macro-encapsulated MSCs attenuate hepatic inflammation and fibrosis by upregulating hypoxia-induced growth hormone secretion in liver disease models.
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Affiliation(s)
- Hyeon Tae Kang
- Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science and Engineering, Seoul, South Korea
| | - Kiseok Jang
- Department of Pathology, Hanyang University School of Medicine, Seoul, South Korea
| | - Dae Won Jun
- Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science and Engineering, Seoul, South Korea.,Department of Internal Medicine, Hanyang University School of Medicine, Seoul, South Korea
| | - Eileen L Yoon
- Department of Internal Medicine, Hanyang University School of Medicine, Seoul, South Korea
| | - Seung Min Lee
- Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science and Engineering, Seoul, South Korea
| | - Waqar Khalid Saeed
- Department of Biomedical Sciences, Pak-Austria Fachhochschule: Institute of Applied Sciences and Technology, Mang, Haripur, Pakistan
| | - Jin Ho Lee
- Department of Advanced Materials, Hannam University, Daejeon, South Korea
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19
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Sevari SP, Ansari S, Moshaverinia A. A narrative overview of utilizing biomaterials to recapitulate the salient regenerative features of dental-derived mesenchymal stem cells. Int J Oral Sci 2021; 13:22. [PMID: 34193832 PMCID: PMC8245503 DOI: 10.1038/s41368-021-00126-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 05/26/2021] [Accepted: 06/03/2021] [Indexed: 02/06/2023] Open
Abstract
Tissue engineering approaches have emerged recently to circumvent many limitations associated with current clinical practices. This elegant approach utilizes a natural/synthetic biomaterial with optimized physiomechanical properties to serve as a vehicle for delivery of exogenous stem cells and bioactive factors or induce local recruitment of endogenous cells for in situ tissue regeneration. Inspired by the natural microenvironment, biomaterials could act as a biomimetic three-dimensional (3D) structure to help the cells establish their natural interactions. Such a strategy should not only employ a biocompatible biomaterial to induce new tissue formation but also benefit from an easily accessible and abundant source of stem cells with potent tissue regenerative potential. The human teeth and oral cavity harbor various populations of mesenchymal stem cells (MSCs) with self-renewing and multilineage differentiation capabilities. In the current review article, we seek to highlight recent progress and future opportunities in dental MSC-mediated therapeutic strategies for tissue regeneration using two possible approaches, cell transplantation and cell homing. Altogether, this paper develops a general picture of current innovative strategies to employ dental-derived MSCs combined with biomaterials and bioactive factors for regenerating the lost or defective tissues and offers information regarding the available scientific data and possible applications.
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Affiliation(s)
- Sevda Pouraghaei Sevari
- Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA
| | - Sahar Ansari
- Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA
| | - Alireza Moshaverinia
- Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
- California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
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Hong L, Sun H, Amendt BA. MicroRNA function in craniofacial bone formation, regeneration and repair. Bone 2021; 144:115789. [PMID: 33309989 PMCID: PMC7869528 DOI: 10.1016/j.bone.2020.115789] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 11/25/2020] [Accepted: 12/01/2020] [Indexed: 02/06/2023]
Abstract
Bone formation in the craniofacial complex is regulated by cranial neural crest (CNC) and mesoderm-derived cells. Different elements of the developing skull, face, mandible, maxilla (jaws) and nasal bones are regulated by an array of transcription factors, signaling molecules and microRNAs (miRs). miRs are molecular modulators of these factors and act to restrict their expression in a temporal-spatial mechanism. miRs control the different genetic pathways that form the craniofacial complex. By understanding how miRs function in vivo during development they can be adapted to regenerate and repair craniofacial genetic anomalies as well as bone diseases and defects due to traumatic injuries. This review will highlight some of the new miR technologies and functions that form new bone or inhibit bone regeneration.
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Affiliation(s)
- Liu Hong
- Iowa Institute for Oral Health Research, The University of Iowa, Iowa City, IA, USA
| | - Hongli Sun
- Iowa Institute for Oral Health Research, The University of Iowa, Iowa City, IA, USA
| | - Brad A Amendt
- Iowa Institute for Oral Health Research, The University of Iowa, Iowa City, IA, USA; The University of Iowa, Department of Anatomy and Cell Biology, Iowa City, IA, USA; Craniofacial Anomalies Research Center, The University of Iowa, Iowa City, IA, USA.
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21
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Al-Hamdan RS, Almutairi B, Kattan HF, Alsuwailem NA, Farooq I, Vohra F, Abduljabbar T. Influence of Hydroxyapatite Nanospheres in Dentin Adhesive on the Dentin Bond Integrity and Degree of Conversion: A Scanning Electron Microscopy (SEM), Raman, Fourier Transform-Infrared (FTIR), and Microtensile Study. Polymers (Basel) 2020; 12:E2948. [PMID: 33321699 PMCID: PMC7764663 DOI: 10.3390/polym12122948] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 12/01/2020] [Accepted: 12/04/2020] [Indexed: 12/18/2022] Open
Abstract
An experimental adhesive incorporated with different nano-hydroxyapatite (n-HA) particle concentrations was synthesized and analyzed for dentin interaction, micro-tensile bond strength (μTBS), and degree of conversion (DC). n-HA powder (5 wt % and 10 wt %) were added in adhesive to yield three groups; gp-1: control experimental adhesive (CEA, 0 wt % HA), gp-2: 5 wt % n-HA (HAA-5%), and gp-3: 10 wt % n-HA (HAA-10%). The morphology of n-HA spheres was evaluated using Scanning Electron Microscopy (SEM). Their interaction in the adhesives was identified with SEM, Energy-Dispersive X-ray (EDX), and Micro-Raman spectroscopy. Teeth were sectioned, divided in study groups, and assessed for μTBS and failure mode. Employing Fourier Transform-Infrared (FTIR) spectroscopy, the DC of the adhesives was assessed. EDX mapping revealed the occurrence of oxygen, calcium, and phosphorus in the HAA-5% and HAA-10% groups. HAA-5% had the greatest μTBS values followed by HAA-10%. The presence of apatite was shown by FTIR spectra and Micro-Raman demonstrated phosphate and carbonate groups for n-HA spheres. The highest DC was observed for the CEA group followed by HAA-5%. n-HA spheres exhibited dentin interaction and formed a hybrid layer with resin tags. HAA-5% demonstrated superior μTBS compared with HAA-10% and control adhesive. The DC for HAA-5% was comparable to control adhesive.
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Affiliation(s)
- Rana S Al-Hamdan
- Department of Restorative Dental Sciences, College of Dentistry, King Saud University, 60169, Riyadh 11545, Saudi Arabia; (R.SA.-H.); (B.A.)
| | - Basil Almutairi
- Department of Restorative Dental Sciences, College of Dentistry, King Saud University, 60169, Riyadh 11545, Saudi Arabia; (R.SA.-H.); (B.A.)
| | - Hiba F Kattan
- Preventive Dental Science Department, Princess Nourah bint Abdulrahman University, Riyadh 11545, Saudi Arabia;
| | | | - Imran Farooq
- Faculty of Dentistry, University of Toronto, Toronto, ON M5S 1A1, Canada;
| | - Fahim Vohra
- Department of Prosthetic Dental Science, College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia;
- Research Chair for Biological Research in Dental Health, College of Dentistry, Riyadh 11545, Saudi Arabia
| | - Tariq Abduljabbar
- Department of Prosthetic Dental Science, College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia;
- Research Chair for Biological Research in Dental Health, College of Dentistry, Riyadh 11545, Saudi Arabia
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Gilchrist AE, Harley BA. Connecting secretome to hematopoietic stem cell phenotype shifts in an engineered bone marrow niche. Integr Biol (Camb) 2020; 12:175-187. [PMID: 32556172 PMCID: PMC7384206 DOI: 10.1093/intbio/zyaa013] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 04/21/2020] [Accepted: 05/08/2020] [Indexed: 01/06/2023]
Abstract
Hematopoietic stem cells (HSCs) primarily reside in the bone marrow, where they receive external cues from their local microenvironment. The complex milieu of biophysical cues, cellular components and cell-secreted factors regulates the process by which HSC produce the blood and immune system. We previously showed direct coculture of primary murine hematopoietic stem and progenitor cells with a population of marrow-derived mesenchymal stromal and progenitor cells (MSPCs) in a methacrylamide-functionalized gelatin (GelMA) hydrogel improves hematopoietic progenitor maintenance. However, the mechanism by which MSPCs influenced HSC fate decisions remained unknown. Herein, we report the use of proteomic analysis to correlate HSC phenotype to a broad candidate pool of 200 soluble factors produced by combined mesenchymal and hematopoietic progeny. Partial least squares regression (PLSR), along with an iterative filter method, identified TGFβ-1, MMP-3, c-RP and TROY as positively correlated with HSC maintenance. Experimentally, we then observe exogenous stimulation of HSC monocultures in GelMA hydrogels with these combined cytokines increases the ratio of hematopoietic progenitors to committed progeny after a 7-day culture 7.52 ± 3.65-fold compared to non-stimulated monocultures. Findings suggest a cocktail of the downselected cytokines amplifies hematopoietic maintenance potential of HSCs beyond that of MSPC-secreted factors alone. This work integrates empirical and computation methods to identify cytokine combinations to improve HSC maintenance within an engineered HSC niche, suggesting a route toward identifying feeder-free culture platforms for HSC expansion. Insight Hematopoietic stem cells within an artificial niche receive maintenance cues in the form of soluble factors from hematopoietic and mesenchymal progeny. Applying a proteomic regression analysis, we identify a reduced set of soluble factors correlated to maintenance of a hematopoietic phenotype during culture in a biomaterial model of the bone marrow niche. We identify a minimum factor cocktail that promotes hematopoietic maintenance potential in a gelatin-based culture, regardless of the presence of mesenchymal feeder cells. By combining empirical and computational methods, we report an experimentally feasible number of factors from a large dataset, enabling exogenous integration of soluble factors into an engineered hematopoietic stem cell for enhanced maintenance potential of a quiescent stem cell population.
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Affiliation(s)
- Aidan E. Gilchrist
- Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Brendan A.C. Harley
- Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
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Shapourzadeh A, Atyabi SM, Irani S, Bakhshi H. Osteoinductivity of polycaprolactone nanofibers grafted functionalized with carboxymethyl chitosan: Synergic effect of β-carotene and electromagnetic field. Int J Biol Macromol 2020; 150:152-160. [DOI: 10.1016/j.ijbiomac.2020.02.036] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 01/21/2020] [Accepted: 02/05/2020] [Indexed: 01/24/2023]
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Oberweis CV, Marchal JA, López-Ruiz E, Gálvez-Martín P. A Worldwide Overview of Regulatory Frameworks for Tissue-Based Products. TISSUE ENGINEERING PART B-REVIEWS 2020; 26:181-196. [DOI: 10.1089/ten.teb.2019.0315] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Affiliation(s)
- Caroline Veronique Oberweis
- Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospitals of Granada—University of Granada, Granada, Spain
| | - Juan Antonio Marchal
- Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospitals of Granada—University of Granada, Granada, Spain
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, Granada, Spain
- Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain
- Excellence Research Unit “Modeling Nature” (MNat), University of Granada, Granada, Spain
| | - Elena López-Ruiz
- Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospitals of Granada—University of Granada, Granada, Spain
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, Granada, Spain
- Excellence Research Unit “Modeling Nature” (MNat), University of Granada, Granada, Spain
- Department of Health Sciences, University of Jaén, Jaén, Spain
| | - Patricia Gálvez-Martín
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Granada, Spain
- R&D Human Health, Bioibérica S.A.U., Barcelona, Spain
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25
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Carvalho CR, Costa JB, Costa L, Silva-Correia J, Moay ZK, Ng KW, Reis RL, Oliveira JM. Enhanced performance of chitosan/keratin membranes with potential application in peripheral nerve repair. Biomater Sci 2020; 7:5451-5466. [PMID: 31642822 DOI: 10.1039/c9bm01098j] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Although surgical management of peripheral nerve injuries (PNIs) has improved over time, autografts are still the current "gold standard" treatment for PNIs, which presents numerous limitations. In an attempt to improve natural biomaterial-based nerve guidance conduits (NGCs), chitosan (CHT), a derivative of the naturally occurring biopolymer chitin, has been explored for peripheral nerve regeneration (PNR). In addition to CHT, keratin has gained enormous attention as a biomaterial and tissue engineering scaffolding. In this study, biomimetic CHT/keratin membranes were produced using a solvent casting technique. These membranes were broadly characterized in terms of their surface topography and physicochemical properties, with techniques such as Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), contact angle, weight loss and water uptake measurements, Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM). Biological in vitro assays were also performed, where a preliminary cytotoxicity screening with the L929 fibroblast cell line revealed that the membranes and respective materials are suitable for cell culture. In addition, Schwann cells, fibroblasts and endothelial cells were directly seeded in the membranes. Quantitative and qualitative assays revealed that the addition of keratin enhanced cell viablity and adhesion. Based on the encouraging in vitro results, the in vivo angiogenic/antiangiogenic potential of CHT and CHT/keratin membranes was assessed, using an optimized chick embryo chorioallantoic membrane assay, where higher angiogenic responses were seen in keratin-enriched materials. Overall, the obtained results indicate the higher potential of CHT/keratin membranes for guided tissue regeneration applications in the field of PNR.
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Affiliation(s)
- Cristiana R Carvalho
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Avepark - Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal.
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26
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Marycz K, Smieszek A, Targonska S, Walsh SA, Szustakiewicz K, Wiglusz RJ. Three dimensional (3D) printed polylactic acid with nano-hydroxyapatite doped with europium(III) ions (nHAp/PLLA@Eu 3+) composite for osteochondral defect regeneration and theranostics. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 110:110634. [PMID: 32204070 DOI: 10.1016/j.msec.2020.110634] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 12/31/2019] [Accepted: 01/03/2020] [Indexed: 12/20/2022]
Abstract
In the current research previously developed composites composed from poly (l-lactide) (PLLA) and nano-hydroxyapatite (10 wt% nHAp/PLLA) were functionalized with different concentrations of europium (III) (Eu3+). The aim of this study was to determine whether Eu3+ ions doped within the 10 wt% nHAp/PLLA scaffolds will improve the bioactivity of composites. Therefore, first set of experiments was designed to evaluate the effect of Eu3+ ions on morphology, viability, proliferation and metabolism of progenitor cells isolated from adipose tissue (hASC). Three different concentration were tested i.e. 1 mol%, 3 mol% and 5%mol. We identified the 10 wt% nHAp/PLLA@3 mol% Eu3+ scaffolds as the most cytocompatible. Further, we investigated the influence of the composites doped with 3 mol% Eu3+ ions on differentiation of hASC toward bone and cartilage forming cells. Our results showed that 10 wt% nHAp/PLLA@3 mol% Eu3+ scaffolds promotes osteogenesis and chondrogenesis of hASCs what was associated with improved synthesis and secretion of extracellular matrix proteins specific for bone and articular cartilage tissue. We also proved that obtained biomaterials have bio-imaging function and their integration with bone can be monitored using micro computed tomography (μCT).
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Affiliation(s)
- Krzysztof Marycz
- University of Environmental and Life Sciences Wroclaw, The Department of Experimental Biology, The Faculty of Biology and Animal Science, 38 C Chelmonskiego St., 50-630 Wroclaw, Poland; Collegium Medicum, Cardinal Stefan Wyszynski University (UKSW), Woycickiego 1/3, 01-938 Warsaw, Poland
| | - Agnieszka Smieszek
- University of Environmental and Life Sciences Wroclaw, The Department of Experimental Biology, The Faculty of Biology and Animal Science, 38 C Chelmonskiego St., 50-630 Wroclaw, Poland
| | - Sara Targonska
- Institute of Low Temperature and Structure Research, Polish Academy of Sciences, Okolna 2, PL-50-422 Wroclaw, Poland
| | - Susan A Walsh
- Small Animal Imaging Core, University of Iowa Carver College of Medicine, Iowa City, IA, United States of America
| | - Konrad Szustakiewicz
- Polymer Engineering and Technology Division, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland
| | - Rafal J Wiglusz
- Institute of Low Temperature and Structure Research, Polish Academy of Sciences, Okolna 2, PL-50-422 Wroclaw, Poland; Centre for Advanced Materials and Smart Structures, Polish Academy of Sciences, Okolna 2, 50-950 Wroclaw, Poland.
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27
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Wang SJ, Jiang D, Zhang ZZ, Chen YR, Yang ZD, Zhang JY, Shi J, Wang X, Yu JK. Biomimetic Nanosilica-Collagen Scaffolds for In Situ Bone Regeneration: Toward a Cell-Free, One-Step Surgery. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2019; 31:e1904341. [PMID: 31621958 DOI: 10.1002/adma.201904341] [Citation(s) in RCA: 124] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 09/26/2019] [Indexed: 05/18/2023]
Abstract
Current approaches to fabrication of nSC composites for bone tissue engineering (BTE) have limited capacity to achieve uniform surface functionalization while replicating the complex architecture and bioactivity of native bone, compromising application of these nanocomposites for in situ bone regeneration. A robust biosilicification strategy is reported to impart a uniform and stable osteoinductive surface to porous collagen scaffolds. The resultant nSC composites possess a native-bone-like porous structure and a nanosilica coating. The osteoinductivity of the nSC scaffolds is strongly dependent on the surface roughness and silicon content in the silica coating. Notably, without the use of exogenous cells and growth factors (GFs), the nSC scaffolds induce successful repair of a critical-sized calvarium defect in a rabbit model. It is revealed that topographic and chemical cues presented by nSC scaffolds could synergistically activate multiple signaling pathways related to mesenchymal stem cell recruitment and bone regeneration. Thus, this facile surface biosilicification approach could be valuable by enabling production of BTE scaffolds with large sizes, complex porous structures, and varied osteoinductivity. The nanosilica-functionalized scaffolds can be implanted via a cell/GF-free, one-step surgery for in situ bone regeneration, thus demonstrating high potential for clinical translation in treatment of massive bone defects.
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Affiliation(s)
- Shao-Jie Wang
- Knee Surgery Department of the Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, 100191, China
- Department of Joint Surgery and Sports Medicine, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, 361000, China
| | - Dong Jiang
- Knee Surgery Department of the Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, 100191, China
| | - Zheng-Zheng Zhang
- Knee Surgery Department of the Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, 100191, China
- Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - You-Rong Chen
- Knee Surgery Department of the Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, 100191, China
| | - Zheng-Dong Yang
- Department of Chemistry, University of California Riverside, Riverside, CA, 92521, USA
| | - Ji-Ying Zhang
- Knee Surgery Department of the Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, 100191, China
| | - Jinjun Shi
- Center for Nanomedicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
| | - Xing Wang
- Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, China
| | - Jia-Kuo Yu
- Knee Surgery Department of the Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, 100191, China
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Rana D, Kumar S, Webster TJ, Ramalingam M. Impact of Induced Pluripotent Stem Cells in Bone Repair and Regeneration. Curr Osteoporos Rep 2019; 17:226-234. [PMID: 31256323 DOI: 10.1007/s11914-019-00519-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW The main objective of this article is to investigate the current trends in the use of induced pluripotent stem cells (iPSCs) for bone tissue repair and regeneration. RECENT FINDINGS Pluripotent stem cell-based tissue engineering has extended innovative therapeutic approaches for regenerative medicine. iPSCs have shown osteogenic differentiation capabilities and would be an innovative resource of stem cells for bone tissue regenerative applications. This review recapitulates the current knowledge and recent progress regarding utilization of iPSCs for bone therapy. A review of current findings suggests that a combination of a three-dimensional scaffolding system with iPSC technology to mimic the physiological complexity of the native stem cell niche is highly favorable for bone tissue repair and regeneration.
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Affiliation(s)
- Deepti Rana
- Department of Biomechanical Engineering, Technical Medical Centre, University of Twente, 7522 NB, Enschede, The Netherlands
| | - Sanjay Kumar
- Centre for Stem Cell Research, Christian Medical College Campus, Vellore, 632002, India
| | - Thomas J Webster
- Department of Chemical Engineering, Northeastern University, Boston, MA, 02115, USA.
| | - Murugan Ramalingam
- Biomaterials and Stem Cell Engineering Lab, Centre for Biomaterials, Cellular and Molecular Theranostics, School of Mechanical Engineering, Vellore Institute of Technology (Deemed to be University), Vellore, 632014, India.
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29
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Ghosh LD, Ravi V, Jain A, Panicker AG, Sundaresan NR, Chatterjee K. Sirtuin 6 mediated stem cell cardiomyogenesis on protein coated nanofibrous scaffolds. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2019; 19:145-155. [PMID: 30926577 DOI: 10.1016/j.nano.2019.03.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Revised: 02/11/2019] [Accepted: 03/12/2019] [Indexed: 12/26/2022]
Abstract
The cellular niche provides combination of biomolecular and biophysical cues to control stem cell fate. Three-dimensional (3D) aligned nanofibrous scaffolds can effectively augment stem cell cardiomyogenesis. This work aims to understand the role of biomolecular signals from extracellular matrix (ECM) proteins and leverage them to further promote cardiomyogenesis on nanofibrous scaffolds. Human mesenchymal stem cells (hMSCs) were cultured on 3D aligned polycaprolactone scaffolds coated with different ECM proteins. Among multiple coatings tested, collagen coated fibers were most effective in promoting cardiomyogenesis as determined from increased expression of cardiac biomarkers and intracellular calcium flux. At molecular level, enhanced differentiation on collagen coated fibers was associated with an increased level of sirtuin 6 (SIRT6). Depletion of SIRT6 using siRNA attenuated the differentiation process through activation of Wnt signaling pathway. This study, thus, demonstrates that protein coated scaffolds can augment cardiomyogenic differentiation of stem cells through a combination of topographical and biomolecular signals.
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Affiliation(s)
- Lopamudra Das Ghosh
- Department of Materials Engineering, Indian Institute of Science, Bangalore, India
| | - Venkatraman Ravi
- Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India
| | - Aditi Jain
- Centre for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, India
| | - Arpana G Panicker
- Department of Materials Engineering, Indian Institute of Science, Bangalore, India
| | - Nagalingam R Sundaresan
- Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India; Centre for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, India.
| | - Kaushik Chatterjee
- Department of Materials Engineering, Indian Institute of Science, Bangalore, India; Centre for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, India.
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30
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Zhang B, Kasoju N, Li Q, Ma J, Yang A, Cui Z, Wang H, Ye H. Effect of Substrate Topography and Chemistry on Human Mesenchymal Stem Cell Markers: A Transcriptome Study. Int J Stem Cells 2019; 12:84-94. [PMID: 30836724 PMCID: PMC6457710 DOI: 10.15283/ijsc18102] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 01/25/2019] [Accepted: 02/04/2019] [Indexed: 02/06/2023] Open
Abstract
Background and Objectives The International Society for Cellular Therapy (ISCT) proposed a set of minimal markers for identifying human mesenchymal stromal cells (hMSCs) in 2007. Since then, with the growing interest of better characterising hMSCs, various additional surface markers have been proposed. However, the impact of how culture conditions, in particular, the culture surface, vary the expression of hMSC markers was overlooked. Methods and Results In this study, we utilized the RNA sequencing data on hMSCs cultured on different surfaces to investigate the variation of the proposed hMSC biomarkers. One of the three ISCT proposed positive biomarker, CD90 was found to be significantly down regulated on hMSCs culture on fibrous surfaces when compared to flat surfaces. The detected gene expression values for 177 hMSCs biomarkers compiled from the literature are reported here. Correlation and cluster analysis revealed the existence of different biomarker communities that displayed a similar expression profile. We found a list of hMSCs biomarkers which are the least sensitive to a change in surface properties and another list of biomarkers which are found to have high sensitivity to a change in surface properties. Conclusions This study demonstrated that substrate properties have paramount effect on altering the expressions of hMSCs biomarkers and the proposed list of substrate-stable and substrate-sensitive biomarkers would better assist in the population characterisation. However, proteomic level analysis would be essential to confirm the observations noted.
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Affiliation(s)
- Bo Zhang
- Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK.,Department of Engineering Science, University of Oxford, Oxford, UK
| | - Naresh Kasoju
- Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK
| | | | - Jinmin Ma
- BGI-Shenzhen, Shenzhen 518083, China
| | - Aidong Yang
- Department of Engineering Science, University of Oxford, Oxford, UK
| | - Zhanfeng Cui
- Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK
| | - Hui Wang
- Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK.,BGI-Shenzhen, Shenzhen 518083, China.,Oxford Suzhou Centre for Advanced Research, Suzhou Industrial Park, Jiangsu, China
| | - Hua Ye
- Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK
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31
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Kwon SG, Kwon YW, Lee TW, Park GT, Kim JH. Recent advances in stem cell therapeutics and tissue engineering strategies. Biomater Res 2018; 22:36. [PMID: 30598836 PMCID: PMC6299977 DOI: 10.1186/s40824-018-0148-4] [Citation(s) in RCA: 126] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Accepted: 12/07/2018] [Indexed: 12/19/2022] Open
Abstract
Background Tissue regeneration includes delivering specific types of cells or cell products to injured tissues or organs for restoration of tissue and organ function. Stem cell therapy has drawn considerable attention since transplantation of stem cells can overcome the limitations of autologous transplantation of patient’s tissues; however, it is not perfect for treating diseases. To overcome the hurdles associated with stem cell therapy, tissue engineering techniques have been developed. Development of stem cell technology in combination with tissue engineering has opened new ways of producing engineered tissue substitutes. Several studies have shown that this combination of tissue engineering and stem cell technologies enhances cell viability, differentiation, and therapeutic efficacy of transplanted stem cells. Main body Stem cells that can be used for tissue regeneration include mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells. Transplantation of stem cells alone into injured tissues exhibited low therapeutic efficacy due to poor viability and diminished regenerative activity of transplanted cells. In this review, we will discuss the progress of biomedical engineering, including scaffolds, biomaterials, and tissue engineering techniques to overcome the low therapeutic efficacy of stem cells and to treat human diseases. Conclusion The combination of stem cell and tissue engineering techniques overcomes the limitations of stem cells in therapy of human diseases, and presents a new path toward regeneration of injured tissues.
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Affiliation(s)
- Seong Gyu Kwon
- 1Department of Physiology, Pusan National University School of Medicine, Yangsan, 50612 Gyeongsangnam-do Republic of Korea
| | - Yang Woo Kwon
- 1Department of Physiology, Pusan National University School of Medicine, Yangsan, 50612 Gyeongsangnam-do Republic of Korea
| | - Tae Wook Lee
- 1Department of Physiology, Pusan National University School of Medicine, Yangsan, 50612 Gyeongsangnam-do Republic of Korea
| | - Gyu Tae Park
- 1Department of Physiology, Pusan National University School of Medicine, Yangsan, 50612 Gyeongsangnam-do Republic of Korea
| | - Jae Ho Kim
- 1Department of Physiology, Pusan National University School of Medicine, Yangsan, 50612 Gyeongsangnam-do Republic of Korea.,2Research Institute of Convergence Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, 50612 Republic of Korea
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Bello AB, Park H, Lee SH. Current approaches in biomaterial-based hematopoietic stem cell niches. Acta Biomater 2018; 72:1-15. [PMID: 29578087 DOI: 10.1016/j.actbio.2018.03.028] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Revised: 02/07/2018] [Accepted: 03/14/2018] [Indexed: 12/20/2022]
Abstract
Hematopoietic stem cells (HSCs) are multipotent progenitor cells that can differentiate and replenish blood and immune cells. While there is a growing demand for autologous and allogeneic HSC transplantation owing to the increasing incidence of hereditary and hematologic diseases, the low population of HSCs in cord-blood and bone marrow (the main source of HSCs) hinders their medical applicability. Several cytokine and growth factor-based methods have been developed to expand the HSCs in vitro; however, the expansion rate is low, or the expanded cells fail to survive upon engraftment. This is at least in part because the overly simplistic polystyrene culture substrates fail to fully replicate the microenvironments or niches where these stem cells live. Bone marrow niches are multi-dimensional, complex systems that involve both biochemical (cells, growth factors, and cytokines) and physiochemical (stiffness, O2 concentration, and extracellular matrix presentation) factors that regulate the quiescence, proliferation, activation, and differentiation of the HSCs. Although several studies have been conducted on in vitro HSC expansion via 2D and 3D biomaterial-based platforms, additional work is required to engineer an effective biomaterial platform that mimics bone marrow niches. In this study, the factors that regulate the HSC in vivo were explained and their applications in the engineering of a bone marrow biomaterial-based platform were discussed. In addition, current approaches, challenges, and the future direction of a biomaterial-based culture and expansion of the HSC were examined. STATEMENT OF SIGNIFICANCE Hematopoietic stem cells (HSC) are multipotent cells that can differentiate and replace the blood and immune cells of the body. However, in vivo, there is a low population of these cells, and thus their use in biotherapeutic and medical applications is limited (i.e., bone marrow transplantation). In this review, the biochemical factors (growth factors, cytokines, co-existing cells, ECM, gas concentrations, and differential gene expression) that may regulate the over-all fate of HSC, in vivo, were summarized and discussed. Moreover, different conventional and recent biomaterial platforms were reviewed, and their potential in generating a biomaterial-based, BM niche-mimicking platform for the efficient growth and expansion of clinically relevant HSCs in-vitro, was discussed.
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Affiliation(s)
- Alvin Bacero Bello
- School of Integrative Engineering, Chung-Ang University, Seoul 06911, Republic of Korea; Department of Biomedical Science, CHA University, Seongnam-Si 13488, Republic of Korea
| | - Hansoo Park
- School of Integrative Engineering, Chung-Ang University, Seoul 06911, Republic of Korea.
| | - Soo-Hong Lee
- Department of Biomedical Science, CHA University, Seongnam-Si 13488, Republic of Korea.
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Robb KP, Shridhar A, Flynn LE. Decellularized Matrices As Cell-Instructive Scaffolds to Guide Tissue-Specific Regeneration. ACS Biomater Sci Eng 2017; 4:3627-3643. [PMID: 33429606 DOI: 10.1021/acsbiomaterials.7b00619] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Decellularized scaffolds are promising clinically translational biomaterials that can be applied to direct cell responses and promote tissue regeneration. Bioscaffolds derived from the extracellular matrix (ECM) of decellularized tissues can naturally mimic the complex extracellular microenvironment through the retention of compositional, biomechanical, and structural properties specific to the native ECM. Increasingly, studies have investigated the use of ECM-derived scaffolds as instructive substrates to recapitulate properties of the stem cell niche and guide cell proliferation, paracrine factor production, and differentiation in a tissue-specific manner. Here, we review the application of decellularized tissue scaffolds as instructive matrices for stem or progenitor cells, with a focus on the mechanisms through which ECM-derived scaffolds can mediate cell behavior to promote tissue-specific regeneration. We conclude that although additional preclinical studies are required, ECM-derived scaffolds are a promising platform to guide cell behavior and may have widespread clinical applications in the field of regenerative medicine.
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Affiliation(s)
- Kevin P Robb
- Biomedical Engineering Graduate Program, The University of Western Ontario, Claudette MacKay Lassonde Pavilion, London, Ontario, Canada N6A 5B9
| | - Arthi Shridhar
- Department of Chemical and Biochemical Engineering, The University of Western Ontario, Thompson Engineering Building, London, Ontario, Canada N6A 5B9
| | - Lauren E Flynn
- Department of Chemical and Biochemical Engineering, The University of Western Ontario, Thompson Engineering Building, London, Ontario, Canada N6A 5B9.,Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada N6A 5C1
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34
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Li X, He X, Yin Y, Wu R, Tian B, Chen F. Administration of signalling molecules dictates stem cell homing for in situ regeneration. J Cell Mol Med 2017; 21:3162-3177. [PMID: 28767189 PMCID: PMC5706509 DOI: 10.1111/jcmm.13286] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2017] [Accepted: 05/29/2017] [Indexed: 12/13/2022] Open
Abstract
Ex vivo-expanded stem cells have long been a cornerstone of biotherapeutics and have attracted increasing attention for treating intractable diseases and improving tissue regeneration. However, using exogenous cellular materials to develop restorative treatments for large numbers of patients has become a major concern for both economic and safety reasons. Advances in cell biological research over the past two decades have expanded the potential for using endogenous stem cells during wound healing processes, and in particular, recent insight into stem cell movement and homing has prompted regenerative research and therapy based on recruiting endogenous cells. Inspired by the natural healing process, artificial administration of specific chemokines as signals systemically or at the injury site, typically using biomaterials as vehicles, is a state-of-the-art strategy that potentiates stem cell homing and recreates an anti-inflammatory and immunomodulatory microenvironment to enhance in situ tissue regeneration. However, pharmacologically coaxing endogenous stem cells to act as therapeutics in the field of biomedicine remains in the early stages; its efficacy is limited by the lack of innovative methodologies for chemokine presentation and release. This review describes how to direct the homing of endogenous stem cells via the administration of specific signals, with a particular emphasis on targeted signalling molecules that regulate this homing process, to enhance in situ tissue regeneration. We also provide an outlook on and critical considerations for future investigations to enhance stem cell recruitment and harness the reparative potential of these recruited cells as a clinically relevant cell therapy.
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Affiliation(s)
- Xuan Li
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral DiseasesDepartment of PeriodontologySchool of StomatologyFourth Military Medical UniversityXi'anChina
| | - Xiao‐Tao He
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral DiseasesDepartment of PeriodontologySchool of StomatologyFourth Military Medical UniversityXi'anChina
| | - Yuan Yin
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral DiseasesDepartment of PeriodontologySchool of StomatologyFourth Military Medical UniversityXi'anChina
| | - Rui‐Xin Wu
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral DiseasesDepartment of PeriodontologySchool of StomatologyFourth Military Medical UniversityXi'anChina
| | - Bei‐Min Tian
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral DiseasesDepartment of PeriodontologySchool of StomatologyFourth Military Medical UniversityXi'anChina
| | - Fa‐Ming Chen
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral DiseasesDepartment of PeriodontologySchool of StomatologyFourth Military Medical UniversityXi'anChina
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Fibrin-Enhanced Canonical Wnt Signaling Directs Plasminogen Expression in Cementoblasts. Int J Mol Sci 2017; 18:ijms18112380. [PMID: 29120400 PMCID: PMC5713349 DOI: 10.3390/ijms18112380] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Revised: 11/06/2017] [Accepted: 11/07/2017] [Indexed: 11/17/2022] Open
Abstract
Cementum is a mineralized layer on the tooth's root surface and facilitates the biomechanical anchoring of fibrous connective tissues as a part of tooth-supportive complexes. Previously, we observed that OCCM30 cementoblasts cultured on fibrin matrices underwent apoptosis due to fibrin degradation through the expression of proteases. Here, we demonstrated that OCCM30 on fibrin matrices (OCCM30-fibrin) enhanced canonical Wnt signaling, which directed to plasminogen expression. The OCCM30-fibrin showed higher levels of Wnt3a expression, nuclear translocation of β-catenin, and T-cell factor (TCF) optimal motif (TOP) reporter activity than the cells on tissue culture dishes (OCCM30-TCD), indicating that the OCCM30-fibrin enhanced canonical Wnt/β-catenin signaling. Also, OCCM30-fibrin expressed biomineralization-associated markers at higher levels than OCCM30-TCD, of which levels were further increased with LiCl, a Wnt signaling activator. The OCCM30 cementoblasts simultaneously showed that high levels of plasminogen, a critical component of fibrinolysis, were expressed in the OCCM30-fibrin. Activation of canonical Wnt signaling with LiCl treatment or with forced lymphoid enhancer factor 1 (LEF1)-expression increased the expression of plasminogen. On the contrary, the inhibition of canonical Wnt signaling with siRNAs against Wnt3a or β-catenin abrogated fibrin-enhanced plasminogen expression. Furthermore, there are three conserved putative response elements for the LEF1/β-catenin complex in the plasminogen proximal promoter regions (-900 to +54). Site-directed mutations and chromatin immunoprecipitation indicated that canonical Wnt signaling directed plasminogen expression. Taken together, this study suggests that fibrin-based materials can modulate functional periodontal formations in controlling cementoblast differentiation and fibrin degradation.
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Feng G, Zhang Z, Dang M, Zhang X, Doleyres Y, Song Y, Chen D, Ma PX. Injectable nanofibrous spongy microspheres for NR4A1 plasmid DNA transfection to reverse fibrotic degeneration and support disc regeneration. Biomaterials 2017; 131:86-97. [PMID: 28376367 PMCID: PMC5448136 DOI: 10.1016/j.biomaterials.2017.03.029] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Revised: 03/17/2017] [Accepted: 03/20/2017] [Indexed: 02/06/2023]
Abstract
Safe and efficient gene therapy is highly desired for controlling pathogenic fibrosis of nucleus pulposus (NP) tissue, which would result in intervertebral disc (IVD) degeneration and disability if left untreated. In this work, a hyperbranched polymer (HP) with high plasmid DNA (pDNA) binding affinity and negligible cytotoxicity is synthesized, which can self-assemble into nano-sized polyplexes with a "double shell" structure that can transfect pDNA into NP cells with very high efficiency. These polyplexes are then encapsulated in biodegradable nanospheres (NS) to enable two-stage delivery: 1) temporally-controlled release of pDNA-carrying polyplexes and 2) highly efficient delivery of pDNA into cells by the released polyplexes. These biodegradable NS are co-injected with nanofibrous spongy microspheres (NF-SMS) to localize the cellular transfection of the pDNA encoding orphan nuclear receptor 4A1 (NR4A1), which was recently reported as a therapeutic agent to delay pathogenic fibrosis. It is shown that HP can transfect human NP cells efficiently in vitro with low cytotoxicity. The two-stage delivery system is able to present the polyplexes over a sustained time period (more than 30 days) in the tail of a rat. The NR4A1 pDNA carried by the HP polyplexes is found to therapeutically reduce the pathogenic fibrosis of NP tissue in a rat-tail degeneration model. In conclusion, the combination of the two-stage NR4A1 pDNA delivery NS and NF-SMS is able to repress fibrosis and to support IVD regeneration.
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Affiliation(s)
- Ganjun Feng
- Department of Biologic and Materials Science, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Zhanpeng Zhang
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Ming Dang
- Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Xiaojin Zhang
- Department of Biologic and Materials Science, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Yasmine Doleyres
- Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Yueming Song
- Department of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Di Chen
- Department of Biochemistry, Rush University, Chicago, IL, 60612, USA
| | - Peter X Ma
- Department of Biologic and Materials Science, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA; Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
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Dhaliwal A, Brenner M, Wolujewicz P, Zhang Z, Mao Y, Batish M, Kohn J, Moghe PV. Profiling stem cell states in three-dimensional biomaterial niches using high content image informatics. Acta Biomater 2016; 45:98-109. [PMID: 27590870 PMCID: PMC5262522 DOI: 10.1016/j.actbio.2016.08.052] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Revised: 08/23/2016] [Accepted: 08/29/2016] [Indexed: 02/06/2023]
Abstract
A predictive framework for the evolution of stem cell biology in 3-D is currently lacking. In this study we propose deep image informatics of the nuclear biology of stem cells to elucidate how 3-D biomaterials steer stem cell lineage phenotypes. The approach is based on high content imaging informatics to capture minute variations in the 3-D spatial organization of splicing factor SC-35 in the nucleoplasm as a marker to classify emergent cell phenotypes of human mesenchymal stem cells (hMSCs). The cells were cultured in varied 3-D culture systems including hydrogels, electrospun mats and salt leached scaffolds. The approach encompasses high resolution 3-D imaging of SC-35 domains and high content image analysis (HCIA) to compute quantitative 3-D nuclear metrics for SC-35 organization in single cells in concert with machine learning approaches to construct a predictive cell-state classification model. Our findings indicate that hMSCs cultured in collagen hydrogels and induced to differentiate into osteogenic or adipogenic lineages could be classified into the three lineages (stem, adipogenic, osteogenic) with ⩾80% precision and sensitivity, within 72h. Using this framework, the augmentation of osteogenesis by scaffold design exerted by porogen leached scaffolds was also profiled within 72h with ∼80% high sensitivity. Furthermore, by employing 3-D SC-35 organizational metrics, differential osteogenesis induced by novel electrospun fibrous polymer mats incorporating decellularized matrix could also be elucidated and predictably modeled at just 3days with high precision. We demonstrate that 3-D SC-35 organizational metrics can be applied to model the stem cell state in 3-D scaffolds. We propose that this methodology can robustly discern minute changes in stem cell states within complex 3-D architectures and map single cell biological readouts that are critical to assessing population level cell heterogeneity. STATEMENT OF SIGNIFICANCE The sustained development and validation of bioactive materials relies on technologies that can sensitively discern cell response dynamics to biomaterials, while capturing cell-to-cell heterogeneity and preserving cellular native phenotypes. In this study, we illustrate the application of a novel high content image informatics platform to classify emergent human mesenchymal stem cell (hMSC) phenotypes in a diverse range of 3-D biomaterial scaffolds with high sensitivity and precision, and track cell responses to varied external stimuli. A major in silico innovation is the proposed image profiling technology based on unique three dimensional textural signatures of a mechanoreporter protein within the nuclei of stem cells cultured in 3-D scaffolds. This technology will accelerate the pace of high-fidelity biomaterial screening.
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Affiliation(s)
- Anandika Dhaliwal
- Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, United States
| | - Matthew Brenner
- Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, United States
| | - Paul Wolujewicz
- Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers University, Newark, NJ, United States
| | - Zheng Zhang
- Department of Chemistry and Chemical Biology, New Jersey Center for Biomaterials, Rutgers University, Piscataway, NJ, United States
| | - Yong Mao
- Department of Chemistry and Chemical Biology, New Jersey Center for Biomaterials, Rutgers University, Piscataway, NJ, United States
| | - Mona Batish
- Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers University, Newark, NJ, United States
| | - Joachim Kohn
- Department of Chemistry and Chemical Biology, New Jersey Center for Biomaterials, Rutgers University, Piscataway, NJ, United States
| | - Prabhas V Moghe
- Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, United States; Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ, United States.
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Yang S, Jang L, Kim S, Yang J, Yang K, Cho SW, Lee JY. Polypyrrole/Alginate Hybrid Hydrogels: Electrically Conductive and Soft Biomaterials for Human Mesenchymal Stem Cell Culture and Potential Neural Tissue Engineering Applications. Macromol Biosci 2016; 16:1653-1661. [DOI: 10.1002/mabi.201600148] [Citation(s) in RCA: 98] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Revised: 06/30/2016] [Indexed: 01/09/2023]
Affiliation(s)
- Sumi Yang
- School of Materials Science and Engineering; Gwangju Institute of Science and Engineering (GIST); Gwangju 500-712 Republic of Korea
| | - LindyK. Jang
- School of Materials Science and Engineering; Gwangju Institute of Science and Engineering (GIST); Gwangju 500-712 Republic of Korea
| | - Semin Kim
- School of Materials Science and Engineering; Gwangju Institute of Science and Engineering (GIST); Gwangju 500-712 Republic of Korea
| | - Jongcheol Yang
- School of Materials Science and Engineering; Gwangju Institute of Science and Engineering (GIST); Gwangju 500-712 Republic of Korea
| | - Kisuk Yang
- Department of Biotechnology; Yonsei University; Seoul 120-749 Republic of Korea
| | - Seung-Woo Cho
- Department of Biotechnology; Yonsei University; Seoul 120-749 Republic of Korea
| | - Jae Young Lee
- School of Materials Science and Engineering; Gwangju Institute of Science and Engineering (GIST); Gwangju 500-712 Republic of Korea
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Zhang Z, Eyster TW, Ma PX. Nanostructured injectable cell microcarriers for tissue regeneration. Nanomedicine (Lond) 2016; 11:1611-28. [PMID: 27230960 PMCID: PMC5619097 DOI: 10.2217/nnm-2016-0083] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Accepted: 05/05/2016] [Indexed: 11/21/2022] Open
Abstract
Biodegradable polymer microspheres have emerged as cell carriers for the regeneration and repair of irregularly shaped tissue defects due to their injectability, controllable biodegradability and capacity for drug incorporation and release. Notably, recent advances in nanotechnology allowed the manipulation of the physical and chemical properties of the microspheres at the nanoscale, creating nanostructured microspheres mimicking the composition and/or structure of natural extracellular matrix. These nanostructured microspheres, including nanocomposite microspheres and nanofibrous microspheres, have been employed as cell carriers for tissue regeneration. They enhance cell attachment and proliferation, promote positive cell-carrier interactions and facilitate stem cell differentiation for target tissue regeneration. This review highlights the recent advances in nanostructured microspheres that are employed as injectable, biomimetic and cell-instructive cell carriers.
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Affiliation(s)
- Zhanpeng Zhang
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-1078, USA
| | - Thomas W Eyster
- Department of Biologic & Materials Sciences, University of Michigan, Ann Arbor, MI 48109-1078, USA
| | - Peter X Ma
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-1078, USA
- Department of Biologic & Materials Sciences, University of Michigan, Ann Arbor, MI 48109-1078, USA
- Macromolecular Science & Engineering Center, University of Michigan, Ann Arbor, MI 48109-1078, USA
- Materials Science & Engineering, University of Michigan, Ann Arbor, MI 48109-1078, USA
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Noh MJ, Lee KH. Orthopedic cellular therapy: An overview with focus on clinical trials. World J Orthop 2015; 6:754-61. [PMID: 26601056 PMCID: PMC4644862 DOI: 10.5312/wjo.v6.i10.754] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Revised: 08/22/2015] [Accepted: 09/25/2015] [Indexed: 02/06/2023] Open
Abstract
In this editorial, the authors tried to evaluate the present state of cellular therapy in orthopedic field. The topics the authors try to cover include not only the clinical trials but the various research areas as well. Both the target diseases for cellular therapy and the target cells were reviewed. New methods to activate the cells were interesting to review. Most advanced clinical trials were also included because several of them have advanced to phase III clinical trials. In the orthopedic field, there are many diseases with a definite treatment gap at this time. Because cellular therapies can regenerate damaged tissues, there is a possibility for cellular therapies to become disease modifying drugs. It is not clear whether cellular therapies will become the standard of care in any of the orthopedic disorders, however the amount of research being performed and the number of clinical trials that are on-going make the authors believe that cellular therapies will become important treatment modalities within several years.
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Ramamoorthy M, Rajiv S. In-vitro release of fragrant l-carvone from electrospun poly(ϵ-caprolactone)/wheat cellulose scaffold. Carbohydr Polym 2015; 133:328-36. [DOI: 10.1016/j.carbpol.2015.07.015] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Revised: 06/17/2015] [Accepted: 07/02/2015] [Indexed: 11/24/2022]
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Li H, Li X, Zhang M, Chen L, Zhang B, Tang S, Fu X. Three-dimensional co-culture of BM-MSCs and eccrine sweat gland cells in Matrigel promotes transdifferentiation of BM-MSCs. J Mol Histol 2015; 46:431-8. [PMID: 26189057 DOI: 10.1007/s10735-015-9632-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Accepted: 07/14/2015] [Indexed: 02/05/2023]
Abstract
Victims with extensive and deep burns are unable to regenerate eccrine sweat glands. Combining of stem cells and biomimetic ECM to generate cell-based 3D tissues is showing promise for tissue repair and regeneration. We co-cultured BrdU-labeled bone marrow-derived mesenchymal stem cells (BM-MSCs) and eccrine sweat gland cells in Matrigel for 2 weeks in vitro and then evaluated for BM-MSCs differentiation into functional eccrine sweat gland cells by morphological assessment and immunohistochemical double staining for BrdU/pancytokeratin, BrdU/ZO-2, BrdU/E-cadherin, BrdU/desmoglein-2, BrdU/Na(+)-K(+)-ATPase α, BrdU/NHE1 and BrdU/CFTR. Cells formed spheroid-like structures in Matrigel, and BrdU-labeled BM-MSCs were involved in the 3D reconstitution of eccrine sweat gland tissues, and the incorporated BM-MSCs expressed an epithelial cell marker (pancytokeratin), epithelial cell junction proteins (ZO-2, E-cadherin and desmoglein-2) and functional proteins of eccrine sweat glands (Na(+)-K(+)-ATPase α, NHE1 and CFTR). In conclusion, three-dimensional co-culture of BM-MSCs and eccrine sweat gland cells in Matrigel promotes the transdifferentiation of BM-MSCs into potentially functional eccrine sweat gland cells.
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Affiliation(s)
- Haihong Li
- Burn and Plastic Surgery, The Second Affiliated Hospital, Shantou University Medical College, North Dongxia Road, Shantou, 515041, Guangdong Province, China,
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Hodonsky C, Mundada L, Wang S, Witt R, Raff G, Kaushal S, Si MS. Effects of scaffold material used in cardiovascular surgery on mesenchymal stem cells and cardiac progenitor cells. Ann Thorac Surg 2014; 99:605-11. [PMID: 25497071 DOI: 10.1016/j.athoracsur.2014.08.071] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2013] [Revised: 08/04/2014] [Accepted: 08/15/2014] [Indexed: 11/29/2022]
Abstract
BACKGROUND Polytetrafluoroethylene (PTFE) and porcine small intestinal submucosa (pSIS) are patch materials used in congenital heart surgery. Porcine SIS is an extracellular-matrix scaffold that may interact with stem or progenitor cells. To evaluate this, we determined the in vitro effects of pSIS and PTFE on human bone marrow mesenchymal stromal cells (MSCs) and cardiac progenitor cells (CPCs) in 3 areas; cell proliferation, angiogenic growth-factor production, and differentiation. METHODS Human MSCs and CPCs were seeded onto pSIS and PTFE patches. Cell-seeded patches were cultured and then assessed for cell viability and proliferation and supernatant vascular endothelial growth factor A (VEGFA) levels. Cell proliferation was quantified by MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). Quantitative real-time polymerase chain reaction was performed on cell-seeded scaffolds to determine relative changes in gene expression related to angiogenesis and cardiogenesis. RESULTS The MSCs and CPCs were able to attach and proliferate on pSIS and PTFE. The proliferation rate of each cell type was similar on pSIS. Total RNA isolation was only possible from the cell-seeded pSIS patches. The MSC VEGFA production was increased by pSIS. Porcine SIS promoted an angiogenic gene profile in MSCs and an early cardiogenic profile in CPCs. CONCLUSIONS Both PTFE and pSIS allow for varying degrees of cell proliferation. Porcine SIS elicits different phenotypical responses in MSCs as compared with CPCs, which indicates that pSIS may be a bioactive scaffold that modulates stem cell activation and proliferation. These findings highlight the differences in scaffold material strategies and suggest potential advantages of bioactive approaches.
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Affiliation(s)
- Chani Hodonsky
- Department of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan
| | - Lakshmi Mundada
- Department of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan
| | - Shuyun Wang
- Department of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan
| | - Russell Witt
- Department of Surgery, University of California at Davis Medical Center, Sacramento, California
| | - Gary Raff
- Department of Surgery, University of California at Davis Medical Center, Sacramento, California
| | - Sunjay Kaushal
- Department of Surgery, University Maryland, Baltimore, Maryland
| | - Ming-Sing Si
- Department of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan.
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Chae SK, Mun CH, Noh DY, Kang E, Lee SH. Simple fabrication method for a porous poly(vinyl alcohol) matrix by multisolvent mixtures for an air-exposed model of the lung epithelial system. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2014; 30:12107-12113. [PMID: 25260012 DOI: 10.1021/la501453h] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
We introduce a simple and easy method for fabricating a thin and porous matrix that can be used as an extracellular matrix (ECM). A porous poly(vinyl alcohol) (PVA) matrix was created through recrystallization by multiple solvents under distilled water (DW), isopropyl alcohol (IPA), and a combination of DW and IPA. The crysatllization was driven by precipitating and dissolving a solute in a solution of a solvent and a nonsolvent, which induced the formation of microspheres in the IPA. The crystal structure depended on the ratio of the solvent/nonsolvent and the concentration of the PVA aqueous solution; these properties were used to tune the thickness, size, and porosity of the matrices. The resulting PVA matrix was chemically stabilized through a reaction with glutaraldehyde in the IPA solution. We demonstrated that a very thin and porous PVA matrix provided an effective functional model of the lung epithelial system. Lung epithelial cells (A549) displayed a high affinity for this matrix, which was permeable to the culture medium. These properties facilitated culturing under the air environment.
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Affiliation(s)
- Su-Kyoung Chae
- Department of Biomedical Engineering, College of Health Science, Korea University , Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea
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Kusuma S, Macklin B, Gerecht S. Derivation and network formation of vascular cells from human pluripotent stem cells. Methods Mol Biol 2014; 1202:1-9. [PMID: 24155232 DOI: 10.1007/7651_2013_39] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
As the lifeline of almost all living tissues, blood vessels are a major focus of tissue-regenerative therapies. Rebuilding blood vessels has vast implications for the study of vascular growth and treatment of diseases in which vascular function is compromised. Toward this end, human pluripotent stem cells have been widely studied for their differentiation capacity toward vascular lineages. We demonstrate methods to derive a bicellular population of early specialized vascular cells from human pluripotent stem cells, to differentiate these toward mature endothelial cells and pericytes, and to utilize a collagen scaffold to facilitate organization into vascular networks.
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Affiliation(s)
- Sravanti Kusuma
- Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences, and Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA
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