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1
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Kao YC, Yang PC, Lin YP, Chen GH, Liu SW, Ho CH, Huang SC, Lee PY, Chen L, Huang CC. Tailoring the therapeutic potential of stem cell spheroid-derived decellularized ECM through post-decellularization BDNF incorporation to enhance brain repair. Biomaterials 2025; 321:123332. [PMID: 40220567 DOI: 10.1016/j.biomaterials.2025.123332] [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: 01/05/2025] [Revised: 04/06/2025] [Accepted: 04/07/2025] [Indexed: 04/14/2025]
Abstract
Decellularized extracellular matrix (dECM) from tissues has significant therapeutic potential but is limited by its rigid molecular composition and reliance on post-decellularization modifications to tailor its functionality. Harsh decellularization processes often result in substantial glycosaminoglycan (GAG) loss, impairing natural growth factor incorporation and necessitating chemical modifications that complicate processing and limit clinical translation. To address these challenges, we developed mesenchymal stem cell (MSC) spheroid-derived three-dimensional (3D) dECM using gentle decellularization techniques. This study demonstrated a crucial advancement-the retention of endogenous GAGs-enabling direct growth factor incorporation without chemical agents. As a proof-of-concept, brain-derived neurotrophic factor (BDNF) was incorporated into the 3D dECM to enhance its therapeutic potential for brain repair. In vitro, BDNF-loaded 3D dECM enabled sustained growth factor release, significantly enhancing the proneuritogenic, neuroprotective, and proangiogenic effects. In a mouse model of traumatic brain injury, the implantation of BDNF-loaded 3D dECM significantly enhanced motor function and facilitated brain repair. These findings highlight the adaptability of MSC spheroid-derived 3D dECM for tissue-specific customization through straightforward and translatable growth factor incorporation, demonstrating its potential as a pro-regenerative biomaterial for advancing regenerative medicine applications.
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Affiliation(s)
- Ying-Chi Kao
- Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan
| | - Pei-Ching Yang
- Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan
| | - Yu-Ping Lin
- Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan
| | - Grace H Chen
- Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan
| | - Shao-Wen Liu
- Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan
| | - Chia-Hsin Ho
- Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan
| | - Shih-Chen Huang
- Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan
| | - Peng-Ying Lee
- Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan
| | - Linyi Chen
- Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, 30013, Taiwan; Department of Medical Science, National Tsing Hua University, Hsinchu, 30013, Taiwan
| | - Chieh-Cheng Huang
- Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan.
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2
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Gulberk Ozcebe S, Tristan M, Zorlutuna P. Adult human heart extracellular matrix improves human iPSC-CM function via mitochondrial and metabolic maturation. Stem Cells 2025; 43:sxaf005. [PMID: 39862185 PMCID: PMC12080356 DOI: 10.1093/stmcls/sxaf005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 01/06/2025] [Indexed: 01/27/2025]
Abstract
Myocardial infarction can lead to the loss of billions of cardiomyocytes, and while cell-based therapies are an option, immature nature of in vitro-generated human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) is a roadblock to their development. Existing iPSC differentiation protocols don't go beyond producing fetal iCMs. Recently, adult extracellular matrix (ECM) was shown to retain tissue memory and have some success driving tissue-specific differentiation in unspecified cells in various organ systems. Therefore, we focused on investigating the effect of adult human heart-derived extracellular matrix (ECM) on iPSC cardiac differentiation and subsequent maturation. By preconditioning iPSCs with ECM, we tested whether creating cardiac environments around iPSCs would drive iPSCs toward cardiac fate and which ECM components might be involved. We report novel high- and low-abundance proteomes of young, adult, and aged human hearts, with relative abundances to total proteins and each other. We found that adult ECM had extracellular galactin-1, fibronectin, fibrillins, and perlecan (HSPG2) which are implicated in normal heart development. We also showed preconditioning iPSCs with adult cardiac ECM resulted in enhanced cardiac differentiation, yielding iCMs with higher functional maturity, more developed mitochondrial network and coverage, enhanced metabolic maturity, and shift towards more energetic profile. These findings demonstrate the potential use of cardiac ECM in iCM maturation and as a promising strategy for developing iCM-based therapies, disease modeling, and drug screening studies. Upon manipulating ECM, we concluded that the beneficial effects observed were not solely due to the ECM proteins, which might be related to the decorative units attached.
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Affiliation(s)
- S Gulberk Ozcebe
- Bioengineering Graduate Program, University of Notre Dame, Notre Dame, 46556 IN, United States
- National Institute of Environmental Health Sciences (NIEHS), Durham, 27709 NC, United States
| | - Mateo Tristan
- Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, 46556 IN, United States
| | - Pinar Zorlutuna
- Bioengineering Graduate Program, University of Notre Dame, Notre Dame, 46556 IN, United States
- Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, 46556 IN, United States
- Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, 46556 IN, United States
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3
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Kumar P, Sharma J, Kumar R, Najser J, Frantik J, Manuja A, Sunnam N, Praveenkumar S. Advances in bioink-based 3D printed scaffolds: optimizing biocompatibility and mechanical properties for bone regeneration. Biomater Sci 2025; 13:2556-2579. [PMID: 40190204 DOI: 10.1039/d4bm01606h] [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: 05/14/2025]
Abstract
The development of bioink-based 3D-printed scaffolds has revolutionized bone tissue engineering (BTE) by enabling patient-specific and biomimetic constructs for bone regeneration. This review focuses on the biocompatibility and mechanical properties essential for scaffold performance, highlighting advancements in bioink formulations, material combinations, and printing techniques. The key biomaterials, including natural polymers (gelatin, collagen, alginate), synthetic polymers (polycaprolactone, polyethylene glycol), and bioactive ceramics (hydroxyapatite, calcium phosphate), are discussed concerning their osteoconductivity, printability, and structural integrity. Despite significant progress, challenges remain in achieving optimal mechanical strength, degradation rates, and cellular interactions. The review explores emerging strategies such as gene-activated bioinks, nanocomposite reinforcements, and crosslinking techniques to enhance scaffold durability and bioactivity. By synthesizing recent developments, this work provides insights into future directions for bioink-based scaffolds, paving the way for more effective and personalized bone regenerative therapies.
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Affiliation(s)
- Pawan Kumar
- Department of Biotechnology, Kurukshetra University, Kurukshetra 136119, India.
| | - Jitender Sharma
- Department of Biotechnology, Kurukshetra University, Kurukshetra 136119, India.
| | - Ravinder Kumar
- School of Mechanical Engineering, Lovely Professional University, City Phagwara, 144411, India.
| | - Jan Najser
- ENET Centre, CEET, VSB-Technical University of Ostrava, Ostrava, 708 00, Czech Republic.
| | - Jaroslav Frantik
- ENET Centre, CEET, VSB-Technical University of Ostrava, Ostrava, 708 00, Czech Republic.
| | - Anju Manuja
- ICAR-National Research Centre on Equines, Hisar, 125001, India.
| | - Nagaraju Sunnam
- Department of Mechanical Engineering, MLR Institute of Technology, Hyderabad, Telangana, India.
| | - Seepana Praveenkumar
- Department of Nuclear and Renewable Energy, Ural Federal University Named After the First President of Russia Boris, 19 Mira Street, 620002, Ekaterinburg, Yeltsin, Russia.
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4
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Wang Z, Liang W, Ao R, An Y. Adipose Decellularized Matrix: A Promising Skeletal Muscle Tissue Engineering Material for Volume Muscle Loss. Biomater Res 2025; 29:0174. [PMID: 40248249 PMCID: PMC12003953 DOI: 10.34133/bmr.0174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 02/06/2025] [Accepted: 03/07/2025] [Indexed: 04/19/2025] Open
Abstract
Volume muscle loss is a severe injury often caused by trauma, fracture, tumor resection, or degenerative disease, leading to long-term dysfunction or disability. The current gold-standard treatment is autologous muscle tissue transplantation, with limitations due to donor site restrictions, complications, and low regeneration efficiency. Tissue engineering shows potential to overcome these challenges and achieve optimal muscle regeneration, vascularization, nerve repair, and immunomodulation. In the field of muscle tissue engineering, skeletal muscle decellularized matrices are regarded as an ideal material due to their similarity to the defect site environment, yet they suffer from difficulties in preparation, severe fibrosis, and inconsistent experimental findings. Adipose decellularized matrices (AdECMs) have demonstrated consistent efficacy in promoting muscle regeneration, and their ease of preparation and abundant availability make them even more attractive. The full potential of AdECMs for muscle regeneration remains to be explored. The aim of this review is to summarize the relevant studies on using AdECMs to promote muscle regeneration, to summarize the preparation methods of various applied forms, and to analyze their advantages and shortcomings, as well as to further explore their mechanisms and to propose possible improvements, so as to provide new ideas for the clinical solution of the problem of volume muscle loss.
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Affiliation(s)
| | - Wei Liang
- Address correspondence to: (W.L.); (Y.A.)
| | - Rigele Ao
- Department of Plastic Surgery,
Peking University Third Hospital, Beijing 100191, China
| | - Yang An
- Department of Plastic Surgery,
Peking University Third Hospital, Beijing 100191, China
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5
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Abou-Shanab AM, Gaser OA, Soliman MW, Oraby A, Salah RA, Gabr M, Edris AAF, Mohamed I, El-Badri N. Human amniotic membrane scaffold enhances adipose mesenchymal stromal cell mitochondrial bioenergetics promoting their regenerative capacities. Mol Cell Biochem 2025; 480:2611-2632. [PMID: 39453499 DOI: 10.1007/s11010-024-05094-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 08/12/2024] [Indexed: 10/26/2024]
Abstract
The human amniotic membrane (hAM) has been applied as a scaffold in tissue engineering to sustain stem cells and enhance their regenerative capacities. We investigated the molecular and biochemical regulations of mesenchymal stromal cells (MSCs) cultured on hAM scaffold in a three-dimensional (3D) setting. Culture of adipose-MSCs (AMSCs) on decellularized hAM showed significant improvement in their viability, proliferative capacity, resistance to apoptosis, and enhanced MSC markers expression. These cultured MSCs displayed altered expression of markers associated with pro-angiogenesis and inflammation and demonstrated increased potential for differentiation into adipogenic and osteogenic lineages. The hAM scaffold modulated cellular respiration by upregulating glycolysis in MSCs as evidenced by increased glucose consumption, cellular pyruvate and lactate production, and upregulation of glycolysis markers. These metabolic changes modulated mitochondrial oxidative phosphorylation (OXPHOS) and altered the production of reactive oxygen species (ROS), expression of OXPHOS markers, and total antioxidant capacity. They also significantly boosted the urea cycle and altered the mitochondrial ultrastructure. Similar findings were observed in bone marrow-derived MSCs (BMSCs). Live cell imaging of BMSCs cultured in the same 3D environment revealed dynamic changes in cellular activity and interactions with its niche. These findings provide evidence for the favorable properties of hAM as a biomimetic scaffold for enhancing the in vitro functionality of MSCs and supporting their potential usefulness in clinical applications.
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Affiliation(s)
- Ahmed M Abou-Shanab
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, 12578, Egypt
| | - Ola A Gaser
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, 12578, Egypt
| | - Mariam Waleed Soliman
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, 12578, Egypt
| | - Alaa Oraby
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, 12578, Egypt
| | - Radwa Ayman Salah
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, 12578, Egypt
| | - Mahmoud Gabr
- Urology and Nephrology Center, Mansoura University, Mansoura, 35516, Egypt
| | | | - Ihab Mohamed
- Department of Zoology, Faculty of Science, Ain Shams University, Cairo, 11566, Egypt
| | - Nagwa El-Badri
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, 12578, Egypt.
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6
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Füge L, Schüssler F, Gerhardus J, Schwab R, Harms G, Hasenburg A, Blaeser A, Brenner W, Peters K. Comparative Analysis of Hydrogels From Porcine Extracellular Matrix for 3D Bioprinting of Adipose Tissue. J Biomed Mater Res A 2025; 113:e37832. [PMID: 40165526 DOI: 10.1002/jbm.a.37832] [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: 07/31/2024] [Revised: 10/19/2024] [Accepted: 10/24/2024] [Indexed: 04/02/2025]
Abstract
The extracellular matrix (ECM) is the natural scaffold of all soft tissues in tissue engineering. Of special interest is the use of ECM as a hydrogel, which can be used to enclose cells and to be molded into any form by 3D bioprinting. Protocols for the preparation of ECM vary in the use of physical and chemical processing steps, the use of different detergents for decellularization, and the removal of DNA and RNA residues and show a different use of solvents and wash buffers. We have, therefore, compared seven different variations for the decellularization of a primary porcine isolate to manufacture decellularized adipose tissue (DAT) for their use in adipose tissue engineering and as a hydrogel in particular. Decellularization efficacy was assessed by DNA quantification while retention of ECM components was evaluated by measuring the content of hydroxyproline and glycosaminoglycan (GAGs). Depending on the decellularization protocol, the composition and DNA content of the resulting DAT were different. All DAT samples were processed into hydrogels to assess their mechanical properties as well as their influence on cellular metabolic activity and cell differentiation. The different compositions of the DAT and the resulting hydrogels had an effect on the stability and printability of the gels. Some DAT that were digested with hydrochloric acid (HCl) were more stable than those that were digested with acetic acid (AA). In addition, depending on the protocol, there was a clear effect on adipose-derived stem cells (ASC), endothelial cells and fibroblasts, cultured with the hydrogels. The differentiation of ASC to adipocytes could be achieved on most of the hydrogels. Human dermal microvascular endothelial cells (HDMEC) showed significantly better metabolic activity on hydrogels digested with HCl than digested with AA. HDMEC cultured on hydrogel #2 digested with HCl showed a 40% higher metabolic activity compared to collagen as a positive control, whereas culturing HDMEC on hydrogel #2 digested with AA resulted in a cellular metabolic activity loss of 60%. In a triculture of all three cell types, the formation of first tubular networks by HDMEC was achieved depending on the hydrogel used.
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Affiliation(s)
- Leonie Füge
- Department of Obstetrics and Women's Health, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Felix Schüssler
- Department of Obstetrics and Women's Health, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Jamina Gerhardus
- BioMedical Printing Technology, Department of Mechanical Engineering, Technical University of Darmstadt, Darmstadt, Germany
| | - Roxana Schwab
- Department of Obstetrics and Women's Health, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Gregory Harms
- Cell Biology Unit, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- Department of Biology, Wilkes University, Wilkes Barre, Pennsylvania, USA
| | - Annette Hasenburg
- Department of Obstetrics and Women's Health, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Andreas Blaeser
- BioMedical Printing Technology, Department of Mechanical Engineering, Technical University of Darmstadt, Darmstadt, Germany
- Centre for Synthetic Biology, Technical University of Darmstadt, Darmstadt, Germany
| | - Walburgis Brenner
- Department of Obstetrics and Women's Health, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- BiomaTiCS - Biomaterials, Tissues and Cells in Science, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Katharina Peters
- Department of Obstetrics and Women's Health, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- BiomaTiCS - Biomaterials, Tissues and Cells in Science, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
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7
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van Hengel EVA, van der Laan LJW, de Jonge J, Verstegen MMA. Towards Safety and Regulation Criteria for Clinical Applications of Decellularized Organ-Derived Matrices. Bioengineering (Basel) 2025; 12:136. [PMID: 40001655 PMCID: PMC11851377 DOI: 10.3390/bioengineering12020136] [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: 12/30/2024] [Revised: 01/25/2025] [Accepted: 01/29/2025] [Indexed: 02/27/2025] Open
Abstract
Whole-organ decellularization generates scaffolds containing native extracellular matrix (ECM) components with preserved tissue microarchitecture, providing a promising advancement in tissue engineering and regenerative medicine. Decellularization retains the ECM integrity which is important for supporting cell attachment, growth, differentiation, and biological function. Although there are consensus guidelines to standardize decellularization processes and ECM characterization, no specific criteria or standards regarding matrix sterility and biosafety have been established so far. This regulatory gap in safety, sterilization, and regulation criteria has hampered the clinical translation of decellularized scaffolds. In this review, we identify essential criteria for the safe clinical use of decellularized products from both human and animal sources. These include the decellularization efficacy, levels of chemical residue, preservation of ECM composition and physical characteristics, and criteria for the aseptic processing of decellularization to assure sterility. Furthermore, we explore key considerations for advancing decellularized scaffolds into clinical practice, focusing on regulatory frameworks and safety requirements. Addressing these challenges is crucial for minimizing risks of adverse reactions or infection transmission, thereby accelerating the adoption of tissue-engineered products. This review aims to provide a foundation for establishing robust guidelines, supporting the safe and effective integration of decellularized scaffolds into regenerative medicine applications.
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Affiliation(s)
| | | | | | - Monique M. A. Verstegen
- Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands; (E.V.A.v.H.); (L.J.W.v.d.L.); (J.d.J.)
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8
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Almeida GHDR, Gibin MS, Rinaldi JDC, Gonzaga VHDS, Thom CR, Iglesia RP, da Silva RS, Fernandes IC, Bergamo RO, Lima LS, Lopomo B, Santos GVC, Nesiyama TNG, Sato F, Baesso ML, Hernandes L, Meirelles FV, Carreira ACO. Development and Biocompatibility Assessment of Decellularized Porcine Uterine Extracellular Matrix-Derived Grafts. Tissue Eng Part C Methods 2024. [PMID: 39311629 DOI: 10.1089/ten.tec.2024.0229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/10/2024] Open
Abstract
Biomaterials derived from biological matrices have been widely investigated due to their great therapeutic potential in regenerative medicine, since they are able to induce cell proliferation, tissue remodeling, and angiogenesis in situ. In this context, highly vascularized and proliferative tissues, such as the uterine wall, present an interesting source to produce acellular matrices that can be used as bioactive materials to induce tissue regeneration. Therefore, this study aimed to establish an optimized protocol to generate decellularized uterine scaffolds (dUT), characterizing their structural, compositional, and biomechanical properties. In addition, in vitro performance and in vivo biocompatibility were also evaluated to verify their potential applications for tissue repair. Results showed that the protocol was efficient to promote cell removal, and dUT general structure and extracellular matrix composition remained preserved compared with native tissue. In addition, the scaffolds were cytocompatible, allowing cell growth and survival. In terms of biocompatibility, the matrices did not induce any signs of immune rejection in vivo in a model of subcutaneous implantation in immunocompetent rats, demonstrating an indication of tissue integration after 30 days of implantation. In summary, these findings suggest that dUT scaffolds could be explored as a biomaterial for regenerative purposes, which is beyond the studies in the reproductive field.
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Affiliation(s)
| | | | | | | | | | - Rebeca Piatniczka Iglesia
- The Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Raquel Souza da Silva
- Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil
| | - Iorrane Couto Fernandes
- Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil
| | - Rafael Oliveira Bergamo
- Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil
| | - Luan Stefani Lima
- Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil
| | - Beatriz Lopomo
- Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil
| | | | - Thais Naomi Gonçalves Nesiyama
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, São Paulo, Brazil
| | - Francielle Sato
- Department of Physics, State University of Maringá, Maringá, Brazil
| | - Mauro Luciano Baesso
- Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil
| | - Luzmarina Hernandes
- Department of Morphological Sciences, State University of Maringá, Maringá, Brazil
| | - Flávio Vieira Meirelles
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, São Paulo, Brazil
| | - Ana Claudia Oliveira Carreira
- Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil
- Center for Natural and Human Sciences, Federal University of ABC, Santo André, Brazil
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9
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Araújo-Gomes N, Zoetebier-Liszka B, van Loo B, Becker M, Nijhuis S, Smink AM, de Haan BJ, de Vos P, Karperien M, Leijten J. Microfluidic Generation of Thin-Shelled Polyethylene Glycol-Tyramine Microgels for Non-Invasive Delivery of Immunoprotected β-Cells. Adv Healthc Mater 2024; 13:e2301552. [PMID: 37548084 DOI: 10.1002/adhm.202301552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 07/21/2023] [Indexed: 08/08/2023]
Abstract
Transplantation of microencapsulated pancreatic cells is emerging as a promising therapy to replenish β-cell mass lost from auto-immune nature of type I diabetes mellitus (T1DM). This strategy intends to use micrometer-sized microgels to provide immunoprotection to transplanted cells to avoid chronic application of immunosuppression. Clinical application of encapsulation has remained elusive due to often limited production throughputs and body's immunological reactions to implanted materials. This article presents a high-throughput fabrication of monodisperse, non-immunogenic, non-degradable, immunoprotective, semi-permeable, enzymatically-crosslinkable polyethylene glycol-tyramine (PEG-TA) microgels for β-cell microencapsulation. Monodisperse β-cell laden microgels of ≈120 µm, with a shell thickness of 20 µm are produced using an outside-in crosslinking strategy. Microencapsulated β-cells rapidly self-assemble into islet-sized spheroids. Immunoprotection of the microencapsulated is demonstrated by inability of FITC-IgG antibodies to diffuse into cell-laden microgels and NK-cell inability to kill microencapsulated β-cells. Multiplexed ELISA analysis on live blood immune reactivity confirms limited immunogenicity. Microencapsulated MIN6β1 spheroids remain glucose responsive for 28 days in vitro, and able to restore normoglycemia 5 days post-implantation in diabetic mice without notable amounts of cell death. In short, PEG-TA microgels effectively protect implanted cells from the host's immune system while being viable and functional, validating this strategy for the treatment of T1DM.
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Affiliation(s)
- Nuno Araújo-Gomes
- Department of Developmental BioEngineering, TechMed Centre, University of Twente, Drienerlolaan 5, Enschede, 7522NB, The Netherlands
| | - Barbara Zoetebier-Liszka
- Department of Developmental BioEngineering, TechMed Centre, University of Twente, Drienerlolaan 5, Enschede, 7522NB, The Netherlands
| | - Bas van Loo
- Department of Developmental BioEngineering, TechMed Centre, University of Twente, Drienerlolaan 5, Enschede, 7522NB, The Netherlands
| | - Malin Becker
- Department of Developmental BioEngineering, TechMed Centre, University of Twente, Drienerlolaan 5, Enschede, 7522NB, The Netherlands
| | - Suzanne Nijhuis
- Department of Developmental BioEngineering, TechMed Centre, University of Twente, Drienerlolaan 5, Enschede, 7522NB, The Netherlands
| | - Alexandra M Smink
- Department of Pathology and Medical Biology, Section of Immunoendocrinology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, 9713 GZ, The Netherlands
| | - Bart J de Haan
- Department of Pathology and Medical Biology, Section of Immunoendocrinology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, 9713 GZ, The Netherlands
| | - Paul de Vos
- Department of Pathology and Medical Biology, Section of Immunoendocrinology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, 9713 GZ, The Netherlands
| | - Marcel Karperien
- Department of Developmental BioEngineering, TechMed Centre, University of Twente, Drienerlolaan 5, Enschede, 7522NB, The Netherlands
| | - Jeroen Leijten
- Department of Developmental BioEngineering, TechMed Centre, University of Twente, Drienerlolaan 5, Enschede, 7522NB, The Netherlands
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10
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Ostadi Y, Khanali J, Tehrani FA, Yazdanpanah G, Bahrami S, Niazi F, Niknejad H. Decellularized Extracellular Matrix Scaffolds for Soft Tissue Augmentation: From Host-Scaffold Interactions to Bottlenecks in Clinical Translation. Biomater Res 2024; 28:0071. [PMID: 39247652 PMCID: PMC11378302 DOI: 10.34133/bmr.0071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 07/29/2024] [Indexed: 09/10/2024] Open
Abstract
Along with a paradigm shift in looking at soft tissue fillers from space-filling to bioactive materials, decellularized extracellular matrix (DEM) fillers have gained more attention considering their superior bioactivity. However, the complex mechanisms that govern the interaction between host tissues and DEMs have been partially understood. This review first covers the mechanisms that determine immunogenicity, angiogenesis and vasculogenesis, and recellularization and remodeling after DEM implantation into host tissue, with a particular focus on related findings from filler materials. Accordingly, the review delves into the dual role of macrophages and their M1/M2 polarization paradigm to form both constructive and destructive immune responses to DEM implants. Moreover, the contribution of macrophages in angiogenesis has been elucidated, which includes but is not limited to the secretion of angiogenic growth factors and extracellular matrix (ECM) remodeling. The findings challenge the traditional view of immune cells as solely destructive entities in biomaterials and indicate their multifaceted roles in tissue regeneration. Furthermore, the review discusses how the compositional factors of DEMs, such as the presence of growth factors and matrikines, can influence angiogenesis, cell fate, and differentiation during the recellularization process. It is also shown that the biomechanical properties of DEMs, including tissue stiffness, modulate cell responses through mechanotransduction pathways, and the structural properties of DEMs, such as scaffold porosity, impact cell-cell and cell-ECM interactions. Finally, we pointed out the current clinical applications, the bottlenecks in the clinical translation of DEM biomaterials into soft tissue fillers, as well as the naïve research areas of the field.
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Affiliation(s)
- Yasamin Ostadi
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Javad Khanali
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh A Tehrani
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ghasem Yazdanpanah
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL, USA
| | - Soheyl Bahrami
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in AUVA Research Center, Vienna, Austria
| | - Feizollah Niazi
- Department of Plastic and Reconstructive Surgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hassan Niknejad
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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11
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Shen J, Ye D, Jin H, Wu Y, Peng L, Liang Y. Porcine nasal septum cartilage-derived decellularized matrix promotes chondrogenic differentiation of human umbilical mesenchymal stem cells without exogenous growth factors. J Mater Chem B 2024; 12:5513-5524. [PMID: 38745541 DOI: 10.1039/d3tb03077f] [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: 05/16/2024]
Abstract
BACKGROUND In the domain of plastic surgery, nasal cartilage regeneration is of significant importance. The extracellular matrix (ECM) from porcine nasal septum cartilage has shown potential for promoting human cartilage regeneration. Nonetheless, the specific biological inductive factors and their pathways in cartilage tissue engineering remain undefined. METHODS The decellularized matrix derived from porcine nasal septum cartilage (PN-DCM) was prepared using a grinding method. Human umbilical cord mesenchymal stem cells (HuMSCs) were cultured on these PN-DCM scaffolds for 4 weeks without exogenous growth factors to evaluate their chondroinductive potential. Subsequently, proteomic analysis was employed to identify potential biological inductive factors within the PN-DCM scaffolds. RESULTS Compared to the TGF-β3-cultured pellet model serving as a positive control, the PN-DCM scaffolds promoted significant deposition of a Safranin-O positive matrix and Type II collagen by HuMSCs. Gene expression profiling revealed upregulation of ACAN, COL2A1, and SOX9. Proteomic analysis identified potential chondroinductive factors in the PN-DCM scaffolds, including CYTL1, CTGF, MGP, ITGB1, BMP7, and GDF5, which influence HuMSC differentiation. CONCLUSION Our findings have demonstrated that the PN-DCM scaffolds promoted HuMSC differentiation towards a nasal chondrocyte phenotype without the supplementation of exogenous growth factors. This outcome is associated with the chondroinductive factors present within the PN-DCM scaffolds.
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Affiliation(s)
- Jinpeng Shen
- Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Guizhou, P. R. China.
- Department of Plastic Surgery and Burn Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, P. R. China.
- Department of Plastic Surgery, Taizhou Enze Medical Center, Zhejiang, P. R. China
| | - Danyan Ye
- Research Center for Translational Medicine, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, P. R. China
| | - Hao Jin
- Department of Cardiology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, P. R. China
| | - Yongxuan Wu
- Department of Plastic Surgery and Burn Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, P. R. China.
| | - Lihong Peng
- Department of Plastic Surgery and Burn Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, P. R. China.
| | - Yan Liang
- Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Guizhou, P. R. China.
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12
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Sreepadmanabh M, Arun AB, Bhattacharjee T. Design approaches for 3D cell culture and 3D bioprinting platforms. BIOPHYSICS REVIEWS 2024; 5:021304. [PMID: 38765221 PMCID: PMC11101206 DOI: 10.1063/5.0188268] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 04/01/2024] [Indexed: 05/21/2024]
Abstract
The natural habitat of most cells consists of complex and disordered 3D microenvironments with spatiotemporally dynamic material properties. However, prevalent methods of in vitro culture study cells under poorly biomimetic 2D confinement or homogeneous conditions that often neglect critical topographical cues and mechanical stimuli. It has also become increasingly apparent that cells in a 3D conformation exhibit dramatically altered morphological and phenotypical states. In response, efforts toward designing biomaterial platforms for 3D cell culture have taken centerstage over the past few decades. Herein, we present a broad overview of biomaterials for 3D cell culture and 3D bioprinting, spanning both monolithic and granular systems. We first critically evaluate conventional monolithic hydrogel networks, with an emphasis on specific experimental requirements. Building on this, we document the recent emergence of microgel-based 3D growth media as a promising biomaterial platform enabling interrogation of cells within porous and granular scaffolds. We also explore how jammed microgel systems have been leveraged to spatially design and manipulate cellular structures using 3D bioprinting. The advent of these techniques heralds an unprecedented ability to experimentally model complex physiological niches, with important implications for tissue bioengineering and biomedical applications.
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Affiliation(s)
- M Sreepadmanabh
- National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, Karnataka, India
| | - Ashitha B. Arun
- National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, Karnataka, India
| | - Tapomoy Bhattacharjee
- National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, Karnataka, India
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13
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Wu TY, Hsieh YC, Yin WR, Cheng KY, Hou YT. Fabrication of a decellularized liver matrix-based hepatic patch for the repair of CCl4-induced liver injury. Biotechnol J 2024; 19:e2300570. [PMID: 38864387 DOI: 10.1002/biot.202300570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 04/23/2024] [Accepted: 05/16/2024] [Indexed: 06/13/2024]
Abstract
This article primarily introduces a new treatment for liver fibrosis/cirrhosis. We developed a hepatic patch by combining decellularized liver matrix (DLM) with the hepatocyte growth factor (HGF)/heparin-complex and evaluated its restorative efficacy. In vitro prophylactic results, the HGF/heparin-DLM patches effectively mitigated CCl4-induced hepatocyte toxicity and restored the cytotoxicity levels to the baseline levels by day 5. Furthermore, these patches restored albumin synthesis of injured hepatocytes to more than 70% of the normal levels within 5 days. In vitro therapeutic results, the urea synthesis of the injured hepatocytes reached 91% of the normal levels after 10 days of culture, indicating successful restoration of hepatic function by the HGF/heparin-DLM patches in both prophylactic and therapeutic models. In vivo results, HGF/heparin-DLM patches attached to the liver and gut exhibited a significant decrease in collagen content (4.44 times and 2.77 times, respectively) and an increase in glycogen content (1.19 times and 1.12 times, respectively) compared to the fibrosis group after 1 week, separately. In summary, liver function was restored and inflammation was inhibited through the combined effects of DLM and the HGF/heparin-complex in fibrotic liver. The newly designed hepatic patch holds promise for both in vitro and in vivo regeneration therapy and preventive health care for liver tissue engineering.
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Affiliation(s)
- Ting-Yi Wu
- Department of Biomechatronics Engineering, National Taiwan University, Taipei, Taiwan
| | - Yi-Cheng Hsieh
- Department of Biomechatronics Engineering, National Taiwan University, Taipei, Taiwan
| | - Wei-Rong Yin
- Department of Biomechatronics Engineering, National Taiwan University, Taipei, Taiwan
| | - Kai-Yi Cheng
- Department of Biomechatronics Engineering, National Taiwan University, Taipei, Taiwan
| | - Yung-Te Hou
- Department of Biomechatronics Engineering, National Taiwan University, Taipei, Taiwan
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14
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Cavallini C, Olivi E, Tassinari R, Zannini C, Ragazzini G, Marcuzzi M, Taglioli V, Ventura C. Deer antler stem cell niche: An interesting perspective. World J Stem Cells 2024; 16:479-485. [PMID: 38817324 PMCID: PMC11135255 DOI: 10.4252/wjsc.v16.i5.479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 04/09/2024] [Accepted: 04/25/2024] [Indexed: 05/24/2024] Open
Abstract
In recent years, there has been considerable exploration into methods aimed at enhancing the regenerative capacity of transplanted and/or tissue-resident cells. Biomaterials, in particular, have garnered significant interest for their potential to serve as natural scaffolds for cells. In this editorial, we provide commentary on the study by Wang et al, in a recently published issue of World J Stem Cells, which investigates the use of a decellularized xenogeneic extracellular matrix (ECM) derived from antler stem cells for repairing osteochondral defects in rat knee joints. Our focus lies specifically on the crucial role of biological scaffolds as a strategy for augmenting stem cell potential and regenerative capabilities, thanks to the establishment of a favorable microenvironment (niche). Stem cell differentiation heavily depends on exposure to intrinsic properties of the ECM, including its chemical and protein composition, as well as the mechanical forces it can generate. Collectively, these physicochemical cues contribute to a bio-instructive signaling environment that offers tissue-specific guidance for achieving effective repair and regeneration. The interest in mechanobiology, often conceptualized as a form of "structural memory", is steadily gaining more validation and momentum, especially in light of findings such as these.
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Affiliation(s)
- Claudia Cavallini
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems - Eldor Lab, Bologna 40128, Italy
- Eldor Lab, Bologna 40128, Italy
| | | | | | | | | | - Martina Marcuzzi
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | | | - Carlo Ventura
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems - Eldor Lab, Bologna 40128, Italy.
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15
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Hu N, Jiang R, Deng Y, Li W, Jiang W, Xu N, Wang J, Wen J, Gu S. Periapical lesion-derived decellularized extracellular matrix as a potential solution for regenerative endodontics. Regen Biomater 2024; 11:rbae050. [PMID: 38872841 PMCID: PMC11170217 DOI: 10.1093/rb/rbae050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Revised: 04/01/2024] [Accepted: 04/17/2024] [Indexed: 06/15/2024] Open
Abstract
Pulp regeneration remains a crucial target in the preservation of natural dentition. Using decellularized extracellular matrix is an appropriate approach to mimic natural microenvironment and facilitate tissue regeneration. In this study, we attempted to obtain decellularized extracellular matrix from periapical lesion (PL-dECM) and evaluate its bioactive effects. The decellularization process yielded translucent and viscous PL-dECM, meeting the standard requirements for decellularization efficiency. Proteomic sequencing revealed that the PL-dECM retained essential extracellular matrix components and numerous bioactive factors. The PL-dECM conditioned medium could enhance the proliferation and migration ability of periapical lesion-derived stem cells (PLDSCs) in a dose-dependent manner. Culturing PLDSCs on PL-dECM slices improved odontogenic/angiogenic ability compared to the type I collagen group. In vivo, the PL-dECM demonstrated a sustained supportive effect on PLDSCs and promoted odontogenic/angiogenic differentiation. Both in vitro and in vivo studies illustrated that PL-dECM served as an effective scaffold for pulp tissue engineering, providing valuable insights into PLDSCs differentiation. These findings pave avenues for the clinical application of dECM's in situ transplantation for regenerative endodontics.
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Affiliation(s)
- Nan Hu
- Department of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road No.639, Shanghai, 200011, China
- College of Stomatology, Shanghai Jiao Tong University, Yanqiao Road No.390, Shanghai, 200125, China
- National Center for Stomatology, Zhizaoju Road No.639, Shanghai, 200011, China
- National Clinical Research Center for Oral Diseases, Zhizaoju Road No.639, Shanghai, 200011, China
- Shanghai Key Laboratory of Stomatology, Yanqiao Road No.390, Shanghai, 200125, China
- Shanghai Research Institute of Stomatology, Zhizaoju Road No.639, Shanghai, 200011, China
| | - Ruixue Jiang
- Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road No.639, Shanghai, 200011, China
- College of Stomatology, Shanghai Jiao Tong University, Yanqiao Road No.390, Shanghai, 200125, China
- National Center for Stomatology, Zhizaoju Road No.639, Shanghai, 200011, China
- National Clinical Research Center for Oral Diseases, Zhizaoju Road No.639, Shanghai, 200011, China
- Shanghai Key Laboratory of Stomatology, Yanqiao Road No.390, Shanghai, 200125, China
- Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Yanqiao Road No.390, Shanghai, 200125, China
| | - Yuwei Deng
- Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road No.639, Shanghai, 200011, China
- College of Stomatology, Shanghai Jiao Tong University, Yanqiao Road No.390, Shanghai, 200125, China
- National Center for Stomatology, Zhizaoju Road No.639, Shanghai, 200011, China
- National Clinical Research Center for Oral Diseases, Zhizaoju Road No.639, Shanghai, 200011, China
- Shanghai Key Laboratory of Stomatology, Yanqiao Road No.390, Shanghai, 200125, China
- Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Yanqiao Road No.390, Shanghai, 200125, China
| | - Weiping Li
- Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road No.639, Shanghai, 200011, China
- College of Stomatology, Shanghai Jiao Tong University, Yanqiao Road No.390, Shanghai, 200125, China
- National Center for Stomatology, Zhizaoju Road No.639, Shanghai, 200011, China
- National Clinical Research Center for Oral Diseases, Zhizaoju Road No.639, Shanghai, 200011, China
- Shanghai Key Laboratory of Stomatology, Yanqiao Road No.390, Shanghai, 200125, China
- Shanghai Research Institute of Stomatology, Zhizaoju Road No.639, Shanghai, 200011, China
- Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Zhizaoju Road No.639, Shanghai, 200011, China
| | - Wentao Jiang
- Department of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road No.639, Shanghai, 200011, China
- College of Stomatology, Shanghai Jiao Tong University, Yanqiao Road No.390, Shanghai, 200125, China
- National Center for Stomatology, Zhizaoju Road No.639, Shanghai, 200011, China
- National Clinical Research Center for Oral Diseases, Zhizaoju Road No.639, Shanghai, 200011, China
- Shanghai Key Laboratory of Stomatology, Yanqiao Road No.390, Shanghai, 200125, China
- Shanghai Research Institute of Stomatology, Zhizaoju Road No.639, Shanghai, 200011, China
| | - Ningwei Xu
- Department of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road No.639, Shanghai, 200011, China
- College of Stomatology, Shanghai Jiao Tong University, Yanqiao Road No.390, Shanghai, 200125, China
- National Center for Stomatology, Zhizaoju Road No.639, Shanghai, 200011, China
- National Clinical Research Center for Oral Diseases, Zhizaoju Road No.639, Shanghai, 200011, China
- Shanghai Key Laboratory of Stomatology, Yanqiao Road No.390, Shanghai, 200125, China
- Shanghai Research Institute of Stomatology, Zhizaoju Road No.639, Shanghai, 200011, China
| | - Jia Wang
- Department of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road No.639, Shanghai, 200011, China
- College of Stomatology, Shanghai Jiao Tong University, Yanqiao Road No.390, Shanghai, 200125, China
- National Center for Stomatology, Zhizaoju Road No.639, Shanghai, 200011, China
- National Clinical Research Center for Oral Diseases, Zhizaoju Road No.639, Shanghai, 200011, China
- Shanghai Key Laboratory of Stomatology, Yanqiao Road No.390, Shanghai, 200125, China
- Shanghai Research Institute of Stomatology, Zhizaoju Road No.639, Shanghai, 200011, China
| | - Jin Wen
- Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road No.639, Shanghai, 200011, China
- College of Stomatology, Shanghai Jiao Tong University, Yanqiao Road No.390, Shanghai, 200125, China
- National Center for Stomatology, Zhizaoju Road No.639, Shanghai, 200011, China
- National Clinical Research Center for Oral Diseases, Zhizaoju Road No.639, Shanghai, 200011, China
- Shanghai Key Laboratory of Stomatology, Yanqiao Road No.390, Shanghai, 200125, China
- Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Yanqiao Road No.390, Shanghai, 200125, China
| | - Shensheng Gu
- Department of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road No.639, Shanghai, 200011, China
- College of Stomatology, Shanghai Jiao Tong University, Yanqiao Road No.390, Shanghai, 200125, China
- National Center for Stomatology, Zhizaoju Road No.639, Shanghai, 200011, China
- National Clinical Research Center for Oral Diseases, Zhizaoju Road No.639, Shanghai, 200011, China
- Shanghai Key Laboratory of Stomatology, Yanqiao Road No.390, Shanghai, 200125, China
- Shanghai Research Institute of Stomatology, Zhizaoju Road No.639, Shanghai, 200011, China
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16
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Barajaa MA, Otsuka T, Ghosh D, Kan HM, Laurencin CT. Development of porcine skeletal muscle extracellular matrix-derived hydrogels with improved properties and low immunogenicity. Proc Natl Acad Sci U S A 2024; 121:e2322822121. [PMID: 38687784 PMCID: PMC11087813 DOI: 10.1073/pnas.2322822121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 03/18/2024] [Indexed: 05/02/2024] Open
Abstract
Hydrogels derived from decellularized extracellular matrices (ECM) of animal origin show immense potential for regenerative applications due to their excellent cytocompatibility and biomimetic properties. Despite these benefits, the impact of decellularization protocols on the properties and immunogenicity of these hydrogels remains relatively unexplored. In this study, porcine skeletal muscle ECM (smECM) underwent decellularization using mechanical disruption (MD) and two commonly employed decellularization detergents, sodium deoxycholate (SDC) or Triton X-100. To mitigate immunogenicity associated with animal-derived ECM, all decellularized tissues were enzymatically treated with α-galactosidase to cleave the primary xenoantigen-the α-Gal antigen. Subsequently, the impact of the different decellularization protocols on the resultant hydrogels was thoroughly investigated. All methods significantly reduced total DNA content in hydrogels. Moreover, α-galactosidase treatment was crucial for cleaving α-Gal antigens, suggesting that conventional decellularization methods alone are insufficient. MD preserved total protein, collagen, sulfated glycosaminoglycan, laminin, fibronectin, and growth factors more efficiently than other protocols. The decellularization method impacted hydrogel gelation kinetics and ultrastructure, as confirmed by turbidimetric and scanning electron microscopy analyses. MD hydrogels demonstrated high cytocompatibility, supporting satellite stem cell recruitment, growth, and differentiation into multinucleated myofibers. In contrast, the SDC and Triton X-100 protocols exhibited cytotoxicity. Comprehensive in vivo immunogenicity assessments in a subcutaneous xenotransplantation model revealed MD hydrogels' biocompatibility and low immunogenicity. These findings highlight the significant influence of the decellularization protocol on hydrogel properties. Our results suggest that combining MD with α-galactosidase treatment is an efficient method for preparing low-immunogenic smECM-derived hydrogels with enhanced properties for skeletal muscle regenerative engineering and clinical applications.
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Affiliation(s)
- Mohammed A. Barajaa
- Department of Biomedical Engineering, College of Engineering, Imam Abdulrahman Bin Faisal University, Dammam34212, Saudi Arabia
| | - Takayoshi Otsuka
- The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut, Farmington, CT06030
| | - Debolina Ghosh
- The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut, Farmington, CT06030
| | - Ho-Man Kan
- The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut, Farmington, CT06030
| | - Cato T. Laurencin
- The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut, Farmington, CT06030
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT06269
- Department of Orthopedic Surgery, University of Connecticut Health Center, Farmington, CT06030
- Department of Materials Science & Engineering, University of Connecticut, Storrs, CT06269
- Department of Chemical & Bimolecular Engineering, University of Connecticut, Storrs, CT06269
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17
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Sepúlveda-García JA, Martínez-Puente DH, Ballesteros-Elizondo RG, Rodríguez-Rocha H, García-García A, Soto-Domínguez A, Saucedo-Cárdenas O, Vilchez-Cavazos JF, Montes de Oca-Luna R, Loera-Arias MDJ. Comparison of three techniques for decellularization of porcine bone-tendon-bone grafts. Biotech Histochem 2024; 99:190-196. [PMID: 38726944 DOI: 10.1080/10520295.2024.2350030] [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] [Indexed: 12/14/2024] Open
Abstract
Anterior cruciate ligament injuries are frequent afflictions related to sports or physical trauma. Autograft reconstruction strategies cause secondary injury to the patient. One alternative, supported by clinical evidence, is porcine xenografts. For clinical use, xenografts must be conditioned to avoid immune rejection. The most widely accepted procedure is tissue decellularization. We analyzed three decellularization strategies: the application of the anionic detergent sodium dodecyl sulfate (SDS), sonication, and freezing and thawing cycles. The treated tissues were evaluated histologically using H&E, Masson's trichrome, Verhoeff-van Gieson staining, and DAPI for fluorescent staining of nuclei. Finally, collagen fiber preservation was evaluated by quantifying this protein by colorimetry. The most efficient decellularization techniques were sonication and SDS. Collagen fibers were preserved in all experimental conditions.
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Affiliation(s)
- Jorge Arturo Sepúlveda-García
- Departamento de Histología, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - David Hernán Martínez-Puente
- Departamento de Histología, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - Raquel Guadalupe Ballesteros-Elizondo
- Departamento de Histología, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - Humberto Rodríguez-Rocha
- Departamento de Histología, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - Aracely García-García
- Departamento de Histología, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - Adolfo Soto-Domínguez
- Departamento de Histología, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - Odila Saucedo-Cárdenas
- Departamento de Histología, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - José Félix Vilchez-Cavazos
- Servicio de Ortopedia y Traumatología, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - Roberto Montes de Oca-Luna
- Departamento de Histología, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - María de Jesús Loera-Arias
- Departamento de Histología, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
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18
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Jin H, Kang Y, Gao H, Lin Z, Huang D, Zheng Z, Zhao J, Wang L, Jiang J. Decellularization-Based Modification Strategy for Bioactive Xenografts Promoting Tendon Repair. Adv Healthc Mater 2024; 13:e2302660. [PMID: 37864473 DOI: 10.1002/adhm.202302660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Revised: 10/09/2023] [Indexed: 10/22/2023]
Abstract
Xenografts have emerged as a promising option for severe tendon defects treatment. However, despite undergoing decellularization, concerns still remain regarding the immunogenicity of xenografts. Because certain components within the extracellular matrix also possess immunogenicity. In this study, a novel strategy of post-decellularization modification aimed at preserving the endogenous capacity of cells on collagen synthesis to mask antigenic epitopes in extracellular matrix is proposed. To implement this strategy, a human-derived rosiglitazone-loaded decellularized extracellular matrix (R-dECM) is developed. R-dECM can release rosiglitazone for over 7 days in vitro. By suppressing M1 macrophage polarization, R-dECM protects the migration and collagen synthesis abilities of tendon-derived stem cells (TDSCs), while also stabilizing the phenotype of M2 macrophages in vitro. RNA sequencing reveals R-dECM can mitigate the detrimental crosstalk between TDSCs and inflammatory cells. When applied to a rat patellar tendon defect model, R-dECM effectively inhibits early inflammation, preventing chronic inflammation. Its duration of function far exceeds the release time of rosiglitazone, implying the establishment of immune evasion, confirming the effectiveness of the proposed strategy. And R-dECM demonstrates superior tendon repair outcomes compared to dECM. Thus, this study provides a novel bioactive scaffold with the potential to enhance the long-term clinical outcomes of xenogeneic tendon grafts.
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Affiliation(s)
- Haocheng Jin
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, P. R. China
| | - Yuhao Kang
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, P. R. China
| | - Haihan Gao
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, P. R. China
| | - Zhiqi Lin
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, P. R. China
| | - Dongcheng Huang
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, P. R. China
| | - Zhi Zheng
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, P. R. China
| | - Jinzhong Zhao
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, P. R. China
| | - Liren Wang
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, P. R. China
| | - Jia Jiang
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, P. R. China
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19
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Anjum S, Li T, Saeed M, Ao Q. Exploring polysaccharide and protein-enriched decellularized matrix scaffolds for tendon and ligament repair: A review. Int J Biol Macromol 2024; 254:127891. [PMID: 37931866 DOI: 10.1016/j.ijbiomac.2023.127891] [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: 07/17/2023] [Revised: 10/07/2023] [Accepted: 11/02/2023] [Indexed: 11/08/2023]
Abstract
Tissue engineering (TE) has become a primary research topic for the treatment of diseased or damaged tendon/ligament (T/L) tissue. T/L injuries pose a severe clinical burden worldwide, necessitating the development of effective strategies for T/L repair and tissue regeneration. TE has emerged as a promising strategy for restoring T/L function using decellularized extracellular matrix (dECM)-based scaffolds. dECM scaffolds have gained significant prominence because of their native structure, relatively high bioactivity, low immunogenicity, and ability to function as scaffolds for cell attachment, proliferation, and differentiation, which are difficult to imitate using synthetic materials. Here, we review the recent advances and possible future prospects for the advancement of dECM scaffolds for T/L tissue regeneration. We focus on crucial scaffold properties and functions, as well as various engineering strategies employed for biomaterial design in T/L regeneration. dECM provides both the physical and mechanical microenvironments required by cells to survive and proliferate. Various decellularization methods and sources of allogeneic and xenogeneic dECM in T/L repair and regeneration are critically discussed. Additionally, dECM hydrogels, bio-inks in 3D bioprinting, and nanofibers are briefly explored. Understanding the opportunities and challenges associated with dECM-based scaffold development is crucial for advancing T/L repairs in tissue engineering and regenerative medicine.
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Affiliation(s)
- Shabnam Anjum
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, Shenyang 110122, China; NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterial, Institute of Regulatory Science for Medical Device, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China
| | - Ting Li
- Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China
| | - Mohammad Saeed
- Dr. A.P.J Abdul Kalam Technical University, Lucknow 226031, India
| | - Qiang Ao
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, Shenyang 110122, China; NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterial, Institute of Regulatory Science for Medical Device, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
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20
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Yang B, Rutkowski N, Elisseeff J. The foreign body response: emerging cell types and considerations for targeted therapeutics. Biomater Sci 2023; 11:7730-7747. [PMID: 37904536 DOI: 10.1039/d3bm00629h] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2023]
Abstract
The foreign body response (FBR) remains a clinical challenge in the field of biomaterials due to its ability to elicit a chronic and sustained immune response. Modulating the immune response to materials is a modern paradigm in tissue engineering to enhance repair while limiting fibrous encapsulation and implant isolation. Though the classical mediators of the FBR are well-characterized, recent studies highlight that our understanding of the cell types that shape the FBR may be incomplete. In this review, we discuss the emerging role of T cells, stromal-immune cell interactions, and senescent cells in the biomaterial response, particularly to synthetic materials. We emphasize future studies that will deepen the field's understanding of these cell types in the FBR, with the goal of identifying therapeutic targets that will improve implant integration. Finally, we briefly review several considerations that may influence our understanding of the FBR in humans, including rodent models, aging, gut microbiota, and sex differences. A better understanding of the heterogeneous host cell response during the FBR can enable the design and development of immunomodulatory materials that favor healing.
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Affiliation(s)
- Brenda Yang
- Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
| | - Natalie Rutkowski
- Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
| | - Jennifer Elisseeff
- Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
- Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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21
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de Paula AP, de Lima JD, Bastos TSB, Czaikovski AP, dos Santos Luz RB, Yuasa BS, Smanioto CCS, Robert AW, Braga TT. Decellularized Extracellular Matrix: The Role of This Complex Biomaterial in Regeneration. ACS OMEGA 2023; 8:22256-22267. [PMID: 37396215 PMCID: PMC10308580 DOI: 10.1021/acsomega.2c06216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 01/12/2023] [Indexed: 07/04/2023]
Abstract
Organ transplantation is understood as a technique where an organ from a donor patient is transferred to a recipient patient. This practice gained strength in the 20th century and ensured advances in areas of knowledge such as immunology and tissue engineering. The main problems that comprise the practice of transplants involve the demand for viable organs and immunological aspects related to organ rejection. In this review, we address advances in tissue engineering for reversing the current challenges of transplants, focusing on the possible use of decellularized tissues in tissue engineering. We address the interaction of acellular tissues with immune cells, especially macrophages and stem cells, due to their potential use in regenerative medicine. Our goal is to exhibit data that demonstrate the use of decellularized tissues as alternative biomaterials that can be applied clinically as partial or complete organ substitutes.
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Affiliation(s)
| | - Jordana Dinorá de Lima
- Department
of Pathology, Federal University of Parana, Curitiba, Parana 80060-000, Brazil
| | | | | | | | - Bruna Sadae Yuasa
- Department
of Pathology, Federal University of Parana, Curitiba, Parana 80060-000, Brazil
| | | | - Anny Waloski Robert
- Stem
Cells Basic Biology Laboratory, Carlos Chagas
Institute − FIOCRUZ/PR, Curitiba, Parana 81350-010, Brazil
| | - Tárcio Teodoro Braga
- Department
of Pathology, Federal University of Parana, Curitiba, Parana 80060-000, Brazil
- Graduate
Program in Biosciences and Biotechnology, Institute Carlos Chagas, Fiocruz, Parana 81310-020, Brazil
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22
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Wong SK, Yee MMF, Chin KY, Ima-Nirwana S. A Review of the Application of Natural and Synthetic Scaffolds in Bone Regeneration. J Funct Biomater 2023; 14:jfb14050286. [PMID: 37233395 DOI: 10.3390/jfb14050286] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 05/12/2023] [Accepted: 05/19/2023] [Indexed: 05/27/2023] Open
Abstract
The management of bone defects is complicated by the presence of clinical conditions, such as critical-sized defects created by high-energy trauma, tumour resection, infection, and skeletal abnormalities, whereby the bone regeneration capacity is compromised. A bone scaffold is a three-dimensional structure matrix serving as a template to be implanted into the defects to promote vascularisation, growth factor recruitment, osteogenesis, osteoconduction, and mechanical support. This review aims to summarise the types and applications of natural and synthetic scaffolds currently adopted in bone tissue engineering. The merits and caveats of natural and synthetic scaffolds will be discussed. A naturally derived bone scaffold offers a microenvironment closer to in vivo conditions after decellularisation and demineralisation, exhibiting excellent bioactivity, biocompatibility, and osteogenic properties. Meanwhile, an artificially produced bone scaffold allows for scalability and consistency with minimal risk of disease transmission. The combination of different materials to form scaffolds, along with bone cell seeding, biochemical cue incorporation, and bioactive molecule functionalisation, can provide additional or improved scaffold properties, allowing for a faster bone repair rate in bone injuries. This is the direction for future research in the field of bone growth and repair.
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Affiliation(s)
- Sok Kuan Wong
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
| | - Michelle Min Fang Yee
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
| | - Kok-Yong Chin
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
| | - Soelaiman Ima-Nirwana
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
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23
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Hu B, Wang R, Wu D, Long R, Ruan J, Jin L, Ma D, Sun C, Liao S. Prospects for fertility preservation: the ovarian organ function reconstruction techniques for oogenesis, growth and maturation in vitro. Front Physiol 2023; 14:1177443. [PMID: 37250136 PMCID: PMC10213246 DOI: 10.3389/fphys.2023.1177443] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 05/04/2023] [Indexed: 05/31/2023] Open
Abstract
Today, fertility preservation is receiving more attention than ever. Cryopreservation, which preserves ovarian tissue to preserve fertility in young women and reduce the risk of infertility, is currently the most widely practiced. Transplantation, however, is less feasible for women with blood-borne leukemia or cancers with a high risk of ovarian metastasis because of the risk of cancer recurrence. In addition to cryopreservation and re-implantation of embryos, in vitro ovarian organ reconstruction techniques have been considered as an alternative strategy for fertility preservation. In vitro culture of oocytes in vitro Culture, female germ cells induction from pluripotent stem cells (PSC) in vitro, artificial ovary construction, and ovaria-related organoids construction have provided new solutions for fertility preservation, which will therefore maximize the potential for all patients undergoing fertility preservation. In this review, we discussed and thought about the latest ovarian organ function reconstruction techniques in vitro to provide new ideas for future ovarian disease research and fertility preservation of patients with cancer and premature ovarian failure.
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Affiliation(s)
- Bai Hu
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Renjie Wang
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Di Wu
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rui Long
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jinghan Ruan
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lei Jin
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ding Ma
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chaoyang Sun
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shujie Liao
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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24
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Namjoo AR, Abrbekoh FN, Saghati S, Amini H, Saadatlou MAE, Rahbarghazi R. Tissue engineering modalities in skeletal muscles: focus on angiogenesis and immunomodulation properties. Stem Cell Res Ther 2023; 14:90. [PMID: 37061717 PMCID: PMC10105969 DOI: 10.1186/s13287-023-03310-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 03/28/2023] [Indexed: 04/17/2023] Open
Abstract
Muscular diseases and injuries are challenging issues in human medicine, resulting in physical disability. The advent of tissue engineering approaches has paved the way for the restoration and regeneration of injured muscle tissues along with available conventional therapies. Despite recent advances in the fabrication, synthesis, and application of hydrogels in terms of muscle tissue, there is a long way to find appropriate hydrogel types in patients with congenital and/or acquired musculoskeletal injuries. Regarding specific muscular tissue microenvironments, the applied hydrogels should provide a suitable platform for the activation of endogenous reparative mechanisms and concurrently deliver transplanting cells and therapeutics into the injured sites. Here, we aimed to highlight recent advances in muscle tissue engineering with a focus on recent strategies related to the regulation of vascularization and immune system response at the site of injury.
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Affiliation(s)
- Atieh Rezaei Namjoo
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Sepideh Saghati
- Department of Tissue Engineering, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hassan Amini
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- General and Vascular Surgery Department, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Reza Rahbarghazi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
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25
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Liu C, Gao H, Sun G, Jiang X, Song S, Zhang J, Shen J. Decellularized Scaffold-Based Artificial Vascular Patch for Porcine Vascular Repair. ACS APPLIED BIO MATERIALS 2023; 6:1071-1080. [PMID: 36876901 DOI: 10.1021/acsabm.2c00957] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/07/2023]
Abstract
Vascular transplantation is an effective strategy against cardiovascular diseases (CVD), and artificial vascular patches are of urgent need across the world. In this work, we designed a multifunctional decellularized scaffolds (DCS)-based vascular patch for porcine vascular repair. Ammonium phosphate zwitter-ion (APZI) and poly(vinyl alcohol) (PVA) hydrogel were coated on the surface of DCS to improve the mechanical properties and biocompatibility of an artificial vascular patch. Then a heparin (Hep)-loaded metal-organic framework (MOF) further decorated the artificial vascular patches to inhibit blood coagulation and promote vascular endothelialization. The obtained artificial vascular patch showed suitable mechanical properties, good biocompatibility, and blood compatibility. In addition, the proliferation and adhesion of endothelial progenitor cells (EPCs) on the surface of artificial vascular patch improved a lot when compared with unmodified PVA/DCS. According to the results of B-ultrasound and CT images, the artificial vascular patch could maintain the patency of the implant site after implanting into the pig carotid artery. The current results solidly support that a MOF-Hep/APZI-PVA/DCS vascular patch would be an excellent vascular replacement material.
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Affiliation(s)
- Cheng Liu
- Department of Vascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Huimin Gao
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
| | - Gaoqi Sun
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
| | - Xuefeng Jiang
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
| | - Saijie Song
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
| | - Jun Zhang
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
| | - Jian Shen
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
- Jiangsu Engineering Research Center of Interfacial Chemistry, Nanjing University, Nanjing 210023, China
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26
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Afzal Z, Huguet EL. Bioengineering liver tissue by repopulation of decellularised scaffolds. World J Hepatol 2023; 15:151-179. [PMID: 36926238 PMCID: PMC10011915 DOI: 10.4254/wjh.v15.i2.151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 11/22/2022] [Accepted: 02/15/2023] [Indexed: 02/24/2023] Open
Abstract
Liver transplantation is the only curative therapy for end stage liver disease, but is limited by the organ shortage, and is associated with the adverse consequences of immunosuppression. Repopulation of decellularised whole organ scaffolds with appropriate cells of recipient origin offers a theoretically attractive solution, allowing reliable and timely organ sourcing without the need for immunosuppression. Decellularisation methodologies vary widely but seek to address the conflicting objectives of removing the cellular component of tissues whilst keeping the 3D structure of the extra-cellular matrix intact, as well as retaining the instructive cell fate determining biochemicals contained therein. Liver scaffold recellularisation has progressed from small rodent in vitro studies to large animal in vivo perfusion models, using a wide range of cell types including primary cells, cell lines, foetal stem cells, and induced pluripotent stem cells. Within these models, a limited but measurable degree of physiologically significant hepatocyte function has been reported with demonstrable ammonia metabolism in vivo. Biliary repopulation and function have been restricted by challenges relating to the culture and propagations of cholangiocytes, though advances in organoid culture may help address this. Hepatic vasculature repopulation has enabled sustainable blood perfusion in vivo, but with cell types that would limit clinical applications, and which have not been shown to have the specific functions of liver sinusoidal endothelial cells. Minority cell groups such as Kupffer cells and stellate cells have not been repopulated. Bioengineering by repopulation of decellularised scaffolds has significantly progressed, but there remain significant experimental challenges to be addressed before therapeutic applications may be envisaged.
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Affiliation(s)
- Zeeshan Afzal
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Emmanuel Laurent Huguet
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
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27
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Kasravi M, Ahmadi A, Babajani A, Mazloomnejad R, Hatamnejad MR, Shariatzadeh S, Bahrami S, Niknejad H. Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine. Biomater Res 2023; 27:10. [PMID: 36759929 PMCID: PMC9912640 DOI: 10.1186/s40824-023-00348-z] [Citation(s) in RCA: 100] [Impact Index Per Article: 50.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 01/30/2023] [Indexed: 02/11/2023] Open
Abstract
Tissue-engineered decellularized extracellular matrix (ECM) scaffolds hold great potential to address the donor shortage as well as immunologic rejection attributed to cells in conventional tissue/organ transplantation. Decellularization, as the key process in manufacturing ECM scaffolds, removes immunogen cell materials and significantly alleviates the immunogenicity and biocompatibility of derived scaffolds. However, the application of these bioscaffolds still confronts major immunologic challenges. This review discusses the interplay between damage-associated molecular patterns (DAMPs) and antigens as the main inducers of innate and adaptive immunity to aid in manufacturing biocompatible grafts with desirable immunogenicity. It also appraises the impact of various decellularization methodologies (i.e., apoptosis-assisted techniques) on provoking immune responses that participate in rejecting allogenic and xenogeneic decellularized scaffolds. In addition, the key research findings regarding the contribution of ECM alterations, cytotoxicity issues, graft sourcing, and implantation site to the immunogenicity of decellularized tissues/organs are comprehensively considered. Finally, it discusses practical solutions to overcome immunogenicity, including antigen masking by crosslinking, sterilization optimization, and antigen removal techniques such as selective antigen removal and sequential antigen solubilization.
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Affiliation(s)
- Mohammadreza Kasravi
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 1985711151, Iran
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Armin Ahmadi
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 1985711151, Iran
| | - Amirhesam Babajani
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 1985711151, Iran
| | - Radman Mazloomnejad
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 1985711151, Iran
| | - Mohammad Reza Hatamnejad
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Siavash Shariatzadeh
- Department of Surgery, University of California Los Angeles, Los Angeles, California, USA
| | - Soheyl Bahrami
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in AUVA Research Center, Vienna, Austria
| | - Hassan Niknejad
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 1985711151, Iran.
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28
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Bian N, Chu C, Rung S, Huangphattarakul V, Man Y, Lin J, Hu C. Immunomodulatory Biomaterials and Emerging Analytical Techniques for Probing the Immune Micro-Environment. Tissue Eng Regen Med 2023; 20:11-24. [PMID: 36241939 PMCID: PMC9852373 DOI: 10.1007/s13770-022-00491-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 08/31/2022] [Accepted: 09/05/2022] [Indexed: 02/01/2023] Open
Abstract
After implantation of a biomaterial, both the host immune system and properties of the material determine the local immune response. Through triggering or modulating the local immune response, materials can be designed towards a desired direction of promoting tissue repair or regeneration. High-throughput sequencing technologies such as single-cell RNA sequencing (scRNA-seq) emerging as a powerful tool for dissecting the immune micro-environment around biomaterials, have not been fully utilized in the field of soft tissue regeneration. In this review, we first discussed the procedures of foreign body reaction in brief. Then, we summarized the influences that physical and chemical modulation of biomaterials have on cell behaviors in the micro-environment. Finally, we discussed the application of scRNA-seq in probing the scaffold immune micro-environment and provided some reference to designing immunomodulatory biomaterials. The foreign body response consists of a series of biological reactions. Immunomodulatory materials regulate immune cell activation and polarization, mediate divergent local immune micro-environments and possess different tissue engineering functions. The manipulation of physical and chemical properties of scaffolds can modulate local immune responses, resulting in different outcomes of fibrosis or tissue regeneration. With the advancement of technology, emerging techniques such as scRNA-seq provide an unprecedented understanding of immune cell heterogeneity and plasticity in a scaffold-induced immune micro-environment at high resolution. The in-depth understanding of the interaction between scaffolds and the host immune system helps to provide clues for the design of biomaterials to optimize regeneration and promote a pro-regenerative local immune micro-environment.
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Affiliation(s)
- Nanyan Bian
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Chenyu Chu
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China
- Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, 14#, 3rd section, Renmin South Road, Chengdu, 610041, Sichuan, China
| | - Shengan Rung
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China
- Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, 14#, 3rd section, Renmin South Road, Chengdu, 610041, Sichuan, China
| | - Vicha Huangphattarakul
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China
- Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, 14#, 3rd section, Renmin South Road, Chengdu, 610041, Sichuan, China
| | - Yi Man
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China
- Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, 14#, 3rd section, Renmin South Road, Chengdu, 610041, Sichuan, China
| | - Jie Lin
- Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, 14#, 3rd section, Renmin South Road, Chengdu, 610041, Sichuan, China.
| | - Chen Hu
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
- Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, 14#, 3rd section, Renmin South Road, Chengdu, 610041, Sichuan, China.
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29
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Justin AW, Cammarata F, Guy AA, Estevez SR, Burgess S, Davaapil H, Stavropoulou-Tatla A, Ong J, Jacob AG, Saeb-Parsy K, Sinha S, Markaki AE. Densified collagen tubular grafts for human tissue replacement and disease modelling applications. BIOMATERIALS ADVANCES 2023; 145:213245. [PMID: 36549149 DOI: 10.1016/j.bioadv.2022.213245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 12/07/2022] [Accepted: 12/09/2022] [Indexed: 12/23/2022]
Abstract
There is a significant need across multiple indications for an off-the-shelf bioengineered tubular graft which fulfils the mechanical and biological requirements for implantation and function but does not necessarily require cells for manufacture or deployment. Herein, we present a tissue-like tubular construct using a cell-free, materials-based method of manufacture, utilizing densified collagen hydrogel. Our tubular grafts are seamless, mechanically strong, customizable in terms of lumen diameter and wall thickness, and display a uniform fibril density across the wall thickness and along the tube length. While the method enables acellular grafts to be generated rapidly, inexpensively, and to a wide range of specifications, the cell-compatible densification process also enables a high density of cells to be incorporated uniformly into the walls of the tubes, which we show can be maintained under perfusion culture. Additionally, the method enables tubes consisting of distinct cell domains with cellular configurations at the boundaries which may be useful for modelling aortic disease. Further, we demonstrate additional steps which allow for luminal surface patterning. These results highlight the universality of this approach and its potential for developing the next generation of bioengineered grafts.
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Affiliation(s)
- Alexander W Justin
- Department of Engineering, University of Cambridge, Trumpington Street, Cambridge CB2 1PZ, UK.
| | - Federico Cammarata
- Department of Engineering, University of Cambridge, Trumpington Street, Cambridge CB2 1PZ, UK
| | - Andrew A Guy
- Department of Engineering, University of Cambridge, Trumpington Street, Cambridge CB2 1PZ, UK
| | - Silas R Estevez
- Department of Engineering, University of Cambridge, Trumpington Street, Cambridge CB2 1PZ, UK
| | - Sebastian Burgess
- Department of Engineering, University of Cambridge, Trumpington Street, Cambridge CB2 1PZ, UK
| | - Hongorzul Davaapil
- Wellcome-Medical Research Council Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, Division of Cardiovascular Medicine, University of Cambridge, Cambridge CB2 0QQ, UK
| | | | - John Ong
- Department of Engineering, University of Cambridge, Trumpington Street, Cambridge CB2 1PZ, UK; East of England Gastroenterology Speciality Training Program, Cambridge, UK
| | - Aishwarya G Jacob
- Wellcome-Medical Research Council Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Biochemistry, University of Cambridge, Downing Site, Tennis Court Road, Cambridge CB2 1QW, UK
| | - Kourosh Saeb-Parsy
- Department of Surgery, University of Cambridge, and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK
| | - Sanjay Sinha
- Department of Medicine, Division of Cardiovascular Medicine, University of Cambridge, Cambridge CB2 0QQ, UK
| | - Athina E Markaki
- Department of Engineering, University of Cambridge, Trumpington Street, Cambridge CB2 1PZ, UK.
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30
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Wan J, Wu T, Wang K, Xia K, Yin L, Chen C. Polydopamine-modified decellularized intestinal scaffolds loaded with adipose-derived stem cells promote intestinal regeneration. J Mater Chem B 2022; 11:154-168. [PMID: 36458582 DOI: 10.1039/d2tb01389d] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Regeneration of gastrointestinal tissues remains a great challenge due to their unique microenvironment. Functional composite decellularized scaffolds have shown great potential in gastrointestinal repair and inducing gastrointestinal tissue-specific proliferation. In this study, polydopamine (PDA)-mediated surface modification of decellularized intestinal scaffolds (DIS), combined with adipose tissue-derived stem cells (ADSC), was used to promote intestinal wound healing while avoiding intestinal resection. The results showed that DIS had good biocompatibility and could maintain the growth and proliferation of ADSC. Moreover, PDA-coated DIS not only had anti-infection ability but could also further promote the secretory activity for the paracrine effects of ADSC. ADSC cultured on PDA-DIS produced significantly higher levels of anti-inflammatory and proangiogenic cytokines than those cultured on plastic plates or DIS. In vivo, ADSC-PDA-DIS significantly promoted intestinal wound closure in rat intestinal defect models. Moreover, ADSC-PDA-DIS was able to induce more neovascularization at 4 weeks postoperatively and promoted macrophage recruitment to accelerate wound healing. Taken together, the results showed that PDA-modified DIS could significantly improve the efficacy of stem cell therapy, and ADSC-PDA-DIS could improve the wound healing process with anti-infection effects, enhancing neovascularization and immunoregulation, which may be of great clinical significance for gastrointestinal regeneration.
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Affiliation(s)
- Jian Wan
- Center for Difficult and Complicated Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China. .,Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Nantong University, Nantong, 226000, China.,Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226000, China
| | - Tianqi Wu
- Center for Difficult and Complicated Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
| | - Keyi Wang
- Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
| | - Kai Xia
- Center for Difficult and Complicated Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
| | - Lu Yin
- Center for Difficult and Complicated Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
| | - Chunqiu Chen
- Center for Difficult and Complicated Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
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31
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Li G, Liu S, Chen W, Jiang Z, Luo Y, Wang D, Zheng Y, Liu Y. Acellularized Uvea Hydrogel as Novel Injectable Platform for Cell-Based Delivering Treatment of Retinal Degeneration and Optimizing Retinal Organoids Inducible System. Adv Healthc Mater 2022; 11:e2202114. [PMID: 36189847 DOI: 10.1002/adhm.202202114] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Indexed: 01/28/2023]
Abstract
Replenishing the retina with retinal pigment epithelial (RPE) cells derived from pluripotent stem cells (PSCs) has great promise for treating retinal degenerative diseases, but it is limited by poor cell survival and integration in vivo. Herein, porcine acellular sclera and uvea extracellular matrix (ECM) and their counterpart hydrogels are developed, and their effects on the biological behavior of human induced pluripotent stem cell (hiPSC)-derived RPE cells (hiPSC-RPE) and embryoid body (hiPSC-EB) differentiation are investigated. Both acellular ECM hydrogels have excellent biocompatibility and suitable biodegradability without evoking an obvious immune response. Most importantly, the decellularized uvea hydrogel-delivered cells' injection remarkably promotes the hiPSC-RPE cells' survival and integration in the subretinal space, rescues the photoreceptor cells' death and retinal gliosis, and restores vision in rats with retinal degeneration for a long duration. In addition, medium supplementation with decellularized uvea peptides promotes hiPSC-EBs onset morphogenesis and neural/retinal differentiation, forming layered retinal organoids. This study demonstrates that ECM hydrogel-delivered hiPSC-RPE cells' injection may be a useful approach for treating retinal degeneration disease, combined with an optimized retinal seeding cells' induction program, which has potential for clinical application.
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Affiliation(s)
- Guilan Li
- Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, #7 Jinsui Road, Tianhe District, Guangzhou, 510060, China.,Research Unit of Ocular Development and Regeneration, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Sheng Liu
- Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, #7 Jinsui Road, Tianhe District, Guangzhou, 510060, China.,Guangzhou Laboratory, No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou, 510005, China
| | - Wenfei Chen
- Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, #7 Jinsui Road, Tianhe District, Guangzhou, 510060, China
| | - Zhijian Jiang
- Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, #7 Jinsui Road, Tianhe District, Guangzhou, 510060, China
| | - Yuanting Luo
- Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, #7 Jinsui Road, Tianhe District, Guangzhou, 510060, China
| | - Dongliang Wang
- Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, #7 Jinsui Road, Tianhe District, Guangzhou, 510060, China
| | - Yingfeng Zheng
- Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, #7 Jinsui Road, Tianhe District, Guangzhou, 510060, China.,Research Unit of Ocular Development and Regeneration, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Yizhi Liu
- Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, #7 Jinsui Road, Tianhe District, Guangzhou, 510060, China.,Research Unit of Ocular Development and Regeneration, Chinese Academy of Medical Sciences, Beijing, 100730, China
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32
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Barbulescu GI, Bojin FM, Ordodi VL, Goje ID, Barbulescu AS, Paunescu V. Decellularized Extracellular Matrix Scaffolds for Cardiovascular Tissue Engineering: Current Techniques and Challenges. Int J Mol Sci 2022; 23:13040. [PMID: 36361824 PMCID: PMC9658138 DOI: 10.3390/ijms232113040] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 10/18/2022] [Accepted: 10/26/2022] [Indexed: 08/13/2023] Open
Abstract
Cardiovascular diseases are the leading cause of global mortality. Over the past two decades, researchers have tried to provide novel solutions for end-stage heart failure to address cardiac transplantation hurdles such as donor organ shortage, chronic rejection, and life-long immunosuppression. Cardiac decellularized extracellular matrix (dECM) has been widely explored as a promising approach in tissue-regenerative medicine because of its remarkable similarity to the original tissue. Optimized decellularization protocols combining physical, chemical, and enzymatic agents have been developed to obtain the perfect balance between cell removal, ECM composition, and function maintenance. However, proper assessment of decellularized tissue composition is still needed before clinical translation. Recellularizing the acellular scaffold with organ-specific cells and evaluating the extent of cardiomyocyte repopulation is also challenging. This review aims to discuss the existing literature on decellularized cardiac scaffolds, especially on the advantages and methods of preparation, pointing out areas for improvement. Finally, an overview of the state of research regarding the application of cardiac dECM and future challenges in bioengineering a human heart suitable for transplantation is provided.
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Affiliation(s)
- Greta Ionela Barbulescu
- Immuno-Physiology and Biotechnologies Center (CIFBIOTEH), Department of Functional Sciences, “Victor Babes” University of Medicine and Pharmacy, No 2 Eftimie Murgu Square, 300041 Timisoara, Romania
- Department of Clinical Practical Skills, “Victor Babes” University of Medicine and Pharmacy, No 2 Eftimie Murgu Square, 300041 Timisoara, Romania
| | - Florina Maria Bojin
- Immuno-Physiology and Biotechnologies Center (CIFBIOTEH), Department of Functional Sciences, “Victor Babes” University of Medicine and Pharmacy, No 2 Eftimie Murgu Square, 300041 Timisoara, Romania
- Clinical Emergency County Hospital “Pius Brinzeu” Timisoara, Center for Gene and Cellular Therapies in the Treatment of Cancer Timisoara-OncoGen, No 156 Liviu Rebreanu, 300723 Timisoara, Romania
| | - Valentin Laurentiu Ordodi
- Clinical Emergency County Hospital “Pius Brinzeu” Timisoara, Center for Gene and Cellular Therapies in the Treatment of Cancer Timisoara-OncoGen, No 156 Liviu Rebreanu, 300723 Timisoara, Romania
- Faculty of Industrial Chemistry and Environmental Engineering, “Politehnica” University Timisoara, No 2 Victoriei Square, 300006 Timisoara, Romania
| | - Iacob Daniel Goje
- Department of Medical Semiology I, “Victor Babes” University of Medicine and Pharmacy, No 2 Eftimie Murgu Square, 300041 Timisoara, Romania
- Advanced Cardiology and Hemostaseology Research Center, “Victor Babes” University of Medicine and Pharmacy, No 2 Eftimie Murgu Square, 300041 Timisoara, Romania
| | - Andreea Severina Barbulescu
- Center for Advanced Research in Gastroenterology and Hepatology, Department of Internal Medicine II, Division of Gastroenterology and Hepatology, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Virgil Paunescu
- Immuno-Physiology and Biotechnologies Center (CIFBIOTEH), Department of Functional Sciences, “Victor Babes” University of Medicine and Pharmacy, No 2 Eftimie Murgu Square, 300041 Timisoara, Romania
- Clinical Emergency County Hospital “Pius Brinzeu” Timisoara, Center for Gene and Cellular Therapies in the Treatment of Cancer Timisoara-OncoGen, No 156 Liviu Rebreanu, 300723 Timisoara, Romania
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Gao C, Huang Y, Zhang L, Wei P, Jing W, Wang H, Yuan Z, Zhang D, Yu Y, Yang X, Cai Q. Self-reinforcement hydrogel with sustainable oxygen-supply for enhanced cell ingrowth and potential tissue regeneration. BIOMATERIALS ADVANCES 2022; 141:213105. [PMID: 36088718 DOI: 10.1016/j.bioadv.2022.213105] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 08/01/2022] [Accepted: 09/02/2022] [Indexed: 06/15/2023]
Abstract
Hydrogels composed of natural biopolymers are attractive for tissue regeneration applications owing to their advantages such as biocompatibility and ease of administration, etc.. Yet, the low oxygen level and the crosslinked network inside bulk hydrogels, as well as the hypoxic status in defect areas, hamper cell viability, function, and eventual tissue repair. Herein, based on Ca2+-crosslinked alginate hydrogel, oxygen-generating calcium peroxide (CaO2) was introduced, which could provide a dynamic crosslinking alongside the CaO2 decomposition. Compared to the CaCl2-crosslinked alginate hydrogel, bone marrow mesenchymal stromal cells cultured with CaO2-contained system displayed remarkably improved biological behaviors. Furthermore, in vivo evaluations were carried out on a subcutaneous implantation in rats, and the results demonstrated the importance of the local oxygen availability in a series of crucial events for tissue regeneration, such as activating cell viability, migration, angiogenesis, and osteogenesis. In summary, the obtained Ca2+-crosslinked alginate hydrogel achieved a better microenvironment for cell ingrowth and potential tissue regeneration as the CaCl2 crosslinker being replaced by oxygen-generating CaO2 nanoparticles, due to its contribution in remedying the local hypoxic condition, promisingly, the release of Ca2+ makes the hydrogel to be a possible candidate scaffold for bone tissue engineering.
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Affiliation(s)
- Chenyuan Gao
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China
| | - Yiqian Huang
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China
| | - Liwen Zhang
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China
| | - Pengfei Wei
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China
| | - Wei Jing
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China
| | - Haijun Wang
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China
| | - Zuoying Yuan
- Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing 100871, China
| | - Daixing Zhang
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China
| | - Yingjie Yu
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China.
| | - Xiaoping Yang
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China; Foshan (Southern China) Institute for New Materials, Foshan 528200, Guangdong, China
| | - Qing Cai
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China.
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34
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Ding Y, Zhang W, Sun B, Mo X, Wu J. Cyclic freeze–thaw grinding to decellularize meniscus for fabricating porous, elastic scaffolds. J Biomed Mater Res A 2022; 110:1824-1839. [PMID: 36082975 DOI: 10.1002/jbm.a.37435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 06/23/2022] [Accepted: 07/27/2022] [Indexed: 11/11/2022]
Affiliation(s)
- Yangfan Ding
- Shanghai Engineering Research Center of Nano‐Biomaterials and Regenerative Medicine, College of Biologial Science and Medical Engineering Donghua University Shanghai China
| | - Weixing Zhang
- Department of Critical Care Medicine, Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
| | - Binbin Sun
- Shanghai Engineering Research Center of Nano‐Biomaterials and Regenerative Medicine, College of Biologial Science and Medical Engineering Donghua University Shanghai China
| | - Xiumei Mo
- Shanghai Engineering Research Center of Nano‐Biomaterials and Regenerative Medicine, College of Biologial Science and Medical Engineering Donghua University Shanghai China
| | - Jinglei Wu
- Shanghai Engineering Research Center of Nano‐Biomaterials and Regenerative Medicine, College of Biologial Science and Medical Engineering Donghua University Shanghai China
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35
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Karimi S, Khorsandi LS, Ai J. Fabrication of bioartificial pancreas using decellularized rat testicular tissue. Acta Histochem 2022; 124:151928. [DOI: 10.1016/j.acthis.2022.151928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 06/26/2022] [Accepted: 06/26/2022] [Indexed: 11/28/2022]
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36
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Doryab A, Schmid O. Bioactive Cell-Derived ECM Scaffold Forms a Unique Cellular Microenvironment for Lung Tissue Engineering. Biomedicines 2022; 10:biomedicines10081791. [PMID: 35892691 PMCID: PMC9394345 DOI: 10.3390/biomedicines10081791] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/19/2022] [Accepted: 07/22/2022] [Indexed: 12/11/2022] Open
Abstract
Chronic lung diseases are one of the leading causes of death worldwide. Lung transplantation is currently the only causal therapeutic for lung diseases, which is restricted to end-stage disease and limited by low access to donor lungs. Lung tissue engineering (LTE) is a promising approach to regenerating a replacement for at least a part of the damaged lung tissue. Currently, lung regeneration is limited to a simplified local level (e.g., alveolar−capillary barrier) due to the sophisticated and complex structure and physiology of the lung. Here, we introduce an extracellular matrix (ECM)-integrated scaffold using a cellularization−decellularization−recellularization technique. This ECM-integrated scaffold was developed on our artificial co-polymeric BETA (biphasic elastic thin for air−liquid interface cell culture conditions) scaffold, which were initially populated with human lung fibroblasts (IMR90 cell line), as the main generator of ECM proteins. Due to the interconnected porous structure of the thin (<5 µm) BETA scaffold, the cells can grow on and infiltrate into the scaffold and deposit their own ECM. After a mild decellularization procedure, the ECM proteins remained on the scaffold, which now closely mimicked the cellular microenvironment of pulmonary cells more realistically than the plain artificial scaffolds. We assessed several decellularization methods and found that 20 mM NH4OH and 0.1% Triton X100 with subsequent DNase treatment completely removed the fibroblasts (from the first cellularization) and maintains collagen I and IV as the key ECM proteins on the scaffold. We also showed the repopulation of the primary fibroblast from human (without chronic lung disease (non-CLD) donors) and human bronchial epithelial (16HBE14o−) cells on the ECM-integrated BETA scaffold. With this technique, we developed a biomimetic scaffold that can mimic both the physico-mechanical properties and the native microenvironment of the lung ECM. The results indicate the potential of the presented bioactive scaffold for LTE application.
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37
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Kim HS, Hwang HJ, Kim HJ, Choi Y, Lee D, Jung HH, Do SH. Effect of Decellularized Extracellular Matrix Bioscaffolds Derived from Fibroblasts on Skin Wound Healing and Remodeling. Front Bioeng Biotechnol 2022; 10:865545. [PMID: 35845393 PMCID: PMC9277482 DOI: 10.3389/fbioe.2022.865545] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Accepted: 03/22/2022] [Indexed: 11/13/2022] Open
Abstract
The mammalian tissue extracellular matrix (ECM) has been used as a scaffold to facilitate the repair and reconstruction of numerous tissues. However, the material properties of decellularized ECM (dECM) from in vitro cell cultures and the effect of these properties on wound remodeling remain unclear. To elucidate its biological activity, we extracted dECM from human lung fibroblasts, fabricated it into a patch, and applied it to a full-thickness skin wound. The fibroblast-derived dECM (fdECM) maintained the content of collagen Ⅰ, collagen Ⅳ, and elastin, and the extraction process did not damage its critical growth factors. The fdECM-conjugated collagen patch (COL-fdECM) facilitated wound contraction and angiogenesis in the proliferative phase when applied to the in vivo full-thickness skin wound model. Moreover, the COL-fdECM treated wound showed increased regeneration of the epidermal barrier function, mature collagen, hair follicle, and subepidermal nerve plexus, suggesting qualitative skin remodeling. This therapeutic efficacy was similarly observed when applied to the diabetic ulcer model. fdECM was shown to help remodel the tissue by regulating fibroblast growth factors, matrix metalloproteinases, and tissue inhibitors of metalloproteinases via the p38 and ERK signaling pathways in an in vitro experiment for understanding the underlying mechanism. These results provide a biological basis for cell-derived ECM as a multi-functional biomaterial applicable to various diseases.
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Affiliation(s)
- Hyo-Sung Kim
- Department of Veterinary Clinical Pathology, College of Veterinary Medicine, Konkuk University, Seoul, South Korea
| | - Hyun-Jeong Hwang
- Department of Veterinary Clinical Pathology, College of Veterinary Medicine, Konkuk University, Seoul, South Korea
| | - Han-Jun Kim
- Department of Veterinary Clinical Pathology, College of Veterinary Medicine, Konkuk University, Seoul, South Korea
- Terasaki Institute for Biomedical Innovation, Los Angeles, CA, United States
| | - Yeji Choi
- Advanced Medical Device R&D Center, HansBiomed Co. Ltd., Seoul, South Korea
| | - Daehyung Lee
- Advanced Medical Device R&D Center, HansBiomed Co. Ltd., Seoul, South Korea
| | - Hong-Hee Jung
- Advanced Medical Device R&D Center, HansBiomed Co. Ltd., Seoul, South Korea
| | - Sun Hee Do
- Department of Veterinary Clinical Pathology, College of Veterinary Medicine, Konkuk University, Seoul, South Korea
- *Correspondence: Sun Hee Do,
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38
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Orozco-Vega A, Montes-Rodríguez MI, Luévano-Colmenero GH, Barros-Gómez J, Muñoz-González PU, Flores-Moreno M, Delgadillo-Holtfort I, Vega-González A, Rojo FJ, Guinea GV, Mendoza-Novelo B. Decellularization of porcine esophageal tissue at three diameters and the bioscaffold modification with EETs-ECM gel. J Biomed Mater Res A 2022; 110:1669-1680. [PMID: 35703732 DOI: 10.1002/jbm.a.37416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 05/30/2022] [Accepted: 06/02/2022] [Indexed: 11/07/2022]
Abstract
Damaged complex modular organs repair is a current clinical challenge in which one of the primary goals is to keep their biological response. An interesting case of study it is the porcine esophagus since it is a tubular muscular tissue selected as raw material for tissue engineering. The design of esophageal constructs can draw on properties of the processed homologous extracellular matrix (ECM). In this work, we report the decellularization of multilayered esophagus tissue from 1-, 21- and 45-days old piglets through the combination of reversible alkaline swelling and detergent perfusion. The bioscaffolds were characterized in terms of their residual composition and tensile mechanical properties. The biological response to esophageal submucosal derived bioscaffolds modified with ECM gel containing epoxyeicosatrienoic acids (EETs) was then evaluated. Results suggest that the composition (laminin, fibronectin, and sulphated glycosaminoglycans/sGAG) depends on the donor age: a better efficiency of the decellularization process combined with a higher retention of sGAG and fibronectin is observed in piglet esophageal scaffolds. The heterogeneity of this esophageal ECM is maintained, which implied the preservation of anisotropic tensile properties. Coating of bioscaffolds with ECM gel is suitable for carrying esophageal epithelial cells and EETs. Bioactivity of EETs-ECM gel modified esophageal submucosal bioscaffolds is observed to promote neovascularization and antiinflammatory after rabbit full-thickness esophageal defect replacement.
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Affiliation(s)
- Adriana Orozco-Vega
- División de Ciencias e Ingenierías, Universidad de Guanajuato, León, Gto, Mexico
| | - Metzeri I Montes-Rodríguez
- División de Ciencias e Ingenierías, Universidad de Guanajuato, León, Gto, Mexico.,Hospital Gineco-Pediatra No 48, Centro Médico Nacional del Bajío, UMAE, Instituto Mexicano del Seguro Social, León, Gto, Mexico
| | - Guadalupe H Luévano-Colmenero
- División de Ciencias e Ingenierías, Universidad de Guanajuato, León, Gto, Mexico.,Unidad Profesional Interdisciplinaria de Ingeniería, Campus Guanajuato, Instituto Politécnico Nacional, Silao de la Victoria, Gto, Mexico
| | - Jimena Barros-Gómez
- División de Ciencias e Ingenierías, Universidad de Guanajuato, León, Gto, Mexico
| | | | | | | | - Arturo Vega-González
- División de Ciencias e Ingenierías, Universidad de Guanajuato, León, Gto, Mexico
| | - Francisco J Rojo
- Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Pozuelo de Alarcón, Spain.,Departamento de Ciencia de Materiales, ETSI de Caminos, Canales y Puertos, Universidad Politécnica de Madrid, Madrid, Spain.,Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Gustavo V Guinea
- Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Pozuelo de Alarcón, Spain.,Departamento de Ciencia de Materiales, ETSI de Caminos, Canales y Puertos, Universidad Politécnica de Madrid, Madrid, Spain.,Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.,Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain
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39
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Liu K, He Y, Lu F. Research Progress on the Immunogenicity and Regeneration of Acellular Adipose Matrix: A Mini Review. Front Bioeng Biotechnol 2022; 10:881523. [PMID: 35733521 PMCID: PMC9207478 DOI: 10.3389/fbioe.2022.881523] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 05/18/2022] [Indexed: 11/13/2022] Open
Abstract
Acellular adipose matrix (AAM) has received increasing attention for soft tissue reconstruction, due to its abundant source, high long-term retention rate and in vivo adipogenic induction ability. However, the current decellularization methods inevitably affect native extracellular matrix (ECM) properties, and the residual antigens can trigger adverse immune reactions after transplantation. The behavior of host inflammatory cells mainly decides the regeneration of AAM after transplantation. In this review, recent knowledge of inflammatory cells for acellular matrix regeneration will be discussed. These advancements will inform further development of AAM products with better properties.
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Talaei-Khozani T, Yaghoubi A. An overview of post transplantation events of decellularized scaffolds. Transpl Immunol 2022; 74:101640. [PMID: 35667545 DOI: 10.1016/j.trim.2022.101640] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/29/2022] [Accepted: 05/31/2022] [Indexed: 12/19/2022]
Abstract
Regenerative medicine and tissue engineering are reasonable techniques for repairing failed tissues and could be a suitable alternative to organ transplantation. One of the most widely used methods for preparing bioscaffolds is the decellularization procedure. Although cell debris and DNA are removed from the decellularized tissues, important compositions of the extracellular matrix including proteins, proteoglycans, and glycoproteins are nearly preserved. Moreover, the obtained scaffolds have a 3-dimensional (3D) structure, appropriate naïve mechanical properties, and good biocompatibility. After transplantation, different types of host cells migrate to the decellularized tissues. Histological and immunohistochemical assessment of the different bioscaffolds after implantation reveals the migration of parenchymal cells, angiogenesis, as well as the invasion of inflammatory and giant foreign cells. In this review, the events after transplantation including angiogenesis, scaffold degradation, and the presence of immune and tissue-specific progenitor cells in the decellularized scaffolds in various hosts, are discussed.
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Affiliation(s)
- Tahereh Talaei-Khozani
- Histotomorphometry and stereology research center, Shiraz University of Medical Sciences, Shiraz, Iran; Tissue engineering lab, Anatomy Department, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Atefeh Yaghoubi
- Tissue engineering lab, Anatomy Department, Shiraz University of Medical Sciences, Shiraz, Iran.
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Baaji K, Pezeshki-Modaress M, Rajabi S. An aorta ECM extracted hydrogel as a biomaterial in vascular tissue engineering application. Prog Biomater 2022; 11:207-217. [PMID: 35583849 DOI: 10.1007/s40204-022-00186-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 04/11/2022] [Indexed: 11/29/2022] Open
Abstract
Biological scaffolds have been undergoing significant growth in tissue engineering applications over the last years. Biopolymers extracted from ECM with various protein factors and other biological agents have been active in restoring damaged tissue. In the present study, bioactive scaffold is prepared from bovine aorta extracted natural polymeric hydrogel with advantages of availability and cost-effectiveness. The biological scaffolds were prepared through freeze-drying method to make a 3D sponge with appropriate structure, well-defined architecture and interconnected pores for vascular tissue engineering, and studied the effect of aorta hydrogel concentrations (1, 2, 3, and 4% w/v) on the scaffolds. The prepared biological scaffolds were analyzed by mechanical tests, FTIR, SEM, porosity and PBS absorption. Moreover, the morphology and proliferation of human umbilical vein cord cells on the 3D sponges were investigated. Histological analysis including, Masson trichrome (MT), hematoxylin and eosin (H&E), Verhoeff/Van Gieson (VVG) and alcian blue (AB) revealed that during this process the main components of aorta extracellular matrix containing collagen, elastin, and glycosaminoglycan were well preserved. The obtained results revealed that the scaffolds porosity were more than 90%. The Aorta-ECM4% enabled HUVECs to survive, proliferate and migrate better than 2% and 3% aorta-ECM.
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Affiliation(s)
- Khadijeh Baaji
- Soft Tissue Engineering Research Center, Tissue Engineering and Regenerative Medicine Institute, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | | | - Sarah Rajabi
- Department of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
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Massaro MS, Kochová P, Pálek R, Rosendorf J, Červenková L, Dahmen U, Liška V, Moulisová V. Decellularization of Porcine Carotid Arteries: From the Vessel to the High-Quality Scaffold in Five Hours. Front Bioeng Biotechnol 2022; 10:833244. [PMID: 35651544 PMCID: PMC9150822 DOI: 10.3389/fbioe.2022.833244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 04/06/2022] [Indexed: 11/13/2022] Open
Abstract
The use of biologically derived vessels as small-diameter vascular grafts in vascular diseases is currently intensely studied. Vessel decellularization provides a biocompatible scaffold with very low immunogenicity that avoids immunosuppression after transplantation. Good scaffold preservation is important as it facilitates successful cell repopulation. In addition, mechanical characteristics have to be carefully evaluated when the graft is intended to be used as an artery due to the high pressures the vessel is subjected to. Here, we present a new and fast decellularization protocol for porcine carotid arteries, followed by investigation of the quality of obtained vessel scaffolds in terms of maintenance of important extracellular matrix components, mechanical resistance, and compatibility with human endothelial cells. Our results evidence that our decellularization protocol minimally alters both the presence of scaffold proteins and their mechanical behavior and human endothelial cells could adhere to the scaffold in vitro. We conclude that if a suitable protocol is used, a high-quality decellularized arterial scaffold of non-human origin can be promptly obtained, having a great potential to be recellularized and used as an arterial graft in transplantation medicine.
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Affiliation(s)
| | - Petra Kochová
- New Technologies for Information Society-NTIS, University of West Bohemia, Pilsen, Czechia
| | - Richard Pálek
- Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
- Department of Surgery, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
| | - Jáchym Rosendorf
- Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
- Department of Surgery, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
| | - Lenka Červenková
- Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
| | - Uta Dahmen
- Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, University Hospital Jena, Jena, Germany
| | - Václav Liška
- Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
- Department of Surgery, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
| | - Vladimíra Moulisová
- Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
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Chen J, Torres-de la Roche LA, Kahlert UD, Isachenko V, Huang H, Hennefründ J, Yan X, Chen Q, Shi W, Li Y. Artificial Ovary for Young Female Breast Cancer Patients. Front Med (Lausanne) 2022; 9:837022. [PMID: 35372399 PMCID: PMC8969104 DOI: 10.3389/fmed.2022.837022] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 02/02/2022] [Indexed: 12/14/2022] Open
Abstract
In recent decades, there has been increasing attention toward the quality of life of breast cancer (BC) survivors. Meeting the growing expectations of fertility preservation and the generation of biological offspring remains a great challenge for these patients. Conventional strategies for fertility preservation such as oocyte and embryo cryopreservation are not suitable for prepubertal cancer patients or in patients who need immediate cancer therapy. Ovarian tissue cryopreservation (OTC) before anticancer therapy and autotransplantation is an alternative option for these specific indications but has a risk of retransplantation malignant cells. An emerging strategy to resolve these issues is by constructing an artificial ovary combined with stem cells, which can support follicle proliferation and ensure sex hormone secretion. This promising technique can meet both demands of improving the quality of life and meanwhile fulfilling their expectation of biological offspring without the risk of cancer recurrence.
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Affiliation(s)
- Jing Chen
- Reproductive Medicine Center, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | | | - Ulf D. Kahlert
- Molecular and Experimental Surgery, University Clinic for General, Visceral and Vascular Surgery, University Medicine Magdeburg and Otto-von Guericke University, Magdeburg, Germany
| | - Vladimir Isachenko
- Research Group for Reproductive Medicine and IVF Laboratory, Department of Obstetrics and Gynecology, Cologne University, Cologne, Germany
| | - Hui Huang
- Reproductive Medicine Center, Women and Children's Hospital, Xiamen University, Xiamen, China
| | - Jörg Hennefründ
- University Hospital for Gynecology, Pius-Hospital, University Medicine Oldenburg, Oldenburg, Germany
| | - Xiaohong Yan
- Reproductive Medicine Center, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Qionghua Chen
- Reproductive Medicine Center, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Wenjie Shi
- University Hospital for Gynecology, Pius-Hospital, University Medicine Oldenburg, Oldenburg, Germany
| | - Youzhu Li
- Reproductive Medicine Center, The First Affiliated Hospital of Xiamen University, Xiamen, China
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