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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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http://dx.doi.org/10.1186/s40824-023-00348-z | DOI Listing |
Front Med Technol
August 2025
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom.
The extracellular matrix (ECM) serves as a dynamic biological framework that orchestrates cellular behavior through biomechanical and biochemical cues, playing a pivotal role in tissue homeostasis and repair. Despite significant advancements in biomaterial design, current regenerative strategies often fail to fully replicate the ECM's complexity, leading to suboptimal healing outcomes. This review comprehensively examines ECM biology and its application in biomaterial engineering, highlighting structural-functional relationships, integrin-mediated signaling, and ECM remodeling mechanisms in wound healing.
View Article and Find Full Text PDFInt J Mol Sci
August 2025
Reconstructive Orthopaedic Surgery and Innovative Techniques-Musculoskeletal Tissue Bank, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.
Peripheral nerve injuries affect over one million individuals annually worldwide due to various causes such as trauma, metabolic disorders, and autoimmune diseases. While autologous nerve grafting remains the gold standard for treating large-gap nerve injuries, its limitations, including limited tissue availability, donor site morbidity, infection risk, and suboptimal functional recovery, have spurred interest in alternative approaches. Among these, allogeneic nerve grafting has emerged as a promising option, offering structural and functional advantages due to the native architecture of donor nerves.
View Article and Find Full Text PDFJ Mater Chem B
August 2025
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Kolkata, West Bengal 700054, India.
A considerable number of xenogeneic tissues are still underutilised due to concerns about immunogenicity, biocompatibility, and structural integrity. Decellularized extracellular matrix (dECM) hydrogels are gaining popularity due to their ability to mimic natural biochemical cues and structural integrity required for tissue regeneration. In this study, we used pig tendon tissues, which are commonly discarded, to create photo-crosslinked dECM hydrogels.
View Article and Find Full Text PDFExtracellular matrix (ECM) and amniotic derivatives have emerged as promising biomaterials in regenerative medicine, particularly for bone and nerve repair. These biologic scaffolds provide structural and biochemical cues that support cellular migration, proliferation, and differentiation, thereby facilitating tissue regeneration. ECM-based therapies leverage native bioactive components to modulate immune responses and enhance healing, while perinatal derivatives, including amniotic membrane, umbilical cord, and placental tissue, offer a rich source of growth factors, cytokines, and stem cells that promote neurogenesis and osteogenesis.
View Article and Find Full Text PDFJ Am Heart Assoc
August 2025
National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education and Hubei Province), School of Life and Health Sciences, Hubei University of Technology Wuhan China.
Heart valve disease contributes to cardiovascular disease-associated death. Bioprosthetic heart valves have emerged as a preferred option for heart valve replacement due to their superior hemodynamic performance and reduced need for lifelong anticoagulation. However, their long-term durability is compromised by calcification, immunogenicity, and structural degeneration, primarily due to glutaraldehyde fixation and residual xenogeneic antigens.
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