Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine

被引:107
作者
Kasravi, Mohammadreza [1 ,2 ]
Ahmadi, Armin [1 ]
Babajani, Amirhesam [1 ]
Mazloomnejad, Radman [1 ]
Hatamnejad, Mohammad Reza [2 ]
Shariatzadeh, Siavash [3 ]
Bahrami, Soheyl [4 ]
Niknejad, Hassan [1 ]
机构
[1] Shahid Beheshti Univ Med Sci, Sch Med, Dept Pharmacol, Tehran 1985711151, Iran
[2] Shahid Beheshti Univ Med Sci, Res Inst Gastroenterol & Liver Dis, Gastroenterol & Liver Dis Res Ctr, Tehran, Iran
[3] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA USA
[4] Ludwig Boltzmann Inst Expt, Clin Traumatol AUVA Res Ctr, Vienna, Austria
关键词
Decellularization; Tissue engineering; Extracellular matrix; Translational medicine; Immune response; Biologic scaffold; Recellularization; N-GLYCOLYLNEURAMINIC ACID; FOREIGN-BODY RESPONSE; HUMAN IMMUNE-RESPONSE; ALPHA-GAL EPITOPE; CROSS-LINKING; ANTIGEN REMOVAL; HEART-VALVE; MACROPHAGE PHENOTYPE; KNOCKOUT PIGS; EMERGING ROLE;
D O I
10.1186/s40824-023-00348-z
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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.
引用
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页数:24
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