Extracellular matrix materials and tissue regeneration and repair_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

ZHAO Longmei ,  XIE Huiqi

Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P. R. China;

Corresponding?author：

XIE Huiqi, Email: xiehuiqi@scu.edu.cn

Keywords：

Extracellular matrix; biological functionality; architectural optimization; application challenges

DOI：

10.7507/1002-1892.202511037

Video：

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Abstract Full text Figures/Tables Video References Cited by

The extracellular matrix (ECM) plays a pivotal role in regulating cellular behavior and driving tissue regeneration. Its unique structural characteristics and bioactivity not only provide physical support for cell growth, but also orchestrate tissue repair and functional reconstruction through multiple signaling pathways. This review systematically synthesizes preparation strategies for natural and engineered ECM materials from the perspective of ECM-mediated tissue regeneration mechanisms, with particular emphasis on recent advances in component preservation, structural biomimicry, and functional optimization. Furthermore, it delves into the application potential of cutting-edge technologies—including artificial intelligence, flexible electronics, and organoids—in ECM engineering, while critically analyzing the standardization and safety challenges hindering clinical translation. This article aims to provide a theoretical foundation and reference for constructing next-generation ECM-based regenerative medicine platforms.

Citation： ZHAO Longmei, XIE Huiqi. Extracellular matrix materials and tissue regeneration and repair. Chinese Journal of Reparative and Reconstructive Surgery, 2026, 40(1): 132-145. doi: 10.7507/1002-1892.202511037 Copy

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4. Shen L, Zhou Y, Gong J, et al. The role of macrophages in hypertrophic scarring: molecular to therapeutic insights. Front Immunol, 2025, 16: 1503985. doi: 10.3389/fimmu.2025.1503985.
5. Berdiaki A, Neagu M, Tzanakakis P, et al. Extracellular matrix components and mechanosensing pathways in health and disease. Biomolecules, 2024, 14(9): 1186. doi: 10.3390/biom14091186.
6. Yang C, Cai W, Xiang P, et al. Viscoelastic hydrogel combined with dynamic compression promotes osteogenic differentiation of bone marrow mesenchymal stem cells and bone repair in rats. Regen Biomater, 2024, 12: rbae136. doi: 10.1093/rb/rbae136.
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8. Keerthivasan S, ?enbabao?lu Y, Martinez-Martin N, et al. Homeostatic functions of monocytes and interstitial lung macrophages are regulated via collagen domain-binding receptor LAIR1. Immunity, 2021, 54(7): 1511-1526.
9. McDonald B, McAvoy EF, Lam F, et al. Interaction of CD44 and hyaluronan is the dominant mechanism for neutrophil sequestration in inflamed liver sinusoids. J Exp Med, 2008, 205(4): 915-927.
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11. Mayorca-Guiliani AE, Leeming DJ, Henriksen K, et al. ECM formation and degradation during fibrosis, repair, and regeneration. NPJ Metab Health Dis, 2025, 3(1): 25. doi: 10.1038/s44324-025-00063-4.
12. Bruyneel AAN, Carr CA. Ambiguity in the presentation of decellularized tissue composition: The need for standardized approaches. Artif Organs, 2017, 41(8): 778-784.
13. Luo JC, Chen W, Chen XH, et al. A multi-step method for preparation of porcine small intestinal submucosa (SIS). Biomaterials, 2011, 32(3): 706-713.
14. Giang NN, Trinh XT, Han J, et al. Effective decellularization of human skin tissue for regenerative medicine by supercritical carbon dioxide technique. J Tissue Eng Regen Med, 2022, 16(12): 1196-1207.
15. Song YH, Maynes MA, Hlavac N, et al. Development of novel apoptosis-assisted lung tissue decellularization methods. Biomater Sci, 2021, 9(9): 3485-3498.
16. Keane TJ, Londono R, Turner NJ, et al. Consequences of ineffective decellularization of biologic scaffolds on the host response. Biomaterials, 2012, 33(6): 1771-1781.
17. Londono R, Dziki JL, Haljasmaa E, et al. The effect of cell debris within biologic scaffolds upon the macrophage response. J Biomed Mater Res A, 2017, 105(8): 2109-2118.
18. Crapo PM, Gilbert TW, Badylak SF. An overview of tissue and whole organ decellularization processes. Biomaterials, 2011, 32(12): 3233-3243.
19. Naso F, Colli A, Zilla P, et al. Correlations between the alpha-Gal antigen, antibody response and calcification of cardiac valve bioprostheses: experimental evidence obtained using an alpha-Gal knockout mouse animal model. Front Immunol, 2023, 14: 1210098. doi: 10.3389/fimmu.2023.1210098.
20. Singelyn JM, Christman KL. Modulation of material properties of a decellularized myocardial matrix scaffold. Macromol Biosci, 2011, 11(6): 731-738.
21. Adamiak K, Sionkowska A. Current methods of collagen cross-linking: Review. Int J Biol Macromol, 2020, 161: 550-560.
22. Da L, Gong M, Chen A, et al. Composite elastomeric polyurethane scaffolds incorporating small intestinal submucosa for soft tissue engineering. Acta Biomater, 2017, 59: 45-57.
23. Zhao LM, Da LC, Wang R, et al. Promotion of uterine reconstruction by a tissue-engineered uterus with biomimetic structure and extracellular matrix microenvironment. Sci Adv, 2023, 9(46): eadi6488. doi: 10.1126/sciadv.adi6488.
24. Grandi C, Baiguera S, Martorina F, et al. Decellularized bovine reinforced vessels for small-diameter tissue-engineered vascular grafts. Int J Mol Med, 2011, 28(3): 315-325.
25. Wang M, Li YQ, Cao J, et al. Accelerating effects of genipin-crosslinked small intestinal submucosa for defected gastric mucosa repair. J Mater Chem B, 2017, 5(34): 7059-7071.
26. Gao X, Xu Z, Liu G, et al. Polyphenols as a versatile component in tissue engineering. Acta Biomater, 2021, 119: 57-74.
27. Nie R, Zhang QY, Tan J, et al. EGCG modified small intestine submucosa promotes wound healing through immunomodulation. Composites Part B: Engineering, 2023, 267: 111005. doi: 10.1016/j.compositesb.2023.111005.
28. Zhang XZ, Jiang YL, Hu JG, et al. Procyanidins-crosslinked small intestine submucosa: A bladder patch promotes smooth muscle regeneration and bladder function restoration in a rabbit model. Bioact Mater, 2020, 6(6): 1827-1838.
29. Patel KH, Dunn AJ, Talovic M, et al. Aligned nanofibers of decellularized muscle ECM support myogenic activity in primary satellite cells in vitro. Biomed Mater, 2019, 14(3): 035010. doi: 10.1088/1748-605X/ab0b06.
30. Kim HS, Mandakhbayar N, Kim HW, et al. Protein-reactive nanofibrils decorated with cartilage-derived decellularized extracellular matrix for osteochondral defects. Biomaterials, 2021, 269: 120214. doi: 10.1016/j.biomaterials.2020.120214.
31. Mao X, Li T, Cheng J, et al. Nerve ECM and PLA-PCL based electrospun bilayer nerve conduit for nerve regeneration. Front Bioeng Biotechnol, 2023, 11: 1103435. doi: 10.3389/fbioe.2023.1103435.
32. Li S, Deng R, Zou X, et al. Development and fabrication of co-axially electrospun biomimetic periosteum with a decellularized periosteal ECM shell/PCL core structure to promote the repair of critical-sized bone defects. Composites Part B: Engineering, 2022, 234: 109620. doi: 10.1016/j.compositesb.2022.109620.
33. Li C, Zhang W, Nie Y, et al. Integrated and bifunctional bilayer 3D printing scaffold for osteochondral defect repair. Advanced Functional Materials, 2023, 33(20): 2214158. doi: 10.1002/adfm.202214158.
34. Sun T, Meng C, Ding Q, et al. In situ bone regeneration with sequential delivery of aptamer and BMP2 from an ECM-based scaffold fabricated by cryogenic free-form extrusion. Bioact Mater, 2021, 6(11): 4163-4175.
35. Li S, Wang R, Huang L, et al. Promotion of diced cartilage survival and regeneration with grafting of small intestinal submucosa loaded with urine-derived stem cells. Cell Prolif, 2024, 57(2): e13542. doi: 10.1111/cpr.13542.
36. Luo M, Lin J, Li J, et al. Biodegradable polyurethane-decellular extracellular matrix based bioscaffolds promote nerve repair after spinal cord injury. Chemical Engineering Journal, 2025, 523: 168336. doi: 10.1016/j.cej.2025.168336.
37. Ma YH, Shi HJ, Wei QS, et al. Developing a mechanically matched decellularized spinal cord scaffold for the in situ matrix-based neural repair of spinal cord injury. Biomaterials, 2021, 279: 121192. doi: 10.1016/j.biomaterials.2021.121192.
38. Lee H, Kim W, Lee J, et al. Effect of hierarchical scaffold consisting of aligned dECM nanofibers and poly (lactide- co-glycolide) struts on the orientation and maturation of human muscle progenitor cells. ACS Appl Mater Interfaces, 2019, 11(43): 39449-39458.
39. Fang Y, Han Y, Wang S, et al. Three-dimensional printing bilayer membranous nanofiber scaffold for inhibiting scar hyperplasia of skin. Biomater Adv, 2022, 138: 212951. doi: 10.1016/j.bioadv.2022.212951.
40. Jin Y, Zhang J, Xu Y, et al. Stem cell-derived hepatocyte therapy using versatile biomimetic nanozyme incorporated nanofiber-reinforced decellularized extracellular matrix hydrogels for the treatment of acute liver failure. Bioact Mater, 2023, 28: 112-131.
41. Ko KW, Park SY, Lee EH, et al. Integrated bioactive scaffold with polydeoxyribonucleotide and stem-cell-derived extracellular vesicles for kidney regeneration. ACS Nano, 2021, 15(4): 7575-7585.
42. Zheng C, Yang Z, Chen S, et al. Nanofibrous nerve guidance conduits decorated with decellularized matrix hydrogel facilitate peripheral nerve injury repair. Theranostics, 2021, 11(6): 2917-2931.
43. Hwangbo H, Lee J, Kim G. Mechanically and biologically enhanced 3D-printed HA/PLLA/dECM biocomposites for bone tissue engineering. Int J Biol Macromol, 2022, 218: 9-21.
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Chinese Journal of Reparative and Reconstructive Surgery

Extracellular matrix materials and tissue regeneration and repair

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