- Department of Orthopedic Surgery and Orthopedic Research Institute, Laboratory of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P. R. China;
XIE Huiqi,
Email: xiehuiqi@scu.edu.cn
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.
Copyright ? the editorial department of Chinese Journal of Reparative and Reconstructive Surgery of West China Medical Publisher. All rights reserved
| 1. | Mouw JK, Ou G, Weaver VM. Extracellular matrix assembly: a multiscale deconstruction. Nat Rev Mol Cell Biol, 2014, 15(12): 771-785. |
| 2. | Brown BN, Badylak SF. Extracellular matrix as an inductive scaffold for functional tissue reconstruction. Transl Res, 2014, 163(4): 268-285. |
| 3. | Davis GE, Bayless KJ, Davis MJ, et al. Regulation of tissue injury responses by the exposure of matricryptic sites within extracellular matrix molecules. Am J Pathol, 2000, 156(5): 1489-1498. |
| 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. |
| 7. | Nicolas-Boluda A, Vaquero J, Vimeux L, et al. Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment. Elife, 2021, 10: e58688. doi: 10.7554/eLife.58688. |
| 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. |
| 10. | Sarris M, Masson JB, Maurin D, et al. Inflammatory chemokines direct and restrict leukocyte migration within live tissues as glycan-bound gradients. Curr Biol, 2012, 22(24): 2375-2382. |
| 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. | 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. |
| 30. | 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. |
| 31. | 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. |
| 32. | Pereira AT, Schneider KH, Henriques PC, et al. Graphene oxide coating improves the mechanical and biological properties of decellularized umbilical cord arteries. ACS Appl Mater Interfaces, 2021, 13(28): 32662-32672. |
| 33. | 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. |
| 34. | Wan HY, Shin RLY, Chen JCH, et al. Dextran sulfate-amplified extracellular matrix deposition promotes osteogenic differentiation of mesenchymal stem cells. Acta Biomater, 2022, 140: 163-177. |
| 35. | Sakimoto Y, Oo PM, Goshima M, et al. Significance of GABAA receptor for cognitive function and hippocampal pathology. Int J Mol Sci, 2021, 22(22): 12456. doi: 10.3390/ijms222212456. |
| 36. | 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. |
| 37. | 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. |
| 38. | 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. |
| 39. | 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. |
| 40. | 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. |
| 41. | 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. |
| 42. | 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. |
| 43. | 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. |
| 44. | 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. |
| 45. | 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. |
| 46. | 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. |
| 47. | Sheng N, Xing F, Zhang QY, et al. A pleiotropic SIS-based hydrogel with immunomodulation via NLRP3 inflammasome inhibition for diabetic bone regeneration. Chemical Engineering Journal, 2024, 480: 147985. doi: 10.1016/j.cej.2023.147985. |
| 48. | Saheli M, Sepantafar M, Pournasr B, et al. Three-dimensional liver-derived extracellular matrix hydrogel promotes liver organoids function. J Cell Biochem, 2018, 119(6): 4320-4333. |
| 49. | Medberry CJ, Crapo PM, Siu BF, et al. Hydrogels derived from central nervous system extracellular matrix. Biomaterials, 2013, 34(4): 1033-1040. |
| 50. | Giobbe GG, Crowley C, Luni C, et al. Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture. Nat Commun, 2019, 10(1): 5658. doi: 10.1038/s41467-019-13605-4. |
| 51. | Spang MT, Middleton R, Diaz M, et al. Intravascularly infused extracellular matrix as a biomaterial for targeting and treating inflamed tissues. Nat Biomed Eng, 2023, 7(2): 94-109. |
| 52. | Elrayah A, Zhi W, Feng S, et al. Preparation of micro/nano-structure copper-substituted hydroxyapatite scaffolds with improved angiogenesis capacity for bone regeneration. Materials (Basel), 2018, 11(9): 1516. doi: 10.3390/ma11091516. |
| 53. | Khandaker M, Nomhwange H, Progri H, et al. Evaluation of polycaprolactone electrospun nanofiber-composites for artificial skin based on dermal fibroblast culture. Bioengineering (Basel), 2022, 9(1): 19. doi: 10.3390/bioengineering9010019. |
| 54. | Hakimi O, Mouthuy PA, Zargar N, et al. A layered electrospun and woven surgical scaffold to enhance endogenous tendon repair. Acta Biomater, 2015, 26: 124-135. |
| 55. | Huang L, Zhu L, Shi X, et al. A compound scaffold with uniform longitudinally oriented guidance cues and a porous sheath promotes peripheral nerve regeneration in vivo. Acta Biomater, 2018, 68: 223-236. |
| 56. | Denning D, Kilpatrick JI, Fukada E, et al. Piezoelectric tensor of collagen fibrils determined at the nanoscale. ACS Biomater Sci Eng, 2017, 3(6): 929-935. |
| 57. | Ji C, McCulloch CA. TRPV4 integrates matrix mechanosensing with Ca2+ signaling to regulate extracellular matrix remodeling. FEBS J, 2021, 288(20): 5867-5887. |
| 58. | Zhao M, Song B, Pu J, et al. Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN. Nature, 2006, 442(7101): 457-460. |
| 59. | Peng S, Wang L, Lu Z, et al. An injectable conductive multifunctional hydrogel dressing with synergistic antimicrobial, ROS scavenging, and electroactive effects for the combined treatment of chronic diabetic wounds. Biomater Adv, 2026, 179: 214498. doi: 10.1016/j.bioadv.2025.214498. |
| 60. | Yong S, Tian L, Huang D, et al. Engineered decalcified bone matrix/barium titanate piezoelectric composite scaffolds for bone regeneration. J Mater Chem B, 2025, 13(29): 8789-8807. |
| 61. | Gao K, Shang S, Wei B, et al. Magneto-motivated intracellular wireless nanodischarge system induces neural stem cell differentiation and spinal cord injury repair. Advanced Functional Materials, 2025. doi: 10.1002/adfm.202512370. |
| 62. | Gong M, Sun J, Liu G, et al. Graphene oxide-modified 3D acellular cartilage extracellular matrix scaffold for cartilage regeneration. Mater Sci Eng C Mater Biol Appl, 2021, 119: 111603. doi: 10.1016/j.msec.2020.111603. |
| 63. | Guo B, Feng X, Wang Y, et al. Biomimetic and immunomodulatory baicalin-loaded graphene oxide-demineralized bone matrix scaffold for in vivo bone regeneration. J Mater Chem B, 2021, 9(47): 9720-9733. |
| 64. | Zhao LM, Wang L, Zhang WQ, et al. Promotion of right ventricular outflow tract reconstruction using a novel cardiac patch incorporated with hypoxia-pretreated urine-derived stem cells. Bioact Mater, 2021, 14: 206-218. |
| 65. | Yin S, Zhou J, Wang J, et al. Preparation and performance of electrically conductive decellularized nerve matrix hydrogel conduits. J Biomater Appl, 2023, 38(4): 471-483. |
| 66. | Liu X, Cui B, Wang X, et al. Nature-skin-derived e-skin as versatile “wound therapy-health monitoring” bioelectronic skin-scaffolds: skin to bio-e-skin. Adv Healthc Mater, 2023, 12(20): e2202971. doi: 10.1002/adhm.202202971. |
| 67. | Silva DMD, Barroca N, Pinto SC, et al. Decellularized extracellular matrix-based 3D nanofibrous scaffolds functionalized with polydopamine-reduced graphene oxide for neural tissue engineering. Chemical Engineering Journal, 2023, 472: 144980. doi: 10.1016/j.cej.2023.144980. |
| 68. | Nyambat B, Chen CH, Wong PC, et al. Genipin-crosslinked adipose stem cell derived extracellular matrix-nano graphene oxide composite sponge for skin tissue engineering. J Mater Chem B, 2018, 6(6): 979-990. |
| 69. | Liang Y, Goh JC. Polypyrrole-incorporated conducting constructs for tissue engineering applications: A review. Bioelectricity, 2020, 2(2): 101-119. |
| 70. | Zhang H, Xu D, Zhang B, et al. PEDOT-integrated fish swim bladders as conductive nerve conduits. Adv Sci (Weinh), 2024, 11(31): e2400827. doi: 10.1002/advs.202400827. |
| 71. | Liu D, Wang X, Gao C, et al. Biodegradable piezoelectric-conductive integrated hydrogel scaffold for repair of osteochondral defects. Adv Mater, 2024, 36(45): e2409400. doi: 10.1002/adma.202409400. |
| 72. | Shi G, Su T, Li J, et al. Biomimetic piezoelectric hydrogel system for energy metabolism reprogramming in spinal cord injury repair. Theranostics, 2025, 15(11): 4955-4969. |
| 73. | Jahani M, Mansouri K, Madani S H, et al. Engineering of a bilayer artificial E-skin biomimicking epidermal and dermal layers with improved angiogenesis and healing potential. ACS Applied Polymer Materials, 2025, 7(15): 9585-9602. |
| 74. | Tseng BY, Cai YC, Conan Guo CW, et al. Reinforcement learning design framework for nacre-like structures optimized for pre-existing crack resistance. Journal of Materials Research and Technology, 2023, 24: 3502-3512. |
| 75. | Liao H, Hu S, Yang H, et al. Data-driven de novo design of super-adhesive hydrogels. Nature, 2025, 644(8075): 89-95. |
| 76. | Yu C, Shi M, He S, et al. Chronological adhesive cardiac patch for synchronous mechanophysiological monitoring and electrocoupling therapy. Nat Commun, 2023, 14(1): 6226. doi: 10.1038/s41467-023-42008-9. |
| 77. | Yu Y, Jin B, Chen J, et al. Nerve-on-a-Chip Derived Biomimicking Microfibers for Peripheral Nerve Regeneration. Adv Sci (Weinh), 2023, 10(20): e2207536. doi: 10.1002/advs.202207536. |
| 78. | Tomofuji K, Fukumitsu K, Kondo J, et al. Liver ductal organoids reconstruct intrahepatic biliary trees in decellularized liver grafts. Biomaterials, 2022, 287: 121614. doi: 10.1016/j.biomaterials.2022.121614. |
| 79. | Kim JW, Nam SA, Yi J, et al. Kidney decellularized extracellular matrix enhanced the vascularization and maturation of human kidney organoids. Adv Sci (Weinh), 2022, 9(15): e2103526. doi: 10.1002/advs.202103526. |
| 80. | Burkhanova U, Harris A, Leir SH. Enhancement of airway epithelial cell differentiation by pulmonary endothelial cell co-culture. Stem Cell Res, 2022, 65: 102967. doi: 10.1016/j.scr.2022.102967. |
| 81. | Ronaldson-Bouchard K, Teles D, Yeager K, et al. A multi-organ chip with matured tissue niches linked by vascular flow. Nat Biomed Eng, 2022, 6(4): 351-371. |
- 1. Mouw JK, Ou G, Weaver VM. Extracellular matrix assembly: a multiscale deconstruction. Nat Rev Mol Cell Biol, 2014, 15(12): 771-785.
- 2. Brown BN, Badylak SF. Extracellular matrix as an inductive scaffold for functional tissue reconstruction. Transl Res, 2014, 163(4): 268-285.
- 3. Davis GE, Bayless KJ, Davis MJ, et al. Regulation of tissue injury responses by the exposure of matricryptic sites within extracellular matrix molecules. Am J Pathol, 2000, 156(5): 1489-1498.
- 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.
- 7. Nicolas-Boluda A, Vaquero J, Vimeux L, et al. Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment. Elife, 2021, 10: e58688. doi: 10.7554/eLife.58688.
- 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.
- 10. Sarris M, Masson JB, Maurin D, et al. Inflammatory chemokines direct and restrict leukocyte migration within live tissues as glycan-bound gradients. Curr Biol, 2012, 22(24): 2375-2382.
- 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. 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.
- 30. 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.
- 31. 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.
- 32. Pereira AT, Schneider KH, Henriques PC, et al. Graphene oxide coating improves the mechanical and biological properties of decellularized umbilical cord arteries. ACS Appl Mater Interfaces, 2021, 13(28): 32662-32672.
- 33. 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.
- 34. Wan HY, Shin RLY, Chen JCH, et al. Dextran sulfate-amplified extracellular matrix deposition promotes osteogenic differentiation of mesenchymal stem cells. Acta Biomater, 2022, 140: 163-177.
- 35. Sakimoto Y, Oo PM, Goshima M, et al. Significance of GABAA receptor for cognitive function and hippocampal pathology. Int J Mol Sci, 2021, 22(22): 12456. doi: 10.3390/ijms222212456.
- 36. 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.
- 37. 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.
- 38. 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.
- 39. 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.
- 40. 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.
- 41. 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.
- 42. 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.
- 43. 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.
- 44. 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.
- 45. 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.
- 46. 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.
- 47. Sheng N, Xing F, Zhang QY, et al. A pleiotropic SIS-based hydrogel with immunomodulation via NLRP3 inflammasome inhibition for diabetic bone regeneration. Chemical Engineering Journal, 2024, 480: 147985. doi: 10.1016/j.cej.2023.147985.
- 48. Saheli M, Sepantafar M, Pournasr B, et al. Three-dimensional liver-derived extracellular matrix hydrogel promotes liver organoids function. J Cell Biochem, 2018, 119(6): 4320-4333.
- 49. Medberry CJ, Crapo PM, Siu BF, et al. Hydrogels derived from central nervous system extracellular matrix. Biomaterials, 2013, 34(4): 1033-1040.
- 50. Giobbe GG, Crowley C, Luni C, et al. Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture. Nat Commun, 2019, 10(1): 5658. doi: 10.1038/s41467-019-13605-4.
- 51. Spang MT, Middleton R, Diaz M, et al. Intravascularly infused extracellular matrix as a biomaterial for targeting and treating inflamed tissues. Nat Biomed Eng, 2023, 7(2): 94-109.
- 52. Elrayah A, Zhi W, Feng S, et al. Preparation of micro/nano-structure copper-substituted hydroxyapatite scaffolds with improved angiogenesis capacity for bone regeneration. Materials (Basel), 2018, 11(9): 1516. doi: 10.3390/ma11091516.
- 53. Khandaker M, Nomhwange H, Progri H, et al. Evaluation of polycaprolactone electrospun nanofiber-composites for artificial skin based on dermal fibroblast culture. Bioengineering (Basel), 2022, 9(1): 19. doi: 10.3390/bioengineering9010019.
- 54. Hakimi O, Mouthuy PA, Zargar N, et al. A layered electrospun and woven surgical scaffold to enhance endogenous tendon repair. Acta Biomater, 2015, 26: 124-135.
- 55. Huang L, Zhu L, Shi X, et al. A compound scaffold with uniform longitudinally oriented guidance cues and a porous sheath promotes peripheral nerve regeneration in vivo. Acta Biomater, 2018, 68: 223-236.
- 56. Denning D, Kilpatrick JI, Fukada E, et al. Piezoelectric tensor of collagen fibrils determined at the nanoscale. ACS Biomater Sci Eng, 2017, 3(6): 929-935.
- 57. Ji C, McCulloch CA. TRPV4 integrates matrix mechanosensing with Ca2+ signaling to regulate extracellular matrix remodeling. FEBS J, 2021, 288(20): 5867-5887.
- 58. Zhao M, Song B, Pu J, et al. Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN. Nature, 2006, 442(7101): 457-460.
- 59. Peng S, Wang L, Lu Z, et al. An injectable conductive multifunctional hydrogel dressing with synergistic antimicrobial, ROS scavenging, and electroactive effects for the combined treatment of chronic diabetic wounds. Biomater Adv, 2026, 179: 214498. doi: 10.1016/j.bioadv.2025.214498.
- 60. Yong S, Tian L, Huang D, et al. Engineered decalcified bone matrix/barium titanate piezoelectric composite scaffolds for bone regeneration. J Mater Chem B, 2025, 13(29): 8789-8807.
- 61. Gao K, Shang S, Wei B, et al. Magneto-motivated intracellular wireless nanodischarge system induces neural stem cell differentiation and spinal cord injury repair. Advanced Functional Materials, 2025. doi: 10.1002/adfm.202512370.
- 62. Gong M, Sun J, Liu G, et al. Graphene oxide-modified 3D acellular cartilage extracellular matrix scaffold for cartilage regeneration. Mater Sci Eng C Mater Biol Appl, 2021, 119: 111603. doi: 10.1016/j.msec.2020.111603.
- 63. Guo B, Feng X, Wang Y, et al. Biomimetic and immunomodulatory baicalin-loaded graphene oxide-demineralized bone matrix scaffold for in vivo bone regeneration. J Mater Chem B, 2021, 9(47): 9720-9733.
- 64. Zhao LM, Wang L, Zhang WQ, et al. Promotion of right ventricular outflow tract reconstruction using a novel cardiac patch incorporated with hypoxia-pretreated urine-derived stem cells. Bioact Mater, 2021, 14: 206-218.
- 65. Yin S, Zhou J, Wang J, et al. Preparation and performance of electrically conductive decellularized nerve matrix hydrogel conduits. J Biomater Appl, 2023, 38(4): 471-483.
- 66. Liu X, Cui B, Wang X, et al. Nature-skin-derived e-skin as versatile “wound therapy-health monitoring” bioelectronic skin-scaffolds: skin to bio-e-skin. Adv Healthc Mater, 2023, 12(20): e2202971. doi: 10.1002/adhm.202202971.
- 67. Silva DMD, Barroca N, Pinto SC, et al. Decellularized extracellular matrix-based 3D nanofibrous scaffolds functionalized with polydopamine-reduced graphene oxide for neural tissue engineering. Chemical Engineering Journal, 2023, 472: 144980. doi: 10.1016/j.cej.2023.144980.
- 68. Nyambat B, Chen CH, Wong PC, et al. Genipin-crosslinked adipose stem cell derived extracellular matrix-nano graphene oxide composite sponge for skin tissue engineering. J Mater Chem B, 2018, 6(6): 979-990.
- 69. Liang Y, Goh JC. Polypyrrole-incorporated conducting constructs for tissue engineering applications: A review. Bioelectricity, 2020, 2(2): 101-119.
- 70. Zhang H, Xu D, Zhang B, et al. PEDOT-integrated fish swim bladders as conductive nerve conduits. Adv Sci (Weinh), 2024, 11(31): e2400827. doi: 10.1002/advs.202400827.
- 71. Liu D, Wang X, Gao C, et al. Biodegradable piezoelectric-conductive integrated hydrogel scaffold for repair of osteochondral defects. Adv Mater, 2024, 36(45): e2409400. doi: 10.1002/adma.202409400.
- 72. Shi G, Su T, Li J, et al. Biomimetic piezoelectric hydrogel system for energy metabolism reprogramming in spinal cord injury repair. Theranostics, 2025, 15(11): 4955-4969.
- 73. Jahani M, Mansouri K, Madani S H, et al. Engineering of a bilayer artificial E-skin biomimicking epidermal and dermal layers with improved angiogenesis and healing potential. ACS Applied Polymer Materials, 2025, 7(15): 9585-9602.
- 74. Tseng BY, Cai YC, Conan Guo CW, et al. Reinforcement learning design framework for nacre-like structures optimized for pre-existing crack resistance. Journal of Materials Research and Technology, 2023, 24: 3502-3512.
- 75. Liao H, Hu S, Yang H, et al. Data-driven de novo design of super-adhesive hydrogels. Nature, 2025, 644(8075): 89-95.
- 76. Yu C, Shi M, He S, et al. Chronological adhesive cardiac patch for synchronous mechanophysiological monitoring and electrocoupling therapy. Nat Commun, 2023, 14(1): 6226. doi: 10.1038/s41467-023-42008-9.
- 77. Yu Y, Jin B, Chen J, et al. Nerve-on-a-Chip Derived Biomimicking Microfibers for Peripheral Nerve Regeneration. Adv Sci (Weinh), 2023, 10(20): e2207536. doi: 10.1002/advs.202207536.
- 78. Tomofuji K, Fukumitsu K, Kondo J, et al. Liver ductal organoids reconstruct intrahepatic biliary trees in decellularized liver grafts. Biomaterials, 2022, 287: 121614. doi: 10.1016/j.biomaterials.2022.121614.
- 79. Kim JW, Nam SA, Yi J, et al. Kidney decellularized extracellular matrix enhanced the vascularization and maturation of human kidney organoids. Adv Sci (Weinh), 2022, 9(15): e2103526. doi: 10.1002/advs.202103526.
- 80. Burkhanova U, Harris A, Leir SH. Enhancement of airway epithelial cell differentiation by pulmonary endothelial cell co-culture. Stem Cell Res, 2022, 65: 102967. doi: 10.1016/j.scr.2022.102967.
- 81. Ronaldson-Bouchard K, Teles D, Yeager K, et al. A multi-organ chip with matured tissue niches linked by vascular flow. Nat Biomed Eng, 2022, 6(4): 351-371.