Research progress of gelatin composites in promoting peripheral nerve regeneration_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

ZHANG Shuai , YOU Chaoqun , ZENG Fanwei , XU Jiuhui , ZHOU Chang ,  WEI Ran ,  TANG Xiaodong

Second Department of Orthopedic Oncology, Peking University People’s Hospital, Beijing, 101100, P. R. China;

Corresponding?author：

WEI Ran, Email: dr.weiran@foxmail.com; TANG Xiaodong, Email: tang15877@126.com

Keywords：

Peripheral nerve injury; gelatin; composite material; peripheral nerve regeneration

DOI：

10.7507/1002-1892.202603032

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To review the research status of gelatin (Gel) composite material in promoting peripheral nerve regeneration (PNR), and point out the current shortcomings and future research directions. Methods Domestic and foreign literature related to Gel composites used in PNR was extensively reviewed, and the material characteristics, mechanism, and experimental effects were systematically analyzed from the structure types of nerve guide conduit (NGC), hydrogel, scaffold, film, and nanofiber bundle. Results Gel composites can improve the biocompatibility, mechanical properties, slow release, and conductivity of NGC, hydrogel, and scaffolds, promote the survival and proliferation of Schwann cells and adipose-derived stem cells, and facilitate the repair of long-distance peripheral nerve injury. The membrane made of Gel composites can reduce the scar formation at the nerve anastomosis, and the nanofiber bundle can help to restore the direct connection of the nerve stump. However, there are also challenges such as insufficient clinical transformation and determination of the best Gel composite scheme. Conclusion Gel composites show good application potential in PNR, but the optimal material ratio, clinical transformation scheme, and long-term effectiveness still need further study.

Citation： ZHANG Shuai, YOU Chaoqun, ZENG Fanwei, XU Jiuhui, ZHOU Chang, WEI Ran, TANG Xiaodong. Research progress of gelatin composites in promoting peripheral nerve regeneration. Chinese Journal of Reparative and Reconstructive Surgery, 2026, 40(8): 1297-1303. doi: 10.7507/1002-1892.202603032 Copy

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8.	Liu BF, Ma J, Xu QY, et al. Regulation of charged groups and laminin patterns for selective neuronal adhesion[J]. Colloid Surf B-biointerfaces, 2006, 53(2): 175-178.
9.	Waidi YO, Kariim I, Datta S. Bioprinting of gelatin-based materials for orthopedic application[J/OL]. Front Bioeng Biotechnol, 2024, 12: 1357460. doi: 10.3389/fbioe.2024.1357460.
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36.	Xu HL, Gao ZH, Wang ZY, et al. Electrospun PCL nerve conduit filled with GelMA gel for CNTF and IGF-1 delivery in promoting sciatic nerve regeneration in rat[J]. Acs Biomater Sci Eng, 2023, 9(11): 6309-6321.
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38.	Su WJ, Xu JK, Pei DT, et al. Hybrid electrically conductive hydrogels with local nerve growth factor release facilitate peripheral nerve regeneration[J]. Acs Appl Bio Mater, 2023, 6(12): 5854-5863.
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1. Yu L, Bennett CJ, Lin CH, et al. Scaffold design considerations for peripheral nerve regeneration[J/OL]. J Neural Eng, 2024, 21(4): 10.1088/1741-2552/ad628d doi: 10.1088/1741-2552/ad628d.
2. Padovano WM, Dengler J, Patterson MM, et al. Incidence of nerve injury after extremity trauma in the United States[J]. Hand (N Y), 2022, 17(4): 615-623.
3. Silverman DA, Martinez VK, Dougherty PM, et al. Cancer-associated neurogenesis and nerve-cancer cross-talk[J]. Cancer Res, 2021, 81(6): 1431-1440.
4. Bangia M, Ahmadzai I, Casselman J, et al. Accuracy of MR neurography as a diagnostic tool in detecting injuries to the lingual and inferior alveolar nerve in patients with iatrogenic post-traumatic trigeminal neuropathy[J]. Eur Radiol, 2024, 34(7): 4619-4627.
5. Zhang X, Duan XC, Liu XY. The role of kinases in peripheral nerve regeneration: mechanisms and implications[J/OL]. Front Neurol, 2024, 15: 1340845. doi: 10.3389/fneur.2024.1340845.
6. Liu K, Yan L, Li R, et al. 3D printed personalized nerve guide conduits for precision repair of peripheral nerve defects[J/OL]. Adv Sci (Weinh), 2022, 9(12): e2103875. doi: 10.1002/advs.202103875.
7. Park SS, Farwa U, Hossain M, et al. Evaluation of gelatin/hyaluronic acid-generated bridging in a 3D-printed titanium cage for bone regeneration[J/OL]. J Func Biomater, 2023, 14(12): 562. doi: 10.3390/jfb14120562.
8. Liu BF, Ma J, Xu QY, et al. Regulation of charged groups and laminin patterns for selective neuronal adhesion[J]. Colloid Surf B-biointerfaces, 2006, 53(2): 175-178.
9. Waidi YO, Kariim I, Datta S. Bioprinting of gelatin-based materials for orthopedic application[J/OL]. Front Bioeng Biotechnol, 2024, 12: 1357460. doi: 10.3389/fbioe.2024.1357460.
10. Jia XY, Fan X, Chen C, et al. Chemical and structural engineering of gelatin-based delivery systems for therapeutic applications: A review[J]. Biomacromolecules, 2024, 25(2): 564-589.
11. Kang NU, Lee SJ, Gwak SJ. Fabrication techniques of nerve guidance conduits for nerve regeneration[J]. Yonsei Med J, 2022, 63(2): 114-123.
12. Rahman M, Dip TM, Padhye R, et al. Review on electrically conductive smart nerve guide conduit for peripheral nerve regeneration[J]. J Biomed Mater Res Part A, 2023, 111(12): 1916-1950.
13. Lopes B, Sousa P, Alvites R, et al. Peripheral nerve injury treatments and advances: One health perspective[J/OL]. Int J Mol Sci, 2022, 23(2): 918. doi: 10.3390/ijms23020918.
14. Wieringa PA, De pinho ARG, Micera S, et al. Biomimetic architectures for peripheral nerve repair: A review of biofabrication strategies[J/OL]. Adv Healthc Mater, 2018, 7(8): 1701164. doi: 10.1002/adhm.201701164.
15. Mligiliche N, Endo K, Okamoto K, et al. Extracellular matrix of human amnion manufactured into tubes as conduits for peripheral nerve regeneration[J]. J Biomed Mater Res, 2002, 63(5): 591-600.
16. Han WH, Wang QY, Kang YY, et al. Cross-linking electrospinning[J]. Nanoscale, 2023, 15(38): 15513-15551.
17. Samadian H, Ehterami A, Sarrafzadeh A, et al. Sophisticated polycaprolactone/gelatin nanofibrous nerve guided conduit containing platelet-rich plasma and citicoline for peripheral nerve regeneration: In vitro and in vivo study[J]. Int J Biol Macromol, 2020, 150: 380-388.
18. Chen SY, Zhao YX, Yan XL, et al. PAM/GO/gel/SA composite hydrogel conduit with bioactivity for repairing peripheral nerve injury[J]. J Biomed Mater Res Part A, 2019, 107(6): 1273-1283.
19. Chen SS, Wang Y, Lai JH, et al. Structure and properties of gelatin methacryloyl (GelMA) synthesized in different reaction systems[J]. Biomacromolecules, 2023, 24(6): 2928-2941.
20. Zhu YR, Yu XG, Liu H, et al. Strategies of functionalized GelMA-based bioinks for bone regeneration: Recent advances and future perspectives[J]. Bioact Mater, 2024, 38: 346-373.
21. Dong Q, Yang X, Liang X, et al. Composite hydrogel conduit incorporated with platelet-rich plasma improved the regenerative microenvironment for peripheral nerve repair[J]. ACS Appl Mater Interfaces. 2023, 15(20): 24120-24133.
22. Wu YY, Wang YJ, Li WL, et al. Construction of piezoelectric, conductive and injectable hydrogels to promote wound healing through electrical stimulation[J]. Acta Biomater, 2025, 191: 205-215.
23. Das S, Jegadeesan JT, Basu B. Advancing peripheral nerve regeneration: 3D bioprinting of GelMA-based cell-laden electroactive bioinks for nerve conduits[J]. Acs Biomater Sci Eng, 2024, 10(3): 1620-1645.
24. Qingning S, Ismail ZIM, Patar MNAA, et al. The limelight of adipose-derived stem cells in the landscape of neural tissue engineering for peripheral nerve injury[J/OL]. Tissue Cell, 2024, 91: 102556. doi: 10.1016/j.tice.2024.102556.
25. Hu Y, Wu Y, Gou ZY, et al. 3D-engineering of cellularized conduits for peripheral nerve regeneration[J/OL]. Sci Rep, 2016, 6: 32184. doi: 10.1038/srep32184.
26. H?ke A. Mechanisms of disease: What factors limit the success of peripheral nerve regeneration in humans?[J]. Nat Clin Pract Neurol, 2006, 2(8): 448-454.
27. Wu S, Kuss M, Qi D, et al. Development of cryogel-based guidance conduit for peripheral nerve regeneration[J]. ACS Appl Bio Mater, 2019, 2(11): 4864-4871.
28. Kriebel A, Hodde D, Kuenzel T, et al. Cell-free artificial implants of electrospun fibres in a three-dimensional gelatin matrix support sciatic nerve regeneration in vivo[J]. J Tissue Eng Regen Med, 2017, 11(12): 3289-3304.
29. Chyzy A, Plonska-brzezinska ME. Hydrogel properties and their impact on regenerative medicine and tissue engineering[J/OL]. Molecules, 2020, 25(24): 5795. doi: 10.3390/molecules25245795.
30. Ho TC, Chang CC, Chan HP, et al. Hydrogels: properties and applications in biomedicine[J/OL]. Molecules, 2022, 27(9): 2902. doi: 10.3390/molecules27092902.
31. Liu BS, Yao CH, Hsu SH, et al. A novel use of genipin-fixed gelatin as extracellular matrix for peripheral nerve regeneration[J]. J Biomater Appl, 2004, 19(1): 21-34.
32. Mohanty S, Swarup J, Priya S, et al. Exploring the potential of polysaccharide-based hybrid hydrogel systems for their biomedical and therapeutic applications: A review[J/OL]. Int J Biol Macromol, 2024, 256: 128348. doi: 10.1016/j.ijbiomac.2023.128348.
33. Vishnoi T, Singh A, Teotia AK, et al. Chitosan-gelatin-polypyrrole cryogel matrix for stem cell differentiation into neural lineage and sciatic nerve regeneration in peripheral nerve injury model[J]. Acs Biomater Sci Eng, 2019, 5(6): 3007-3021.
34. Wang T, Han Y, Wu Z, et al. Tissue-specific hydrogels for three-dimensional printing and potential application in peripheral nerve regeneration[J]. Tissue Eng Part A, 2022, 28(3-4): 161-174.
35. Lv ZS, Dong C, Zhang TJ, et al. Hydrogels in spinal cord injury repair: A review[J/OL]. Front Bioeng Biotechnol, 2022, 10: 931800. doi: 10.3389/fbioe.2022.931800.
36. Xu HL, Gao ZH, Wang ZY, et al. Electrospun PCL nerve conduit filled with GelMA gel for CNTF and IGF-1 delivery in promoting sciatic nerve regeneration in rat[J]. Acs Biomater Sci Eng, 2023, 9(11): 6309-6321.
37. Liu KQ, Wei S, Song LX, et al. Conductive hydrogels-a novel material: Recent advances and future perspectives[J]. J Agric Food Chem, 2020, 68(28): 7269-7280.
38. Su WJ, Xu JK, Pei DT, et al. Hybrid electrically conductive hydrogels with local nerve growth factor release facilitate peripheral nerve regeneration[J]. Acs Appl Bio Mater, 2023, 6(12): 5854-5863.
39. Wang S, Wang Z, Yang W, et al. In situ-sprayed bioinspired adhesive conductive hydrogels for cavernous nerve repair[J/OL]. Adv Mater, 2024, 36(19): e2311264. doi: 10.1002/adma.202311264.
40. Zhao Q, Jiang CY, Zhao L, et al. Unleashing axonal regeneration capacities: neuronal and non-neuronal changes after injuries to dorsal root ganglion neuron central and peripheral axonal branches[J]. Mol Neurobiol, 2024, 61(1): 423-433.
41. Singh A, Shiekh PA, Das M, et al. Aligned chitosan-gelatin cryogel-filled polyurethane nerve guidance channel for neural tissue engineering: Fabrication, characterization, and in vitro evaluation[J]. Biomacromolecules, 2019, 20(2): 662-673.
42. Doblado LR, Martínez-ramos C, Pradas MM. Multimodular bio-inspired organized structures guiding long-distance axonal regeneration[J/OL]. Biomedicines, 2022, 10(9): 2228. doi: 10.3390/biomedicines10092228.
43. Dong XH, Yang YY, Bao ZH, et al. Micro-nanofiber composite biomimetic conduits promote long-gap peripheral nerve regeneration in canine models[J]. Bioact Mater, 2023, 30: 98-115.
44. Li GC, Li SJ, Zhang LL, et al. Construction of biofunctionalized anisotropic hydrogel micropatterns and their effect on Schwann cell behavior in peripheral nerve regeneration[J]. Acs Appl Mater Interfaces, 2019, 11(41): 37397-37410.
45. Cheng KW, Alhasan L, Rezk AR, et al. Fast three-dimensional micropatterning of PC12 cells in rapidly crosslinked hydrogel scaffolds using ultrasonic standing waves[J/OL]. Biofabrication, 2020, 12(1): 015013. doi: 10.1088/1758-5090/ab4cca.
46. Li XK, Cai SX, Liu B, et al. Characteristics of PLGA-gelatin complex as potential artificial nerve scaffold[J]. Colloid Surf B-biointerfaces, 2007, 57(2): 198-203.
47. Ghorbani F, Zamanian A, Nojehdehian H. Effects of pore orientation on in-vitro properties of retinoic acid-loaded PLGA/gelatin scaffolds for artificial peripheral nerve application[J]. Mater Sci Eng C-mater Biol Appl, 2017, 77: 159-172.
48. Gong H, Chen ZT. Adipose-derived stem cells and ginkgo biloba extract-loaded PCL/gelatin nanofibrous scaffolds for peripheral nerve injury repair: the impact of physical activity[J]. Acta Bioeng Biomech, 2023, 25(4): 35-47.
49. Baniasadi H, Ramazani SAA, Mashayekhan S. Fabrication and characterization of conductive chitosan/gelatin-based scaffolds for nerve tissue engineering[J]. Int J Biol Macromol, 2015, 74: 360-366.
50. Huang Y, Xu K, Liu J, et al. Promotion of adrenal pheochromocytoma (PC-12) cell proliferation and outgrowth using schwann cell-laden gelatin methacrylate substrate[J/OL]. Gels, 2022, 8(2): 84. doi: 10.3390/gels8020084. doi: 10.3390/gels8020084.
51. Chen JL, Huang D, Wang L, et al. 3D bioprinted multiscale composite scaffolds based on gelatin methacryloyl (GelMA)/chitosan microspheres as a modular bioink for enhancing 3D neurite outgrowth and elongation[J]. J Colloid Interface Sci, 2020, 574: 162-173.
52. Li T, Javed R, Ao Q. Xenogeneic decellularized extracellular matrix-based biomaterials for peripheral nerve repair and regeneration[J]. Curr Neuropharmacol, 2021, 19(12): 2152-2163.
53. Chen L, Song XB, Yao ZC, et al. Gelatin nanofiber-reinforced decellularized amniotic membrane promotes axon regeneration and functional recovery in the surgical treatment of peripheral nerve injury[J/OL]. Biomaterials, 2023, 300: 122207. doi: 10.1016/j.biomaterials.2023.122207.
54. Heydari P, Mojahedi M, Javaherchi P, et al. Advances and impact of human amniotic membrane and human amniotic-based materials in wound healing application[J/OL]. Int J Biol Macromol, 2024, 281: 136596. doi: 10.1016/j.ijbiomac.2024.136596.
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56. Elkhenany H, El-derby A, Abd elkodous M, et al. Applications of the amniotic membrane in tissue engineering and regeneration: the hundred-year challenge[J/OL]. Stem Cell Res Ther, 2022, 13(1): 8. doi: 10.1186/s13287-021-02684-0.
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