OpenLB
Open Library of Bioscience
Advanced Search
Neural regeneration research
Dec 01, 2025;20 (12): 3476-3500.

Biomaterial-based strategies: a new era in spinal cord injury treatment.

Shihong Zhu, Sijun Diao, Xiaoyin Liu, Zhujun Zhang, Fujun Liu, Wei Chen, Xiyue Lu, Huiyang Luo, Xu Cheng, Qiang Liao, Zhongyu Li, Jing Chen
Author Information
  1. Shihong Zhu: Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China. ORCID
  2. Sijun Diao: Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China.
  3. Xiaoyin Liu: Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China.
  4. Zhujun Zhang: Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China.
  5. Fujun Liu: Department of Ophthalmology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
  6. Wei Chen: Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China.
  7. Xiyue Lu: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
  8. Huiyang Luo: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
  9. Xu Cheng: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
  10. Qiang Liao: Department of Pharmacy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China.
  11. Zhongyu Li: Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China.
  12. Jing Chen: Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China. ORCID
PMID: 40095657 DOI: 10.4103/NRR.NRR-D-24-00844

Abstract

Enhancing neurological recovery and improving the prognosis of spinal cord injury have gained research attention recently. Spinal cord injury is associated with a complex molecular and cellular microenvironment. This complexity has prompted researchers to elucidate the underlying pathophysiological mechanisms and changes and to identify effective treatment strategies. Traditional approaches for spinal cord injury repair include surgery, oral or intravenous medications, and administration of neurotrophic factors; however, the efficacy of these approaches remains inconclusive, and serious adverse reactions continue to be a concern. With advancements in tissue engineering and regenerative medicine, emerging strategies for spinal cord injury repair now involve nanoparticle-based nanodelivery systems, scaffolds, and functional recovery techniques that incorporate biomaterials, bioengineering, stem cell, and growth factors as well as three-dimensional bioprinting. Ideal biomaterial scaffolds should not only provide structural support for neuron migration, adhesion, proliferation, and differentiation but also mimic the mechanical properties of natural spinal cord tissue. Additionally, these scaffolds should facilitate axon growth and neurogenesis by offering adjustable topography and a range of physical and biochemical cues. The three-dimensionally interconnected porous structure and appropriate physicochemical properties enabled by three-dimensional biomimetic printing technology can maximize the potential of biomaterials used for treating spinal cord injury. Therefore, correct selection and application of scaffolds, coupled with successful clinical translation, represent promising clinical objectives to enhance the treatment efficacy for and prognosis of spinal cord injury. This review elucidates the key mechanisms underlying the occurrence of spinal cord injury and regeneration post-injury, including neuroinflammation, oxidative stress, axon regeneration, and angiogenesis. This review also briefly discusses the critical role of nanodelivery systems used for repair and regeneration of injured spinal cord, highlighting the influence of nanoparticles and the factors that affect delivery efficiency. Finally, this review highlights tissue engineering strategies and the application of biomaterial scaffolds for the treatment of spinal cord injury. It discusses various types of scaffolds, their integrations with stem cells or growth factors, and approaches for optimization of scaffold design.

References

  1. Albu S, Kumru H, Coll R, Vives J, Vall��s M, Benito-Penalva J, Rodr��guez L, Codinach M, Hern��ndez J, Navarro X, Vidal J (2021) Clinical effects of intrathecal administration of expanded Wharton jelly mesenchymal stromal cells in patients with chronic complete spinal cord injury: a randomized controlled study. Cytotherapy 23:146���156.
  2. Andrabi SS, Yang J, Gao Y, Kuang Y, Labhasetwar V (2020) Nanoparticles with antioxidant enzymes protect injured spinal cord from neuronal cell apoptosis by attenuating mitochondrial dysfunction. J Control Release 317:300���311.
  3. Azizi M, Farahmandghavi F, Joghataei MT, Zandi M, Imani M, Bakhtiari M, Omidian H (2020) ChABC-loaded PLGA nanoparticles: A comprehensive study on biocompatibility, functional recovery, and axonal regeneration in animal model of spinal cord injury. Int J Pharm 577:119037.
  4. Babaloo H, Ebrahimi-Barough S, Derakhshan MA, Yazdankhah M, Lotfibakhshaiesh N, Soleimani M, Joghataei MT, Ai J (2019) PCL/gelatin nanofibrous scaffolds with human endometrial stem cells/Schwann cells facilitate axon regeneration in spinal cord injury. J Cell Physiol 234:11060���11069.
  5. Bartlett RD, Eleftheriadou D, Evans R, Choi D, Phillips JB (2020) Mechanical properties of the spinal cord and brain: Comparison with clinical-grade biomaterials for tissue engineering and regenerative medicine. Biomaterials 258:120303.
  6. Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS, Eisenberg HM, Flamm E, Leo-Summers L, Maroon J, et al. (1990) A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med 322:1405���1411.
  7. Ca��li K, Ula�� MM, Ozi��ik K, Kale A, Bakuy V, Emir M, Balci M, Topba�� M, Sener E, Ta��demir O (2005) The intraoperative effect of pentoxifylline on the inflammatory process and leukocytes in cardiac surgery patients undergoing cardiopulmonary bypass. Perfusion 20:45���51.
  8. Cao J, Wu J, Mu J, Feng S, Gao J (2021) The design criteria and therapeutic strategy of functional scaffolds for spinal cord injury repair. Biomater Sci 9:4591���4606.
  9. Cao T, Chen H, Huang W, Xu S, Liu P, Zou W, Pang M, Xu Y, Bai X, Liu B, Rong L, Cui ZK, Li M (2022) hUC-MSC-mediated recovery of subacute spinal cord injury through enhancing the pivotal subunits ��3 and ��2 of the GABA(A) receptor. Theranostics 12:3057���3078.
  10. Carone TW, Hasenwinkel JM (2006) Mechanical and morphological characterization of homogeneous and bilayered poly(2-hydroxyethyl methacrylate) scaffolds for use in CNS nerve regeneration. J Biomed Mater Res B Appl Biomater 78:274���282.
  11. Chedly J, Soares S, Montembault A, von Boxberg Y, Veron-Ravaille M, Mouffle C, Benassy MN, Taxi J, David L, Nothias F (2017) Physical chitosan microhydrogels as scaffolds for spinal cord injury restoration and axon regeneration. Biomaterials 138:91���107.
  12. Chen W, Zhang Y, Yang S, Sun J, Qiu H, Hu X, Niu X, Xiao Z, Zhao Y, Zhou Y, Dai J, Chu T (2020) NeuroRegen scaffolds combined with autologous bone marrow mononuclear cells for the repair of acute complete spinal cord injury: a 3-year clinical study. Cell Transplant 29:963689720950637.
  13. Chen Y, Zhang H, Hu X, Cai W, Ni W, Zhou K (2022) Role of NETosis in central nervous system injury. Oxid Med Cell Longev 2022:3235524.
  14. Chen Z, Sun Z, Fan Y, Yin M, Jin C, Guo B, Yin Y, Quan R, Zhao S, Han S, Cheng X, Liu W, Chen B, Xiao Z, Dai J, Zhao Y (2023) Mimicked spinal cord fibers trigger axonal regeneration and remyelination after injury. ACS Nano 17:25591���25613.
  15. Ciciriello AJ, Smith DR, Munsell MK, Boyd SJ, Shea LD, Dumont CM (2020) Acute implantation of aligned hydrogel tubes supports delayed spinal progenitor implantation. ACS Biomater Sci Eng 6:5771���5784.
  16. Ciciriello AJ, Surnar B, Medy GD, Su X, Dhar S, Dumont CM (2022) Biomaterial-targeted precision nanoparticle delivery to the injured spinal cord. Acta Biomater 152:532���545.
  17. Cnops V, Chin JS, Milbreta U, Chew SY (2020) Biofunctional scaffolds with high packing density of aligned electrospun fibers support neural regeneration. J Biomed Mater Res A 108:2473���2483.
  18. Crowley ST, Fukushima Y, Uchida S, Kataoka K, Itaka K (2019) Enhancement of motor function recovery after spinal cord injury in mice by delivery of brain-derived neurotrophic factor mRNA. Mol Ther Nucleic Acids 17:465���476.
  19. Cruz LJ, Stammes MA, Que I, van Beek ER, Knol-Blankevoort VT, Snoeks TJA, Chan A, Kaijzel EL, L��wik C (2016) Effect of PLGA NP size on efficiency to target traumatic brain injury. J Control Release 223:31���41.
  20. Cui X, Wang L, Gao X, Wu J, Hu T, Zhang J, Zhou X, Zhang K-Q, Cheng L (2024) Self-assembled silk fibroin injectable hydrogels based on layered double hydroxides for spinal cord injury repair. Matter 7:620���639.
  21. Curt A, Hsieh J, Schubert M, Hupp M, Friedl S, Freund P, Huber E, Pfyffer D, Sutter R, Jutzeler C, W��thrich RP, Min K, Casha S, Fehlings MG, Guzman R (2020) The damaged spinal cord is a suitable target for stem cell transplantation. Neurorehabil Neural Repair 34:758���768.
  22. Dai H, Fan Q, Wang C (2022a) Recent applications of immunomodulatory biomaterials for disease immunotherapy. Exploration (Beijing) 2:20210157.
  23. Dai Y, Lu T, Shao M, Lyu F (2022b) Recent advances in PLLA-based biomaterial scaffolds for neural tissue engineering: Fabrication, modification, and applications. Front Bioeng Biotechnol 10:1011783.
  24. Easthope CS, Traini LR, Awai L, Franz M, Rauter G, Curt A, Bolliger M (2018) Overground walking patterns after chronic incomplete spinal cord injury show distinct response patterns to unloading. J Neuroeng Rehabil 15:102.
  25. Echave MC, Saenz del Burgo L, Pedraz JL, Orive G (2017) Gelatin as biomaterial for tissue engineering. Curr Pharm Des 23:3567���3584.
  26. Elci SG, Jiang Y, Yan B, Kim ST, Saha K, Moyano DF, Yesilbag Tonga G, Jackson LC, Rotello VM, Vachet RW (2016) Surface charge controls the suborgan biodistributions of gold nanoparticles. ACS Nano 10:5536���5542.
  27. Fan C, Yang W, Zhang L, Cai H, Zhuang Y, Chen Y, Zhao Y, Dai J (2022) Restoration of spinal cord biophysical microenvironment for enhancing tissue repair by injury-responsive smart hydrogel. Biomaterials 288:121689.
  28. Feng F, Song X, Tan Z, Tu Y, Xiao L, Xie P, Ma Y, Sun X, Ma J, Rong L, He L (2023) Cooperative assembly of a designer peptide and silk fibroin into hybrid nanofiber gels for neural regeneration after spinal cord injury. Sci Adv 9:eadg0234.
  29. Francos-Quijorna I, S��nchez-Petidier M, Burnside ER, Badea SR, Torres-Espin A, Marshall L, de Winter F, Verhaagen J, Moreno-Manzano V, Bradbury EJ (2022) Chondroitin sulfate proteoglycans prevent immune cell phenotypic conversion and inflammation resolution via TLR4 in rodent models of spinal cord injury. Nat Commun 13:2933.
  30. Gao X, Cheng W, Zhang X, Zhou Z, Ding Z, Zhou X, Lu Q, Kaplan DL (2022a) Nerve growth factor-laden anisotropic silk nanofiber hydrogels to regulate neuronal/astroglial differentiation for scarless spinal cord repair. ACS Appl Mater Interfaces 14:3701���3715.
  31. Gao X, Han Z, Huang C, Lei H, Li G, Chen L, Feng D, Zhou Z, Shi Q, Cheng L, Zhou X (2022b) An anti-inflammatory and neuroprotective biomimetic nanoplatform for repairing spinal cord injury. Bioact Mater 18:569���582.
  32. Ghane N, Beigi MH, Labbaf S, Nasr-Esfahani MH, Kiani A (2020) Design of hydrogel-based scaffolds for the treatment of spinal cord injuries. J Mater Chem B 8:10712���10738.
  33. Giandomenico SL, Mierau SB, Gibbons GM, Wenger LMD, Masullo L, Sit T, Sutcliffe M, Boulanger J, Tripodi M, Derivery E, Paulsen O, Lakatos A, Lancaster MA (2019) Cerebral organoids at the air-liquid interface generate diverse nerve tracts with functional output. Nat Neurosci 22:669���679.
  34. Golestani A, Shobeiri P, Sadeghi-Naini M, Jazayeri SB, Maroufi SF, Ghodsi Z, Dabbagh Ohadi MA, Mohammadi E, Rahimi-Movaghar V, Ghodsi SM (2022) Epidemiology of traumatic spinal cord injury in developing countries from 2009 to 2020: a systematic review and meta-analysis. Neuroepidemiology 56:219���239.
  35. Gu Y, Cheng X, Huang X, Yuan Y, Qin S, Tan Z, Wang D, Hu X, He C, Su Z (2019) Conditional ablation of reactive astrocytes to dissect their roles in spinal cord injury and repair. Brain Behav Immun 80:394���405.
  36. Guo S, Redenski I, Levenberg S (2021) Spinal cord repair: from cells and tissue engineering to extracellular vesicles. Cells 10:1872.
  37. Han IB, Thakor DK, Ropper AE, Yu D, Wang L, Kabatas S, Zeng X, Kim SW, Zafonte RD, Teng YD (2019a) Physical impacts of PLGA scaffolding on hMSCs: recovery neurobiology insight for implant design to treat spinal cord injury. Exp Neurol 320:112980.
  38. Han Q, Xie Y, Ordaz JD, Huh AJ, Huang N, Wu W, Liu N, Chamberlain KA, Sheng ZH, Xu XM (2020) Restoring cellular energetics promotes axonal regeneration and functional recovery after spinal cord injury. Cell Metab 31:623���641.e628.
  39. Han S, et al. (2019b) Pre-clinical evaluation of CBD-NT3 modified collagen scaffolds in completely spinal cord transected non-human primates. J Neurotrauma 36:2316���2324.
  40. Harris GM, Madigan NN, Lancaster KZ, Enquist LW, Windebank AJ, Schwartz J, Schwarzbauer JE (2017) Nerve guidance by a decellularized fibroblast extracellular matrix. Matrix Biol 60-61:176���189.
  41. He W, Wang Q, Tian X, Pan G (2022) Recapitulating dynamic ECM ligand presentation at biomaterial interfaces: Molecular strategies and biomedical prospects. Exploration (Beijing) 2:20210093.
  42. He Z, Du J, Zhang Y, Xu Y, Huang Q, Zhou Q, Wu M, Li Y, Zhang X, Zhang H, Cai Y, Ye K, Wang X, Zhang Y, Han Q, Xiao J (2023) Kruppel-like factor 2 contributes to blood-spinal cord barrier integrity and functional recovery from spinal cord injury by augmenting autophagic flux. Theranostics 13:849���866.
  43. Holmes TC, de Lacalle S, Su X, Liu G, Rich A, Zhang S (2000) Extensive neurite outgrowth and active synapse formation on self-assembling peptide scaffolds. Proc Natl Acad Sci U S A 97:6728���6733.
  44. Hong JY, Seo Y, Davaa G, Kim HW, Kim SH, Hyun JK (2020) Decellularized brain matrix enhances macrophage polarization and functional improvements in rat spinal cord injury. Acta Biomater 101:357���371.
  45. Iwasaki M, Wilcox JT, Nishimura Y, Zweckberger K, Suzuki H, Wang J, Liu Y, Karadimas SK, Fehlings MG (2014) Synergistic effects of self-assembling peptide and neural stem/progenitor cells to promote tissue repair and forelimb functional recovery in cervical spinal cord injury. Biomaterials 35:2617���2629.
  46. Jaffer H, Andrabi SS, Petro M, Kuang Y, Steinmetz MP, Labhasetwar V (2023) Catalytic antioxidant nanoparticles mitigate secondary injury progression and promote functional recovery in spinal cord injury model. J Control Release 364:109���123.
  47. Jiang D, Yang X, Ge M, Hu H, Xu C, Wen S, Deng H, Mei X (2023) Zinc defends against Parthanatos and promotes functional recovery after spinal cord injury through SIRT3-mediated anti-oxidative stress and mitophagy. CNS Neurosci Ther 29:2857���2872.
  48. Jiang X, Liu X, Yu Q, Shen W, Mei X, Tian H, Wu C (2022) Functional resveratrol-biodegradable manganese doped silica nanoparticles for the spinal cord injury treatment. Mater Today Bio 13:100177.
  49. Jo HJ, Perez MA (2020) Corticospinal-motor neuronal plasticity promotes exercise-mediated recovery in humans with spinal cord injury. Brain 143:1368���1382.
  50. Ju D, Dong C (2024) The combined application of stem cells and three-dimensional bioprinting scaffolds for the repair of spinal cord injury. Neural Regen Res 19:1751���1758.
  51. Kang J, Li Z, Zhi Z, Wang S, Xu G (2019) MiR-21 derived from the exosomes of MSCs regulates the death and differentiation of neurons in patients with spinal cord injury. Gene Ther 26:491���503.
  52. Khoueir P, Oh BC, DiRisio DJ, Wang MY (2007) Multilevel anterior cervical fusion using a collagen-hydroxyapatite matrix with iliac crest bone marrow aspirate: an 18-month follow-up study. Neurosurgery 61:963���970; discussion 970-971.
  53. Kim BS, Das S, Jang J, Cho DW (2020) Decellularized extracellular matrix-based bioinks for engineering tissue- and organ-specific microenvironments. Chem Rev 120:10608���10661.
  54. Kitade K, Kobayakawa K, Saiwai H, Matsumoto Y, Kawaguchi K, Iida K, Kijima K, Iura H, Tamaru T, Haruta Y, Ono G, Konno D, Maeda T, Okada S, Nakashima K, Nakashima Y (2023) Reduced neuroinflammation via astrocytes and neutrophils promotes regeneration after spinal cord injury in neonatal mice. J Neurotrauma 40:2566���2579.
  55. Koffler J, Zhu W, Qu X, Platoshyn O, Dulin JN, Brock J, Graham L, Lu P, Sakamoto J, Marsala M, Chen S, Tuszynski MH (2019) Biomimetic 3D-printed scaffolds for spinal cord injury repair. Nat Med 25:263���269.
  56. Kong F, Yu H, Gao L, Xing E, Yu Y, Sun X, Wang W, Zhao D, Li X (2024) Multifunctional hierarchical nanoplatform with anisotropic bimodal mesopores for effective neural circuit reconstruction after spinal cord injury. ACS Nano 18:13333���13345.
  57. Lai BQ, Che MT, Du BL, Zeng X, Ma YH, Feng B, Qiu XC, Zhang K, Liu S, Shen HY, Wu JL, Ling EA, Zeng YS (2016) Transplantation of tissue engineering neural network and formation of neuronal relay into the transected rat spinal cord. Biomaterials 109:40���54.
  58. Langer R, Vacanti JP (1993) Tissue engineering. Science 260:920���926.
  59. Li G, Zhang B, Sun JH, Shi LY, Huang MY, Huang LJ, Lin ZJ, Lin QY, Lai BQ, Ma YH, Jiang B, Ding Y, Zhang HB, Li MX, Zhu P, Wang YQ, Zeng X, Zeng YS (2021a) An NT-3-releasing bioscaffold supports the formation of TrkC-modified neural stem cell-derived neural network tissue with efficacy in repairing spinal cord injury. Bioact Mater 6:3766���3781.
  60. Li L, Xiao B, Mu J, Zhang Y, Zhang C, Cao H, Chen R, Patra HK, Yang B, Feng S, Tabata Y, Slater NKH, Tang J, Shen Y, Gao J (2019) A MnO(2) nanoparticle-dotted hydrogel promotes spinal cord repair via regulating reactive oxygen species microenvironment and synergizing with mesenchymal stem cells. ACS Nano 13:14283���14293.
  61. Li L, Mu J, Zhang Y, Zhang C, Ma T, Chen L, Huang T, Wu J, Cao J, Feng S, Cai Y, Han M, Gao J (2022a) Stimulation by exosomes from hypoxia preconditioned human umbilical vein endothelial cells facilitates mesenchymal stem cells angiogenic function for spinal cord repair. ACS Nano 16:10811���10823.
  62. Li S, Yang Y, Wang S, Gao Y, Song Z, Chen L, Chen Z (2022b) Advances in metal graphitic nanocapsules for biomedicine. Exploration (Beijing) 2:20210223.
  63. Li S, Ke Z, Peng X, Fan P, Chao J, Wu P, Xiao P, Zhou Y (2022c) Injectable and fast gelling hyaluronate hydrogels with rapid self-healing ability for spinal cord injury repair. Carbohydr Polym 298:120081.
  64. Li X, Zhang C, Haggerty AE, Yan J, Lan M, Seu M, Yang M, Marlow MM, Maldonado-Lasunci��n I, Cho B, Zhou Z, Chen L, Martin R, Nitobe Y, Yamane K, You H, Reddy S, Quan DP, Oudega M, Mao HQ (2020) The effect of a nanofiber-hydrogel composite on neural tissue repair and regeneration in the contused spinal cord. Biomaterials 245:119978.
  65. Li XH, Zhu X, Liu XY, Xu HH, Jiang W, Wang JJ, Chen F, Zhang S, Li RX, Chen XY, Tu Y (2021b) The corticospinal tract structure of collagen/silk fibroin scaffold implants using 3D printing promotes functional recovery after complete spinal cord transection in rats. J Mater Sci Mater Med 32:31.
  66. Li Y, Lei Z, Ritzel RM, He J, Li H, Choi HMC, Lipinski MM, Wu J (2022d) Impairment of autophagy after spinal cord injury potentiates neuroinflammation and motor function deficit in mice. Theranostics 12:5364���5388.
  67. Li Y, Cheng S, Wen H, Xiao L, Deng Z, Huang J, Zhang Z (2023a) Coaxial 3D printing of hierarchical structured hydrogel scaffolds for on-demand repair of spinal cord injury. Acta Biomater 168:400���415.
  68. Li Z, Qi Y, Sun L, Li Z, Chen S, Zhang Y, Ma Y, Han J, Wang Z, Zhang Y, Geng H, Huang B, Wang J, Li G, Li X, Wu S, Ni S (2023b) Three-dimensional nanofibrous sponges with aligned architecture and controlled hierarchy regulate neural stem cell fate for spinal cord regeneration. Theranostics 13:4762���4780.
  69. Lin J, Anopas D, Milbreta U, Lin PH, Chin JS, Zhang N, Wee SK, Tow A, Ang WT, Chew SY (2019) Regenerative rehabilitation: exploring the synergistic effects of rehabilitation and implantation of a bio-functional scaffold in enhancing nerve regeneration. Biomater Sci 7:5150���5160.
  70. Lin S, Li D, Zhou Z, Xu C, Mei X, Tian H (2021a) Therapy of spinal cord injury by zinc modified gold nanoclusters via immune-suppressing strategies. J Nanobiotechnology 19:281.
  71. Lin S, Zhao HS, Xu C, Zhou ZP, Wang DH, Chen SR, Mei XF (2021b) Bioengineered zinc oxide nanoparticle-loaded hydrogel for combinative treatment of spinal cord transection. Front Bioeng Biotechnol 9:796361.
  72. Liu D, Shu M, Liu W, Shen Y, Long G, Zhao Y, Hou X, Xiao Z, Dai J, Li X (2021a) Binary scaffold facilitates in situ regeneration of axons and neurons for complete spinal cord injury repair. Biomater Sci 9:2955���2971.
  73. Liu H, Feng Y, Che S, Guan L, Yang X, Zhao Y, Fang L, Zvyagin AV, Lin Q (2023a) An electroconductive hydrogel scaffold with injectability and biodegradability to manipulate neural stem cells for enhancing spinal cord injury repair. Biomacromolecules 24:86���97.
  74. Liu J, Yan R, Wang B, Chen S, Hong H, Liu C, Chen X (2024a) Decellularized extracellular matrix enriched with GDNF enhances neurogenesis and remyelination for improved motor recovery after spinal cord injury. Acta Biomater 180:308���322.
  75. Liu K, Wang Y, Dong X, Xu C, Yuan M, Wei W, Pang Z, Wu X, Dai H (2024b) Injectable hydrogel system incorporating black phosphorus nanosheets and tazarotene drug for enhanced vascular and nerve regeneration in spinal cord injury repair. Small 20:e2310194.
  76. Liu M, Zhang W, Han S, Zhang D, Zhou X, Guo X, Chen H, Wang H, Jin L, Feng S, Wei Z (2024c) Multifunctional conductive and electrogenic hydrogel repaired spinal cord injury via immunoregulation and enhancement of neuronal differentiation. Adv Mater 36:e2313672.
  77. Liu S, Yang H, Chen D, Xie Y, Tai C, Wang L, Wang P, Wang B (2022a) Three-dimensional bioprinting sodium alginate/gelatin scaffold combined with neural stem cells and oligodendrocytes markedly promoting nerve regeneration after spinal cord injury. Regen Biomater 9:rbac038.
  78. Liu W, Xu B, Xue W, Yang B, Fan Y, Chen B, Xiao Z, Xue X, Sun Z, Shu M, Zhang Q, Shi Y, Zhao Y, Dai J (2020a) A functional scaffold to promote the migration and neuronal differentiation of neural stem/progenitor cells for spinal cord injury repair. Biomaterials 243:119941.
  79. Liu W, Xu B, Zhao S, Han S, Quan R, Liu W, Ji C, Chen B, Xiao Z, Yin M, Yin Y, Dai J, Zhao Y (2023b) Spinal cord tissue engineering via covalent interaction between biomaterials and cells. Sci Adv 9:eade8829.
  80. Liu X, Hao M, Chen Z, Zhang T, Huang J, Dai J, Zhang Z (2021b) 3D bioprinted neural tissue constructs for spinal cord injury repair. Biomaterials 272:120771.
  81. Liu X, Jiang X, Yu Q, Shen W, Tian H, Mei X, Wu C (2022b) Sodium alginate and naloxone loaded macrophage-derived nanovesicles for the treatment of spinal cord injury. Asian J Pharm Sci 17:87���101.
  82. Liu X, Zhang L, Xu Z, Xiong X, Yu Y, Wu H, Qiao H, Zhong J, Zhao Z, Dai J, Suo G (2022c) A functionalized collagen-I scaffold delivers microRNA 21-loaded exosomes for spinal cord injury repair. Acta Biomater 154:385���400.
  83. Liu XY, Chen C, Xu HH, Zhang YS, Zhong L, Hu N, Jia XL, Wang YW, Zhong KH, Liu C, Zhu X, Ming D, Li XH (2021c) Integrated printed BDNF/collagen/chitosan scaffolds with low temperature extrusion 3D printer accelerated neural regeneration after spinal cord injury. Regen Biomater 8:rbab047.
  84. Liu Y, Zhang Z, Zhang Y, Luo B, Liu X, Cao Y, Pei R (2023c) Construction of adhesive and bioactive silk fibroin hydrogel for treatment of spinal cord injury. Acta Biomater 158:178���189.
  85. Liu Z, Yao X, Jiang W, Li W, Zhu S, Liao C, Zou L, Ding R, Chen J (2020b) Advanced oxidation protein products induce microglia-mediated neuroinflammation via MAPKs-NF-��B signaling pathway and pyroptosis after secondary spinal cord injury. J Neuroinflammation 17:90.
  86. Liu ZH, Huang YC, Kuo CY, Kuo CY, Chin CY, Yip PK, Chen JP (2020c) Docosahexaenoic acid-loaded polylactic acid core-shell nanofiber membranes for regenerative medicine after spinal cord injury: in vitro and in vivo study. Int J Mol Sci 21:7031.
  87. Lu Y, Shang Z, Zhang W, Pang M, Hu X, Dai Y, Shen R, Wu Y, Liu C, Luo T, Wang X, Liu B, Zhang L, Rong L (2024) Global incidence and characteristics of spinal cord injury since 2000-2021: a systematic review and meta-analysis. BMC Med 22:285.
  88. Luo J, Shi R (2007) Polyethylene glycol inhibits apoptotic cell death following traumatic spinal cord injury. Brain Res 1155:10���16.
  89. Luo Y, Fan L, Liu C, Wen H, Wang S, Guan P, Chen D, Ning C, Zhou L, Tan G (2022) An injectable, self-healing, electroconductive extracellular matrix-based hydrogel for enhancing tissue repair after traumatic spinal cord injury. Bioact Mater 7:98���111.
  90. Ma CC, Wang XC, Tao NP (2021) Hydroxyapatite from the skull of tuna (Thunnus obesus) head combined with chitosan to restore locomotive function after spinal cord injury. Front Nutr 8:734498.
  91. Ma D, Zhao Y, Huang L, Xiao Z, Chen B, Shi Y, Shen H, Dai J (2020) A novel hydrogel-based treatment for complete transection spinal cord injury repair is driven by microglia/macrophages repopulation. Biomaterials 237:119830.
  92. Ma D, Fu C, Li F, Ruan R, Lin Y, Li X, Li M, Zhang J (2024) Functional biomaterials for modulating the dysfunctional pathological microenvironment of spinal cord injury. Bioact Mater 39:521���543.
  93. Madhavan K, Frid MG, Hunter K, Shandas R, Stenmark KR, Park D (2018) Development of an electrospun biomimetic polyurea scaffold suitable for vascular grafting. J Biomed Mater Res B Appl Biomater 106:278���290.
  94. Man W, Yang S, Cao Z, Lu J, Kong X, Sun X, Zhao L, Guo Y, Yao S, Wang G, Wang X (2021) A multi-modal delivery strategy for spinal cord regeneration using a composite hydrogel presenting biophysical and biochemical cues synergistically. Biomaterials 276:120971.
  95. Maynard G, Kannan R, Liu J, Wang W, Lam TKT, Wang X, Adamson C, Hackett C, Schwab JM, Liu C, Leslie DP, Chen D, Marino R, Zafonte R, Flanders A, Block G, Smith E, Strittmatter SM (2023) Soluble Nogo-receptor-Fc decoy (AXER-204) in patients with chronic cervical spinal cord injury in the USA: a first-in-human and randomised clinical trial. Lancet Neurol 22:672���684.
  96. Monahan M, Homer M, Zhang S, Zheng R, Chen CL, De Yoreo J, Cossairt BM (2022) Impact of nanoparticle size and surface chemistry on peptoid self-assembly. ACS Nano 16:8095���8106.
  97. Mou C, Wang X, Li W, Li Z, Liu N, Xu Y (2023) Efficacy of mesenchymal stromal cells intraspinal transplantation for patients with different degrees of spinal cord injury: A systematic review and meta-analysis. Cytotherapy 25:530���536.
  98. Mu J, Wu J, Cao J, Ma T, Li L, Feng S, Gao J (2021) Rapid and effective treatment of traumatic spinal cord injury using stem cell derived exosomes. Asian J Pharm Sci 16:806���815.
  99. Pink DL, Loruthai O, Ziolek RM, Wasutrasawat P, Terry AE, Lawrence MJ, Lorenz CD (2019) On the structure of solid lipid nanoparticles. Small 15:e1903156.
  100. Pointillart V, Petitjean ME, Wiart L, Vital JM, Lassi�� P, Thicoip�� M, Dabadie P (2000) Pharmacological therapy of spinal cord injury during the acute phase. Spinal Cord 38:71���76.
  101. Poulen G, Aloy E, Bringuier CM, Mestre-Franc��s N, Artus EVF, Cardoso M, Perez JC, Goze-Bac C, Boukhaddaoui H, Lonjon N, Gerber YN, Perrin FE (2021) Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates. Theranostics 11:8640���8659.
  102. Rahimi B, Behroozi Z, Motamednezhad A, Jafarpour M, Hamblin MR, Moshiri A, Janzadeh A, Ramezani F (2023) Study of nerve cell regeneration on nanofibers containing cerium oxide nanoparticles in a spinal cord injury model in rats. J Mater Sci Mater Med 34:9.
  103. Ran N, Li W, Zhang R, Lin C, Zhang J, Wei Z, Li Z, Yuan Z, Wang M, Fan B, Shen W, Li X, Zhou H, Yao X, Kong X, Feng S (2023) Autologous exosome facilitates load and target delivery of bioactive peptides to repair spinal cord injury. Bioact Mater 25:766���782.
  104. Rao JS, Zhao C, Zhang A, Duan H, Hao P, Wei RH, Shang J, Zhao W, Liu Z, Yu J, Fan KS, Tian Z, He Q, Song W, Yang Z, Sun YE, Li X (2018) NT3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury. Proc Natl Acad Sci U S A 115:E5595���E5604.
  105. Roh EJ, Kim DS, Kim JH, Lim CS, Choi H, Kwon SY, Park SY, Kim JY, Kim HM, Hwang DY, Han DK, Han I (2023) Multimodal therapy strategy based on a bioactive hydrogel for repair of spinal cord injury. Biomaterials 299:122160.
  106. Sandhu MS, Gray E, Kocherginsky M, Jayaraman A, Mitchell GS, Rymer WZ (2019) Prednisolone pretreatment enhances intermittent hypoxia-induced plasticity in persons with chronic incomplete spinal cord injury. Neurorehabil Neural Repair 33:911���921.
  107. Santi S, Corridori I, Pugno NM, Motta A, Migliaresi C (2021) Injectable scaffold-systems for the regeneration of spinal cord: advances of the past decade. ACS Biomater Sci Eng 7:983���999.
  108. Schwaiger C, Haider T, Endmayr V, Zrzavy T, Gruber VE, Ricken G, Simonovska A, Hametner S, Schwab JM, H��ftberger R (2023) Dynamic induction of the myelin-associated growth inhibitor Nogo-A in perilesional plasticity regions after human spinal cord injury. Brain Pathol 33:e13098.
  109. Sekine Y, Kannan R, Wang X, Strittmatter SM (2022) Rabphilin3A reduces integrin-dependent growth cone signaling to restrict axon regeneration after trauma. Exp Neurol 353:114070.
  110. Sen S, Lagas S, Roy A, Kumar H (2022) Cytoskeleton saga: its regulation in normal physiology and modulation in neurodegenerative disorders. Eur J Pharmacol 925:175001.
  111. Sha Q, Wang Y, Zhu Z, Wang H, Qiu H, Niu W, Li X, Qian J (2023) A hyaluronic acid/silk fibroin/poly-dopamine-coated biomimetic hydrogel scaffold with incorporated neurotrophin-3 for spinal cord injury repair. Acta Biomater 167:219���233.
  112. Shang Z, Wang M, Zhang B, Wang X, Wanyan P (2022) Clinical translation of stem cell therapy for spinal cord injury still premature: results from a single-arm meta-analysis based on 62 clinical trials. BMC Med 20:284.
  113. Shen H, Chen X, Li X, Jia K, Xiao Z, Dai J (2019) Transplantation of adult spinal cord grafts into spinal cord transected rats improves their locomotor function. Sci China Life Sci 62:725���733.
  114. Shi R, Borgens RB, Blight AR (1999) Functional reconnection of severed mammalian spinal cord axons with polyethylene glycol. J Neurotrauma 16:727���738.
  115. Sitoci-Ficici KH, Matyash M, Uckermann O, Galli R, Leipnitz E, Later R, Ikonomidou C, Gelinsky M, Schackert G, Kirsch M (2018) Non-functionalized soft alginate hydrogel promotes locomotor recovery after spinal cord injury in a rat hemimyelonectomy model. Acta Neurochir (Wien) 160:449���457.
  116. Sousa JPM, Stratakis E, Mano J, Marques P (2023) Anisotropic 3D scaffolds for spinal cord guided repair: Current concepts. Biomater Adv 148:213353.
  117. Squair JW, B��langer LM, Tsang A, Ritchie L, Mac-Thiong JM, Parent S, Christie S, Bailey C, Dhall S, Charest-Morin R, Street J, Ailon T, Paquette S, Dea N, Fisher CG, Dvorak MF, West CR, Kwon BK (2019) Empirical targets for acute hemodynamic management of individuals with spinal cord injury. Neurology 93:e1205-e1211.
  118. Stahel PF, VanderHeiden T, Flierl MA, Matava B, Gerhardt D, Bolles G, Beauchamp K, Burlew CC, Johnson JL, Moore EE (2013) The impact of a standardized ���spine damage-control��� protocol for unstable thoracic and lumbar spine fractures in severely injured patients: a prospective cohort study. J Trauma Acute Care Surg 74:590���596.
  119. Stern S, Hilton BJ, Burnside ER, Dupraz S, Handley EE, Gonyer JM, Brakebusch C, Bradke F (2021) RhoA drives actin compaction to restrict axon regeneration and astrocyte reactivity after CNS injury. Neuron 109:3436���3455.e3439.
  120. Stewart AN, McFarlane KE, Vekaria HJ, Bailey WM, Slone SA, Tranthem LA, Zhang B, Patel SP, Sullivan PG, Gensel JC (2021) Mitochondria exert age-divergent effects on recovery from spinal cord injury. Exp Neurol 337:113597.
  121. Stewart AN, Glaser EP, Mott CA, Bailey WM, Sullivan PG, Patel SP, Gensel JC (2022) Advanced age and neurotrauma diminish glutathione and impair antioxidant defense after spinal cord injury. J Neurotrauma 39:1075���1089.
  122. Sun X, Bai Y, Zhai H, Liu S, Zhang C, Xu Y, Zou J, Wang T, Chen S, Zhu Q, Liu X, Mao H, Quan D (2019) Devising micro/nano-architectures in multi-channel nerve conduits towards a pro-regenerative matrix for the repair of spinal cord injury. Acta Biomater 86:194���206.
  123. Tan Z, Wang H, Gao X, Liu T, Tan Y (2016) Composite vascular grafts with high cell infiltration by co-electrospinning. Mater Sci Eng C Mater Biol Appl 67:369���377.
  124. Ter Wengel PV, De Witt Hamer PC, Pauptit JC, van der Gaag NA, Oner FC, Vandertop WP (2019) Early surgical decompression improves neurological outcome after complete traumatic cervical spinal cord injury: a meta-analysis. J Neurotrauma 36:835���844.
  125. Thomas AM, Shea LD (2013) Polysaccharide-modified scaffolds for controlled lentivirus delivery in vitro and after spinal cord injury. J Control Release 170:421���429.
  126. Tran KA, Partyka PP, Jin Y, Bouyer J, Fischer I, Galie PA (2020) Vascularization of self-assembled peptide scaffolds for spinal cord injury repair. Acta Biomater 104:76���84.
  127. Tsai EC, Dalton PD, Shoichet MS, Tator CH (2006) Matrix inclusion within synthetic hydrogel guidance channels improves specific supraspinal and local axonal regeneration after complete spinal cord transection. Biomaterials 27:519���533.
  128. Tysseling VM, Sahni V, Pashuck ET, Birch D, Hebert A, Czeisler C, Stupp SI, Kessler JA (2010) Self-assembling peptide amphiphile promotes plasticity of serotonergic fibers following spinal cord injury. J Neurosci Res 88:3161���3170.
  129. Vismara I, Papa S, Veneruso V, Mauri E, Mariani A, De Paola M, Affatato R, Rossetti A, Sponchioni M, Moscatelli D, Sacchetti A, Rossi F, Forloni G, Veglianese P (2020) Selective modulation of A1 astrocytes by drug-loaded nano-structured gel in spinal cord injury. ACS Nano 14:360���371.
  130. Wan KR, Ng ZYV, Wee SK, Fatimah M, Lui W, Phua MW, So QYR, Maszczyk TK, Premchand B, Saffari SE, Ker RXJ, Ng WH (2024a) Recovery of volitional motor control and overground walking in participants with chronic clinically motor complete spinal cord injury: restoration of rehabilitative function with epidural spinal stimulation (RESTORES) trial-a preliminary study. J Neurotrauma 41:1146���1162.
  131. Wan X, Zhao Y, Li Z, Li L (2022) Emerging polymeric electrospun fibers: From structural diversity to application in flexible bioelectronics and tissue engineering. Exploration (Beijing) 2:20210029.
  132. Wan Y, Lin Y, Tan X, Gong L, Lei F, Wang C, Sun X, Du X, Zhang Z, Jiang J, Liu Z, Wang J, Zhou X, Wang S, Zhou X, Jing P, Zhong Z (2024b) Injectable hydrogel to deliver bone mesenchymal stem cells preloaded with azithromycin to promote spinal cord repair. ACS Nano 18:8934���8951.
  133. Wang D, Wang K, Liu Z, Wang Z, Wu H (2021a) Valproic acid labeled chitosan nanoparticles promote the proliferation and differentiation of neural stem cells after spinal cord injury. Neurotox Res 39:456���466.
  134. Wang D, Zhao H, Xu C, Lin S, Guo Y (2023a) Enhancing neuroprotective effect of aminosalicylic acid-grafted chitosan electrospun fibers for spinal cord injury. Mater Today Bio 18:100529.
  135. Wang J, Chu R, Ni N, Nan G (2020) The effect of Matrigel as scaffold material for neural stem cell transplantation for treating spinal cord injury. Sci Rep 10:2576.
  136. Wang J, Kong X, Li Q, Li C, Yu H, Ning G, Xiang Z, Liu Y, Feng S (2021b) The spatial arrangement of cells in a 3D-printed biomimetic spinal cord promotes directional differentiation and repairs the motor function after spinal cord injury. Biofabrication 13:045016.
  137. Wang L, Shi Q, Dai J, Gu Y, Feng Y, Chen L (2018) Increased vascularization promotes functional recovery in the transected spinal cord rats by implanted vascular endothelial growth factor-targeting collagen scaffold. J Orthop Res 36:1024���1034.
  138. Wang S, Wang R, Chen J, Yang B, Shu J, Cheng F, Tao Y, Shi K, Wang C, Wang J, Xia K, Zhang Y, Chen Q, Liang C, Tang J, Li F (2023b) Controlled extracellular vesicles release from aminoguanidine nanoparticle-loaded polylysine hydrogel for synergistic treatment of spinal cord injury. J Control Release 363:27���42.
  139. Woods I, O���Connor C, Frugoli L, Kerr S, Gutierrez Gonzalez J, Stasiewicz M, McGuire T, Cavanagh B, Hibbitts A, Dervan A, O���Brien FJ (2022) Biomimetic scaffolds for spinal cord applications exhibit stiffness-dependent immunomodulatory and neurotrophic characteristics. Adv Healthc Mater 11:e2101663.
  140. Wu W, Jia S, Xu H, Gao Z, Wang Z, Lu B, Ai Y, Liu Y, Liu R, Yang T, Luo R, Hu C, Kong L, Huang D, Yan L, Yang Z, Zhu L, Hao D (2023) Supramolecular hydrogel microspheres of platelet-derived growth factor mimetic peptide promote recovery from spinal cord injury. ACS Nano 17:3818���3837.
  141. Xi K, Gu Y, Tang J, Chen H, Xu Y, Wu L, Cai F, Deng L, Yang H, Shi Q, Cui W, Chen L (2020) Microenvironment-responsive immunoregulatory electrospun fibers for promoting nerve function recovery. Nat Commun 11:4504.
  142. Xiao Z, Tang F, Zhao Y, Han G, Yin N, Li X, Chen B, Han S, Jiang X, Yun C, Zhao C, Cheng S, Zhang S, Dai J (2018) Significant improvement of acute complete spinal cord injury patients diagnosed by a combined criteria implanted with neuroregen scaffolds and mesenchymal stem cells. Cell Transplant 27:907���915.
  143. Xie Y, Sun Y, Liu Y, Zhao J, Liu Q, Xu J, Qin Y, He R, Yuan F, Wu T, Duan C, Jiang L, Lu H, Hu J (2023) Targeted delivery of RGD-CD146(+)CD271(+) human umbilical cord mesenchymal stem cell-derived exosomes promotes blood-spinal cord barrier repair after spinal cord injury. ACS Nano 17:18008���18024.
  144. Xu ZX, Zhang LQ, Zhou YN, Chen XM, Xu WH (2020) Histological and functional outcomes in a rat model of hemisected spinal cord with sustained VEGF/NT-3 release from tissue-engineered grafts. Artif Cells Nanomed Biotechnol 48:362���376.
  145. Xue X, Wu X, Fan Y, Han S, Zhang H, Sun Y, Yin Y, Yin M, Chen B, Sun Z, Zhao S, Zhang Q, Liu W, Zhang J, Li J, Shi Y, Xiao Z, Dai J, Zhao Y (2024) Heterogeneous fibroblasts contribute to fibrotic scar formation after spinal cord injury in mice and monkeys. Nat Commun 15:6321.
  146. Yang Y, Fan Y, Zhang H, Zhang Q, Zhao Y, Xiao Z, Liu W, Chen B, Gao L, Sun Z, Xue X, Shu M, Dai J (2021) Small molecules combined with collagen hydrogel direct neurogenesis and migration of neural stem cells after spinal cord injury. Biomaterials 269:120479.
  147. Yang Z, Zhang A, Duan H, Zhang S, Hao P, Ye K, Sun YE, Li X (2015) NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury. Proc Natl Acad Sci U S A 112:13354���13359.
  148. Yao M, Li J, Zhang J, Ma S, Wang L, Gao F, Guan F (2021) Dual-enzymatically cross-linked gelatin hydrogel enhances neural differentiation of human umbilical cord mesenchymal stem cells and functional recovery in experimental murine spinal cord injury. J Mater Chem B 9:440���452.
  149. Yao S, Liu X, Yu S, Wang X, Zhang S, Wu Q, Sun X, Mao H (2016) Co-effects of matrix low elasticity and aligned topography on stem cell neurogenic differentiation and rapid neurite outgrowth. Nanoscale 8:10252���10265.
  150. Yao Y, Yan J, Jiang F, Zhang S, Qiu J (2020) Comparison of anterior and posterior decompressions in treatment of traumatic thoracolumbar spinal fractures complicated with spinal cord injury. Med Sci Monit 26:e927284.
  151. Yin P, Liang W, Han B, Yang Y, Sun D, Qu X, Hai Y, Luo D (2024) Hydrogel and nanomedicine-based multimodal therapeutic strategies for spinal cord injury. Small Methods 8:e2301173.
  152. You Z, Gao X, Kang X, Yang W, Xiong T, Li Y, Wei F, Zhuang Y, Zhang T, Sun Y, Shen H, Dai J (2023) Microvascular endothelial cells derived from spinal cord promote spinal cord injury repair. Bioact Mater 29:36���49.
  153. Yuan T, Shao Y, Zhou X, Liu Q, Zhu Z, Zhou B, Dong Y, Stephanopoulos N, Gui S, Yan H, Liu D (2021) Highly permeable DNA supramolecular hydrogel promotes neurogenesis and functional recovery after completely transected spinal cord injury. Adv Mater 33:e2102428.
  154. Yuan T, Wang T, Zhang J, Liu P, Xu J, Gu Z, Xu J, Li Y (2023) Robust and multifunctional nanoparticles assembled from natural polyphenols and metformin for efficient spinal cord regeneration. ACS Nano 17:18562���18575.
  155. Zeng X, Wei QS, Ye JC, Rao JH, Zheng MG, Ma YH, Peng LZ, Ding Y, Lai BQ, Li G, Cheng SX, Ling EA, Han I, Zeng YS (2023) A biocompatible gelatin sponge scaffold confers robust tissue remodeling after spinal cord injury in a non-human primate model. Biomaterials 299:122161.
  156. Zhai H, Zhou J, Xu J, Sun X, Xu Y, Qiu X, Zhang C, Wu Z, Long H, Bai Y, Quan D (2020) Mechanically strengthened hybrid peptide-polyester hydrogel and potential applications in spinal cord injury repair. Biomed Mater 15:055031.
  157. Zhang J, Li X, Guo L, Gao M, Wang Y, Xiong H, Xu T, Xu R (2024a) 3D hydrogel microfibers promote the differentiation of encapsulated neural stem cells and facilitate neuron protection and axon regrowth after complete transactional spinal cord injury. Biofabrication 16:035015.
  158. Zhang M, Bai Y, Xu C, Lin J, Jin J, Xu A, Lou JN, Qian C, Yu W, Wu Y, Qi Y, Tao H (2021) Novel optimized drug delivery systems for enhancing spinal cord injury repair in rats. Drug Deliv 28:2548���2561.
  159. Zhang Q, Shi B, Ding J, Yan L, Thawani JP, Fu C, Chen X (2019) Polymer scaffolds facilitate spinal cord injury repair. Acta Biomater 88:57���77.
  160. Zhang S, Li Q, Zhang S (2023) Neural regeneration ability of Polypyrrole-Collagen-Quercetin composite in the spinal cord injury. Regen Ther 24:85���93.
  161. Zhang X, Liu H (2022) A commentary on ���Comparative analysis of the efficacy of early and late surgical intervention for acute spinal cord injury: a systematic review and meta-analysis based on 16 studies��� [Int. J. Surg. 94 (2021) 106098]. Int J Surg 101:106606.
  162. Zhang X, Meng L, Lu Q (2009) Cell behaviors on polysaccharide-wrapped single-wall carbon nanotubes: a quantitative study of the surface properties of biomimetic nanofibrous scaffolds. ACS Nano 3:3200���3206.
  163. Zhang Y, Wang J, Yang C, Geng H, Li Z, Zhao K, Wang Z, Li Z, Han J, Shao Y, Xia J, Li J, Sun L, Cui J, Sun F, Ni S (2024b) Polyphenol-integrated carboxymethyl chitosan hydrogels with immunoregulatory properties remodeling of inflammatory microenvironment for spinal cord injury repair. Chem Eng J 484:149522.
  164. Zhao H, Xiong T, Chu Y, Hao W, Zhao T, Sun X, Zhuang Y, Chen B, Zhao Y, Wang J, Chen Y, Dai J (2024) Biomimetic dual-network collagen fibers with porous and mechanical cues reconstruct neural stem cell niche via AKT/YAP mechanotransduction after spinal cord injury. Small 20:e2311456.
  165. Zhao X, Lu X, Li K, Song S, Luo Z, Zheng C, Yang C, Wang X, Wang L, Tang Y, Wang C, Liu J (2023) Double crosslinked biomimetic composite hydrogels containing topographical cues and WAY-316606 induce neural tissue regeneration and functional recovery after spinal cord injury. Bioact Mater 24:331���345.
  166. Zheng B, Tuszynski MH (2023) Regulation of axonal regeneration after mammalian spinal cord injury. Nat Rev Mol Cell Biol 24:396���413.
  167. Zheng G, Yu W, Xu Z, Yang C, Wang Y, Yue Z, Xiao Q, Zhang W, Wu X, Zang F, Wang J, Wang L, Yuan WE, Hu B, Chen H (2024) Neuroimmune modulating and energy supporting nanozyme-mimic scaffold synergistically promotes axon regeneration after spinal cord injury. J Nanobiotechnology 22:399.
  168. Zhou H, Li Z, Jing S, Wang B, Ye Z, Xiong W, Liu Y, Liu Y, Xu C, Kumeria T, He Y, Ye Q (2024) Repair spinal cord injury with a versatile anti-oxidant and neural regenerative nanoplatform. J Nanobiotechnology 22:351.
  169. Zhou LY, Tian ZR, Yao M, Chen XQ, Song YJ, Ye J, Yi NX, Cui XJ, Wang YJ (2019a) Riluzole promotes neurological function recovery and inhibits damage extension in rats following spinal cord injury: a meta-analysis and systematic review. J Neurochem 150:6���27.
  170. Zhou T, Zheng Y, Sun L, Badea SR, Jin Y, Liu Y, Rolfe AJ, Sun H, Wang X, Cheng Z, Huang Z, Zhao N, Sun X, Li J, Fan J, Lee C, Megraw TL, Wu W, Wang G, Ren Y (2019b) Microvascular endothelial cells engulf myelin debris and promote macrophage recruitment and fibrosis after neural injury. Nat Neurosci 22:421���435.
  171. Zhu X, Vo C, Taylor M, Smith BR (2019) Non-spherical micro- and nanoparticles in nanomedicine. Mater Horiz 6:1094���1121.
  172. Zuo Y, Ye J, Cai W, Guo B, Chen X, Lin L, Jin S, Zheng H, Fang A, Qian X, Abdelrahman Z, Wang Z, Zhang Z, Chen Z, Yu B, Gu X, Wang X (2023) Controlled delivery of a neurotransmitter-agonist conjugate for functional recovery after severe spinal cord injury. Nat Nanotechnol 18:1230���1240.
  173. Zweckberger K, Ahuja CS, Liu Y, Wang J, Fehlings MG (2016) Self-assembling peptides optimize the post-traumatic milieu and synergistically enhance the effects of neural stem cell therapy after cervical spinal cord injury. Acta Biomater 42:77���89.
Journal Article

Word Cloud

Created with Highcharts 10.0.0cordspinalinjuryscaffoldstreatmentfactorsstrategiesapproachesrepairtissuegrowthreviewregenerationrecoveryprognosisunderlyingmechanismsefficacyengineeringnanodeliverysystemsbiomaterialsstemthree-dimensionalbiomaterialalsopropertiesaxonusedapplicationclinicaldiscussesEnhancingneurologicalimprovinggainedresearchattentionrecentlySpinalassociatedcomplexmolecularcellularmicroenvironmentcomplexitypromptedresearcherselucidatepathophysiologicalchangesidentifyeffectiveTraditionalincludesurgeryoralintravenousmedicationsadministrationneurotrophichoweverremainsinconclusiveseriousadversereactionscontinueconcernadvancementsregenerativemedicineemergingnowinvolvenanoparticle-basedfunctionaltechniquesincorporatebioengineeringcellwellbioprintingIdealprovidestructuralsupportneuronmigrationadhesionproliferationdifferentiationmimicmechanicalnaturalAdditionallyfacilitateneurogenesisofferingadjustabletopographyrangephysicalbiochemicalcuesthree-dimensionallyinterconnectedporousstructureappropriatephysicochemicalenabledbiomimeticprintingtechnologycanmaximizepotentialtreatingThereforecorrectselectioncoupledsuccessfultranslationrepresentpromisingobjectivesenhanceelucidateskeyoccurrencepost-injuryincludingneuroinflammationoxidativestressangiogenesisbrieflycriticalroleinjuredhighlightinginfluencenanoparticlesaffectdeliveryefficiencyFinallyhighlightsvarioustypesintegrationscellsoptimizationscaffolddesignBiomaterial-basedstrategies:newera

Similar Articles

Cited By