中国组织工程研究 ›› 2022, Vol. 26 ›› Issue (28): 4562-4568.doi: 10.12307/2022.314
• 生物材料综述 biomaterial review • 上一篇 下一篇
赵兴昌1,2 ,宋世强1,何 峰1 ,唐毓金3,刘 佳3
收稿日期:
2021-02-05
接受日期:
2021-04-10
出版日期:
2022-10-08
发布日期:
2022-03-24
通讯作者:
刘佳,博士,教授,主任医师,硕士生导师,右江民族医学院附属医院,广西壮族自治区百色市 533000
作者简介:
赵兴昌,男,1982年生,河北省邯郸市人,汉族,硕士,主治医师,主要从事脊柱脊髓损伤、组织工程材料的研究。
基金资助:
Zhao Xingchang1, 2, Song Shiqiang1, He Feng1, Tang Yujin3, Liu Jia3
Received:
2021-02-05
Accepted:
2021-04-10
Online:
2022-10-08
Published:
2022-03-24
Contact:
Liu Jia, MD, Professor, Chief physician, Master’s supervisor, Affilialted Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
About author:
Zhao Xingchang, Master, Attending physician, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China; Handan Hospital of Traditional Chinese Medicine, Handan 056000, Hebei Province, China
Supported by:
摘要:
文题释义:
生物材料:是用于与生命系统接触和发生相互作用,并能对其细胞、组织和器官进行诊断治疗、替换修复或诱导再生的一类天然或人工合成的特殊功能材料,又称生物医用材料。
脱细胞脊髓支架:是将从实验动物体内获取的脊髓,经化学脱细胞、物理洗涤、超声、冰融及混合方法处理去除脊髓神经细胞,经冰冻干燥所得的多孔脱细胞支架。
背景:由于脊髓损伤后神经神经再生能力弱,修复受损脊髓组织并使其实现功能正常化仍是目前医学难题。生物组织材料学的快速发展以及其在医学中广泛应用为脊髓损伤修复提供了新的治疗理念和方法。
目的:总结生物材料支架对脊髓损伤后神经组织再生修复研究并对其发展趋势进行展望,以探讨修复脊髓损伤的方法并总结经验。
方法:应用PubMed数据库高级检索功能,检索 2011年1月至2021年1月的文献,检索词为“Spinal cord injury;Biomaterials;Nerve regeneration;Material”; 应用知网、万方、维普等数据库高级检索功能,检索2011年1月至2021年1月的相关文献,检索词为“脊髓损伤;生物材料;支架”。
结果与结论:随着生物工程研究和医学结合的进一步深入,生物材料支架已被广泛应用于脊髓损伤修复的研究,生物材料的组织相容性、降解性等方面均有了改善;生物材料种类较多,各有其利弊,取其优点制备成复合支架并负载种子细胞、细胞因子或药物对神经再生效果更佳。但复合支架如何选择材料组合,如何选择种子细胞、细胞因子或药物,使生物材料支架联合种子细胞、细胞因子或药物成为最佳组合值得深入研究。总之,生物材料修复脊髓损伤是一个新思路,可能成为促进脊髓损伤修复的突破点。
https://orcid.org/0000-0002-7264-1988(赵兴昌)
中国组织工程研究杂志出版内容重点:生物材料;骨生物材料;口腔生物材料;纳米材料;缓释材料;材料相容性;组织工程
中图分类号:
赵兴昌, 宋世强, 何 峰, 唐毓金, 刘 佳. 生物材料支架在治疗脊髓损伤中的应用[J]. 中国组织工程研究, 2022, 26(28): 4562-4568.
Zhao Xingchang, Song Shiqiang, He Feng, Tang Yujin, Liu Jia. Application of biomaterial scaffolds in the treatment of spinal cord injury[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(28): 4562-4568.
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[1] AHUJA CS, NORI S, TETREAULT L, et al. Traumatic Spinal Cord Injury-Repair and Regeneration. Neurosurgery. 2017;80(3s):S9-s22.
[2] WU J, LIPINSKI MM. Autophagy in Neurotrauma: Good, Bad, or Dysregulated. Cells. 2019;8(7):693.
[3] FAN B, WEI Z, YAO X, et al. Microenvironment Imbalance of Spinal Cord Injury. Cell Transplant. 2018;27(6):853-866.
[4] COFANO F, BOIDO M, MONTICELLI M, et al. Mesenchymal Stem Cells for Spinal Cord Injury: Current Options, Limitations, and Future of Cell Therapy. Int J Mol Sci. 2019;20(11):2698.
[5] 刘佳.脊髓脱细胞支架复合人脐血间充质干细胞促进大鼠脊髓长节段缺损轴突长入再生及功能恢复[D].广州:南方医科大学,2013.
[6] KATOH H, YOKOTA K, FEHLINGS MG. Regeneration of Spinal Cord Connectivity Through Stem Cell Transplantation and Biomaterial Scaffolds. Front Cell Neurosci. 2019;13:248.
[7] LI X, LIU D, XIAO Z, et al. Scaffold-facilitated locomotor improvement post complete spinal cord injury: Motor axon regeneration versus endogenous neuronal relay formation. Biomaterials. 2019;197:20-31.
[8] DEAL DN, GRIFFIN JW, HOGAN MV. Nerve conduits for nerve repair or reconstruction. J Am Acad Orthop Surg. 2012;20(2):63-68.
[9] CHEN JC, LI LM, GAO JQ. Biomaterials for local drug delivery in central nervous system. Int J Pharm. 2019;560:92-100.
[10] ZHANG J, YUN S, BI J, et al. Enhanced multi-lineage differentiation of human mesenchymal stem/stromal cells within poly(N-isopropy lacrylamide-acrylic acid) microgel-formed three-dimensional constructs. J Mater Chem B Mater Biol Med. 2018;6(12):1799-1814.
[11] OLIVEIRA MB, RIBEIRO MP, MIGUEL SP, et al. In vivo high-content evaluation of three-dimensional scaffolds biocompatibility. Tissue Eng Part C Methods. 2014;20(11):851-864.
[12] ZHOU HL, ZHANG XJ, ZHANG MY, et al. Transplantation of Human Amniotic Mesenchymal Stem Cells Promotes Functional Recovery in a Rat Model of Traumatic Spinal Cord Injury. Neurochem Res. 2016; 41(10):2708-2718.
[13] WANG M, ZHAI P, CHEN X, et al.Bioengineered scaffolds for spinal cord repair. Tissue Eng Part B Rev. 2011;17(3):177-194.
[14] LANG BT, CREGG JM, DEPAUL MA, et al. Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury. Nature. 2015; 518(7539):404-408.
[15] JIANG T, REN XJ, TANG JL, et al. Preparation and characterization of genipin-crosslinked rat acellular spinal cord scaffolds. Mater Sci Eng C Mater Biol Appl. 2013;33(6):3514-3521.
[16] WANG YH, CHEN J, ZHOU J, et al. Reduced inflammatory cell recruitment and tissue damage in spinal cord injury by acellular spinal cord scaffold seeded with mesenchymal stem cells. Exp Ther Med. 2017;13(1):203-207.
[17] BAN DX, LIU Y, CAO TW, et al. The preparation of rat’s acellular spinal cord scaffold and co-culture with rat’s spinal cord neuron in vitro. Spinal Cord. 2017;55(4):411-418.
[18] LIU J, LI K, ZHOU J, et al. Bisperoxovanadium induces M2-type macrophages and promotes functional recovery after spinal cord injury. Mol Immunol. 2019;116:56-62.
[19] XING H, REN X, YIN H, et al. Construction of a NT-3 sustained-release system cross-linked with an acellular spinal cord scaffold and its effects on differentiation of cultured bone marrow mesenchymal stem cells. Mater Sci Eng C Mater Biol Appl. 2019;104:109902.
[20] XU HL, TIAN FR, LU CT, et al. Thermo-sensitive hydrogels combined with decellularised matrix deliver bFGF for the functional recovery of rats after a spinal cord injury. Sci Rep. 2016;6:38332.
[21] XU ZX, ZHANG LQ, WANG CS, et al. Acellular Spinal Cord Scaffold Implantation Promotes Vascular Remodeling with Sustained Delivery of VEGF in a Rat Spinal Cord Hemisection Model. Curr Neurovasc Res. 2017; 14(3):274-289.
[22] ZHAO F, GRAYSON WL, MA T, et al. Effects of hydroxyapatite in 3-D chitosan-gelatin polymer network on human mesenchymal stem cell construct development. Biomaterials. 2011;27(9):1859-1867.
[23] CHEDLY J, SOARES S, MONTEMBAULT A, et al. Physical chitosan microhydrogels as scaffolds for spinal cord injury restoration and axon regeneration. Biomaterials. 2017;138:91-107.
[24] NOMURA H, BALADIE B, KATAYAMA Y, et al. Delayed implantation of intramedullary chitosan channels containing nerve grafts promotes extensive axonal regeneration after spinal cord injury. Neurosurgery. 2008;63(1):141-143.
[25] YAO ZA, CHEN FJ, CUI HL, et al. Efficacy of chitosan and sodium alginate scaffolds for repair of spinal cord injury in rats. Neural Regen Res. 2018; 13(3):502-509.
[26] 刘东,朱冬昀,彭长亮,等.脊髓损伤修复的复合透明质酸水凝胶支架的构建及其评价[J].山东大学学报(医学版),2017,55(9):53-59.
[27] MUKHAMEDSHINA YO, AKHMETZYANOVA ER, KOSTENNIKOV AA, et al. Adipose-Derived Mesenchymal Stem Cell Application Combined With Fibrin Matrix Promotes Structural and Functional Recovery Following Spinal Cord Injury in Rats. Front Pharmacol. 2018;9:343.
[28] SHARP KG, DICKSON AR, MARCHENKO SA, et al.Salmon fibrin treatment of spinal cord injury promotes functional recovery and density of serotonergic innervation. Exp Neurol. 2012;235(1):345-356.
[29] YAO S, YU S, CAO Z, et al. Hierarchically aligned fibrin nanofiber hydrogel accelerated axonal regrowth and locomotor function recovery in rat spinal cord injury. Int J Nanomedicine. 2018;13:2883-2895.
[30] JALALI MONFARED M, NASIRINEZHAD F, EBRAHIMI-BAROUGH S, et al. Transplantation of miR-219 overexpressed human endometrial stem cells encapsulated in fibrin hydrogel in spinal cord injury. J Cell Physiol. 2019;234(10):18887-18896.
[31] CHEN X, ZHAO Y, LI X, et al. Functional Multichannel Poly(Propylene Fumarate)-Collagen Scaffold with Collagen-Binding Neurotrophic Factor 3 Promotes Neural Regeneration After Transected Spinal Cord Injury. Adv Healthc Mater. 2018;7(14):e1800315.
[32] WANG L, SHI Q, DAI J, et al. Increased vascularization promotes functional recovery in the transected spinal cord rats by implanted vascular endothelial growth factor-targeting collagen scaffold. J Orthop Res. 2018; 36(3):1024-1034.
[33] SHI Q, GAO W, HAN X, et al. Collagen scaffolds modified with collagen-binding bFGF promotes the neural regeneration in a rat hemisected spinal cord injury model. Sci China Life Sci. 2014;57(2):232-340.
[34] WANG N, XIAO Z, ZHAO Y, et al. Collagen scaffold combined with human umbilical cord-derived mesenchymal stem cells promote functional recovery after scar resection in rats with chronic spinal cord injury. J Tissue Eng Regen Med. 2018;12(2):e1154-e1163.
[35] FAN C, LI X, XIAO Z, et al. A modified collagen scaffold facilitates endogenous neurogenesis for acute spinal cord injury repair. Acta Biomater. 2017;51: 304-316.
[36] ZHOU X, SHI G, FAN B, et al. Polycaprolactone electrospun fiber scaffold loaded with iPSCs-NSCs and ASCs as a novel tissue engineering scaffold for the treatment of spinal cord injury. Int J Nanomedicine0 2018;13:6265-6277.
[37] ZHANG S, WANG XJ, LI WS, et al. Polycaprolactone/polysialic acid hybrid, multifunctional nanofiber scaffolds for treatment of spinal cord injury. Acta Biomater. 2018;77:15-27.
[38] BABALOO H, EBRAHIMI-BAROUGH S, DERAKHSHAN MA, et al. PCL/gelatin nanofibrous scaffolds with human endometrial stem cells/Schwann cells facilitate axon regeneration in spinal cord injury. J Cell Physiol. 2019;234(7): 11060-11069.
[39] TERRAF P, KOUHSARI SM, AI J, et al. Tissue-Engineered Regeneration of Hemisected Spinal Cord Using Human Endometrial Stem Cells, Poly ¦Å-C aprolactone Scaffolds, and Crocin as a Neuroprotective Agent. Mol Neurobiol. 2017;54(7):5657-5667.
[40] SHU B, LIU XB, ZHOU JF, et al. Polypyrrole/polylactic acid nanofibrous scaffold cotransplanted with bone marrow stromal cells promotes the functional recovery of spinal cord injury in rats. CNS Neurosci Ther. 2019; 25(9):951-964.
[41] SANTHOSH KT, ALIZADEH A, KARIMI-ABDOLREZAEE S. Design and optimization of PLGA microparticles for controlled and local delivery of Neuregulin-1 in traumatic spinal cord injury. J Control Release. 2017;261: 147-162.
[42] PAN S, QI Z, LI Q, et al. Graphene oxide-PLGA hybrid nanofibres for the local delivery of IGF-1 and BDNF in spinal cord repair. Artif Cells Nanomed Biotechnol. 2019;47(1):651-664.
[43] WEN Y, YU S, WU Y, et al. Spinal cord injury repair by implantation of structured hyaluronic acid scaffold with PLGA microspheres in the rat. Cell Tissue Res. 2016;364(1):17-28.
[44] WANG C, SUN C, HU Z, et al. Improved Neural Regeneration with Olfactory Ensheathing Cell Inoculated PLGA Scaffolds in Spinal Cord Injury Adult Rats. Neurosignals. 2017;25(1):1-14.
[45] CALDWELL AS, RAO VV, GOLDEN AC, et al. Porous bio-click microgel scaffolds control hMSC interactions and promote their secretory properties. Biomaterials. 2020;232:119725.
[46] SHI R. Polyethylene glycol repairs membrane damage and enhances functional recovery: a tissue engineering ap proach to spinal cord injury. Neurosci Bull. 2013;29(4):460-466.
[47] KIM CY. PEG-assisted reconstruction of the cervical spinal cord in rats: effects on motor conduction at 1h. Spinal Cord. 2016;54(10):910-912.
[48] 朱旭,于国渊,杨华堂,等.胶原-壳聚糖支架对脊髓损伤后运动功能恢复作用的实验研究[J].中国实用神经疾病杂志,2020,23(23):2032-2038.
[49] WANG C, YUE H, FENG Q, et al. Injectable Nanoreinforced Shape-Memory Hydrogel System for Regenerating Spinal Cord Tissue from Traumatic Injury. ACS Appl Mater Interfaces. 2018;10(35):29299-29307.
[50] HAN GH, KIM SJ, KO WK, et al. Injectable Hydrogel Containing Tauroursodeoxycholic Acid for Anti-neuroinflammatory Therapy After Spinal Cord Injury in Rats. Mol Neurobiol. 2020;57(10):4007-4017.
[51] 赵宣淇,张钰,秦川,等.神经营养因子-3基因修饰的骨髓间充质干细胞和水凝胶联合应用对脊髓损伤模型大鼠的治疗作用研究[J].中国比较医学杂志,2020,30(7):1-12.
[52] NAZEMI Z, NOURBAKHSH MS, KIANI S, et al. Co-delivery of minocycline and paclitaxel from injectable hydrogel for treatment of spinal cord injury. J Control Release. 2020;321:145-158.
[53] ALBASHARI A, HE Y, ZHANG Y, et al. Thermosensitive BFGF-Modified Hydrogel with Dental Pulp Stem Cells on Neuroinflammation of Spinal Cord Injury. ACS Omega. 2020;5(26):16064-16075.
[54] HU X, LI R, WU Y, et al. Thermosensitive heparin-poloxamer hydrogel encapsulated bFGF and NGF to treat spinal cord injury . J Cell Mol Med. 2020;24(14):8166-8178.
[55] 王维,齐社宁,赵红斌,等.地塞米松复合聚己内酯胶原支架材料的构建及性能评价[J].中国组织工程研究,2016,20(3):402-407.
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[32] WANG L, SHI Q, DAI J, et al. Increased vascularization promotes functional recovery in the transected spinal cord rats by implanted vascular endothelial growth factor-targeting collagen scaffold. J Orthop Res. 2018; 36(3):1024-1034.
[33] SHI Q, GAO W, HAN X, et al. Collagen scaffolds modified with collagen-binding bFGF promotes the neural regeneration in a rat hemisected spinal cord injury model. Sci China Life Sci. 2014;57(2):232-340.
[34] WANG N, XIAO Z, ZHAO Y, et al. Collagen scaffold combined with human umbilical cord-derived mesenchymal stem cells promote functional recovery after scar resection in rats with chronic spinal cord injury. J Tissue Eng Regen Med. 2018;12(2):e1154-e1163.
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[36] ZHOU X, SHI G, FAN B, et al. Polycaprolactone electrospun fiber scaffold loaded with iPSCs-NSCs and ASCs as a novel tissue engineering scaffold for the treatment of spinal cord injury. Int J Nanomedicine0 2018;13:6265-6277.
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[38] BABALOO H, EBRAHIMI-BAROUGH S, DERAKHSHAN MA, et al. PCL/gelatin nanofibrous scaffolds with human endometrial stem cells/Schwann cells facilitate axon regeneration in spinal cord injury. J Cell Physiol. 2019;234(7): 11060-11069.
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[44] WANG C, SUN C, HU Z, et al. Improved Neural Regeneration with Olfactory Ensheathing Cell Inoculated PLGA Scaffolds in Spinal Cord Injury Adult Rats. Neurosignals. 2017;25(1):1-14.
[45] CALDWELL AS, RAO VV, GOLDEN AC, et al. Porous bio-click microgel scaffolds control hMSC interactions and promote their secretory properties. Biomaterials. 2020;232:119725.
[46] SHI R. Polyethylene glycol repairs membrane damage and enhances functional recovery: a tissue engineering ap proach to spinal cord injury. Neurosci Bull. 2013;29(4):460-466.
[47] KIM CY. PEG-assisted reconstruction of the cervical spinal cord in rats: effects on motor conduction at 1h. Spinal Cord. 2016;54(10):910-912.
[48] 朱旭,于国渊,杨华堂,等.胶原-壳聚糖支架对脊髓损伤后运动功能恢复作用的实验研究[J].中国实用神经疾病杂志,2020,23(23):2032-2038.
[49] WANG C, YUE H, FENG Q, et al. Injectable Nanoreinforced Shape-Memory Hydrogel System for Regenerating Spinal Cord Tissue from Traumatic Injury. ACS Appl Mater Interfaces. 2018;10(35):29299-29307.
[50] HAN GH, KIM SJ, KO WK, et al. Injectable Hydrogel Containing Tauroursodeoxycholic Acid for Anti-neuroinflammatory Therapy After Spinal Cord Injury in Rats. Mol Neurobiol. 2020;57(10):4007-4017.
[51] 赵宣淇,张钰,秦川,等.神经营养因子-3基因修饰的骨髓间充质干细胞和水凝胶联合应用对脊髓损伤模型大鼠的治疗作用研究[J].中国比较医学杂志,2020,30(7):1-12.
[52] NAZEMI Z, NOURBAKHSH MS, KIANI S, et al. Co-delivery of minocycline and paclitaxel from injectable hydrogel for treatment of spinal cord injury. J Control Release. 2020;321:145-158.
[53] ALBASHARI A, HE Y, ZHANG Y, et al. Thermosensitive BFGF-Modified Hydrogel with Dental Pulp Stem Cells on Neuroinflammation of Spinal Cord Injury. ACS Omega. 2020;5(26):16064-16075.
[54] HU X, LI R, WU Y, et al. Thermosensitive heparin-poloxamer hydrogel encapsulated bFGF and NGF to treat spinal cord injury . J Cell Mol Med. 2020;24(14):8166-8178.
[55] 王维,齐社宁,赵红斌,等.地塞米松复合聚己内酯胶原支架材料的构建及性能评价[J].中国组织工程研究,2016,20(3):402-407.
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脊髓损伤是一种高致残率的损伤,多由暴力伤所致,表现为损伤节段以下感觉、运动和括约肌功能障碍等一系列临床病症。脊髓损伤后缺血缺氧,使溶酶体内容物过度释放及钙离子依赖的消化酶激活,导致脊髓神经元细胞进一步坏死,可在较短时间甚至数小时内使轴突发生变性、坏死[1];神经元细胞坏死后各种炎症因子的渗入、自噬启动等均会使微环境这种让细胞发挥正常生理功能的“土壤”发生改变[2-3]。因原发性损伤因素不可控,目前治疗集中在继发性损伤,包括减轻脊髓水肿、改善微环境、缩短继发损伤时间而减轻神经细胞进一步损伤。神经干细胞移植是较早应用的治疗手段,方法有移植、血管注射、鞘内注射等[4],对神经功能修复有一定的效果,但干细胞存活率低、缺乏有效支撑、细胞成团而不能定向生长,往往使得神经功能恢复有限[5]。
随着组织工程技术的快速发展,生物材料与医学结合为修复脊髓损伤提供了一个新的思路。生物材料支架修复受损脊髓损伤的机制大致有:可作为“桥梁”填补脊髓神经细胞液化坏死后形成的空腔,使两断端连接起来,同时能抑制胶质细胞生长[6];为神经细胞再生指明“方向”,避免无序并沿“桥梁”定向生长[7-8];作为“载体”可装载多种有利于神经生长的要素[9],如干细胞、神经营养因子、通过局部调控信号通路激发神经细胞分化与再生的药物及可提供理想微环境的水凝胶等[10]。生物材料主要有天然组织材料、人工合成材料、水凝胶等,各类材料有其自身特性。该综述将总结各类材料在脊髓损伤中的应用。
中国组织工程研究杂志出版内容重点:生物材料;骨生物材料;口腔生物材料;纳米材料;缓释材料;材料相容性;组织工程
1.4 数据的提取 共检索到 813 篇文献,其中中文文献174篇、英文文献639篇,排除重复、观点相似、与研究目的不同及质量不高的文献,最终收录55篇文献,其中中文文献 5 篇、英文文献 50 篇,见图1。
脊髓损伤后的功能恢复是世界性的医学难题之一,随着生物医学组织工程学的发展,生物材料支架被广泛应用在脊髓损伤修复领域,并取得了很多科研成果。生物材料支架治疗脊髓损伤的理念已形成,从分子、细胞层面考虑制备负载药物或神经生长因子支架,改善脊髓损伤区微环境,诱导神经轴突再生,抑制胶质瘢痕的形成。由于生物材料的多样性,研究集中在支架材料、种子细胞、生长因子的选择等方面。脊髓损伤模型主要有脊髓挫伤、脊髓半切、脊髓全横断等,将生物材料支架植入或注射到损伤区域,通过对动物术后肢体功能恢复及损伤区组织病理分析而评估治疗效果。因此,理想的生物材料支架应具备良好的组织相容性、合适机械的强度及降解速率、三维多孔结构,并可为神经细胞生长提供“桥梁”作用。各类生物材料的特性不同:①天然生物材料主要有脱细胞脊髓支架、胶原、纤维蛋白、透明质酸、壳聚糖等,该类生物材料优点主要是组织相容性好、能改善局部微环境、降解产物无炎症反应,但存在机械强度小、降解速度快、吸水膨胀后支架塌陷致使三维多孔结构等缺点,不能满足神经轴突再生及定向生长。②人工合成生物材料主要有聚己内酯、聚乳酸、聚乳酸-聚羟基乙酸、聚乙二醇等,这类材料的主要优点是机械强度、降解速率可调,能满足神经轴突再生所需时间及定向生长的需要,且具备三维多孔结构,为细胞生长提供空间;缺点是降解产物产生局部炎症反应而破坏局部微环境,细胞成活率低或不利于生长,这类材料对细胞亲和力弱,多需要与天然材料制备成复合支架而使细胞与材料黏附,进一步诱导神经轴突再生。③水凝胶目前已成为研究热点,被广泛应用在脊髓损伤修复领域,可以多种材料为原料制作而成。水凝胶具有三维多孔网状结构,在吸水后膨胀率较高,可为神经干细胞分化、再生、繁殖提供微环境,使环境类似细胞外基质,使细胞更好地黏附并生长;同时具有较好的组织相容性,并可控制降解率;可单独应用或作为载体,载入细胞、药物、神经生长因子等,通过调控某个通路而促进轴突再生,修复脊髓损伤。
目前生物材料支架治疗脊髓损伤已基本形成共识,从单一材料到复合材料,能弥补单一材料的不足,如胶原蛋白/聚己内酯复合支架[55],可以利用胶原蛋白细胞亲和力好来弥补聚已内酯细胞亲和力弱的缺点,而聚己内酯机械强度好能弥补胶原蛋白力学性能差、易变形的缺点。单一支架或复合支架负载种子细胞、细胞因子、药物较单独应用支架对脊髓损伤的修复效果佳,大部分研究倾向于这个观念,使脊髓损伤修复取得了很大进步。但现在面临的问题是支架材料、种子细胞、细胞因子、药物怎么组合才能达到最佳效果仍需深入研究。随着3D打印技术的普及和精细化,为生物材料治疗脊髓损伤增加了更多可能性。
脊髓损伤修复策略是将生物材料科学与细胞再生医学相结合,通过体内和体外实验来探索较好的治疗方案。各类生物材料支架各有其利弊,大部分研究采用制备复合支架来抵消材料自身的缺点,“复合支架+种子细胞+细胞因子+药物”研究方法较单一方法往往能取得更好的效果,而生物材料、种子细胞、细胞因子、药物的选择成为研究重点,随着研究的深入,相信未来会有更多的成果,为治疗脊髓损伤探索更好的治疗方案。
中国组织工程研究杂志出版内容重点:生物材料;骨生物材料;口腔生物材料;纳米材料;缓释材料;材料相容性;组织工程
文题释义:
生物材料:是用于与生命系统接触和发生相互作用,并能对其细胞、组织和器官进行诊断治疗、替换修复或诱导再生的一类天然或人工合成的特殊功能材料,又称生物医用材料。
脱细胞脊髓支架:是将从实验动物体内获取的脊髓,经化学脱细胞、物理洗涤、超声、冰融及混合方法处理去除脊髓神经细胞,经冰冻干燥所得的多孔脱细胞支架。
文章对各类生物材料进行了较为全面、系统的总结,从单一材料支架到复合支架,阐述了各自的优缺点及在脊髓损伤修复中的应用。在大量查阅文献的基础上,从实验研究论文中获得生物材料的理化性质。分析了目前生物材料治疗脊髓损伤的热点及总体思路,并对存在的困难及末来发展方向进行了说明。
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