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    原位成胶型丝素蛋白基脊髓仿生水凝胶的构筑

    Fabrication of In Situ-Gelling Silk Fibroin-Based Biomimetic Hydrogel for Spinal Cord Repair

    • 摘要: 为获得原位凝胶时间适中、低模量且生物相容性佳的脊髓修复用水凝胶支架,以辣根过氧化物酶温和介导交联的丝素蛋白(SF)基水凝胶为基体,进一步利用酪胺接枝改性后的透明质酸(HA-Tyr)对SF基复合水凝胶进行改性和调控。综合考察不同HA-Tyr含量对SF基复合水凝胶的凝胶时间、压缩模量及细胞相容性的影响。结果表明:HA-Tyr含量升高会缩短复合水凝胶的凝胶时间,提升水凝胶的压缩模量。当SF与HA-Tyr在水凝胶反应体系中体积比为8:2时(S8H2组)为最优配方,凝胶时间符合手术植入窗口时间需求,且水凝胶模量特征亦可达到较好的脊髓组织仿生需求。在水凝胶表面培养的小鼠胚胎成纤维细胞(NIH3T3)的增殖能力随着水凝胶中HA-Tyr含量的提升大体呈现出先增加后减少的趋势,S8H2组表面培养细胞的活力最高。综合凝胶时间、压缩模量、细胞相容性等特征,S8H2组水凝胶展现出更优的综合性能,在脊髓损伤修复中有较大应用潜力。

       

      Abstract: To develop a hydrogel scaffold for spinal cord repair with appropriate in situ gelation time, low modulus, and good biocompatibility, a horseradish peroxidase (HRP)-mediated, mildly crosslinked silk fibroin (SF)-based hydrogel was used as the matrix material. This SF-based composite hydrogel was further modified and tuned by incorporating tyramine-grafted hyaluronic acid (HA-Tyr). The effects of different HA-Tyr contents on the gelation time, compressive modulus, and cytocompatibility of SF-based composite hydrogels were investigated. Results indicated that higher HA-Tyr content led to shorter gelation time and hi/gher compressive modulus of the composite hydrogels. The S8H2 formulation (volume ratio of SF to HA-Tyr is 8/2) exhibited a gelation time highly consistent with the surgical implantation window, and its modulus also met the biomimetic requirements for spinal cord tissue. The proliferation capacity of mouse embryonic fibroblasts (NIH3T3) cultured on the hydrogel surfaces generally displayed an initial increase followed by a decrease with rising HA-Tyr content, with cells on the S8H2 group showing the highest viability. Considering the gelation time, compressive modulus, and cytocompatibility collectively, the S8H2 hydroge demonstrated superior overall performance, showing promising potential for effective application in spinal cord injury repair.

       

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