Sericin, as the major component of Bombyx mori silk, is a useful biomaterial for tissue engineering due to its hydrophilicity, biocompatibility and biodegradability. Here, we report the fabrication of a human acidic fibroblast growth factor(FGF1)-functionalized sericin hydrogel using a transgenic silkworm spun silk with FGF1 incorporated in its sericin layer. Sericin, together with FGF1, were simultaneously extracted from the silk fiber and then exposed to cold-induced hydrogel formation without additional crosslinking. The fabricated FGF1 sericin hydrogels demonstrated injectability, useful mechanical properties and a porous microstructure, which contributed to cell adhesion and survival. In addition, FGF1 achieved long-term storage in the sericin hydrogels over a wide range of temperatures. Further, the sericin-FGF1 demonstrated sustained release to promote cell proliferation and wound healing. Furthermore, cellular inflammatory responses showed that the FGF1 sericin hydrogels exhibited biocompatibility and no immunogenicity. This study revealed the successful exploration of FGF1-functionalized sericin hydrogels as a new protein-based biomaterial to expand applications of FGF1 and sericin in tissue and medical engineering. Further, we demonstrated a strategy for the predesign of exogenous protein-functionalized sericin hydrogels through genetically modifying silk fibers as sources for their cost effective production at a large scale.

Statement of Significance

Sericin from the Bombyx mori silk, is regarded as a desirable biomaterial for tissue engineering due to its hydrophilicity, biocompatibility and biodegradability. Genetically engineering the sericin with functional exogenous proteins would enhance its biofunctions and further expand its application in tissue engineering. In this study, we demonstrated a method to fabricate a human acidic fibroblast growth factor(FGF1)-functionalized sericin hydrogel using a transgenic silkworm spun silk with FGF1 incorporated in its sericin layer. The fabricated FGF1 sericin hydrogels demonstrated injectability, porous microstructure, biocompatibility and no immunogenicity which contributed to cell adhesion and survival. Remarkably, FGF1 could achieve a long-term stability in the sericin hydrogels over a wide range of temperatures and sustained release to promote cell proliferation and wound healing. This study revealed the successful exploration of FGF1-functionalized sericin hydrogels as a new protein-based biomaterial in tissue and medical engineering application, and provided a strategy for the predesign of exogenous protein-functionalized sericin hydrogels through genetically modifying silk fibers as sources for their cost effective production at a large scale.

Sericin，作为家蚕的主要成分丝绸由于其亲水性，生物相容性和生物降解性，是用于组织工程的有用生物材料。在这里，我们报道了人类酸性成纤维细胞生长因子（FGF1）-功能的丝胶蛋白水凝胶的制造，该蛋白使用转基因蚕丝纺丝，丝胶层中掺入了FGF1。从丝纤维中同时提取丝胶和FGF1，然后暴露于冷诱导的水凝胶形成中，而无需另外的交联。制成的FGF1丝胶蛋白水凝胶具有可注射性，有用的机械性能和多孔微结构，可促进细胞粘附和存活。此外，FGF1可在很宽的温度范围内长期保存在丝胶水凝胶中。进一步，sericin-FGF1表现出持续释放，可促进细胞增殖和伤口愈合。此外，细胞炎症反应表明FGF1丝胶蛋白水凝胶表现出生物相容性，没有免疫原性。这项研究揭示了FGF1功能化的丝胶蛋白水凝胶作为一种新的基于蛋白质的生物材料的成功探索，以扩大FGF1和丝胶蛋白在组织和医学工程中的应用。此外，我们证明了通过遗传修饰丝纤维作为大规模低成本生产的来源，对外源蛋白质功能化丝胶蛋白水凝胶进行预设计的策略。这项研究揭示了FGF1功能化的丝胶蛋白水凝胶作为一种新的基于蛋白质的生物材料的成功探索，以扩大FGF1和丝胶蛋白在组织和医学工程中的应用。此外，我们证明了通过遗传修饰丝纤维作为大规模低成本生产的来源，对外源蛋白质功能化丝胶蛋白水凝胶进行预设计的策略。这项研究揭示了FGF1功能化的丝胶蛋白水凝胶作为一种新的基于蛋白质的生物材料的成功探索，以扩大FGF1和丝胶蛋白在组织和医学工程中的应用。此外，我们展示了一种通过遗传修饰蚕丝纤维作为大规模低成本生产的来源来预先设计外源蛋白质功能化丝胶蛋白水凝胶的策略。

重要声明

家蚕的丝胶蚕丝由于其亲水性，生物相容性和生物降解性而被认为是组织工程中理想的生物材料。用功能性外源蛋白对丝胶蛋白进行基因工程改造将增强其生物功能，并进一步扩大其在组织工程中的应用。在这项研究中，我们演示了一种使用转基因蚕丝纺丝技术，在其丝胶蛋白层中掺入FGF1的方法，以制备人酸性成纤维细胞生长因子（FGF1）功能化的丝胶蛋白水凝胶。所制备的FGF1丝胶蛋白水凝胶显示出可注射性，多孔微结构，生物相容性并且没有免疫原性，这有助于细胞粘附和存活。值得注意的是 FGF1可以在很宽的温度范围内在丝胶蛋白水凝胶中实现长期稳定性，并可以持续释放以促进细胞增殖和伤口愈合。这项研究揭示了FGF1功能化的丝胶蛋白水凝胶作为一种新的基于蛋白质的生物材料在组织和医学工程应用中的成功探索，并通过基因修饰丝纤维作为其成本来源，为外源蛋白功能化的丝胶蛋白水凝胶的预先设计提供了策略。大规模有效生产。