Naturally derived extracellular matrix scaffolds can effectively promote tissue repair and regeneration due to their remarkable bioactivity. However, their rapid degradation leads to the decrease of mechanical retention and the failure of physical support in vivo which limit their applications. In this paper, we modified a classic extracellular matrix scaffold – small intestinal submucosa (SIS) – by a silk fibroin (SF) layer-by-layer (LbL) assembly to replace the existing chemical crosslinking methods for improving its mechanical and structural stability. Experimental results showed that the SF LbL surface functionalized SIS scaffold had tunable mechanical properties and degradation rate by adjusting the number of layers of the SF deposited on the surface. For biological responses, in vitro NIH3T3 fibroblast culture studies demonstrated that SF surface modification did not affect the excellent biocompatibility of the SIS. In vivo subcutaneous implantation results showed that the SF modification could effectively extend the residence time of the SIS in the body, and elicit a more moderate inflammatory response compared to the traditional glutaraldehyde chemical crosslinking. Furthermore, we found that SF modification could maintain the ability of bioactive components of the SIS to regulate the transformation of M1 into M2 in macrophages in vivo. This SF LbL modification strategy offers a green process for the development of high-performance extracellular matrix-based scaffolds with tunable biodegradability.

中文翻译：

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丝绸的逐层表面修饰对细胞外基质支架的机械和结构保留的影响。

天然来源的细胞外基质支架由于其卓越的生物活性，可以有效地促进组织修复和再生。然而，它们的快速降解导致机械保留力的降低和体内物理支持的失败，这限制了它们的应用。在本文中，我们通过丝素蛋白（SF）逐层（LbL）组装修改了经典的细胞外基质支架-小肠粘膜下层（SIS），以取代现有的化学交联方法以改善其机械和结构稳定性。实验结果表明，通过调节沉积在表面上的SF层数，SF LbL表面官能化SIS支架具有可调的机械性能和降解速率。对于生物反应，体外NIH3T3成纤维细胞培养研究表明，SF表面修饰不会影响SIS的出色生物相容性。体内皮下植入的结果表明，与传统的戊二醛化学交联相比，SF修饰可以有效延长SIS在体内的停留时间，并引起更适度的炎症反应。此外，我们发现SF修饰可以维持SIS的生物活性成分调节体内巨噬细胞中M1向M2转化的能力。SF LbL修饰策略为开发具有可调节生物降解性的高性能细胞外基质基支架提供了绿色过程。