Sustained release of inhibitor from bionic scaffolds for wound healing and functional regeneration.
Sustained release of inhibitor from bionic scaffolds for wound healing and functional regeneration.
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DOI：
10.1039/d0bm00929f
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发表时间：
2020-10
影响因子：
6.6
通讯作者：
Jifang Yuan;Qian Hou;Lingzhi Zhong;Xin Dai;Q. Lu;Meirong Li;Xiaobing Fu
中科院分区：
文献类型：
--
作者：
Jifang Yuan;Qian Hou;Lingzhi Zhong;Xin Dai;Q. Lu;Meirong Li;Xiaobing Fu
小分子在促进组织再生中发挥着重要作用，但受其爆发释放的限制。去铁胺（DFO）等小分子从蚕丝水凝胶中缓慢释放，刺激血管生成和伤口愈合，但未能实现皮肤的功能恢复。各种生物活性分子需要通过控制其释放行为来创造一个合适的生态位，以更好地实现皮肤再生。本研究将GSK-3抑制剂SB216763小分子负载于丝素纳米纤维（SNF）上，与壳聚糖（CS）混合制备小分子负载复合仿生支架（CSNF-SB）。考虑到SNF与SB216763的相互作用，SNF和CSNF-SB复合支架均实现了SB216763 21天以上的缓释。与无药CSNF支架相比，CSNF- sb具有更好的细胞粘附能力和增殖能力，表明其具有生物活性。β-catenin在体外成纤维细胞中表达上调，表明释放的小分子在复合支架中保持了其功能。载药支架可实现更快、更好的伤口愈合，明显优于无药支架。与dfo负载的丝水凝胶系统不同，在药物负载支架处理的伤口中也发现了毛囊新生，显示出功能恢复。因此，丝纳米纤维作为不同生物活性小分子的多功能载体，可用于制备具有优化壁龛的支架，从而实现组织的功能恢复。小分子负载仿生支架在皮肤组织再生中具有广阔的应用前景。
Small molecules play remarkable roles in promoting tissue regeneration, but are limited by their burst release. Small molecules such as deferoxamine (DFO) have been released slowly from silk hydrogels and stimulated angiogenesis and wound healing, but failed to achieve functional recovery of skin. Various bioactive molecules are required to create a suitable niche for better skin regeneration by controlling their release behaviors. Herein, a small molecule SB216763, a GSK-3 inhibitor, was loaded on silk fibroin nanofibers (SNF), and then mixed with chitosan (CS) to prepare the small molecule-loaded composite bionic scaffolds (CSNF-SB). Given the interaction of SNF and SB216763, the sustained release of SB216763 for more than 21 days was achieved for SNF and CSNF-SB composite scaffolds. Compared to drug-free CSNF scaffolds, CSNF-SB showed better cell adhesion and proliferation capacity, suggesting bioactivity. The upregulated expression of β-catenin in fibroblasts in vitro revealed that the released small molecules maintained their function in composite scaffolds. Quicker and better wound healing was realized with the drug-loaded scaffolds, which was significantly superior to that treated with drug-free scaffolds. Unlike the DFO-loaded silk hydrogel system, hair follicle neogenesis was also found in the drug-loaded-scaffold treatment wounds, demonstrating functional recovery. Therefore, silk nanofibers as versatile carriers for different small bioactive molecules could be used to fabricate scaffolds with optimized niches and then achieve functional recovery of tissues. The small molecule-loaded bionic scaffolds have a promising future in skin tissue regeneration.