State Key Laboratory of Metal Matrix Composites, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.
School of Physical Science and Technology, Shanghai Tech University, Shanghai, 201210, P. R. China.
Adv Healthc Mater. 2023 Nov;12(28):e2301310. doi: 10.1002/adhm.202301310. Epub 2023 Aug 11.
Uncontrollable blood loss poses fatality risks and most recently developed sealants still share common limitations on controversial components, degradability, mechanical strength or gelation time. Herein, series of injectable sealants based on silk fibroin (SF) is developed. Random coil/β-sheet conformation transition in SF is achieved by forming dendritic intermediates under induction of the structurally compatible and chemically complementary assembly peptide (Ac-KAEA-KAEA-KAEA-KAEA-NH , KA ). A ratio of 1:5 (KA-SF-15) shown an accelerating gelation process (≈12 s) and enhanced mechanical strength at physiological conditions. The interweaved nanofibers effectively impeded the bleeding within 30 s and no obvious adverse effects are observed. The supramolecular interactions and in vivo degradation benefit the inflammatory host cells infiltration and cytokines diffusion. Without any exogenous factors, the increased expression of VEGF and PDGF led to a positive feedback regulation on fibroblasts and vascular endothelial cell growth/proliferation and promoted the wound healing. These findings indicated the few assembly-peptide can accelerate fibroin gelation transition at a limited physiological condition, and the injectable amino acid-based sealants show obvious advantages on biocompatibility, degradability, rapid gelation and matched strength, with strong potential to act as next generation of biomedical materials.
无法控制的出血会带来致命风险,而最近开发的密封剂在有争议的成分、可降解性、机械强度或胶凝时间方面仍然存在共同的局限性。在此,开发了一系列基于丝素蛋白(SF)的可注射密封剂。通过在结构相容且化学互补的组装肽(Ac-KAEA-KAEA-KAEA-KAEA-NH ,KA )诱导下形成树枝状中间物,实现 SF 中无规卷曲/β-折叠构象转变。比例为 1:5(KA-SF-15)显示出加速的胶凝过程(≈12 s)和在生理条件下增强的机械强度。交织的纳米纤维可在 30 s 内有效阻止出血,且未观察到明显的不良反应。超分子相互作用和体内降解有利于炎症宿主细胞的浸润和细胞因子的扩散。在没有任何外源性因素的情况下,VEGF 和 PDGF 的表达增加导致成纤维细胞和血管内皮细胞生长/增殖的正反馈调节,并促进伤口愈合。这些发现表明,少量的组装肽可以在有限的生理条件下加速丝素蛋白的胶凝转变,而可注射的基于氨基酸的密封剂在生物相容性、可降解性、快速胶凝和匹配强度方面具有明显优势,具有作为下一代生物医学材料的强大潜力。