Coaxial nanofibrous scaffolds mimicking the extracellular matrix transition in the wound healing process promoting skin regeneration through enhancing immunomodulation
Coaxial nanofibrous scaffolds mimicking the extracellular matrix transition in the wound healing process promoting skin regeneration through enhancing immunomodulation
复制标题
DOI：
10.1039/d0tb01933j
复制
发表时间：
2021-02-07
影响因子：
7
通讯作者：
Chen, Xiaofeng
中科院分区：
文献类型：
--
作者：
Sun, Luyao;Li, Jing;Chen, Xiaofeng
大量研究表明，与细胞外基质（ECM）蛋白结合的支架可以调节细胞行为并改善伤口愈合。然而，大多数包含 ECM 的支架无法捕获原生 ECM 的动态特征。在这方面，模拟伤口愈合过程中ECM成分转变的纳米纤维支架可能在通过动态调节微环境促进皮肤再生方面具有巨大潜力。在此，我们报告了一种用于修复慢性伤口的新型皮肤 ECM 仿生同轴纳米纤维支架。纤维蛋白原和 I 型胶原蛋白这两种必需的 ECM 蛋白分别被纳入纳米纤维的外壳和核心中，以模拟纤维蛋白原和 I 型胶原蛋白在伤口愈合过程中的顺序出现。将仿生同轴支架对脂肪间充质基质细胞（ASC）的调节与 PLGA/纤维蛋白原、PLGA/胶原蛋白 I 和 PLGA 单轴支架进行比较。我们的结果表明，仿生同轴支架显着促进 ASC 的免疫调节旁分泌分泌。通过用 ASC 条件培养基孵育巨噬细胞，巨噬细胞 M1 至 M2 极化的增强证实了仿生同轴支架上 ASC 免疫调节的增强。此外，仿生同轴支架通过解决糖尿病大鼠的炎症，有效促进伤口修复。这些发现有助于揭示动态 ECM 变化在调节伤口愈合中的作用，并表明仿生同轴支架作为治疗慢性伤口的有前途的替代方案的潜在用途。
Numerous studies have shown that scaffolds incorporated with extracellular matrix (ECM) proteins could regulate cell behaviors and improve wound healing. However, most ECM-containing scaffolds fail to capture the dynamic features of the native ECM. In this regard, nanofibrous scaffolds which mimic the composition transition of the ECM during wound healing may have great potential in promoting skin regeneration through dynamically modulating the microenvironment. Herein, we report a novel skin ECM-biomimetic coaxial nanofibrous scaffold for the repair of chronic wounds. Two essential ECM proteins, fibrinogen and collagen I, were incorporated into the shell and the core of nanofibers, respectively, to mimic the sequential appearance of fibrinogen and collagen I in the wound healing process. The regulation of the biomimetic coaxial scaffolds on adipose-derived mesenchymal stromal cells (ASCs) was compared with that of the PLGA/fibrinogen, PLGA/collagen I and PLGA uniaxial scaffolds. Our results showed that the biomimetic coaxial scaffolds remarkably promoted the immunomodulatory paracrine secretion of ASCs. By incubating macrophages with ASC conditioned medium, the enhanced immunomodulation of ASCs on the biomimetic coaxial scaffolds was confirmed by the enhanced M1-to-M2 polarization of macrophages. Furthermore, the biomimetic coaxial scaffolds effectively promoted wound repair through resolving inflammation in diabetic rats. These findings helped reveal the role of the dynamic ECM change in regulating wound healing and suggest the potential utility of the biomimetic coaxial scaffolds as a promising alternative to treat chronic wounds.