Vascular Endothelial Growth Factor-Recruiting Nanofiber Bandages Promote Multifunctional Skin Regeneration via Improved Angiogenesis and Immunomodulation
Vascular Endothelial Growth Factor-Recruiting Nanofiber Bandages Promote Multifunctional Skin Regeneration via Improved Angiogenesis and Immunomodulation
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血管内皮生长因子招募纳米纤维绷带通过改善血管生成和免疫调节促进多功能皮肤再生
DOI：
10.1007/s42765-022-00226-8
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发表时间：
2022-11-14
影响因子：
16.1
通讯作者：
Chen, Chang
中科院分区：
文献类型：
--
作者：
Chen, Yi;Yuan, Zhengchao;Chen, Chang
组织损伤导致趋化因子的梯度，其驱动组织修复的多个过程，包括炎症反应以及内源性细胞募集。然而，化学引诱物的梯度的有限时间窗口以及它们在损伤部位的差的稳定性可能不会转化为健康的组织修复。因此，具有稳定损伤诱导的细胞因子和趋化因子的能力的智能多功能支架为组织修复带来了巨大的希望。血管内皮生长因子（VEGF）通过促进血管生成在创伤愈合中起重要作用。本研究的总体目标是开发智能多功能支架，具有内源性募集VEGF的能力，并通过血管生成和免疫调节双重功能促进伤口愈合。将Prominin-1衍生肽（PR 1 P）包封到基于静电纺丝的聚（L-丙交酯-共乙交酯）/明胶（P/G）绷带中。PR 1 P的持续释放原位募集VEGF，从而稳定体内蛋白浓度峰值，并在伤口部位提供具有足够血管生成能力的修复性微环境。同时，PR 1 P募集的VEGF诱导的巨噬细胞向M2样表型重编程进一步赋予绷带免疫调节功能。这些促血管生成和免疫调节的双重功能形成级联放大，通过VEGF/巨噬细胞/微环境轴调节伤口微环境中的基质金属蛋白酶（MMP-9）以及炎症因子（核因子（NF）-κ B、肿瘤坏死因子（TNF）-α）。因此，绷带在有或没有糖尿病的大鼠的夹板切除伤口中实现了多功能再生，提供了更高的皮肤附件新生、感觉功能和胶原蛋白重塑。总之，我们的方法包括在损伤部位原位招募VEGF，具有促进免疫调节介导的组织修复的能力，为无瘢痕伤口再生提供了一个有前途的途径，这也可能对其他组织工程学科产生影响。
Tissue injury leads to gradients of chemoattractants, which drive multiple processes for tissue repair, including the inflammatory response as well as endogenous cell recruitment. However, a limited time window for the gradients of chemoattractants as well as their poor stability at the injury site may not translate into healthy tissue repair. Consequently, intelligent multifunctional scaffolds with the capability to stabilize injury-induced cytokines and chemokines hold great promise for tissue repair. Vascular endothelial growth factor (VEGF) plays a significant role in wound healing by promoting angiogenesis. The overarching objective of this research was to develop intelligent multifunctional scaffolds with the capability to endogenously recruit VEGF and promote wound healing via angiogenic and immunomodulatory dual functions. Prominin-1-derived peptide (PR1P) was encapsulated into electrospun poly(L-lactide-coglycolide)/gelatin (P/G)-based bandages. The sustained release of PR1P recruited VEGF in situ, thereby stabilizing the protein concentration peak in vivo and affording a reparative microenvironment with an adequate angiogenic ability at the wound site. Meanwhile, PR1P-recruited VEGF-induced macrophage reprogramming towards M2-like phenotypes further conferred immunomodulatory functions to the bandages. These dual functions of proangiogenesis and immunomodulation formed a cascade amplification, which regulated matrix metalloproteinases (MMP-9) as well as inflammatory factors (nuclear factor (NF)-kappa b, tumor necrosis factor (TNF)-alpha) in the wound microenvironment via the VEGF/macrophages/microenvironment axis. Consequently, the bandages realized multifunctional regeneration in splinted excisional wounds in rats, with or without diabetes, affording a higher skin appendage neogenesis, sensory function, and collagen remodeling. Conclusively, our approach encompassing in situ recruitment of VEGF at the injury site with the capability to promote immunomodulation-mediated tissue repair affords a promising avenue for scarless wound regeneration, which may also have implications for other tissue engineering disciplines.