Author(s): Duan, Lian ; Liu, Ga ; Liao, Fuying ; Xie, Chunyu ; Shi, Jiahao ; Yang, Xiao ; Zheng, Fan ; Reis, R. L. ; Kundu, Subhas C ; Xiao, Bo
Date: 2025
Persistent ID: https://hdl.handle.net/1822/97822
Origin: RepositóriUM - Universidade do Minho
Subject(s): Antheraea pernyi silk nanofibril; Diabetic wound; Macrophage polarization; RGD motif; Hemostasis
The chronic inflammation and matrix metalloprotease (MMP)-induced tissue degradation significantly disrupt re-epithelization and delay the healing process of diabetic wounds. To address these issues, we produced nanofibrils from Antheraea pernyi (Ap) silk fibers via a facile and green treatment of swelling and shearing. The integrin receptors on the cytomembrane could specifically bind to the Ap nanofibrils (ApNFs) due to their inherent Arg-Gly-Asp (RGD) motifs, which activated platelets to accelerate coagulation and promoted fibroblast migration, adhesion and spreading. These degradable nanofibrils served as effective competitive substrates to reduce MMP-induced tissue degradation. ApNFs and their enzymatic hydrolysates could modulate macrophage polarization due to their RGD motifs. RNA sequencing further revealed that ApNFs treatment activated the JAK2- STAT5b and PI3K-Akt signaling pathways while suppressed the NF-κB, IL-17 and TNF signaling pathways in macrophages. The full-thickness skin wound experiments confirmed that ApNFs significantly accelerated wound healing in both diabetic and non-diabetic rats. Notably, in diabetic wound, ApNFs and their enzymatic hydrolysates polarized the accumulated M1-type macrophages into M2-type, which promoted the wound to get rid of the inflammatory stage and transition to the following proliferative stage, improving the wound healing percentage on day 14 from 74.9 % to 93.2 % by facilitating collagen deposition, angiogenesis and re-epithelization. These results demonstrate that ApNFs are promising drug-free diabetic wound dressings with favorable inherent immunoregulatory properties for biomedical translation.
