Abstract
Impaired angiogenesis is one of the predominant reasons for non-healing diabetic wounds. Herein, a nanofiber/hydrogel core–shell scaffold with three-dimensional (3D) multilayer patterned structure (3D-PT-P/GM) was introduced for promoting diabetic wound healing with improved angiogenesis. The results showed that the 3D-PT-P/GM scaffolds possessed multilayered structure with interlayer spacing of about 15–80 μm, and the hexagonal micropatterned structures were uniformly distributed on the surface of each layer. The nanofibers in the scaffold exhibited distinct core–shell structures with Gelatin methacryloyl (GelMA) hydrogel as the shell and Poly (d, l-lactic acid) (PDLLA) as the core. The results showed that the porosity, water retention time and water vapor permeability of the 3D-PT-P/GM scaffolds increased to 1.6 times, 21 times, and 1.9 times than that of the two-dimensional (2D) PDLLA nanofibrous scaffolds, respectively. The in vitro studies showed that the 3D-PT-P/GM scaffolds could significantly promote cell adhesion, proliferation, infiltration and migration throughout the scaffolds, and the expression of cellular communication protein-related genes, as well as angiogenesis-related genes in the same group, was remarkably upregulated. The in vivo results further demonstrated that the 3D-PT-P/GM scaffolds could not only effectively absorb exudate and provide a moist environment for the wound sites, but also significantly promote the formation of a 3D network of capillaries. As a result, the healing of diabetic wounds was accelerated with enhanced angiogenesis, granulation tissue formation, and collagen deposition. These results indicate that nanofiber/hydrogel core–shell scaffolds with 3D multilayer patterned structures could provide a new strategy for facilitating chronic wound healing.Graphical
Highlights
As a kind of serious complication of diabetes mellitus with high morbidity and risk of amputation, diabetic wounds have become a global health concern with the increase in the incidence of diabetes [1, 2]
Nanofibers in PT-P/GM (c2) and 3D-PT-P/GM (c3) scaffolds showed rougher surface than PT-P scaffold (c1), which might be due to the swelling effect of Gelatin methacryloyl (GelMA) hydrogel and surface pultrusion effect of CO2 fluid
The water contact angle (WCA) of the three kinds of scaffolds (Fig. 2A (e1–e3)) was investigated and the results revealed that compared with the PT-P scaffolds, both the PT-P/GM and 3D-PTP/GM scaffolds exhibited excellent hydrophilic behaviors, which might be due to the hydrophilic GelMA hydrogel coated on the surfaces of nanofibers
Summary
As a kind of serious complication of diabetes mellitus with high morbidity and risk of amputation, diabetic wounds have become a global health concern with the increase in the incidence of diabetes [1, 2]. The 3D multilayer micropatterned structure and high porosity of the scaffold will promote cell infiltration, migration, and 3D vascular network formation, which eventually accelerate diabetic wound healing (as shown in Scheme 1).
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