Wound dressings with asymmetric wettability surfaces can effectively prevent bacterial colonization and tissue dehydration and have shown great potential for diabetic wound healing applications. However, the construction of a highly hydrophobic outer surface with high biocompatibility and permeability is still the major challenge in the preparation of asymmetric wettable dressings. Inspired by the superhydrophobic surface structures existing in nature, an asymmetric wettable composite wound dressing with a highly hydrophobic outer layer was successfully prepared for diabetic wound healing in this study. The hydrophobic outer layer was fabricated by the electrospinning of poly(ε-caprolactone) (PCL) on a micron-pore-size nylon mesh template, and the hydrophilic inner layer was obtained by the electrospinning of pioglitazone-incorporated gelatin (Gel-pio). The hydrophobic outer layer of the dressing with a hierarchical micro−nanostructure exhibits excellent ability to waterproof and prevent bacterial adhesion, whereas the hydrophilic inner layer can promote cell proliferation, migration, and angiogenesis by its nanofiber structure and biocompatible gelatin composition. The presented dressing has good mechanical properties, permeability, and high biocompatibility. More importantly, the results of full-thickness skin wound model evaluation on db/db mice (type 2 diabetes) and STZ rats (type 1 diabetes) indicate that the developed dressing can promote wound healing by stimulating cell proliferation, angiogenesis, collagen deposition, and re-epithelialization. The findings of this study suggest that the bioinspired asymmetric wettable composite wound dressing can be used as a promising candidate for diabetic wound healing.

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Kidney fibrosis is accompanied by vascular dysfunction. Discovering new ways to ameliorate dysfunctional angiogenesis may bypass kidney fibrosis. YAP (Yes-associated protein) plays a multifaceted role during angiogenesis. Here, we found that selectively targeting YAP signaling in the endothelium ameliorates unilateral ureteral obstruction (UUO)-induced kidney fibrosis. Genetic deletion of Yap1, encoding YAP protein, in VEcadherin + endothelial cells inhibited endothelial-to-mesenchymal transition (EndMT) and dysfunctional angiogenesis and improved obstructive nephropathy and kidney fibrosis. Treatment with the systemic YAP inhibitor verteporfin worsened kidney fibrosis symptoms because of its lack of cell specificity. In an attempt to identify endothelial-specific YAP modulators, we found that Gprotein-coupled receptor coagulation factor II receptor-like 1 (F2RL1) was highly expressed in vessels after UUO-induced kidney fibrosis. The F2RL1 peptide antagonist FSLLRY-NH2 selectively blocked YAP activity in endothelial cells and ameliorated kidney fibrosis. Thus, selective antagonization of endothelial YAP activity might bypass kidney fibrosis and provide new avenues for the design of antifibrotic therapies.

Epigenetic targeting of the maladaptive vascular niche in fibrotic liver blocks fibrosis by alleviating fibrogenic angiocrine IGFBP7 and ADAMTS1.