Wound healing in diabetes is retarded by the dysfunctional local microenvironment. Although there are many studies using hydrogels as substitutes for natural extracellular matrices (ECMs), hydrogels that can mimic both the structure and functions of natural ECM remain a challenge. Self‐assembling peptide RADA16 nanofiber has distinct advantages to provide a biomimetic extracellular matrix nanofiber structure. However, it still lacks biological cues to promote angiogenesis that is of vital significance for diabetic wound healing. With a customized copper peptide glycyl‐histidyl‐lysine (GHK) functionalized RADA16, an integrated approach using functionalized RADA16 nanofiber to chelate copper ion, is innovatively proposed in this present study. The acquired composite hydrogel holds the biomimetic nanofiber architecture, and exhibits promoting angiogenesis by both enhancing adhesion and proliferation of endothelial cells (EC) in vitro and neovascularization in vivo. It shows that the functionalized nanofiber scaffolds significantly accelerated wound closure, collagen deposition, and tissue remodeling both in healthy and diabetic mice. Furthermore, immunohistochemical analysis give evidence that an upregulated expression of eNOS and CD31 in the copper peptide‐functionalized RADA16 treated group. It can be envisioned that this scaffold can serve as a promising dressing for diabetic wound healing.

Carbon monoxide (CO) is a bioactive molecule with high potential as it shows promising efficacy for regulating inflammation. Materials capable of storing and delivering CO are of great potential therapeutic value. Although CO-releasing molecules (CORMs) have been developed to deliver CO, the short CO duration of minutes to 2 h confines their practical use. In this study, partially reduced MIL-100(Fe) as a new CO-releasing nanoMOF was developed and used for sustained CO release and macrophage (MA) phenotypic polarization regulation. MIL-100(Fe) was synthesized and mildly annealed in vacuum for partial reduction. When the annealing temperature was lower than 250 °C, less Fe(II) present in MIL-100(Fe) and the subsequent CO adsorption and desorption profiles displayed typical features of physisorption. While it was annealed at 250 °C, it showed about 20% of Fe(III) was reduced, which resulted in chemisorption of CO due to the high coordination affinity of Fe(II) to CO. The loading amount of CO was increased, and the CO release was prolonged for about 24 h. Furthermore, the CO release from this nanoMOF could alter the lipopolysaccharide (LPS)-induced macrophage from M1 to the alternative M2 phenotype and promoted the growth of endothelial cells (ECs) by paracrine regulation of MA. It can be envisioned as a promising CO-releasing solid for biomedical application.