Sprayable hydrogel sponge for neurovascular microenvironment reconstruction and inflammation modulation in diabetic wound healing

作者：Xiaozhen Zhou, Pengchao Ma, Yihao Liu, Zhaojian Wang, S Chen, Zekun Cheng, Songlu Tseng, Hui Wu, Mengdi Zhang, Fengzhou Du, Nanze Yu, Long Xiao, Jiuzuo Huang, Xiumei Wang · 发表于：Bioactive Materials · 年份：2025 · DOI：10.1016/j.bioactmat.2025.08.008 · 被引用次数：16 · 研究领域：Wound Healing and Treatments、Electrospun Nanofibers in Biomedical Applications、Mesenchymal stem cell research

Diabetic wounds are characterized by chronic inflammation, vascular insufficiency, and peripheral neuropathy, which collectively disrupt the neurovascular microenvironment essential for coordinated tissue regeneration. However, strategies targeting neurovascular regeneration remain limited. Here, we developed a sprayable hydrogel sponge based on gelatin methacryloyl and methacrylamide-modified ε-poly-L-lysine (S-GPL), co-functionalized with VEGF-mimetic peptide (KLT) and BDNF-mimetic peptide (RGI). The sprayable format conforms to irregular wound geometries, while the pneumatic spraying technique generates high-pressure microbubbles that create a porous structure, thereby enhancing exudate absorption and sustained peptide release as a sponge dressing. Additionally, the incorporation of KLT and RGI facilitates the reconstruction of the neurovascular microenvironment. In vitro, KLT promoted endothelial cell maturation and cytokine secretion, whereas RGI enhanced Schwann cell activity. Notably, S-GPL KLT/RGI facilitated intercellular interactions between RSCs and HUVECs, highlighting the cellular mechanisms underlying neurovascular communication. In a full-thickness diabetic wound model in rats, the hydrogel accelerated wound closure, re-epithelialization, and matrix remodeling. These effects were accompanied by enhanced neovascularization and axonal regeneration, along with the formation of a spatially organized neurovascular niche, as evidenced by CD31 + capillaries closely al...