Anchoring of Probiotic-Membrane Vesicles in Hydrogels Facilitates Wound Vascularization

Inadequate vascularization significantly hampers wound recovery by limiting nutrient delivery. To address this challenge, we extracted membrane vesicles from Lactobacillus reuteri (LMVs) and identified their angiogenic potential via transcriptomic analysis. We further developed a composite hydrogel system (Gel-LMVs) by anchoring LMVs within carboxylated chitosan and cross-linking it with oxidized hyaluronic acid through a Schiff base reaction. The resulting Gel-LMVs exhibit good biocompatibility and retain the bioactivity of LMVs, which are released in a controlled manner to stimulate cell proliferation, migration, and angiogenesis in vitro by modulating gene expression in critical signaling pathways. Moreover, in an in vivo model, Gel-LMVs upregulate vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule (CD31), leading to accelerated vascularization in early healing stages, while concurrently reducing inflammation and augmenting collagen deposition to enhance wound healing quality. This approach to functionalizing biomaterials with probiotic-MVs offers an advanced strategy for wound healing.