MicroRNA-126 from stem cell extracellular vesicles encapsulated in a tri-layer hydrogel scaffold promotes bladder angiogenesis by activating CXCR4/SDF-1α pathway

Restricted by insufficient waterproofness and stretching resistance, hydrogel alone is seldomly applied in bladder wall regeneration. A tri-layer scaffold comprising acellular matrix graft-alginate di-aldehyde-gelatin hydrogel-silk mesh (BAMG-HS) was designed to encapsulate human adipose stem cells (ASCs)-derived extracellular vesicles (EVs), aiming facilitate The proangiogenic composite biomaterial evaluated a rat model of augmentation, where rats were randomly allocated BAMG-HS-EVs (n = 6 sampled at 2, 4, 12 weeks, respectively), BAMG-HS 6, weeks) sham operation control groups weeks). has excellent mechanical biodegradable properties, promotes angiogenesis facilitates morphological regenerations urothelium, smooth muscle neural fibers, functional restoration without unmitigated fibrosis or dysregulated inflammation. Human ASCs-EVs activate CXCR4/SDF-1α pathway, enhance umbilical vein endothelial (HUVEC) proliferation, invasiveness tube-like structure formation. After internalization HUVEC, they up-regulate microRNA-126 inhibit RGS16 thus enhancing VEGF secretion via ERK1/2 phosphorylation.