Biodegradable Mg/polymer composite fibers offer a promising therapeutic option for tissue injury because of bioactive Mg2+ and biomimetic microstructure. However, current studies are limited to the contribution of Mg2+ and the single microstructure. In this study, we designed Mg/poly (lactic-co-glycolic acid) (Mg/PLGA) composite microfibers that significantly enhanced angiogenesis and tissue regeneration synergistically by Mg2+ and self-sculptured microstructure, due to spontaneous in situ microphase separation in response to the weakly alkaline microenvironment. Our composite microfiber patch exhibited superior performance in the adhesion, spreading, and angiogenesis functions of human umbilical vein endothelial cells (HUVECs) due to the joint contribution of the hierarchically porous microstructure and Mg2+. Genomics and proteomics analyses revealed that the Mg/PLGA composite microfibers activated the cell focal adhesion and angiogenesis-related signaling pathways. Furthermore, the repair of typical soft tissue defects, including refractory urethral wounds and easily healed skin wounds, validated that our Mg/PLGA composite microfiber patch could provide favorable surface topography and ions microenvironment for tissue infiltration and accelerated revascularization. It could cause rapid urethral tissue regeneration and recovery of rabbit urethral function within 6 weeks and accelerate rat skin wound closure within 16 days. This work provides new insight into soft tissue regeneration through the bioactive alkaline substance/block copolymer composites interactions.
Keywords: Angiogenesis; Electrospun fibers; Hierarchical microstructure; Microphase separation; Tissue regeneration; pH response.
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