Biological Signal Integrated Microfluidic Hydrogel Microspheres for Promoting Bone Regeneration

Biological signal peptides can regulate a variety of biological functions and have been extensively studied. However, it is still a challenge on how to effectively deliver integrated biological signal peptides and apply them to bone tissue repair. Herein, based on microfluidic technology, an integrated biological signal peptide system (SVVYGLR-BFP) was first constructed by coupling osteogenic and angiogenic signal peptides via solid-phase synthesis method, and then crosslinked into a biological signal integrated microspheres composed of methacrylate gelatin (GelMA) by clicking reaction of sulfhydryl and double bonds (GelMA-S-B), which realized effective delivery of integrated biological signal peptides to promote bone repair. The results of the pharmacokinetics study showed that GelMA-S-B could achieve an efficient sustained release in the bone defect area, and continuously deliver integrated biological signals. Compared with the control group, GelMA-S-B can effectively deliver osteogenesis and angiogenesis biosignal peptides to activate the ALP and PI3K signaling pathways, thereby significantly promoting the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and the vascularization of human umbilical vein endothelial cells (HUVECs). In vivo experiments have shown that GelMA-S-B can remarkably facilitate bone tissue regeneration at bone defects by inducing osteogenic differentiation and neovascularization. In summary, a tissue engineering system for local delivery of integrated biological signal peptides is designed to ensure long-term peptide release, minimal invasiveness, and easy preparation, and ultimately realize effective treatment of bone defect regeneration.