Angiogenic sticky porous microgels as injectable stem cell carriers for site-directed treatment of osteoporosis

초록

Injectable stem cell therapy has emerged as a promising approach for treating various bone diseases from bony defects to osteoporosis. While microgels serve as preformed scaffolds for cell transplantation with minimal surgical intervention, off-target administration and poor vascularization limit their clinical translation, especially for treating vascularized tissues. Here, we propose sticky porous microgels with bioengineered angiogenic mussel adhesive protein (MAP-VEGF) as injectable cell carriers to accomplish site-directed delivery of stem cells with augmented vascularization. A suit of highly homogeneous porous microgels (MVPs) microfluidically fabricated using the oxidation-induced covalent crosslinking of MAP-VEGF showed a superior adhesion ability and appropriate physical properties, enabling the maintenance of the viability and stemness of loaded mesenchymal stem cells (MSCs) after syringe injection and supporting differentiation toward the desired lineages upon inductive culture. Injection of the MSC-laden MVPs induced the ectopic formation of vascularized bone constructs in target sites of the subcutaneous layer and accelerated bone regeneration in cranial bone defects and osteoporotic cancellous bone spaces in vivo. Thus, the developed MVPs hold great potential for the in situ construction of vascularized tissues via a minimally invasive administration procedure with further expansion to stem cell-mediated regenerative therapies for various intractable diseases in humans.

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