仿生多孔水凝胶支架促进血管化组织工程骨再生的血管向内生长和成骨分化

Abstract

The construction of vascularized tissue-engineered bone ( VTEB ) has been a promising alternative for bone defect repair but remains a remarkable challenge. To date, there have been very limited breakthroughs in VTEB regeneration based on hydrogel scaffolds due to nutrient exchange obstacle caused by a dense hydrogel network, as well as the lack of an osteogenic microenvironment and vascularized pipeline. Here, we developed a novel strategy to prepare porous hydrogel scaffolds with bone biomimetic microenvironments to promote vascular ingrowth and osteogenic differentiation for VTEB regeneration. Based on the phase-separation void-formation technology, porous hydrogel scaffolds with satisfactory mass transport capability were conveniently prepared using gelatin methacryloyl ( GelMA ) and poly (ethylene oxide) ( PEO ) emulsified two-phase aqueous solutions. By further combining the osteogenic ingredient, decalcified bone matrix ( DBM ) particles, and poly (lactic-co-glycolic acid)-encapsulated angiogenic vascular endothelial growth factor ( PLGA / VEGF ) microspheres, the porous hydrogel scaffolds with biomimetic osteogenic/angiogenic microenvironments were successfully constructed. Moreover, the osteogenic/angiogenic designs based on the DBM particles, porous structure, and VEGF -released microspheres efficiently enhanced the survival, spreading, migration, and osteogenic differentiation of BMSCs in the hydrogels in vitro , and significantly prompted bone regeneration of BMSC-laden hydrogels in vivo . More importantly, in situ bone defects in a rabbit skull model were successfully repaired with VTEB regenerated by BMSC-laden biomimetic porous hydrogels. This study developed a novel bone-biomimetic porous hydrogel scaffold, which provided promising strategies for ectopic VTEB regeneration and in situ bone defect repair.