Generation of rhBMP-2-induced juvenile ossicles in aged mice

Critical-sized bone defects and nonunions following fracture are common among elderly patients and severely reduce the quality of life. Dysfunctional senescent endothelial and mesenchymal stromal cells (MSCs) inhibit bone defect repair. Here we provide a method to obtain surrogate vascularized juvenile bone by subcutaneous implantation of recombinant human bone morphogenic protein-2 (rhBMP-2)-loaded absorbable gelatin scaffolds. RhBMP-2-induced ossicles showed fewer senenscent MSCs whereas much more type H blood vessels (strongly positive for CD31 and endomucin (Emcn)) and osteoprogenitor cells than native bone (femur and tibiae) even in old mice. Treatment with this juvenile ossicles improved the regenerative capacity in critical-sized cranial defects versus standard treatment in both young and old mice. Furthermore, ossicles with custom size shape were obtained by 3D-printing for irregular bone defects repair. These customizable juvenile ossicles developed in aged individuals provide an alternative to resecting native bone in autologous bone transplantation, with superior regenerative efficacy in elderly patients due to their juvenile phenotype.