Administration of mRNA-Nanomedicine-Augmented Calvarial Defect Healing via Endochondral Ossification

Large-area craniofacial defects remain a challenge for orthopaedists, hastening the need to develop facile and safe tissue engineering strategy; osteoconductive material combination of optimal growth factors microenvironment should be considered. Faced with unmet need, we propose that abundant cytokines chemokines can secreted from bone defect, provoking infiltration endogenous stem cells assist regeneration. We provide potent mRNA medicine cocktail promptly initiate formation templates, osteogenesis, subsequent matrix deposition via endochondral ossification, which may retard rapid fibroblast prevent atrophic non-union. explored mutual interaction BMP2 TGFβ3 mRNA, both chondrogenic factors, on inducing ossification; examined influence in vitro transcribed polyA tail length stability; prepared nanomedicine using PEGylated polyaspartamide block copolymer loaded gelatin sponge grafted critical-sized calvarial defect; evaluated regeneration histological μCT examination. The composite resulted over 10-fold new volume (BV) 8 weeks than administration alone, demonstrating synergistically enhances bone’s capability, is induced by nanomedicine. Our data demonstrated mRNA-medicine-mediated ossification provides an alternative cell-free methodology guiding defect healing.