Synergistic osteogenesis after co-administration of cmRNAs encoding BMP-2 and BMP-7

Bone morphogenetic proteins -2 and -7 (BMP-2 and BMP-7) are effective in treating large bone defects, but the required doses are high, resulting in side effects and elevated costs. Previously, we have demonstrated that a chemically modified messenger RNA (cmRNA) coding for BMP-2 induced rapid and reliable healing until consolidation in a bone segmental defect in rats. Here, we show that the simultaneous transfer of BMP-2 and BMP-7 cmRNAs to stem cells leads to increased osteogenic gene expression, extracellular matrix deposition, and mineralization, compared to single or sequential delivery of these cmRNAs. Using a murine model of ectopic ossification, we found that dual BMP-2/BMP-7 cmRNA delivery using collagen-hydroxyapatite scaffolds, designed specifically for bone repair, ensured local BMP-2 and -7 expression with abundant osteogenesis in the absence of adverse effects. This confirms the superior osteogenic potency achieved by local, controlled dual delivery of cmRNAs encoding BMP-2 and BMP-7, further enhancing the potential of this highly translatable technology for promoting bone healing.