Authors: Rodolfo E. De La Vega, Martijn van Griensven, Wen Zhang, Michael J. Coenen, Christopher V. Nagelli, Joseph A. Panos, Carlos J. Peniche Silva, Johannes Geiger, Christian Plank, Christopher H. Evans, Elizabeth R. Balmayor
Published: 2022-02-16
Source: Full article
Large segmental osseous defects heal poorly. Recombinant, human bone morphogenetic protein-2 (rhBMP-2) is used clinically to promote bone healing, but it is applied at very high doses that cause adverse side effects and raise costs while providing only incremental benefit. We describe a previously unexplored, alternative approach to bone regeneration using chemically modified messenger RNA (cmRNA). An optimized cmRNA encoding BMP-2 was delivered to critical-sized femoral osteotomies in rats. The cmRNA remained orthotopically localized and generated BMP locally for several days. Defects healed at doses ≥25 μg of BMP-2 cmRNA. By 4 weeks, all animals treated with 50 μg of BMP-2 cmRNA had bridged bone defects without forming the massive callus seen with rhBMP-2. Moreover, such defects recovered normal mechanical strength quicker and initiated bone remodeling faster. cmRNA regenerated bone via endochondral ossification, whereas rhBMP-2 drove intramembranous osteogenesis; cmRNA provides an innovative, safe, and highly translatable technology for bone healing.