| Autor: |
De La Vega RE; Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, USA.; cBITE, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands., van Griensven M; Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, USA.; cBITE, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands., Zhang W; Ethris GmbH, Planegg, Germany., Coenen MJ; Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, USA., Nagelli CV; Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, USA., Panos JA; Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, USA., Peniche Silva CJ; cBITE, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands., Geiger J; Ethris GmbH, Planegg, Germany., Plank C; Ethris GmbH, Planegg, Germany., Evans CH; Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, USA., Balmayor ER; Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, USA.; IBE, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands. |
| Abstrakt: |
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. |
