Efficient healing of large osseous segmental defects using optimized chemically modified messenger RNA encoding BMP-2.
Sci Adv
; 8(7): eabl6242, 2022 02 18.
Article
em En
| MEDLINE
| ID: mdl-35171668
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regeneração Óssea
/
Proteína Morfogenética Óssea 2
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article