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

DOI

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.

Identifier
DOI https://doi.org/10.34894/PT4QLL
Metadata Access https://dataverse.nl/oai?verb=GetRecord&metadataPrefix=oai_datacite&identifier=doi:10.34894/PT4QLL
Provenance
Creator Del Toro Runzer, Claudia ORCID logo; Sadowska, Joanna M.; Roumans, Nadia ORCID logo; Christian Plank ORCID logo; Evans, Christopher H.; O’Brien, Fergal J. ORCID logo; van Griensven, Martijn ORCID logo; Rosado Balmayor, Elizabeth ORCID logo
Publisher DataverseNL
Contributor Rosado Balmayor, Elizabeth; Hebels, Dennie; Dataverse Support Contact
Publication Year 2025
Rights CC-BY-4.0; info:eu-repo/semantics/openAccess; http://creativecommons.org/licenses/by/4.0
OpenAccess true
Contact Rosado Balmayor, Elizabeth (RWTH Aachen University Hospital); Hebels, Dennie (Maastricht University); Dataverse Support Contact (Maastricht University)
Representation
Resource Type Dataset
Format application/pdf
Size 48093; 218653
Version 1.0
Discipline Life Sciences; Medicine