Osteogenic-differentiated mesenchymal stem cell-secreted extracellular matrix as a bone morphogenetic protein-2 delivery system for ectopic bone formation

• Published in: Acta biomaterialia 2020-10, Vol.116, p.186-200
• Main Authors: Larochette, Nathanael, El-Hafci, Hanane, Potier, Esther, Setterblad, Niclas, Bensidhoum, Morad, Petite, Hervé, Logeart-Avramoglou, Delphine
• Format: Article
• Language: English
• Subjects: Animals; Biomedical materials; BMP-2 delivery system; Bone growth; Bone matrix; Bone Morphogenetic Protein 2; Bone morphogenetic proteins; Bone Regeneration; Cell Differentiation; Cells, Cultured; Critical components; Crystals; Extracellular Matrix; Growth factors; in vivo; Mesenchymal Stem Cells; Mice; Ossification (ectopic); Osteogenesis; Proteins; Regeneration; Regeneration (physiology); Stem cell transplantation; Stem cells; Surgical implants
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2020.09.003

While human bone morphogenetic protein-2 (BMP-2) is a promising growth factor for bone regeneration, a major challenge in biomedical applications is finding an optimal carrier for its delivery at the site of injury. Because of their natural affinities for growth factors (including BMP-2) as well as their role in instructing cell function, cultured cell-derived extracellular matrices (ECM) are of special interest. We hereby hypothesized that a “bony matrix” containing mineralized, osteogenic ECM is a potential efficacious carrier of BMP-2 for promoting bone formation and, therefore, compared the efficacy of the decellularized ECM derived from osteogenic-differentiated human mesenchymal stem cells (hMSCs) to the one obtained from ECM from undifferentiated hMSCs. Our results provided evidence that both ECMs can bind BMP-2 and promote bone formation when implanted ectopically in mice. The osteoinductive potential of BMP-2, however, was greater when loaded within an osteogenic MSC-derived ECM; this outcome was correlated with higher sequestration capacity of BMP-2 over time in vivo. Interestingly, although the BMP-2 mainly bound onto the mineral crystals contained within the osteogenic MSC derived-ECM, these mineral components were not involved in the observed higher osteoinductivity, suggesting that the organic components were the critical components for the matrix efficacy as BMP-2 carrier. [Display omitted]