Strategies to engineer bone have focused on the use of natural or synthetic biodegradable materials to support cell transplantation or as substrates to guide bone regeneration. The deposition of a biomineral on the surface of synthetic polymers has resulted in the formation of hybrid biomaterials with desired biodegradability and enhanced osteoconductivity. It is widely accepted that osteoconductive materials provide a superior environment to promote osteogenesis in vivo. However, the impact of the osteoconductive substrate coupled with soluble signals on progenitor cell differentiation within the three-dimensional substrates is not well known. In this study, we investigated the influence of carbonate apatite on the osteogenic differentiation of human mesenchymal stem cells (hMSCs) seeded in biodegradable poly(lactide-co-glycolide) scaffolds. Two schemes for depositing carbonate apatite were examined: a postmineralized process involved surface hydrolysis of the scaffold followed by incubation in a modified simulated body fluid (mSBF) and a premineralized process entailed microparticle hydrolysis, subsequent incubation in mSBF and then scaffold formation. Under scanning electron microscopy, we observed phenotypic differences in structure between each scaffold. We cultured hMSCs on the scaffolds for 28 days in osteogenic media supplemented with 100 ng/mL BMP-2. Compared with nonmineralized scaffolds, hMSCs cultured on biomineralized substrates exhibited increased cellular proliferation, along with reduced levels of osteogenic differentiation markers as determined by intracellular alkaline phosphatase, osteocalcin, and osteopontin secretion. No significant differences in osteogenic differentiation were observed between the two biomineralized substrates. However, we detected significantly higher levels of scaffold-associated calcium in premineralized scaffolds versus postmineralized and nonmineralized substrates. These results suggest that in the presence of soluble signals, mineralization may prove counterproductive to promoting the osteogenic differentiation of hMSCs. In light of these observations, multiple signaling strategies may be necessary to achieve optimal bone regeneration.
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