Engineering of bone using rhBMP-2-loaded mesoporous silica bioglass and bone marrow stromal cells for oromaxillofacial bone regeneration

Abstract

In present study, CaO–P2O5–SiO2-system mesoporous silica (MS) scaffolds were synthesized and loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2), while their protein release properties and other characteristics were investigated. Furthermore, rabbit bone marrow stromal cells (bMSCs) were cultured and seeded on rhBMP-2-loaded MS (rhBMP-2/MS) scaffolds. Cell adhesion and proliferation were evaluated by scanning electron microscopy (SEM) and MTT assays, while osteogenic differentiation was measured by ALP activity and real-time PCR analysis on the osteogenic markers of runt-related transcription factor 2 (Runx2), collagen type 1 (COL1), osteocalcin (OCN), and osteopontin (OPN). Finally, twenty-four rabbits received unilateral maxillary sinus floor elevation surgery at each time point (2 and 8weeks), and randomly filled with one of the following four materials: MS alone; autologous bMSCs/MS complexes; rhBMP-2/MS complexes; or autologous bMSCs/rhBMP-2/MS complexes. New bone formation and mineralization were detected by histological/histomorphometric analysis, and fluorochrome labeling. The results showed that MS scaffolds presented excellent hierarchically large pore and well-ordered mesopore properties; moreover, rhBMP-2/MS scaffolds efficiently released rhBMP-2 in a sustained manner. Furthermore, rhBMP-2/MS scaffolds significantly enhanced the proliferation and osteogenic differentiation of bMSCs. In the maxillary sinus floor elevation experiments, rhBMP-2/MS scaffolds promoted new bone formation and augmented the height of the sinus floor, while the addition of bMSCs further enhanced new bone formation and mineralization. The present study revealed that CaO–P2O5–SiO2-system MS scaffolds could act as drug delivery carriers for rhBMP-2 and could be used to construct tissue-engineered bone with bMSCs for oromaxillofacial bone regeneration.