Administration of bone morphogenetic protein-2 (BMP-2), which is commercially approved by the food and drug administration to damaged bone sites has been investigated for the purpose of bone tissue regeneration. BMP-2 can promote osteoblastic differentiation of mesenchymal stem cells as well as regeneration of bone formation in early phase. This review highlights various factors such as vitamin D, dexamethasone, platelet-derived growth factor, placental growth factor, BMP-7, and NEL-like protein-1 that enhance and stimulate angiogenesis, cell differentiation, and bone regeneration. These biochemical signals and growth factors (GFs) accelerate bone repair and remodeling either synergistically or individually. Delivery systems and scaffolds are used for sustained release of these cargo molecules and support at damaged bone sites. Compared with direct administration of BMP-2, current studies have demonstrated that a combination of multiple GFs and/or therapeutic chemical factors with delivery platforms synergistically facilitates bone regeneration. Therefore, in the future, multiple combinations of various GFs, chemicals, and materials could provide patients and surgeons with non-invasive treatment options without secondary surgery and pain. To the end, this review summarizes the biological functions and synergistic effects of dual administration modalities involving BMP-2 as well as recent developments in bone tissue engineering applications.
Keywords: Bone morphogenetic Protein-2; Bone tissue engineering; Chemical supplements; Co-delivery; Cytokines; Osteogenesis.