Bone morphogenetic protein-2 associated multiple growth factor delivery for bone tissue regeneration

Administration of growth factors (GFs) and cytokines to damaged bone tissue for the purpose of bone tissue regeneration has been investigated. Among GFs and cytokines, bone morphogenetic protein-2 (BMP-2) is one of the most important stimulatory factors for enhancing the osteoblastic differentiation of progenitor cells and promoting bone formation. Co-delivery of other GFs, including vascular endothelial growth factor, fibroblast growth factor, insulin-like growth factor, and stromal cell-derived factor, with BMP-2 is known to facilitate repair and remodeling of damaged bone tissue. These GFs stimulate various cellular activities, including angiogenesis, migration, proliferation, regulation of proteoglycan level, and stem cell recruitment. Although bone repair and regeneration are dynamic and complex physiological processes involving multiple cell types and cytokines in timed healing cascade stages, BMP-2-associated delivery of dual and/or multiple GFs could promote bone tissue regeneration based on the synergistic effects of GFs compared with single GF treatment. Current engineering approaches emphasize the importance of design parameters for GF delivery systems, such as optimization of the release profiles, stabilities, and bioactivities of cargo GFs, and the physico-chemical properties of scaffold/hydrogel materials. Therefore, this review summarizes BMP-2-associated GF combinations, biological functions, and current delivery strategies utilized in bone tissue engineering for the development of feasible clinical applications.