Biomaterials for the Delivery of Growth Factors and Other Therapeutic Agents in Tissue Engineering Approaches to Bone Regeneration.

Bone fracture followed by delayed or non-union typically requires bone graft intervention. Autologous bone grafts remain the clinical "gold standard". Recently, synthetic bone grafts such as Medtronic's Infuse Bone Graft have opened the possibility to pharmacological and tissue engineering strategies to bone repair following fracture. This clinically-available strategy uses an absorbable collagen sponge as a carrier material for recombinant human bone morphogenetic protein 2 (rhBMP-2) and a similar strategy has been employed by Stryker with BMP-7, also known as osteogenic protein-1 (OP-1). A key advantage to this approach is its "off-the-shelf" nature, but there are clear drawbacks to these products such as edema, inflammation, and ectopic bone growth. While there are clinical challenges associated with a lack of controlled release of rhBMP-2 and OP-1, these are among the first clinical examples to wed understanding of biological principles with biochemical production of proteins and pharmacological principles to promote tissue regeneration (known as regenerative pharmacology). After considering the clinical challenges with such synthetic bone grafts, this review considers the various biomaterial carriers under investigation to promote bone regeneration. This is followed by a survey of the literature where various pharmacological approaches and molecular targets are considered as future strategies to promote more rapid and mature bone regeneration. From the review, it should be clear that pharmacological understanding is a key aspect to developing these strategies.