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Highlights: [•] Regenerative engineering has been recently proposed to regenerate complex tissue. [•] Therapeutic proteins have many limitations for their use in regenerating tissues. [•] Small-molecule-based therapeutics is emerging as an alternative strategy. [•] Small molecules may represent the next generation in musculoskeletal regenerative medicine. [ABSTRACT FROM AUTHOR]

Abstract: Over the past several decades, recombinant human bone morphogenetic proteins (rhBMPs) have been the most extensively studied and widely used osteoinductive agents for clinical bone repair. Since rhBMP-2 and rhBMP-7 were cleared by the U.S. Food and Drug Administration for certain clinical uses, millions of patients worldwide have been treated with rhBMPs for various musculoskeletal disorders. Current clinical applications include treatment of long bone fracture non-unions, spinal surgeries, and oral maxillofacial surgeries. Considering the growing number of recent publications related to clincal research of rhBMPs, there exists enormous promise for these proteins to be used in bone regenerative medicine. The authors take this opportunity to review the rhBMP literature paying specific attention to the current applications of rhBMPs in bone repair and spine surgery. The prospective future of rhBMPs delivered in combination with tissue engineered scaffolds is also reviewed. [Copyright &y& Elsevier]

Osteoblast cell adhesion on biomaterials is an important goal for implants to be useful in bone regeneration technologies. The adhesion of osteoblastic cells to biomaterials has been investigated in the field of bone regenerative engineering. Previous work from our group demonstrated that osteoblastic cells adhering to biodegradable biomaterials require the expression of integrins on the cell surface. However, the underlying molecular signaling mechanism is still not fully clear. We report here that cyclic adenosine monophosphate (cAMP), a small signaling molecule, regulates osteoblast cell adhesion to biomaterial surfaces. We used an in vitro cell adhesion assay to demonstrate that at 0.1 mM, 8-Br-cAMP, a cell-permeable cAMP analog, significantly enhances osteoblast-like cells' (MC3T3-E1) adherence to biomaterials. Moreover, we demonstrate that a commonly used cAMP-elevating agent, forskolin, promotes cell adhesion similar to that of the cell permeable cAMP analog. By using different target-specific cAMP analogs: 8-CPT-2Me-cAMP which specifically activates exchange protein activated by cAMP (Epac), and 6-Bnz-cAMP which specifically activates protein kinase A (PKA), we observed that the PKA signaling pathway plays a dominant role in this process. Thus, this report suggests a new method to enhance osteoblast cell adhesion on biodegradable biomaterials for bone regenerative engineering applications. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:602-608, 2011 [ABSTRACT FROM AUTHOR]

Bone scientists are actively investigating a range of methods to promote skeletal tissue regeneration. A review of recent literature has revealed that several ions are uniquely capable of inducing stem cell differentiation down desired lineages. There exists enormous promise for these ions to be used in bone regenerative medicine. Given that these ions can be released from biodegradable polymeric materials, their long-term delivery can be achieved through a variety of controlled-release strategies compared with the relatively few options available for expensive and fragile polypeptide-based growth factors. In this review, we highlight the developments in using ions in conjunction with biomaterials for bone regeneration. [ABSTRACT FROM AUTHOR]