Chad Smith

 Introduction: Musculoskeletal disorders are the leading cause of disability in the United States, with an estimated 5.5 million fractures occurring annually¹⁶. Every bone fracture has the potential to develop into a nonunion fracture, with an occurrence rate of 5-10%¹⁶. Current bone grafting procedures for the treatment of nonunion fractures are undergoing a transition from autograft/allografts to synthetic scaffolding⁵. These osteoconductive platforms promote osteogenic proliferation while minimizing graft rejection and complications. Incorporating bone morphogenic protein coating holds potential to regulate the release rate of osteoinductive transcription factors acting on SMAD and non-SMAD phosphorylation cascade transduction pathways involved in progenitor differentiation¹⁵. With greater experimentation, a synthetic graft can be produced to promote more efficient homeostatic bone repair processes for the treatment of nonunion fractures. Methods: A study was conducted to utilize the osteoinductive abilities of rh-BMPs to improve the porous scaffold provided osteoconduction for enhanced bone repair. The researchers of this study utilized BMP-2 with a chitosan film. Various methodologies were utilized to assess the level of osteogenic activity of the testing groups. X-ray diffraction and electron microscopy were used to measure physiochemical responses to bone generation. Bioassays observing levels of APL and MTT were utilized to measure biomarker levels indicating higher levels of osteogenic activity. Results: Bioassay levels revealed higher levels of alkaline phosphatase levels in the scaffoldings containing rh-BMP2¹. The APL levels were studied as an indication of osteogenesis because the increase of this enzyme in cell culture is a direct consequence of the differentiation toward osteogenic lineage. Elevated ALP activity only appeared in rhBMP-2 treatments, while control ceramics do not induce this cell reaction¹. MTT levels were found to be present only with ceramic scaffoldings as opposed to control subjects, revealing proliferation activity increased in the modified scaffoldings due to the osteoconductive properties¹. In vivo observations of the rh-BMP2 coated scaffolding material revealed new bone formation only three weeks following surgery, earlier than the control ceramics without BMP coating¹. Conclusion: These results demonstrated that rhBMP-2 remains active in assayed immobilization processes and that these coated ceramics allow both in vitro cell adhesion and proliferation in addition to differentiation of adhered cells to osteogenic lineage in vivo¹. The significance of this research reveals that recombinant BMPs are a viable methodology to augment current synthetic scaffolding in order to combine the osteoconductive and osteoinductive abilities of bioengineered material to yield more rapid and effective bone formation post injury.

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