期刊
SCIENCE ADVANCES
卷 7, 期 24, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abh4302
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资金
- University of Chicago
A new translational protein engineering-based approach has been developed to reduce the required dosage of rhBMP-2 in clinical spinal fusion, increasing safety when delivered in a collagen sponge. This method has shown improved efficacy at low doses of rhBMP-2 in two mouse models of bone regeneration and may have applications in various regenerative medicine fields.
The revolutionizing efficacy of recombinant human bone morphogenetic protein (rhBMP-2) for clinical spinal fusion is hindered by safety issues associated with the high dose required. However, it continues to be widely used, for example, in InFUSE Bone Graft (Medtronic). Here, we developed a translational protein engineering-based approach to reduce the dose and thereby improve the safety of rhBMP-2 delivered in a collagen sponge, as in InFUSE Bone Graft. We engineered a bridge protein with high affinity for rhBMP-2 and collagen that can be simply added to the product's formulation, demonstrating improved efficacy at low dose of rhBMP- 2 in two mouse models of bone regeneration, including a newly developed spinal fusion model. Moreover, the bridge protein can control the retention of rhBMP-2 from endogenous collagenous extracellular matrix of tissue. Our approach may be generalizable to other growth factors and collagen-based materials, for use in many other applications in regenerative medicine.
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