Although 90% of fractures typically heal without complications, there remains a small proportion (≤ 10%) of fractures that experience delayed healing or non-union. In patients with such healing complications, there appears to be an important contribution of an inappropriately maintained pro-inflammatory environment to the defective fracture healing process. Interestingly, growth factors e.g. BMP-2, used in bone regenerative approaches have recently been shown to induce pro-inflammatory cytokine release. Thus, immunomodulation of the local fracture microenvironment could be an effective way to enhance fracture healing in troublesome healing environments. The preceding project HealBone showed that local administration of IL-1Ra, the receptor antagonist of the pro-inflammatory cytokine IL-1β, can improve BMP-2 induced bone healing in a segmental femoral defect in rats. However, the rapid degradation of IL-1Ra in vivo suggests that improved bone healing efficacy may be observed with more effective strategies to inhibit IL-1β activity, such as anti-IL-1β monoclonal antibody therapy. Therefore, the current project focuses on investigating the therapeutic efficacy of systemic anti-IL-1β administration to improve BMP-2 induced bone healing in challenging healing environments.
The goals of this project include the characterization of BMP-induced cytokine and proteomic profiles during bone healing, and to test the efficacy of systemic anti-IL-1β administration to improve BMP-2 induced bone healing in challenging healing environments.