Systemic administration of anti-IL-1β to enhance bone healing

ARI Exploratory Research
M Stoddart, E Wehrle

Background

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.

Histological healing assessment of a rat femoral defect within the preceding HealBone project. Giemsa-eosin stained section of a methyl methacrylate-embedded femur at 14 weeks following implantation of a collagen-hydroxyapatite scaffold loaded with BMP-2 and IL-1 receptor antagonist (IL-1ra). Scale bar = 2 mm.

 

Goal

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.

  • Presentation
    Wehrle E, Günther D, Mathavan N, Correia Marques F, Singh A, Müller R. Spatial transcriptomics of musculoskeletal tissues during bone healing in mice. 2023 ORS (poster)

    Schröder M, Gens L, Bernhard L, Arens D, Gehweiler D, Zeiter S, Stoddart M, Wehrle E. Effects of low dose BMP-2 on cytokine levels during fracture healing in a femur segmental defect in rats. 2023 eCM (oral)

    Hatt LP, Armiento AR, van der Heide D, Pirera ME, Stoddart MJ. β-TCP from 3D-printed scaffold can act as an effective phosphate source during the osteogenic differentiation of human mesenchymal stromal cell. 2023 ESB (Biomaterials) / (poster) 

    Schröder M, Gens L, Bernhard L, Arens D, Gehweiler D, Zeiter S, Stoddart M, Wehrle E. Effects of low dose BMP-2 on fracture healing and cytokine levels in a femur segmental defect in rats.
    2023 ESB (Biomaterials) / (poster) 
     
     
     

     

     
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