In vitro and in vivo evaluation of a bio-inspired adhesive for bone fixation

Abstract

Background: Compared to metallic hardware, an effective bone adhesive can revolutionize the treatment of clinically challenging situations such as comminuted, articular and pediatric fractures. The present study aims at developing such a bio-inspired bone adhesive, based upon a modified mineral-organic adhesive with tetracalcium phosphate (TTCP) and phosphoserine (OPS) by incorporating nanoparticles of polydopamine (nPDA). Methods: The optimal formulation was screened using in vitro instrumental traction tests. Adhesion to bone, cohesion, setting time, and biomineralization of the optimized adhesive was then assessed with ex vivo instrumental and manual tests, compression tests, setting time measurement and simulated body fluid assay. Cytotoxicity was assessed by extraction test (ISO 10993-5). A new in vivo model was developed: the rat fibula was glued to the ipsilateral tibia, simulating the clinical scenario of autograft fixation under low mechanical load. Analysis was performed clinically, radiologically with micro-computed tomography and histologically (without decalcification). Results: The optimal formulation was found as 50%molTTCP/50%molOPS-2%wtnPDA with a liquid-to-powder ratio of 0.21 mL/g. This adhesive has a substantially stronger adhesive strength (1.0–1.6 MPa) to bovine cortical bone (after a 24-hour soak in a physiological saline) than the adhesive without nPDA (0.5–0.6 MPa), and is more quickly induced and has more abundant surface mineralization when immersed in simulated body fluid. Moreover, non-cytotoxicity of this adhesive was confirmed in vitro. In vivo, the TTCP/OPS-nPDA adhesive (n=7) was shown to be effective in stabilizing the graft without displacement (clinical success rate of 86% and 71% respectively at 5 and 12 weeks) compared to a sham control (0%). Significant coverage of newly formed bone was particularly observed on the surface of the adhesive, thanks to the osteoinductive property of nPDA. Conclusions: To conclude, the TTCP/OPS-nPDA adhesive fulfilled many clinical requirements for the bone fixation, and potentially could be functionalized via nPDA to offer more biological activities, e.g. anti-infection after antibiotics loading. Trial Registration: Not applicable