Rational Design of Hot‐Melt Biodegradable Tissue Adhesive for Bone Fracture Repair

ABSTRACT Biodegradable bone adhesives can be an effective alternative to metallic implants for stabilizing bone fractures, promoting healing, and restoring full function and mobility. Nonetheless, achieving strong adhesion to the bone under physiological conditions is complex. Herein, a polymer‐based hot‐melt biodegradable bone‐tissue adhesive was developed for bone fracture repair to provide strong bone adhesion in physiological (wet) conditions and is easy to apply. The incorporation of 3,4‐dihydroxyhydrocinnamic acid (HCA) and monobasic calcium phosphate monohydrate (MCPM) into the poly(ε‐caprolactone) (PCL) matrix via melt blending demonstrated successful adhesion of bovine bone slices under wet conditions. A mixture design of experiments was applied to optimize the adhesive formulation to maximize adhesion strength while minimizing the adhesive's melting temperature ( T m ). The optimized composition of 50% PCL, 25% HCA, 25% MCPM achieved a T m of 52°C ± 0.6°C and a lap shear adhesion strength of 294 ± 88 kPa after 30 min and 226 ± 51 kPa after 2 h of application. Time‐dependent oscillatory shear measurements revealed that HCA prolongs the setting time while MCPM reduces it. Furthermore, in vivo feasibility testing demonstrated successful adhesion of fractured bones. The hot‐melt adhesive represents a promising approach toward bone fracture repair.