3D-printed polycaprolactone scaffolds functionalized with poly(lactic-co-glycolic) acid microparticles enhance bone...

Numerous tissue engineering strategies aim to enable the in situ and controlled release of both cells and biologically relevant factors, mimicking physiological regenerative processes. A notable example is the release of rhBMP-2 for treating bone nonunion. By adopting a quasi-physiological approach, we can mitigate the side effects that have hindered its clinical application. Here, we present a customizable 3D-printed polycaprolactone (PCL) scaffold functionalized with poly(lactic-co-glycolic) acid (PLGA) microparticles through covalent binding, designed to mimic the periosteum structure. This scaffold was then functionalized with PLGA microparticles through covalent binding, enabling in situ delivery of rhBMP-2. This construct exhibits significant osteogenic and osteoinductive potential in vitro, promoting the differentiation of periosteum-derived mesenchymal progenitor cells into osteoblasts. Moreover, in vivo testing using a nonunion model (critical size defect) demonstrated therapeutic efficacy with a reduced net morphogen dose. Therefore, this customizable 3D scaffold represents a valuable approach for enhancing bone regeneration and holds significant potential for promoting healing in cases of nonunion fractures. This approach combines a customizable 3D scaffold with controlled rhBMP-2 release, offering a potentially more effective and safer solution for bone regeneration compared to current methods. STATEMENT OF SIGNIFICANCE: As the incidence of bone fractures continues to rise, nonunion remains a significant challenge in orthopedics, becoming a major clinical and economic burden. We present a tissue engineering strategy employing a customizable 3D-printed polycaprolactone scaffold functionalized with covalently bound poly(lactic-co-glycolic acid) microparticles for the localized release of rhBMP-2. By mimicking key features of the periosteum, this scaffold promotes bone regeneration while minimizing the risk of ectopic bone formation. In vivo tests conducted in a critical-size defect model demonstrated effective bone bridging, highlighting the therapeutic potential of the scaffold. The simple manufacturing process, potential for scale-up production, long-term storage capability, and options for customization, including combinations of different molecules or adjuvants, demonstrate that this approach possesses significant translational potential.