Continuously released Zn²⁺ in 3D-printed PLGA/β-TCP/Zn scaffolds for bone defect repair by improving osteoinductive and anti-inflammatory properties.

Abstract

Long-term nonunion of bone defects has always been a major problem in orthopedic treatment. Artificial bone graft materials such as Poly (lactic-co-glycolic acid)/β-tricalcium phosphate (PLGA/β-TCP) scaffolds are expected to solve this problem due to their suitable degradation rate and good osteoconductivity. However, insufficient mechanical properties, lack of osteoinductivity and infections after implanted limit its large-scale clinical application. Hence, we proposed a novel bone repair bioscaffold by adding zinc submicron particles to PLGA/β-TCP using low temperature rapid prototyping 3D printing technology. We first screened the scaffolds with 1 wt% Zn that had good biocompatibility and could stably release a safe dose of zinc ions within 16 weeks to ensure long-term non-toxicity. As designed, the scaffold had a multi-level porous structure of biomimetic cancellous bone, and the Young's modulus (63.41 ± 1.89 MPa) and compressive strength (2.887 ± 0.025 MPa) of the scaffold were close to those of cancellous bone. In addition, after a series of <i>in vitro</i> and <i>in vivo</i> experiments, the scaffolds proved to have no adverse effects on the viability of BMSCs and promoted their adhesion and osteogenic differentiation, as well as exhibiting higher osteogenic and anti-inflammatory properties than PLGA/β-TCP scaffold without zinc particles. We also found that this osteogenic and anti-inflammatory effect might be related to Wnt/β-catenin, P38 MAPK and NFkB pathways. This study lay a foundation for the follow-up study of bone regeneration mechanism of Zn-containing biomaterials. We envision that this scaffold may become a new strategy for clinical treatment of bone defects.