Dual-functional 3D-printed composite scaffold for inhibiting bacterial infection and promoting bone regeneration in infected bone defect models

Infection is one of the pivotal causes of nonunion in large bone defect after trauma or tumor resection. Three-dimensional (3D) composite scaffold with multifunctional-therapeutic properties offer many advantages over allogenic or xenogenic bone grafting for the restoration of challenging infected bone defects. In the previous study, we demonstrated that quaternized chitosan (HACC)-grafted polylactide-co-glycolide (PLGA)/hydroxyapatite (HA) scaffold (PLGA/HA/HACC) via 3D-printing technique exhibited significantly improved antimicrobial and osteoconductive property in vitro, together with good biocompatibility in vivo. Hence, the present study further investigated whether such an innovative bone substitute could effectively inhibit the bacterial biofilm formation and promote bone regeneration in vivo. To evaluate the bone repairing effects of the 3D-printed scaffolds on infected cortical and cancellous bone defects scenarios, eighty female Sprague Dawley rats and thirty-six female New Zealand white rabbits were used to establish infected femoral shaft defect and condyle defect model, respectively. X-ray, micro-CT, microbiological and histopathological analyses were used to assess the anti-infection and bone repairing potential of the dual-functional porous scaffolds. We observed that HACC-grafted PLGA/HA scaffolds exhibited significantly enhanced anti-infection and bone regeneration capability in different infected bone defect models. In addition, the degradation rate of the scaffolds appeared to be closely related to the progress of infection, influencing the bone repairing potential of the scaffolds in infected bone defects models. In general, this investigation is of great significance as it demonstrates promising applications of the 3D-printed dual-functional PLGA/HA/HACC scaffold for repairing different types of bone defect under infection.Currently, it is clinically urgent to exploit bone substitutes with potential of bacterial inhibition and bone regeneration. However, bone scaffolds with relatively low risks of bacterial resistance and tissue toxicity used for combating infected bone defects remain to be developed. We have reported that quaternized chitosan (HACC)-grafted 3D-printed PLGA/HA composite scaffold had enhanced in vitro antimicrobial and osteoconductive property, and well cytocompatibility in our published study. This continuing study further confirmed that HACC-grafted PLGA/HA scaffolds exhibited significantly enhanced anti-infection and bone regeneration efficacy in both cortical bone defect in rat and cancellous bone defect in rabbit under infection. Meanwhile, we also found that the degradation rate of the scaffolds seemed to be closely related to the progress of infection, influencing the bone repairing potential of the scaffolds in infected bone defects models. In conclusion, this study provides significant opportunities to develop a 3D-printed bone scaffold with dual functions used for infected bone defects in future plastic and orthopaedic surgery.