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.

Statement of Significance

Currently, thereit is clinically urgenta pressing clinical need to exploitdevelop innovative bone substitutes that provide dual functionality of with potential of bacterial inhibition and bone regeneration. However, bone scaffolds with relatively lowdecreased risks of bacterial resistance and tissue toxicity used for combating infected bone defects remain to be developedexploited. We have reported that quaternized chitosan (HACC)HACC-grafted 3D-printed PLGA/HA composite scaffold had enhanced in vitro antibacterial and antimicrobial and osteocondutive property osteogenic activity, and goodwell biocytocompatibility in our published study. This continuingcontinuous 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 appearedseemed 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-printednew generation of truly multibone scaffold with dual functionnal bone scaffoldss toused for address infected bone defects in future plastic and orthopaedic and plastic surgery.

中文翻译：

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双功能3D打印复合支架可在感染的骨缺损模型中抑制细菌感染并促进骨骼再生

感染是创伤或肿瘤切除后大骨缺损中骨不连的关键原因之一。具有多功能治疗特性的三维（3D）复合支架在修复具有挑战性的感染性骨缺损方面，比同种异体或异种异体植骨具有许多优势。在先前的研究中，我们证明了通过3D打印技术将季铵化壳聚糖（HACC）接枝的聚丙交酯-共-乙交酯（PLGA）/羟基磷灰石（HA）支架（PLGA / HA / HACC）表现出显着改善的体外抗菌和骨传导性能以及良好的体内生物相容性。因此，本研究进一步研究了这种创新的骨替代物是否能有效抑制细菌生物膜的形成并促进体内的骨再生。。为了评估3D打印支架对感染的皮质和松质骨缺损情况的骨修复效果，分别使用80只雌性Sprague Dawley大鼠和36只雌性新西兰白兔分别建立了感染的股骨干缺损和con突缺损模型。X射线，显微CT，微生物学和组织病理学分析被用于评估双功能多孔支架的抗感染和骨修复潜力。我们观察到，在不同的感染性骨缺损模型中，HACC移植的PLGA / HA支架表现出显着增强的抗感染和骨再生能力。另外，支架的降解速率似乎与感染的进展密切相关，影响了在感染的骨缺损模型中支架的骨修复潜力。

重要声明

目前，临床上迫切需要开发具有创新性的骨替代物的临床迫切需求，所述替代物提供具有细菌抑制和骨再生潜力的双重功能。然而，用于抵抗感染的骨缺损的细菌抵抗力和组织毒性降低的风险相对较低的骨支架仍有待开发。我们已经报道了季铵化壳聚糖（HACC）HACC嫁接的3D打印PLGA / HA复合支架在体外具有增强作用在我们发表的研究中，抗菌，抗微生物和骨传导特性具有成骨活性，并具有良好的生物细胞相容性。这项持续不断的研究进一步证实，HACC移植的PLGA / HA支架在感染的大鼠皮质骨缺损和兔子的松质骨缺损中均表现出显着增强的抗感染和骨再生功效。同时，我们还发现支架的降解速率似乎与感染的进展密切相关，影响了在感染的骨缺损模型中支架的骨修复潜力。综上所述，