Dual-functional 3D-printed composite scaffold for inhibiting bacterial infection and promoting bone regeneration in infected bone defect models
Dual-functional 3D-printed composite scaffold for inhibiting bacterial infection and promoting bone regeneration in infected bone defect models
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DOI：
10.1016/j.actbio.2018.08.015
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发表时间：
2018-10-01
影响因子：
9.7
通讯作者：
Tang, Tingting
中科院分区：
文献类型：
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作者：
Yang, Ying;Chu, Linyang;Tang, Tingting
感染是创伤或肿瘤切除后大面积骨缺损不愈合的主要原因之一。三维（3D）复合支架具有多功能治疗特性，在修复感染性骨缺损方面比同种异体或异种骨移植具有许多优点。在之前的研究中，我们通过3d打印技术证明了季铵化壳聚糖（HACC）接枝聚乳酸-乙醇酸酯(PLGA)/羟基磷灰石（HA）支架（PLGA/HA/HACC）在体外具有显著提高的抗菌和导骨性能，并且具有良好的体内生物相容性。因此，本研究进一步研究这种创新的骨替代物是否能在体内有效抑制细菌生物膜的形成，促进骨再生。为评价3d打印支架对感染皮质骨缺损和松质骨缺损情况的骨修复效果，采用80只雌性Sprague Dawley大鼠和36只雌性新西兰大白兔分别建立感染股骨干缺损和髁突缺损模型。采用x线、micro-CT、微生物学和组织病理学分析评估双功能多孔支架的抗感染和骨修复潜力。我们观察到hacc移植的PLGA/HA支架在不同感染骨缺损模型中表现出显著增强的抗感染和骨再生能力。此外，支架的降解速率似乎与感染的进展密切相关，影响了支架在感染骨缺陷模型中的骨修复潜力。总之，本研究具有重要的意义，它展示了3d打印PLGA/HA/HACC双功能支架在不同类型感染下骨缺损修复中的应用前景。目前，临床迫切需要开发具有细菌抑制和骨再生潜力的骨替代物。然而，用于治疗感染性骨缺损的细菌耐药性和组织毒性风险相对较低的骨支架仍有待开发。在我们发表的研究中，我们报道了季铵化壳聚糖（HACC）接枝3d打印PLGA/HA复合支架具有增强的体外抗菌和骨导向性，以及良好的细胞相容性。本研究进一步证实，hacc移植的PLGA/HA支架在感染大鼠皮质骨缺损和家兔松质骨缺损中均表现出显著增强的抗感染和骨再生效果。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，影响了支架在感染骨缺损模型中的骨修复潜力。总之，这项研究为开发具有双重功能的3d打印骨支架提供了重要的机会，该支架可用于未来的整形和矫形手术中感染的骨缺陷。(C) 2018材料学报Elsevier Ltd.出版。版权所有。
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 polylactideco-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 SignificanceCurrently, 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 infectedbone 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. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.