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Novel Therapeutic Strategy for Bacteria-Contaminated Bone Defects: Reconstruction with Multi-Biofunctional GO/Cu-Incorporated 3D Scaffolds
Advanced Therapeutics ( IF 4.6 ) Pub Date : 2022-06-03 , DOI: 10.1002/adtp.202200043
Ying Yang 1, 2, 3 , Min Li 4 , Bixia Zhou 1, 3 , Xulei Jiang 1, 3 , Dou Zhang 2 , Hang Luo 2 , Shaorong Lei 1, 3
Affiliation  

Large-scale bone defects caused by traumatic injury or tumor resection, are accompanied by relatively high bacterial infection rates. Relevant clinical therapy encounters challenges of infection recurrence, poor vascularization, and bone destruction. Engineered substitutes endowed with multiple functions of bacterial eradication, osteoconductivity, and angiogenesis are urgently needed to address these challenges. Herein, graphene oxide/copper (GO/Cu) nanocomposite-decorated polylactide-co-glycolide (PLGA)/β-tricalcium phosphate (TCP) (P/T/GO/Cu) scaffolds are fabricated using 3D printing technology. A comprehensive evaluation of material characteristics and biological activities of these scaffolds is conducted and compared. This novel bone substitute has unique surface characteristics, and the incorporation of GO/Cu nanocomposites into the scaffolds exhibits improved antimicrobial and osteogenic potential and displays acceptable cytocompatibility. A subcutaneous implantation model in rats confirms the effective inhibition of abscess formation and inflammatory reactions, satisfactory neovascularization and tissue integration, and good biosafety of the implanted P/T/GO/Cu scaffolds. Eventually, a bacteria-contaminated bone defect model is established in rabbits and significantly better new cancellous bone formation featuring collagen or osteoid deposition is clearly found in the defect regions implanted with P/T/GO/Cu scaffolds. Thus, this novel bone substitute with excellent bacterial inhibition, osteogenesis, and angiogenesis capabilities represents a promising strategy to satisfy the multiple demands for the repair of bacteria-contaminated bone defects.

中文翻译:

细菌污染骨缺损的新治疗策略:用多生物功能 GO/Cu 结合的 3D 支架进行重建

外伤或肿瘤切除引起的大面积骨缺损,伴有较高的细菌感染率。相关临床治疗面临感染复发、血管化不良和骨质破坏的挑战。迫切需要具有细菌根除、骨传导性和血管生成等多种功能的工程替代品来应对这些挑战。在此,氧化石墨烯/铜 (GO/Cu) 纳米复合材料修饰的聚乳酸-乙交酯 (PLGA)/β-磷酸三钙 (TCP) (P/T/GO/Cu) 支架采用 3D 打印技术制造。对这些支架的材料特性和生物活性进行了综合评估和比较。这种新型骨替代物具有独特的表面特性,将 GO/Cu 纳米复合材料掺入支架中显示出改善的抗菌和成骨潜力,并显示出可接受的细胞相容性。大鼠皮下植入模型证实了植入的 P/T/GO/Cu 支架能有效抑制脓肿形成和炎症反应、令人满意的新生血管形成和组织整合以及良好的生物安全性。最终,在兔子中建立了细菌污染的骨缺损模型,在植入 P/T/GO/Cu 支架的缺损区域明显发现了以胶原或类骨质沉积为特征的明显更好的新松质骨形成。因此,这种具有优异细菌抑制、成骨和血管生成能力的新型骨替代物代表了一种有前途的策略,可以满足修复受细菌污染的骨缺损的多种需求。
更新日期:2022-06-03
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