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用于感染性骨缺损再生的反义yycF与骨形态发生蛋白-2共递送甲基丙烯酸明胶和羧甲基壳聚糖水凝胶复合材料

Antisense yycF and BMP-2 co-delivery gelatin methacryloyl and carboxymethyl chitosan hydrogel composite for infective bone defects regeneration.

作者信息

Qin Boquan, Dong Hongxian, Tang Xiaofang, Liu Yunjie, Feng Guoying, Wu Shizhou, Zhang Hui

机构信息

Department of Orthopedic Surgery and Orthopedic Research Institute, Laboratory of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.

Department of Emergency, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.

出版信息

Int J Biol Macromol. 2023 Dec 31;253(Pt 5):127233. doi: 10.1016/j.ijbiomac.2023.127233. Epub 2023 Oct 2.

Abstract

Repairing infected bone defects remains a challenge in clinical work. Intractable bacterial infections and insufficient osseointegration are major concerns for infected bone defects. To address these issues, we developed a gelatin methacryloyl (GelMA) and carboxymethyl chitosan (CMCS) composite hydrogel with BMP-2 growth factor and GO based antisense technology supported by a PLGA spring. In vitro, photo-crosslinked GelMA composite hydrogels shown excellent biocompatibility and degradability. Relying on the release of BMP-2 from the composite hydrogel provides osteogenic effects. The antisense yycF and BMP-2 were released with the degradation of GelMA and CMCS composite hydrogel. In terms of antimicrobial properties, CMCS, GO and post-transcriptional regulatory antisense yycF from the composite hydrogel synergistically kill S. aureus. In vivo, we implanted the composite hydrogel in a rat model of S. aureus infected femur defect, effectively accelerating bone healing in an infectious microenvironment. This research provides a novel biomaterial that is both antimicrobial and promotes bone regeneration, with the potential to treat infected bone defects.

摘要

修复感染性骨缺损在临床工作中仍然是一项挑战。顽固性细菌感染和骨整合不足是感染性骨缺损的主要问题。为了解决这些问题,我们开发了一种甲基丙烯酰化明胶(GelMA)和羧甲基壳聚糖(CMCS)复合水凝胶,其含有骨形态发生蛋白-2(BMP-2)生长因子,并基于聚乳酸-羟基乙酸共聚物(PLGA)弹簧支撑的氧化石墨烯(GO)反义技术。在体外,光交联的GelMA复合水凝胶表现出优异的生物相容性和可降解性。复合水凝胶中BMP-2的释放具有成骨作用。反义yycF和BMP-2随着GelMA和CMCS复合水凝胶的降解而释放。在抗菌性能方面,复合水凝胶中的CMCS、GO和转录后调控反义yycF协同杀灭金黄色葡萄球菌。在体内,我们将复合水凝胶植入金黄色葡萄球菌感染的大鼠股骨缺损模型中,有效加速了感染微环境中的骨愈合。本研究提供了一种新型生物材料,它既能抗菌又能促进骨再生,具有治疗感染性骨缺损的潜力。

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