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具有增强的近红外控制原位生物矿化功能的氧化石墨烯/黑磷功能化胶原蛋白支架,通过PI3K/Akt途径促进感染性骨缺损修复

Graphene Oxide/Black Phosphorus Functionalized Collagen Scaffolds with Enhanced Near-Infrared Controlled In Situ Biomineralization for Promoting Infectious Bone Defect Repair through PI3K/Akt Pathway.

作者信息

Chen Xiangru, Sun Zhiwei, Peng Ximing, Meng Na, Ma Liya, Fu Jie, Chen Junwei, Liu Yuanhang, Yang Yanqing, Zhou Chuchao

机构信息

Department of Plastic Surgery, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan 430060, China.

Department of Cardiovascular Medicine, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan 430060, China.

出版信息

ACS Appl Mater Interfaces. 2024 Sep 25;16(38):50369-50388. doi: 10.1021/acsami.4c10284. Epub 2024 Sep 12.

Abstract

Infectious bone defects resulting from surgery, infection, or trauma are a prevalent clinical issue. Current treatments commonly used include systemic antibiotics and autografts or allografts. Nevertheless, therapies come with various disadvantages, including multidrug-resistant bacteria, complications arising from the donor site, and immune rejection, which makes artificial implants desirable. However, artificial implants can fail due to bacterial infections and inadequate bone fusion after implantation. Thus, the development of multifunctional bone substitutes that are biocompatible, antibacterial, osteoconductive, and osteoinductive would be of great clinical importance. This study designs and prepares 2D graphene oxide (GO) and black phosphorus (BP) reinforced porous collagen (Col) scaffolds as a viable strategy for treating infectious bone defects. The fabricated Col-GO@BP scaffold exhibited an efficient photothermal antibacterial effect under near-infrared (NIR) irradiation. A further benefit of the NIR-controlled degradation of BP was to promote biomineralization by phosphorus-driven and calcium-extracted phosphorus in situ. The abundant functional groups in GO could synergistically capture the ions and enhance the in situ biomineralization. The Col-GO@BP scaffold facilitated osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSC) by leveraging its mild photothermal effect and biomineralization process, which upregulated heat shock proteins (HSPs) and activated PI3K/Akt pathways. Additionally, systematic in vivo experiments demonstrated that the Col-GO@BP scaffold obviously promotes infectious bone repair through admirable photothermal antibacterial performance and enhanced vascularization. As a result of this study, we provide new insights into the photothermal activity of GO@BP nanosheets, their degradation, and a new biological application for them.

摘要

由手术、感染或创伤导致的感染性骨缺损是一个普遍存在的临床问题。目前常用的治疗方法包括全身使用抗生素以及自体移植或异体移植。然而,这些治疗方法存在各种缺点,包括多重耐药菌、供体部位出现的并发症以及免疫排斥反应,这使得人工植入物成为理想选择。然而,人工植入物可能会因细菌感染和植入后骨融合不足而失败。因此,开发具有生物相容性、抗菌性、骨传导性和骨诱导性的多功能骨替代物具有重要的临床意义。本研究设计并制备了二维氧化石墨烯(GO)和黑磷(BP)增强的多孔胶原蛋白(Col)支架,作为治疗感染性骨缺损的可行策略。制备的Col-GO@BP支架在近红外(NIR)照射下表现出高效的光热抗菌效果。BP的近红外控制降解的另一个好处是通过磷驱动和原位钙提取磷促进生物矿化。GO中丰富的官能团可以协同捕获离子并增强原位生物矿化。Col-GO@BP支架通过利用其温和的光热效应和生物矿化过程促进骨髓间充质干细胞(BMSC)的成骨分化,该过程上调了热休克蛋白(HSPs)并激活了PI3K/Akt途径。此外,系统的体内实验表明,Col-GO@BP支架通过出色的光热抗菌性能和增强的血管生成明显促进感染性骨修复。这项研究的结果为GO@BP纳米片的光热活性、它们的降解以及它们的新生物应用提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db35/11441399/81bd55db8394/am4c10284_0001.jpg

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