骨再生中基于石墨烯的3D支架：MRONJ治疗的新兴机遇

摘要(中文译文)

药物相关性颌骨坏死（MRONJ）仍然是抗骨吸收和抗血管生成治疗相关的一种具有挑战性的并发症，其特征为骨愈合受损、感染和血管化不良。能够促进骨再生并调节局部微环境的先进生物材料正被研究作为潜在的治疗策略。石墨烯基生物材料因其独特的理化性质和多功能的生物学效应，近年来已成为有前景的候选材料。本系统综述旨在分析和综合当前关于石墨烯基三维支架及相关石墨烯基生物材料用于骨再生的证据，特别关注其在MRONJ治疗和预防中的潜在相关性。在PubMed和Scopus数据库进行了系统性文献检索，并辅以对相关出版物参考文献列表的手工筛查。纳入研究石墨烯基支架、复合材料或石墨烯衍生生物材料用于骨再生的研究。纳入涉及成骨、血管生成、抗菌活性、免疫调节或与骨愈合和MRONJ相关的药物递送特性的体外和体内实验研究以及转化研究。排除社论、会议摘要和非英文出版物。由作者独立筛选标题和摘要，随后进行全文评估以确定合格性。由于研究设计和结局指标的异质性，对支架组成、石墨烯衍生物、生物学机制和再生结局的数据进行了定性综合。所识别的文献强调了石墨烯基生物材料在骨再生中的多方面作用。石墨烯及其衍生物增强成骨分化、促进血管生成、调节免疫反应，并具有内在的抗菌特性。此外，石墨烯基支架为药物递送和光热或光动力治疗策略提供了多功能平台。这些多功能特性可能针对MRONJ涉及的关键病理生理机制，包括骨重塑受损、感染控制和组织再生。现有证据主要来自临床前研究，在MRONJ特异性模型中的直接研究有限，且支架设计和实验方法学存在相当大的异质性。石墨烯基三维支架代表了一种有前景且多功能的骨再生策略平台，可能适用于MRONJ管理。需要进一步的转化研究以及精心设计的临床前和临床研究来阐明其安全性、有效性和治疗适用性。本综述按照PRISMA 2020指南进行。综述方案未注册。

Abstract

: Medication-related osteonecrosis of the jaw (MRONJ) remains a challenging complication associated with antiresorptive and antiangiogenic therapies, characterized by impaired bone healing, infection, and compromised vascularization. Advanced biomaterials capable of promoting bone regeneration and modulating the local microenvironment are being investigated as potential therapeutic strategies. Graphene-based biomaterials have recently emerged as promising candidates due to their unique physicochemical properties and multifunctional biological effects. : This systematic review aimed to analyze and synthesize current evidence on graphene-based 3D scaffolds and related graphene-based biomaterials for bone regeneration, with particular attention to their potential relevance in MRONJ treatment and prevention. : A systematic literature search was conducted in PubMed and Scopus databases, complemented by manual screening of reference lists from relevant publications. : Studies investigating graphene-based scaffolds, composites, or graphene-derived biomaterials for bone regeneration were considered. Experimental in vitro and in vivo studies, as well as translational studies addressing osteogenesis, angiogenesis, antimicrobial activity, immunomodulation, or drug-delivery properties relevant to bone healing and MRONJ, were included. Editorials, conference abstracts, and non-English publications were excluded. : Titles and abstracts were independently screened by the authors, followed by full-text assessment for eligibility. Data regarding scaffold composition, graphene derivatives, biological mechanisms, and regenerative outcomes were qualitatively synthesized due to heterogeneity in study designs and outcome measures. : The identified literature highlights the multifaceted role of graphene-based biomaterials in bone regeneration. Graphene and its derivatives enhance osteogenic differentiation, promote angiogenesis, modulate immune responses, and exhibit intrinsic antimicrobial properties. In addition, graphene-based scaffolds provide versatile platforms for drug delivery and photothermal or photodynamic therapeutic strategies. These multifunctional properties may address key pathophysiological mechanisms involved in MRONJ, including impaired bone remodeling, infection control, and tissue regeneration. : The available evidence is predominantly derived from preclinical studies, with limited direct investigation in MRONJ-specific models and considerable heterogeneity in scaffold design and experimental methodologies. : Graphene-based 3D scaffolds represent a promising and versatile platform for bone regenerative strategies potentially applicable to MRONJ management. Further translational research and well-designed preclinical and clinical studies are required to clarify their safety, efficacy, and therapeutic applicability. : This review was conducted according to PRISMA 2020 guidelines. The review protocol was not registered.

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