石墨烯族纳米材料调控骨再生微环境的研究进展

Research progress on graphene and its derivatives modulating the bone regeneration microenvironment

摘要

石墨烯族纳米材料（graphene-family nanomaterials，GFNs）以其卓越的机械性能、生物相容性和促进干细胞成骨分化的能力而在骨组织工程领域备受关注。GFNs在调控骨再生微环境中发挥了多方面的作用。首先，GFNs本身微观形态能够激活黏着斑激酶/细胞外调节蛋白激酶（focal adhesion kinase/ extracellular regulated protein kinase，FAK/ERK）信号通路，促进成骨相关基因的表达。其次，GFNs适应骨组织的机械强度，有助于维持骨整合，并通过调整细胞外基质的硬度，借助黏着斑（focal adhesions，FAs）将基质的力学信号传递到胞内，创造良好的理化微环境；此外，它们还能调节骨缺损部位的免疫微环境，引导巨噬细胞向M2型极化，并影响相关细胞因子的分泌。GFNs还可作为生物活性分子的缓释载体，兼具促进血管形成和抗菌能力，从而加速骨缺损的修复过程。同时，GFNs通过多种形式调控骨再生微环境，包括支架材料、水凝胶、生物薄膜和植入物涂层等。尽管GFNs在骨组织工程领域引起广泛关注，但其在骨组织再生方面的应用仍处于基础实验阶段。为了推动GFNs进入临床应用阶段，需要提供更充分的生物相容性证据，明确诱导干细胞成骨分化的机制，并开发更高效的材料应用形式。

Abstract

Graphene family nanomaterials (GFNs) are highly popular in the field of bone tissue engineering because of their excellent mechanical properties, biocompatibility, and ability to promote the osteogenic differentiation of stem cells. GFNs play a multifaceted role in promoting the bone regeneration microenvironment. First, GFNs activate the adhesion kinase/extracellularly regulated protein kinase (FAK/ERK) signaling pathway through their own micromorphology and promote the expression of osteogenesis-related genes. Second, GFNs adapt to the mechanical strength of bone tissue, which helps to maintain osseointegration; by adjusting the stiffness of the extracellular matrix, they transmit the mechanical signals of the matrix to the intracellular space with the help of focal adhesions (FAs), thus creating a favorable physiochemical microenvironment. Moreover, they regulate the immune microenvironment at the site of bone defects, thus directing the polarization of macrophages to the M2 type and influencing the secretion of relevant cytokines. GFNs also act as slow-release carriers of bioactive molecules with both angiogenic and antibacterial abilities, thus accelerating the repair process of bone defects. Multiple types of GFNs regulate the bone regeneration microenvironment, including scaffold materials, hydrogels, biofilms, and implantable coatings. Although GFNs have attracted much attention in the field of bone tissue engineering, their application in bone tissue regeneration is still in the basic experimental stage. To promote the clinical application of GFNs, there is a need to provide more sufficient evidence of their biocompatibility, elucidate the mechanism by which they induce the osteogenic differentiation of stem cells, and develop more effective form of applications.

关键词

石墨烯 / 氧化石墨烯 / 骨组织工程 / 支架材料 / 水凝胶 / 骨再生 / 成骨诱导 / 细胞微环境 / 免疫微环境 / 理化特征

Key words

graphene / graphene oxide / bone-tissue engineering / scaffold material / hydrogel / bone regeneration / osteogenesis / cell microenvironment / immune microenvironment / physiochemical property

Author summay

兰元辰，硕士研究生，Email：[e-mail]