糖胺聚糖在骨组织工程中的作用机制及应用

Mechanism and application of glycosaminoglycan in bone tissue engineering

背景:复杂骨缺损修复一直是临床上亟待解决的难题,利用生物功能化的组织工程材料促进骨组织再生修复是目前的研究热点之一。以往关于骨组织材料生物化修饰的研究集中于细胞内信号分子的修饰,而对胞外信号分子的修饰和调控作用研究较少。糖胺聚糖作为细胞外基质的重要信号分子,修饰于支架材料中发挥成骨作用是目前新兴研究方向。目的:对糖胺聚糖在骨组织工程的作用机制和应用进展做一综述。方法:检索PubMed数据库和中国知网收录的有关糖胺聚糖参与调控骨组织再生修复及其在骨组织工程中的作用机制与应用的文章,英文检索词为“glycosaminoglycans,proteoglycans,bone tissue engineering,bone tissue engineering materials,osteogenic differentiation”,中文检索词为“糖胺聚糖链、蛋白聚糖、骨组织工程、骨组织工程材料、成骨分化”。根据纳入与排除标准对所有文章进行初筛后,保留质量和相关性较高的文章85篇进行综述。结果与结论:(1)糖胺聚糖作为细胞外基质的重要组成部分和信号分子,不仅可以与生长因子结合协助其扩散,还可以促进受体与配体之间的相互作用从而调控骨再生信号通路传导。(2)在骨组织工程中,糖胺聚糖经过化学修饰和交联,或与其他天然或合成聚合物联合修饰于细胞支架中支持细胞黏附和增殖,以及作为信号分子为生长因子提供结合位点稳定生长因子并促进内外源性生长因子与其相应受体结合,可以实现有效的骨组织再生。(3)关于糖胺聚糖在骨组织工程中的应用还有诸多问题未解决,如糖胺聚糖局部长期应用的形式和安全性、对成骨细胞命运的确切作用机制以及合成纯化等问题,还需后续研究不断完善。

BACKGROUND:The repair of complex bone defects remains a worldwide public health issue.Currently,utilizing biofunctionalized tissue engineering materials to achieve bone regeneration has been an important research focus.Previous studies on the biochemical repair of bone tissue focused on the exploration of intracellular signaling regulatory networks,while the modification and regulation of extracellular signaling molecules were less studied.The modification of glycosaminoglycans as important signaling molecules in the extracellular matrix to play an osteogenic role in scaffold materials is an emerging research direction.OBJECTIVE:To review the mechanism and application of glycosaminoglycan in bone tissue engineering.METHODS:PubMed and CNKI databases were searched for articles concerning glycosaminoglycans to regulate bone tissue regeneration and repair and its role and functional application in bone tissue engineering with the search terms“glycosaminoglycans,proteoglycans,bone tissue engineering,bone tissue engineering materials,osteogenic differentiation”in English and Chinese respectively.After primarily screening based on the inclusion and exclusion criteria,85 articles with high quality and relevance were included for review.RESULTS AND CONCLUSION:(1)As an important component of the extracellular matrix,glycosaminoglycan not only binds to growth factors to facilitate their diffusion,but also promotes the interaction between receptors and ligands to regulate the signaling pathway of bone regeneration.(2)In bone tissue engineering,glycosaminoglycans are chemically modified and cross-linked,or co-modified with other natural or synthetic polymers in cell scaffolds to support cell adhesion and proliferation,and serve as signaling molecules to provide binding sites for growth factors to stabilize growth factors and promote the binding of endogenous and exogenous growth factors to their corresponding receptors,which can achieve effective bone tissue regeneration.(3)There are still many unresolved issues regarding the application of glycosaminoglycans in bone tissue engineering,such as the form and safety of the local long-term application of glycosaminoglycan,the exact mechanism of action on the fate of osteoblasts,synthesis and purification,which needs to be further improved.