The Auxiliary Role of Heparin in Bone Regeneration and its Application in Bone Substitute Materials.
The Auxiliary Role of Heparin in Bone Regeneration and its Application in Bone Substitute Materials.
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肝素对骨再生的辅助作用及其在骨替代材料中的应用。
DOI：
10.3389/fbioe.2022.837172
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发表时间：
2022
影响因子：
5.7
通讯作者：
Wang, Xin
中科院分区：
文献类型：
--
作者：
Wang, Jing;Xiao, Lan;Wang, Weiqun;Zhang, Dingmei;Ma, Yaping;Zhang, Yi;Wang, Xin
关键词：
大段骨缺损的骨再生依赖于成骨细胞的作用和新血管的长入。因此，促进成骨/血管生成生长因子的释放是重要的。自肝素被发现以来，其抗凝血、抗炎和抗癌功能已被广泛研究了世纪。肝素虽然在骨科领域应用广泛，但其对骨再生的辅助作用还有待揭开。具体而言，约三分之一的转化生长因子（TGF）超家族与肝素和硫酸乙酰肝素结合，其中TGF-β1、TGF-β2和骨形态发生蛋白（BMP）是最常用的生长因子。此外，肝素还可以改善BMP-2在体内的递送和保留，以超生理剂量促进大骨缺损的愈合。在血管形成中，肝素通过与血小板衍生生长因子（PDGF）合作仍然发挥骨折愈合的组成部分。重要的是，由于肝素与生长因子结合并释放纳米材料中的组分，因此它可以显著促进生长因子[如成纤维细胞生长因子（FGF）、BMP和PDGF]在体内的受控释放和保留。因此，由肝素和不同生物材料（包括有机、无机、金属和天然聚合物）组成的支架或递送系统的知识对于材料引导的骨再生研究至关重要。本文系统地综述了肝素的结构特性和辅助功能，重点介绍了生理条件下的骨再生及其在生物材料中的应用。
Bone regeneration in large segmental defects depends on the action of osteoblasts and the ingrowth of new blood vessels. Therefore, it is important to promote the release of osteogenic/angiogenic growth factors. Since the discovery of heparin, its anticoagulant, anti-inflammatory, and anticancer functions have been extensively studied for over a century. Although the application of heparin is widely used in the orthopedic field, its auxiliary effect on bone regeneration is yet to be unveiled. Specifically, approximately one-third of the transforming growth factor (TGF) superfamily is bound to heparin and heparan sulfate, among which TGF-β1, TGF-β2, and bone morphogenetic protein (BMP) are the most common growth factors used. In addition, heparin can also improve the delivery and retention of BMP-2 in vivo promoting the healing of large bone defects at hyper physiological doses. In blood vessel formation, heparin still plays an integral part of fracture healing by cooperating with the platelet-derived growth factor (PDGF). Importantly, since heparin binds to growth factors and release components in nanomaterials, it can significantly facilitate the controlled release and retention of growth factors [such as fibroblast growth factor (FGF), BMP, and PDGF] in vivo. Consequently, the knowledge of scaffolds or delivery systems composed of heparin and different biomaterials (including organic, inorganic, metal, and natural polymers) is vital for material-guided bone regeneration research. This study systematically reviews the structural properties and auxiliary functions of heparin, with an emphasis on bone regeneration and its application in biomaterials under physiological conditions.
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