Wang Jing, Xiao Lan, Wang Weiqun, Zhang Dingmei, Ma Yaping, Zhang Yi, Wang Xin
Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Centre for Biomedical Technologies, School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, Australia.
Front Bioeng Biotechnol. 2022 May 12;10:837172. doi: 10.3389/fbioe.2022.837172. eCollection 2022.
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 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] 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.
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很重要。自肝素被发现以来，其抗凝、抗炎和抗癌功能已被广泛研究了一个多世纪。尽管肝素在骨科领域应用广泛，但其对骨再生的辅助作用仍有待揭示。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，肝素还可以提高BMP-2的递送和保留率，在超生理剂量下促进大骨缺损的愈合。在血管形成方面，肝素通过与血小板衍生生长因子（PDGF）协同作用，在骨折愈合中仍发挥着不可或缺的作用。重要的是，由于肝素与生长因子以及纳米材料中的释放成分结合，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]的控释和保留。因此，了解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对于材料引导的骨再生研究至关重要。本研究系统综述了肝素的结构特性和辅助功能，重点关注其在生理条件下对骨再生的作用及其在生物材料中的应用。
