Hyaluronic acid hydrogels with controlled degradation properties for oriented bone regeneration.

Hyaluronic acid hydrogels with controlled degradation properties for oriented bone regeneration.
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DOI:
10.1016/j.biomaterials.2010.05.047
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发表时间:
2010-09
期刊:
影响因子:
14
通讯作者:
Stayton PS
Stayton PS
中科院分区:
工程技术1区
文献类型:
--
作者:
Patterson J;Siew R;Herring SW;Lin AS;Guldberg R;Stayton PS

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无法愈合的骨折可由创伤、疾病或与年龄相关的骨丢失引起。虽然许多治疗方法侧重于恢复骨容量,但很少有人尝试重塑骨组织。然而,骨骼的天然结构经过优化,以提供其必要的力学性能。透明质酸(HA)水凝胶支架系统具有可调节的降解性能,用于控制骨诱导生长因子和血管生成生长因子的释放,从而影响再生组织的数量和质量。HA水凝胶被设计为由于水解而以快、中、慢的速度降解,并由于静电相互作用进一步提供阳离子蛋白质的受控释放。在大鼠颅骨临界大小缺损模型中对骨形态发生蛋白-2(BMP-2)支架进行了评价。从HA水凝胶中释放BMP-2在体内有明显的骨诱导作用,并且,对于所有类型的水凝胶,与对照水凝胶相比,BMP-2释放导致显著的矿化。这种效应的时间进程可以通过改变支架的降解率来调节。在最近一次(六周)测试的时间点上,三种降解率都导致了相似数量的矿物形成。然而,有趣的是,降解最快和最慢的支架似乎比中等降解的支架产生更有组织的骨,中等降解支架被设计为在6-8周内降解,以匹配愈合时间。此外,血管内皮生长因子和骨形态发生蛋白-2的共同输送可以促进愈合。
Non-healing fractures can result from trauma, disease, or age-related bone loss. While many treatments focus on restoring bone volume, few try to recapitulate bone organization. However, the native architecture of bone is optimized to provide its necessary mechanical properties. Hyaluronic acid (HA) hydrogel scaffold systems with tunable degradation properties were developed for the controlled delivery of osteoinductive and angiogenic growth factors, thus affecting the quantity and quality of regenerated tissue. HA hydrogels were designed to degrade at fast, intermediate, and slow rates due to hydrolysis and further provided controlled release of cationic proteins due to electrostatic interactions. Scaffolds delivering bone morphogenetic protein-2 (BMP-2) were evaluated in a rat calvarial bone critical size defect model. BMP-2 delivery from the HA hydrogels had a clear osteoinductive effect in vivo and, for all hydrogel types, BMP-2 delivery resulted in significant mineralization compared to control hydrogels. The temporal progression of this effect could be modulated by altering the degradation rate of the scaffold. All three degradation rates tested resulted in similar amounts of mineral formation at the latest (six week) time point examined. Interestingly, however, the fastest and slowest degrading scaffolds seemed to result in more organized bone than the intermediate degrading scaffold, which was designed to degrade in 6–8 weeks to match the healing time. Additionally, healing could be enhanced by co-delivery of vascular endothelial growth factor along with BMP-2.
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