Stimulation of bone regeneration following the controlled release of water-insoluble oxysterol from biodegradable hydrogel
Stimulation of bone regeneration following the controlled release of water-insoluble oxysterol from biodegradable hydrogel
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DOI：
10.1016/j.biomaterials.2014.03.018
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发表时间：
2014-07-01
期刊：
影响因子：
14
通讯作者：
Jarrahy, Reza
中科院分区：
文献类型：
--
作者：
Hokugo, Akishige;Saito, Takashi;Jarrahy, Reza
最近，使用骨形态发生蛋白（BMP）的骨移植替代物已被预示为传统骨重建程序的潜在替代品。然而，当用于头部和颈部区域时，基于BMP的产品与显著的和潜在的危及生命的副作用相关，此外，价格过高。氧固醇是胆固醇氧化的产物，代表了一类分子，由于其副作用和成本低，因此是BMP治疗的有利替代品或辅助剂。为了建立氧固醇的最佳临床效用，必须开发最佳支架，其允许以持续和有效的方式释放氧固醇。在这项研究中，我们准备了一种临床适用的骨移植替代工程的最佳释放氧固醇。我们首先通过使用L-乳酸低聚物（LAo）接枝明胶的聚合物胶束在水中增溶氧甾醇。然后，将水溶性氧甾醇掺入生物可降解水凝胶中，该水凝胶在体内酶促降解。以这种方式，氧固醇可以以降解驱动的方式从水凝胶中释放。将水溶性氧化固醇生物可降解水凝胶植入大鼠颅骨缺损，并诱导成功的骨再生。这项研究的创新意义在于开发一种骨移植替代品，该替代品将氧固醇的成骨活性与为优化氧固醇释放动力学而设计的支架相结合，所有这些都能更好地修复骨缺损。(C)2014爱思唯尔有限公司版权所有。
Recently bone graft substitutes using bone morphogenetic proteins (BMPs) have been heralded as potential alternatives to traditional bone reconstruction procedures. BMP-based products, however, are associated with significant and potentially life-threatening side effects when used in the head and neck region and furthermore, are exorbitantly priced. Oxysterols, products of cholesterol oxidation, represent a class of molecules that are favorable alternatives or adjuncts to BMP therapy due to their low side effect profile and cost. In order to establish the optimal clinical utility of oxysterol, an optimal scaffold must be developed, one that allows the release of oxysterol in a sustained and efficient manner. In this study, we prepare a clinically applicable bone graft substitute engineered for the optimal release of oxysterol. We first solubilized oxysterol in water by making use of polymeric micelles using L-lactic acid oligomer (LAo) grafted gelatin. Then, the water-solubilized oxysterol was incorporated into a biodegradable hydrogel that was enzymatically degraded intracorporeally. In this manner, oxysterol could be released from the hydrogel in a degradation-driven manner. The water-solubilized oxysterol incorporated biodegradable hydrogel was implanted into rat calvarial defects and induced successful bone regeneration. The innovative significance of this study lies in the development of a bone graft substitute that couples the osteogenic activity of oxysterol with a scaffold designed for optimized oxysterol release kinetics, all of which lead to better repair of bone defects. (C) 2014 Elsevier Ltd. All rights reserved.