Bone reservoir: Injectable hyaluronic acid hydrogel for minimal invasive bone augmentation
Bone reservoir: Injectable hyaluronic acid hydrogel for minimal invasive bone augmentation
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DOI：
10.1016/j.jconrel.2011.02.003
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发表时间：
2011-06-10
影响因子：
10.8
通讯作者：
Varghese, Oommen P.
中科院分区：
文献类型：
--
作者：
Martinez-Sanz, Elena;Ossipov, Dmitri A.;Varghese, Oommen P.
设计了一种策略，利用微创技术开发透明质酸(HA)水凝胶，用于体内骨强化。采用温和的合成工艺，通过酰胺化反应和侧基的选择性氧化，引入氨基甘油侧链，制备了醛修饰的透明质酸。该改性后的HA与酰肼混合后，在30 S范围内形成了一种在生理pH条件下稳定的肼类交联水凝胶。体外实验表明，具有活性骨形态发生蛋白-2(BMP-2)控释的水凝胶没有细胞毒性。通过在大鼠颅骨上注射凝胶对该凝胶作为BMP-2载体进行了体内评估，结果显示8周内骨形成与凝胶中BMP-2的载入量(0、1和30头猪)相关。此外，与骨膜下植入相比，含有30公斤BMP-2的水凝胶皮下注射诱导的骨形成较少。组织学检查显示，BMP-2浓度较高时，新骨形成，骨钙素、骨桥蛋白高表达，并有血管生成的骨髓。我们的结果表明，新型HA水凝胶可以作为BMP-2的载体，并可以促进骨强化，具有潜在的骨科应用。(C)2011爱思唯尔B.V.保留所有权利。
A strategy has been designed to develop hyaluronic acid (HA) hydrogel for in vivo bone augmentation using minimal invasive technique. A mild synthetic procedure was developed to prepare aldehyde modified HA by incorporating an amino-glycerol side chain via amidation reaction and selective oxidation of the pendent group. This modification, upon mixing with hydrazide modified HA formed hydrazone-crosslinked hydrogel within 30 s that was stable at physiological pH. In vitro experiments showed no cytotoxicity of hydrogel with the controlled release of active bone morphogenic protein-2 (BMP-2). In vivo evaluation of this gel as a BMP-2 carrier was performed by injecting gels over the rat calvarium and showed bone formation in 8 weeks in correlation with the amount of BMP-2 loaded (0, 1 and 30 pig) within the gel. Furthermore, hydrogels with 30 Kg of BMP-2 induced less bone formation upon subcutaneous injection in comparison with subperiosteal implantation. Histological examination showed newly formed bone with a high expression of osteocalcin, osteopontin and with angiogenic bone marrow when higher BMP-2 concentration was employed. Our result suggests that novel HA hydrogels could be used as a BMP-2 carrier and can promote bone augmentation for potential orthopedic applications. (C) 2011 Elsevier B.V. All rights reserved.