The use of injectable sonication-induced silk hydrogel for VEGF(165) and BMP-2 delivery for elevation of the maxillary sinus floor.
The use of injectable sonication-induced silk hydrogel for VEGF(165) and BMP-2 delivery for elevation of the maxillary sinus floor.
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DOI：
10.1016/j.biomaterials.2011.08.047
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发表时间：
2011-12
期刊：
影响因子：
14
通讯作者：
Jiang, Xinquan
中科院分区：
文献类型：
--
作者：
Zhang, Wenjie;Wang, Xiuli;Wang, Shaoyi;Zhao, Jun;Xu, Lianyi;Zhu, Chao;Zeng, Deliang;Chen, Jake;Zhang, Zhiyuan;Kaplan, David L.;Jiang, Xinquan
超声诱导的丝水凝胶先前被制备为可注射的骨替代生物材料，需要改善成骨特征。血管内皮生长因子（VEGF 165）和骨形态发生蛋白-2（BMP-2）分别是骨再生过程中血管生成和骨生成的关键调节因子。因此，本研究的目的是评估原位形成的丝水凝胶作为载体，以封装兔上颌窦底提升的双重因素。体外制备了超声诱导的丝素水凝胶，并通过ELISA评价了这些丝素凝胶对VEGF 165和BMP-2的缓释作用。对于每个时间点（4周和12周）的体内研究，在12只兔中双侧进行24次窦底提升手术，用于以下四个治疗组：蚕丝凝胶（蚕丝凝胶组）、蚕丝凝胶/VEGF 165（VEGF组）、蚕丝凝胶/BMP-2（BMP-2组）、蚕丝凝胶/VEGF 165/BMP-2（V+B组）（每组n=6）。使用连续的荧光标记和放射学观察记录新骨形成和矿化，沿着组织学和组织形态计量学分析。在第4周，VEGF 165促进更多的组织浸润到凝胶中，并加速凝胶材料的降解。此时，V+B组的骨面积明显大于其他三组。第12周时，BMP-2组和V+B组的窦底高度高于Silk gel组和VEGF组，V+B组的新骨面积最大。此外，VEGF组和V+B组的剩余凝胶区域中形成了较大的血管区域。总之，从可注射和可生物降解的丝凝胶中释放的VEGF 165和BMP-2促进了血管生成和新骨形成，这两个因素对骨再生具有相加作用。这些结果表明，丝水凝胶可用作可注射载体，以微创方法递送多种生长因子以再生不规则骨腔。
Sonication-induced silk hydrogels were previously prepared as an injectable bone replacement biomaterial, with a need to improve osteogenic features. Vascular endothelial growth factor (VEGF165) and bone morphogenic protein-2 (BMP-2) are key regulators of angiogenesis and osteogenesis, respectively, during bone regeneration. Therefore, the present study aimed at evaluating in situ forming silk hydrogels as a vehicle to encapsulate dual factors for rabbit maxillary sinus floor augmentation. Sonication-induced silk hydrogels were prepared in vitro and the slow release of VEGF165 and BMP-2 from these silk gels was evaluated by ELISA. For in vivo studies for each time point (4 and 12 weeks), 24 sinus floors elevation surgeries were made bilaterally in 12 rabbits for the following four treatment groups: silk gel (group Silk gel), silk gel/VEGF165 (group VEGF), silk gel/BMP-2 (group BMP-2), silk gel/VEGF165/BMP-2 (group V+B) (n=6 per group). Sequential florescent labeling and radiographic observations were used to record new bone formation and mineralization, along with histological and histomorphometric analysis. At week 4, VEGF165 promoted more tissue infiltration into the gel and accelerated the degradation of the gel material. At this time point, the bone area in group V+B was significantly larger than those in the other three groups. At week 12, elevated sinus floor heights of groups BMP-2 and V+B were larger than those of the Silk gel and VEGF groups, and the V+B group had the largest new bone area among all groups. In addition, a larger blood vessel area formed in the remaining gel areas in groups VEGF and V+B. In conclusion, VEGF165 and BMP-2 released from injectable and biodegradable silk gels promoted angiogenesis and new bone formation, with the two factors demonstrating an additive effect on bone regeneration. These results indicate that silk hydrogels can be used as an injectable vehicle to deliver multiple growth factors in a minimally invasive approach to regenerate irregular bony cavities.
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