Enhancement of bone regeneration by dual release of a macrophage recruitment agent and platelet-rich plasma from gelatin hydrogels
Enhancement of bone regeneration by dual release of a macrophage recruitment agent and platelet-rich plasma from gelatin hydrogels
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DOI：
10.1016/j.biomaterials.2013.09.103
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发表时间：
2014-01-01
期刊：
影响因子：
14
通讯作者：
Tabata, Yasuhiko
中科院分区：
文献类型：
--
作者：
Kim, Yang-Hee;Furuya, Hiroyuki;Tabata, Yasuhiko
巨噬细胞在调节炎症反应和组织再生中发挥重要作用。在本研究中，通过同时应用巨噬细胞招募剂、鞘氨醇-1磷酸激动剂SEW2871和富血小板血浆（PRP）来研究它们对骨重塑的影响。将非水溶性SEW2871与l -乳酸接枝的明胶形成胶束，将胶束与PRP结合制成明胶水凝胶。sew2871 -胶束和PRP混合在明胶水凝胶中以受控的方式在体外和体内释放。体外迁移实验显示，PRP的存在协同促进了sew2871诱导的巨噬细胞迁移。当应用于大鼠骨缺损时，混合sew2871 -胶束和PRP的水凝胶比混合sew2871 -胶束或PRP的水凝胶募集了更多的巨噬细胞。sew2871 -胶束与PRP混合的水凝胶在应用后3天增强促炎细胞因子中肿瘤坏死因子(TNE)- α的水平，而在术后10天出现促炎反应，同时抗炎细胞因子中骨保护素（OPG）、白细胞介素(IL)-10和转化生长因子(TGF)- β(1)的表达水平显著升高。与PBS、sew2871 -胶束或PRP混合的水凝胶相比，sew2871 -胶束和PRP混合的水凝胶在很大程度上促进了骨再生。由此可见，巨噬细胞的募集有助于prp诱导的骨再生。(C) 2013 Elsevier Ltd.版权所有。
Macrophages play an important role in regulating inflammatory responses and tissue regeneration. In the present study, their effect on bone remodeling is investigated by the simultaneous application of a macrophage recruiting agent, SEW2871 of a sphingosine-1 phosphate agonist, and platelet-rich plasma (PRP). The non-water soluble SEW2871 was solubilized in water through micelles formation with L-lactic acid grafted gelatin, and the resulting micelles with PRP were incorporated into gelatin hydrogels. Mixed SEW2871-micelles and PRP were released from gelatin hydrogels in a controlled fashion both in vitro and in vivo. In vitro migration assay revealed that the presence of PRP synergistically promoted SEW2871-induced macrophages migration. When applied to a bone defect of rats, the hydrogels incorporating mixed SEW2871-micelles and PRP recruited a higher number of macrophages than those hydrogels incorporating either SEW2871-micelles or PRP. The hydrogels incorporating mixed SEW2871-micelles and PRP enhanced the level of tumor necrosis factor (TNE)-alpha of pro-inflammatory cytokine, 3 days after application, while pro-inflammatory responses coupled with a significant increase in the expression level of osteoprotegerin (OPG) and interleukin (IL)-10 and transforming growth factor (TGF)-beta(1) of anti-inflammatory cytokine were observed 10 days postoperatively. The hydrogels incorporating mixed SEW2871-micelles and PRP promoted bone regeneration to a significant great extent compared with those incorporating PBS and either SEW2871-micelles or PRP. It is concluded that macrophages recruitment contributed to PRP-induced bone regeneration. (C) 2013 Elsevier Ltd. All rights reserved.