Enhancement of bone regeneration by dual release of a macrophage recruitment agent and platelet-rich plasma from gelatin hydrogels

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• 作者：Yang-Hee Kim ; Hiroyuki Furuya ; Yasuhiko Tabata
• 关键词：Macrophages ; Gelatin hydrogel ; Controlled release ; S1P1 agonist (SEW2871) ; Platelet rich plasma (PRP) ; Bone regeneration
• 刊名：Biomaterials
• 出版年：January, 2014
• 年：2014
• 卷：35
• 期：1
• 页码：214-224
• 全文大小：2464 K

文摘

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聽vitro and in聽vivo. In聽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 (TNF)-伪 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)-尾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.