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

Kim, Y.-H., Furuya, H. and Tabata, Yasuhiko (2014) Enhancement of bone regeneration by dual release of a macrophage recruitment agent and platelet-rich plasma from gelatin hydrogels. Biomaterials, 35 (1), 214-224. (doi:10.1016/j.biomaterials.2013.09.103).

Abstract

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 (TNF)-α 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)-β1 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

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Contributors

Author: Y.-H. Kim

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