Local Administration of Bone Morphogenetic Protein-2 Using a Hydrogel Carrier for Robust Bone Regeneration in a Large Animal Model of Legg-Calvé-Perthes disease

使用水凝胶载体局部施用骨形态发生蛋白-2,在 Legg-Calvé-Perthes 病大型动物模型中实现稳健的骨再生

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作者:Harry Kim, Chi Ma, Minsung Park, Felipe Monte, Vishal Gokani, Olumide Aruwajoye, Yinshi Ren, Xiaohua Liu

Abstract

Legg-Calvé-Perthes disease is juvenile idiopathic osteonecrosis of the femoral head (ONFH) that has no effective clinical resolutions. Previously, local injection of bone morphogenetic protein-2 (BMP2) for ONFH treatment showed a heterogeneous bone repair and a high incidence of heterotopic ossification (HO) due to the BMP2 leakage. Here, we developed a BMP2-hydrogel treatment via a transphyseal bone wash and subsequential injection of BMP2-loaded hydrogel. In vivo studies showed that a hydrogel of gelatin-heparin-tyramine retained the BMP2 for four weeks. The injection of the hydrogel can efficiently prevent leakage. With the bone wash, the injected hydrogel had a broad distribution in the head. In vivo studies on pigs revealed that the BMP2-hydrogel treatment produced a homogeneous bone regeneration without HO. It preserved the subchondral contour and restored the subchondral endochondral ossification, although it increased growth plate fusions. In summary, the study demonstrated a promising BMP2-hydrogel treatment for ONFH treatment, especially for teenagers.

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