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BMP-2-coated mineral coated microparticles improve bone repair in atrophic non-unions

机译：BMP-2-涂层矿物涂层微粒可改善萎缩性骨不连的骨修复

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Atrophic non-unions are a major clinical problem. Mineral coated microparticles (MCM) are electrolyte-coated hydroxyapatite particles that have been shown in vitro to bind growth factors electrostatically and enable a tuneable sustained release. Herein, we studied whether MCM can be used in vivo to apply Bone Morphogenetic Protein-2 (BMP-2) to improve bone repair of atrophic non-unions. For this purpose, atrophic non-unions were induced in femurs of CD-1 mice (n = 48). Animals either received BMP-2-coated MCM (MCM + BMP; n = 16), uncoated MCM (MCM; n = 16) or no MCM (NONE; n = 16). Bone healing was evaluated 2 and 10 weeks postoperatively by micro-computed tomographic (µCT), biomechanical, histomorphometric and immunohistochemical analyses. µCT revealed more bone volume with more highly mineralised bone in MCM + BMP femurs. Femurs of MCM + BMP animals showed a significantly higher bending stiffness compared to other groups. Histomorphometry further demonstrated that the callus of MCM + BMP femurs was larger and contained more bone and less fibrous tissue. After 10 weeks, 7 of 8 MCM + BMP femurs presented with complete osseous bridging, whereas NONE femurs exhibited a non-union rate of 100 %. Of interest, immunohistochemistry could not detect macrophages within the callus, indicating a good biocompatibility of MCM. In conclusion, the local application of BMP-2-coated MCM improved bone healing in a challenging murine non-union model and, thus, should be of clinical interest in the treatment of non-unions.
机译：萎缩性骨不连是主要的临床问题。矿物包被的微粒（MCM）是电解质包被的羟基磷灰石颗粒，已在体外显示出可静电结合生长因子并实现可调节的持续释放。在这里，我们研究了MCM是否可以在体内用于应用骨形态发生蛋白2（BMP-2）来改善萎缩性骨不连的骨修复。为此，在CD-1小鼠的股骨中诱发了萎缩性骨不连（n = 48）。动物或者接受了BMP-2包被的MCM（MCM + BMP; n = 16），未包被的MCM（MCM; n = 16）或不接受MCM（无; n = 16）。术后2周和10周通过显微计算机断层扫描（µCT），生物力学，组织形态学和免疫组织化学分析评估骨愈合。 µCT显示MCM + BMP股骨中的骨量更多，矿化度更高。与其他组相比，MCM + BMP动物的股骨显示出明显更高的弯曲刚度。组织形态计量学进一步证明，MCM + BMP股骨的愈伤组织较大，含有更多的骨骼和较少的纤维组织。 10周后，8个MCM + BMP股骨中有7个呈现完整的骨桥，而无股骨表现出100％的骨不连率。有趣的是，免疫组织化学无法检测到愈伤组织内的巨噬细胞，表明MCM具有良好的生物相容性。总之，在具有挑战性的小鼠不愈合模型中局部应用BMP-2涂层的MCM可以改善骨愈合，因此，在不愈合治疗中应引起临床关注。

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