In the present study, we describe autologous blood coagulum (ABC) as a physiological carrier for BMP6 to induce new bone formation. Recombinant human BMP6 (rhBMP6), dispersed within ABC and formed as an autologous bone graft substitute (ABGS), was evaluated either with or without allograft bone particles (ALLO) in rat subcutaneous implants and in a posterolateral lumbar fusion (PLF) model in rabbits. ABGS induced endochondral bone differentiation in rat subcutaneous implants. Coating ALLO by ABC significantly decreased the formation of multinucleated foreign body giant cells (FBGCs) in implants, as compared with ALLO alone. However, addition of rhBMP6 to ABC/ALLO induced a robust endochondral bone formation with little or no FBGCs in the implant. In rabbit PLF model, ABGS induced new bone formation uniformly within the implant resulting in a complete fusion when placed between two lumbar transverse processes in the posterolateral gutter with an optimum dose of 100‐μg rhBMP6 per ml of ABC. ABGS containing ALLO also resulted in a fusion where the ALLO was replaced by the newly formed bone via creeping substitution. Our findings demonstrate for the first time that rhBMP6, with ABC as a carrier, induced a robust bone formation with a complete spinal fusion in a rabbit PLF model. RhBMP6 was effective at low doses with ABC serving as a physiological substratum providing a permissive environment by protecting against foreign body reaction elicited by ALLO.

中文翻译：

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自体血凝块是BMP6的生理载体，可诱导兔新骨形成并促进后外侧腰椎融合。

在本研究中，我们将自体血凝块（ABC）描述为BMP6诱导新骨形成的生理载体。重组人BMP6（rhBMP6）分散在ABC中并形成为自体骨移植替代物（ABGS），在大鼠皮下植入物和兔后外侧腰椎融合（PLF）模型中，评估有无同种异体骨颗粒（ALLO） 。ABGS诱导大鼠皮下植入物中的软骨内骨分化。与单独使用ALLO相比，通过ABC涂层ALLO可以显着减少植入物中多核异物巨细胞（FBGC）的形成。但是，向ABC / ALLO中添加rhBMP6会导致植入物中软骨细胞很少或没有FBGC的坚固的软骨内骨形成。在兔子PLF模型中 ABGS可以在植入物内均匀地诱导新的骨形成，当放置在后外侧沟的两个腰椎横突之间时，可以实现完全融合，最佳剂量为每毫升ABC 100μgrhBMP6。含有ALLO的ABGS也导致融合，其中ALLO通过蠕变取代被新形成的骨头所取代。我们的研究结果首次证明，以ABC为载体的rhBMP6在兔PLF模型中通过完整的脊柱融合诱导了坚固的骨形成。RhBMP6在低剂量时有效，以ABC作为生理基质，通过防止ALLO引起的异物反应，提供了允许的环境。含有ALLO的ABGS也导致融合，其中ALLO通过蠕变取代被新形成的骨头所取代。我们的发现首次证明，以ABC为载体的rhBMP6在兔PLF模型中通过完全的脊柱融合诱导了坚固的骨形成。RhBMP6在低剂量时有效，以ABC作为生理基质，通过防止ALLO引起的异物反应，提供了允许的环境。含有ALLO的ABGS也导致融合，其中ALLO通过蠕变取代被新形成的骨头所取代。我们的研究结果首次证明，以ABC为载体的rhBMP6在兔PLF模型中通过完整的脊柱融合诱导了坚固的骨形成。RhBMP6在低剂量时有效，以ABC作为生理基质，通过防止ALLO引起的异物反应，提供了允许的环境。