Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia.
Department of Orthopedic Surgery, Washington University, St. Louis, MO 63110, USA.
Bone. 2020 Sep;138:115448. doi: 10.1016/j.bone.2020.115448. Epub 2020 May 22.
In the present study, we evaluated an autologous bone graft substitute (ABGS) composed of recombinant human BMP6 (rhBMP6) dispersed within autologous blood coagulum (ABC) used as a physiological carrier for new bone formation in spine fusion sheep models. The application of ABGS included cervical cage for use in the anterior lumbar interbody fusion (ALIF), while for the posterolateral lumbar fusion (PLF) sheep model allograft devitalized bone particles (ALLO) were applied with and without use of instrumentation. In the ALIF model, ABGS (rhBMP6/ABC/cage) implants fused significantly when placed in between the L4-L5 vertebrae as compared to control (ABC/cage) which appears to have a fibrocartilaginous gap, as examined by histology and micro CT analysis at 16 weeks following surgery. In the PLF model, ABGS implants with or without ALLO showed a complete fusion when placed ectopically in the gutter bilaterally between two decorticated L4-L5 transverse processes at a success rate of 88% without instrumentation and at 80% with instrumentation; however the bone volume was 50% lower in the instrumentation group than without, as examined by histology, radiographs, micro CT analyses and biomechanical testing at 27 weeks following surgery. The newly formed bone was uniform within ABGS implants resulting in a biomechanically competent and histologically qualified fusion with an optimum dose in the range of 100 μg rhBMP6 per mL ABC, while in the implants that contained ALLO, the mineralized bone particles were substituted by the newly formed remodeling bone via creeping substitution. These findings demonstrate for the first time that ABGS (rhBMP6/ABC) without and with ALLO particles induced a robust bone formation with a successful fusion in sheep models of ALIF and PLF, and that autologous blood coagulum (ABC) can serve as a preferred physiological native carrier to induce new bone at low doses of rhBMP6 and to achieve a successful spinal fusion.
在本研究中，我们评估了一种由重组人 BMP6（rhBMP6）分散在自体血凝块（ABC）中的自体骨移植物替代物（ABGS），将其用作脊柱融合绵羊模型中新骨形成的生理载体。ABGS 的应用包括用于前路腰椎间融合术（ALIF）的颈椎笼，而对于后路腰椎融合术（PLF）绵羊模型，应用和不应用器械的同种异体脱细胞骨颗粒（ALLO）。在 ALIF 模型中，与对照（ABC/cage）相比，ABGS（rhBMP6/ABC/cage）植入物在 L4-L5 椎体之间融合得非常明显，对照（ABC/cage）似乎有纤维软骨间隙，通过组织学和微 CT 分析在手术后 16 周检查。在 PLF 模型中，ABGS 植入物（无论是否含有 ALLO）在双侧无器械放置在两个去皮质的 L4-L5 横突之间的沟槽中，异位融合率为 88%，而在有器械的情况下为 80%；然而，在手术后 27 周的组织学、X 射线、微 CT 分析和生物力学测试中，器械组的骨量比无器械组低 50%。在 ABGS 植入物中形成的新骨是均匀的，导致具有生物力学能力和组织学合格的融合，最佳剂量为 100μg rhBMP6/ml ABC，而在含有 ALLO 的植入物中，新形成的骨通过爬行替代替代了矿化骨颗粒。这些发现首次表明，ABGS（rhBMP6/ABC）无论是否含有 ALLO 颗粒，均可在 ALIF 和 PLF 绵羊模型中诱导出强大的骨形成和成功的融合，并且自体血凝块（ABC）可作为一种优选的生理天然载体，以低剂量 rhBMP6 诱导新骨形成并实现成功的脊柱融合。
