Abstract：
Osteoinductive BMPs require a suitable delivery system for treating various pathological conditions of the spine and segmental bone defects. INFUSE, the only commercially available BMP-based osteoinductive device, consisting of rhBMP2 on bovine absorbable collagen sponge (ACS) showed major disadvantages due to serious side effects. A novel osteoinductive device, OSTEOGROW, comprised of rhBMP6 dispersed within autologous blood coagulum (ABC) is a promising therapy for bone regeneration, subjected to several clinical trials for diaphysial bone repair and spinal fusion. In the present study, we have examined the release dynamics showing that the ABC carrier provided a slower, more steady BMP release in comparison to the ACS. Rat subcutaneous assay was employed to evaluate cellular events and the time course of ectopic osteogenesis. The host cellular response to osteoinductive implants was evaluated by flow cytometry, while dynamics of bone formation and maintenance in time were evaluated by histology, immunohistochemistry and micro CT analyses. Flow cytometry revealed that the recruitment of lymphoid cell populations was significantly higher in rhBMP6/ABC implants, while rhBMP2/ACS implants recruited more myeloid populations. Furthermore, rhBMP6/ABC implants more efficiently attracted early and committed progenitor cells. Dynamics of bone formation induced by rhBMP2/ACS was characterized by a delayed endochondral ossification process in comparison to rhBMP6/ABC implants. Besides, rhBMP6/ABC implants induced more ectopic bone volume in all observed time points in comparison to rhBMP2/ACS implants. These results indicate that OSTEOGROW was superior to INFUSE due to ABC\'s advantages as a carrier and rhBMP6 superior efficacy in inducing bone.
摘要：
骨诱导性BMP需要合适的递送系统来治疗脊柱的各种病理状况和节段性骨缺损。INFUSE,唯一可商购的基于BMP的骨诱导装置，由rhBMP2组成的牛可吸收胶原海绵（ACS）由于严重的副作用而显示出主要的缺点。一种新型骨诱导装置，OSTEOGROW,由分散在自体血凝块（ABC）中的rhBMP6组成是一种有前途的骨再生疗法，接受了几项用于骨干骨修复和脊柱融合的临床试验。在本研究中,我们检查了释放动态，表明ABC载体提供了较慢的，与ACS相比，BMP释放更稳定。采用大鼠皮下测定来评估细胞事件和异位成骨的时间过程。通过流式细胞术评估宿主细胞对骨诱导性植入物的反应，虽然通过组织学评估了骨形成和维持的动力学，免疫组织化学和显微CT分析。流式细胞术显示，rhBMP6/ABC植入物中淋巴细胞群的募集明显更高，而rhBMP2/ACS植入物招募了更多的骨髓群体。此外，rhBMP6/ABC植入物更有效地吸引早期和定向祖细胞。与rhBMP6/ABC植入物相比，rhBMP2/ACS诱导的骨形成动力学的特征在于软骨内骨化过程延迟。此外,与rhBMP2/ACS植入物相比,rhBMP6/ABC植入物在所有观察到的时间点诱导更多的异位骨体积。这些结果表明，由于ABC作为载体的优势和rhBMP6在诱导骨方面的优势，OSTEOGROW优于INFUSE。
