Laboratory for Mineralized Tissues, School of Medicine, University of Zagreb, Zagreb, Croatia; Scientific Center of Excellence for Reproductive and Regenerative Medicine, Zagreb, Croatia.
Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria.
Biomed Pharmacother. 2023 Dec 31;169:115844. doi: 10.1016/j.biopha.2023.115844. Epub 2023 Nov 9.
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.
骨诱导型 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 是唯一市售的基于 BMP 的骨诱导装置，由牛可吸收胶原海绵（ACS）上的 rhBMP2 组成，由于严重的副作用，它存在很大的缺点。一种新型的骨诱导装置，OSTEOGROW，由分散在自体血凝块（ABC）中的 rhBMP6 组成，是一种很有前途的骨再生治疗方法，已在骨干修复和脊柱融合的多项临床试验中进行了研究。在本研究中，我们检查了释放动力学，结果表明，与 ACS 相比，ABC 载体提供了更慢、更稳定的 BMP 释放。采用大鼠皮下试验评估异位成骨的细胞事件和时间过程。通过流式细胞术评估宿主对骨诱导植入物的细胞反应，通过组织学、免疫组织化学和微 CT 分析评估骨形成和维持的时间动态。流式细胞术显示，rhBMP6/ABC 植入物中淋巴样细胞群体的募集明显更高，而 rhBMP2/ACS 植入物中募集的髓样细胞群体更多。此外，rhBMP6/ABC 植入物更有效地吸引了早期和定向祖细胞。与 rhBMP6/ABC 植入物相比，rhBMP2/ACS 诱导的骨形成动力学特征是软骨内骨化过程延迟。此外，rhBMP6/ABC 植入物在所有观察到的时间点都比 rhBMP2/ACS 植入物诱导更多的异位骨量。这些结果表明，由于 ABC 作为载体的优势和 rhBMP6 诱导骨的更高功效，OSTEOGROW 优于 INFUSE。
