{Reference Type}: Journal Article
{Title}: rhBMP6 in autologous blood coagulum is a preferred osteoinductive device to rhBMP2 on bovine collagen sponge in the rat ectopic bone formation assay.
{Author}: Ivanjko N;Stokovic N;Milesevic M;Rumenovic V;Windhager R;Sampath KT;Kovacic N;Grcevic D;Vukicevic S;
{Journal}: Biomed Pharmacother
{Volume}: 169
{Issue}: 0
{Year}: 2023 Dec 31
{Factor}: 7.419
{DOI}: 10.1016/j.biopha.2023.115844
{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.