Bone morphogenetic proteins: From discovery to development of a novel autologous bone graft substitute consisting of recombinant human BMP6 delivered in autologous blood coagulum carrier.

Vukičević, Slobodan; Perić, Mihaela; Oppermann, Hermann; Stoković, Nikola; Ivanjko, Natalia; Erjavec, Igor; Kufner, Vera; Vnuk, Dražen; BubićŠpoljar, Jadranka; Pećin, Marko; Novak, Ruđer; Jelić, Ivona Matić; Bakić, Kristian; Milešević, Marina; Rumenović, Viktorija; Popek, Irena; Pehar, Sanja; Martinović, Snježana; Blažević, Valentina; Rogina, Lucija

Bone Morphogenetic Proteins (BMPs) are growth and differentiation factors within the TGFβ superfamily of proteins. They induce ectopic and orthotopic endochondral bone formation and are involved in the regulation of cell proliferation, differentiation, apoptosis and mesenchymal-epithelial interactions in critical morphogenetic processes of tissues beyond bone. BMP2 and BMP7 osteogenic devices have been approved for enhancing healing in patients with long bone defects and anterior spinal fusion procedures. However, due to a high price and various serious adverse events including heterotopic ossification, retrograde ejaculation and pain their clinical use have been limited. In this review we discuss the BMP discovery, biology and their use in clinical studies with particular reference to the newly developed BMP6 based autologous bone graft substitute (ABGS). A novel ABGS consisting of an autologous bone coagulum (ABC) carrier with dispersed BMP6 to initiate the differentiation of mesenchymal cells into endochondral bone. The ABC met the conditions for an optimal delivery system for BMP6 due to handling simplicity, without an immunogenic and inflammatory response at the implantation site. Addition of allograft or synthetic ceramics to ABGS demonstrated in animal models significantly increased volume and better microarchitecture of the newly formed bone. The first clinical study was conducted in patients with distal radial fractures (Phase I study) and the second in patients undergoing high tibial osteotomy (Phase I/II study) and no serious adverse events have been observed. Finally, in the ongoing OSTEO-proSPINE study ABGS enforced with allograft bone is evaluated in patients with chronic back pain due to degenerative disc diseases. The novel ABGS bone mimetic is a major breakthrough and contribution to bone biology and regenerative medicine of skeletal repair.

BONE morphogenetic proteins; BONE substitutes; AUTOTRANSPLANTATION; BONE grafting; SPINAL fusion; LUMBAR pain; AUTOTRANSFUSION of blood

Rad Hrvatske Akademije Znanosti i Umjetnosti. Medicinske Znanosti, 2020, Issue 52/53, p26

1330-5301

Academic Journal

10.21857/mnlqgc5vgy