Review article
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
Slobodan Vukičević
Mihaela Perić
Hermann Oppermann
Nikola Štoković
Natalia Ivanjko
Igor Erjavec
Vera Kufner
Dražen Vnuk
Jadranka Bubić-Špoljar
Marko Pećin
Ruđer Novak
Ivona Matić Jelić
Kristina Bakić
Marina Milešević
Viktorija Blažević
Lucija Rogina
Smiljka Vikić-Topić
Tamara Božić
Donatella Verbanac
Tatjana Bordukalo Nikšić
T Kuber Sampath
Marko Pećina
Dražen Matičić
Lovorka Grgurević
Abstract
Bone Morphogenetic Proteins (BMPs) are growth and differentiation factors within the TGFβ superfam- ily 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 proce- dures. However, due to a high price and various serious adverse events including heterotopic ossifica- tion, 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 han- dling 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.
Keywords
Hrčak ID:
248880
URI
Publication date:
15.12.2020.
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