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

Abstract

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

State-of-the-art of the Bone Morphogenetic Protein research field: 13th International BMP Conference, Dubrovnik 2022

“…e following requirements are met with the introduction of Osteogrow, a novel therapeutic solution comprised of rhBMP6 delivered within autologous blood coagulum (142,143). To improve the biomechanical properties of Osteogrow implants might be supplemented with allograft bone (Osteogrow A), host bone (Osteogrow B) and synthetic ceramics (Osteogrow C) (144)(145)(146).…”

Bone Morphogenetic Proteins, Carriers, and Animal Models in the Development of Novel Bone Regenerative Therapies

“…We have recently developed an autologous bone graft substitute (ABGS) comprised of BMP6 delivered within an autologous blood coagulum to which a compression-resistant matrix, such as allograft or synthetic ceramics, can be added [22,73,74,76,[86][87][88][89][90][91][92]. Moreover, the volume of newly induced bone increased with the elevation of the CRM amount, which might be attributed to the enlargement in an overall surface area [73].…”

Zoledronate Bound to Ceramics Increases Ectopic Bone Volume Induced by rhBMP6 Delivered in Autologous Blood Coagulum in Rats

“…Bone morphogenetic proteins (BMPs) are growth and differentiation factors known for their ability to induce cartilage and bone and have a morphogenic role in the development and maintenance of tissue structure throughout the body [1,2]. The ability of BMPs to induce bone was evaluated in various animal models used for the translation of the bone regeneration principle for clinical use [3][4][5][6].…”

“…We have demonstrated that our novel autologous bone graft substitute (ABGS) containing rhBMP6 within autologous blood coagulum (ABC) with or without compression resistant matrix (CRM) restores large bone defects and achieves successful lumbar fusion in rabbits and sheep [2,[12][13][14][15][16][17][18][19]. Importantly, newly induced bone successfully fused with native bone, achieving complete osseointegration, which can be defined as functional fusion between new and old bone [20].…”

“…In addition, ABC serves as a physiological biocompatible carrier [12], promoting the tight binding of rhBMP6 to plasma proteins within the fibrin meshwork. ABC further allows a sustained release of rhBMP6 and suppresses foreign body responses elicited by the mineral-rich ceramics used as CRM [2,13,14]. Furthermore, synthetic ceramics are more preferred CRM than allografts [16,17,23] due to the reduced risk of viral transmission and immunogenicity [24].…”