
Recombinant Human Bone Morphogenetic Protein 6 Delivered Within Autologous Blood Coagulum Restores Critical Size Segmental Defects of Ulna in Rabbits
Author(s) -
Grgurevic Lovorka,
Oppermann Hermann,
Pecin Marko,
Erjavec Igor,
Capak Hrvoje,
Pauk Martina,
Karlovic Sven,
Kufner Vera,
Lipar Marija,
Bubic Spoljar Jadranka,
BordukaloNiksic Tatjana,
Maticic Drazen,
Peric Mihaela,
Windhager Reinhard,
Sampath T Kuber,
Vukicevic Slobodan
Publication year - 2019
Publication title -
jbmr plus
Language(s) - English
Resource type - Journals
ISSN - 2473-4039
DOI - 10.1002/jbm4.10085
Subject(s) - nonunion , bone morphogenetic protein 6 , bone morphogenetic protein , bone healing , medicine , endochondral ossification , bone morphogenetic protein 7 , anatomy , biology , cartilage , biochemistry , gene
BMP2 and BMP7, which use bovine Achilles tendon–derived absorbable collagen sponge and bovine bone collagen as scaffold, respectively, have been approved as bone graft substitutes for orthopedic and dental indications. Here, we describe an osteoinductive autologous bone graft substitute (ABGS) that contains recombinant human BMP6 (rhBMP6) dispersed within autologous blood coagulum (ABC) scaffold. The ABGS is created as an injectable or implantable coagulum gel with rhBMP6 binding tightly to plasma proteins within fibrin meshwork, as examined by dot‐blot assays, and is released slowly as an intact protein over 6 to 8 days, as assessed by ELISA. The biological activity of ABGS was examined in vivo in rats ( Rattus norvegicus ) and rabbits ( Oryctolagus cuniculus ). In a rat subcutaneous implant assay, ABGS induced endochondral bone formation, as observed by histology and micro‐CT analyses. In the rabbit ulna segmental defect model, a reproducible and robust bone formation with complete bridging and restoration of the defect was observed, which is dose dependent, as determined by radiographs, micro‐CT, and histological analyses. In ABGS, ABC scaffold provides a permissive environment for bone induction and contributes to the use of lower doses of rhBMP6 compared with BMP7 in bovine bone collagen as scaffold. The newly formed bone undergoes remodeling and establishes cortices uniformly that is restricted to implant site by bridging with host bone. In summary, ABC carrier containing rhBMP6 may serve as an osteoinductive autologous bone graft substitute for several orthopedic applications that include delayed and nonunion fractures, anterior and posterior lumbar interbody fusion, trauma, and nonunions associated with neurofibromatosis type I. © 2018 American Society for Bone and Mineral Research.