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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\u2010blot 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 (<jats:italic>Rattus norvegicus<\/jats:italic>) and rabbits (<jats:italic>Oryctolagus cuniculus<\/jats:italic>). In a rat subcutaneous implant assay, ABGS induced endochondral bone formation, as observed by histology and micro\u2010CT 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\u2010CT, 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. \u00a9 2018 American Society for Bone and Mineral Research.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jbm4.10085","type":"journal-article","created":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T17:30:29Z","timestamp":1541439029000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Recombinant Human Bone Morphogenetic Protein 6 Delivered Within Autologous Blood Coagulum Restores Critical Size Segmental Defects of Ulna in Rabbits"],"prefix":"10.1093","volume":"3","author":[{"given":"Lovorka","family":"Grgurevic","sequence":"first","affiliation":[{"name":"Laboratory for Mineralized Tissues School of Medicine University of Zagreb Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Oppermann","sequence":"additional","affiliation":[{"name":"Genera Research Kalinovica Sveta Nedelja Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Pecin","sequence":"additional","affiliation":[{"name":"Clinics for Surgery, Orthopedics, and Ophthalmology School of Veterinary Medicine University of Zagreb Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Erjavec","sequence":"additional","affiliation":[{"name":"Laboratory for Mineralized Tissues School of Medicine University of Zagreb Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hrvoje","family":"Capak","sequence":"additional","affiliation":[{"name":"Department of Radiology School of Veterinary Medicine University of Zagreb Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Pauk","sequence":"additional","affiliation":[{"name":"Laboratory for Mineralized Tissues School of Medicine University of Zagreb Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Karlovic","sequence":"additional","affiliation":[{"name":"Faculty of Food Technology and Biotechnology University of Zagreb Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Kufner","sequence":"additional","affiliation":[{"name":"Laboratory for Mineralized Tissues School of Medicine University of Zagreb Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Lipar","sequence":"additional","affiliation":[{"name":"Clinics for Surgery, Orthopedics, and Ophthalmology School of Veterinary Medicine University of Zagreb Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jadranka","family":"Bubic Spoljar","sequence":"additional","affiliation":[{"name":"Laboratory for Mineralized Tissues School of Medicine University of Zagreb Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Bordukalo\u2010Niksic","sequence":"additional","affiliation":[{"name":"Laboratory for Mineralized Tissues School of Medicine University of Zagreb Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drazen","family":"Maticic","sequence":"additional","affiliation":[{"name":"Clinics for Surgery, Orthopedics, and Ophthalmology School of Veterinary Medicine University of Zagreb Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Peric","sequence":"additional","affiliation":[{"name":"Laboratory for Mineralized Tissues School of Medicine University of Zagreb Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Windhager","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Trauma Surgery Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T Kuber","family":"Sampath","sequence":"additional","affiliation":[{"name":"perForm Biologics Inc. 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