Recombinant human bone morphogenetic protein 6 delivered within autologous blood coagulum restores critical size segmental defects of ulna in rabbits

Grgurević, Lovorka and Oppermann, Hermann and Pećin, Marko and Erjavec, Igor and Capak, Hrvoje and Pauk, Martina and Karlović, Sven and Kufner, Vera and Lipar, Marija and Bubić Špoljar, Jadranka and Bordukalo-Nikšić, Tatjana and Matičić, Dražen and Perić, Mihaela and Windhager, Reinhard and Sampath, T Kuber and Vukičević, Slobodan (2018) Recombinant human bone morphogenetic protein 6 delivered within autologous blood coagulum restores critical size segmental defects of ulna in rabbits. JBMR Plus, 3 (5). e10085. ISSN 2473-4039

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Abstract

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.

Item Type: Article
Departments: Katedra za anatomiju i kliničku anatomiju
Depositing User: Kristina Berketa
Status: Published
Creators:
CreatorsEmail
Grgurević, LovorkaUNSPECIFIED
Oppermann, HermannUNSPECIFIED
Pećin, MarkoUNSPECIFIED
Erjavec, IgorUNSPECIFIED
Capak, HrvojeUNSPECIFIED
Pauk, MartinaUNSPECIFIED
Karlović, SvenUNSPECIFIED
Kufner, VeraUNSPECIFIED
Lipar, MarijaUNSPECIFIED
Bubić Špoljar, JadrankaUNSPECIFIED
Bordukalo-Nikšić, TatjanaUNSPECIFIED
Matičić, DraženUNSPECIFIED
Perić, MihaelaUNSPECIFIED
Windhager, ReinhardUNSPECIFIED
Sampath, T KuberUNSPECIFIED
Vukičević, SlobodanUNSPECIFIED
Date: 2018
Date Deposited: 16 Oct 2019 10:57
Last Modified: 16 Oct 2019 10:57
Subjects: /
Related URLs:
URI: http://medlib.mef.hr/id/eprint/3455

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