engleski

Recombinant Human Bone Morphogenetic Protein 6Delivered Within Autologous Blood Coagulum RestoresCritical Size Segmental Defects of Ulna in Rabbits

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 anosteoinductive autologous bone graft substitute (ABGS) that contains recombinant human BMP6 (rhBMP6) dispersed withinautologous blood coagulum (ABC) scaffold. The ABGS is created as an injectable or implantable coagulum gel with rhBMP6 bindingtightly to plasma proteins withinfibrin meshwork, as examined by dot-blot assays, and is released slowly as an intact protein over 6to 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 histologyand micro-CT analyses. In the rabbit ulna segmental defect model, a reproducible and robust bone formation with completebridging and restoration of the defect was observed, which is dose dependent, as determined by radiographs, micro-CT, andhistological analyses. In ABGS, ABC scaffold provides a permissive environment for bone induction and contributes to the use oflower doses of rhBMP6 compared with BMP7 in bovine bone collagen as scaffold. The newly formed bone undergoes remodelingand establishes cortices uniformly that is restricted to implant site by bridging with host bone. In summary, ABC carrier containingrhBMP6 may serve as an osteoinductive autologous bone graft substitute for several orthopedic applications that include delayedand nonunion fractures, anterior and posterior lumbar interbody fusion, trauma, and nonunions associated with neurofibromatosistype I.

BONE MORPHOGENETIC PROTEIN 6 ; AUTOLOGOUS BLOOD COAGULUM CARRIER ; CRITICAL SIZE DEFECT ; AUTOLOGOUS BONEGRAFT SUBSTITUTE ; FRACTURE HEALING

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