Biological repair of thyroid cartilage defects by osteogenic protein-1 (bone morphogenetic protein-7) in dog

The efficacy of human recombinant osteogenic protein-1 (OP-1; bone morphoge netic protein-7) in regeneration of dog larynx,vas examined by treating thy roid cartilage defects (1.5 cm(2)) in dogs with thyroid allografts covered with host perichondrium or fascia, Prior to implantation allografts were fr ozen, thawed and demineralized, The treatment groups were as follows: I - A llograft control implant (n = 3); n - Implants coated with 500 mu g OP-1 (n = 4); III - Implants coated with 100 mu g OP-1 (n = 3); IV - Implants coat ed with 500 mu g OP-l and covered with neck fascia (n = 3); and V - Implant s extracted with 1 M NaCl and guanidine hydrochloride, and coated,vith 500 mu g OP-1 (n = 4). Dogs were sacrificed four months following surgery. Each larynx was removed, carefully dissected and a three-dimensional reconstruc tion of the defect area was performed on serial sections. The results revea led that the implants of control dogs remained intact with no apparent redu ction in size and new tissue formation. OP-1 enriched thyroid allografts, d ose dependently induced bone, cartilage and Ligament-like structures compri sing up to 80% of the total regenerated defect area. Boundaries of the defe cts healed by formation of new bone when bone resided within the old thyroi d cartilage layers. Old cartilage not containing bone within its layers hea led by complete integration with newly formed cartilage. Both new bone and cartilage were embedded into layers of new ligament-like tissue which expre ssed specific morphologic and molecular markers. The three newly formed tis sues were tightly connected into a "bone-cartilage-ligament continuum" of t issues, suggesting that OP-1 served as a multiple tissue morphogen, in this specific microenvironment.