Background: Commonly occurring extensive osseous
defects in the oral and maxillofacial area are seen following complete
or partial resection of the mandible and other facial bones in oncologic
surgery or following traumatic injury. Autogenous osseous grafts
have been used to restore these defects. Additionally, bone graft
substitute materials and autogenous osseous grafts are applied to
congenital defects such as cleft palate, facial clefts, and facial
asymmetry. We have simulated these types of defects in appropriately
aged Macaca fascicularis and Macaca mulatta monkeys to study the
efficacy of using bone morphogenetic protein (BMP) as an osseous inductor.
The objective of these studies was to obtain information on the
feasibility of employing bone inductors to regenerate large continuity
critical-sized maxillofacial defects without using bone grafts.
Methods and Results: In one study, involving eight
animals, the body of the mandible was removed, simulating hemi-mandibulectomy
defects following traumatic bone loss or oncologic surgery. Recombinant
human (rh) BMP-2 (Genetics Institute, Cambridge, Massachusetts)
in a collagen carrier (Colla-Tec Inc., Plainsboro, New Jersey) then
was placed in the hemi-mandibulectomy defect with use of titanium
orthopaedic mesh fixation (Sofamor Danek-Medtronic, Memphis, Tennessee).
Entire bone regeneration of the defect was observed 5 and 6 months
postoperatively. In another group of subhuman primates, the restored
area was functionally stimulated at the 5-month post-BMP implantation
level by placement of intraoral titanium implants. The animals were allowed
to function for 8 months with these titanium implants. Microscopic
results showed increased density, bone volume, and thickness of the
trabecular bone pattern. The bone cortex in the restored defect
also increased in thickness compared with the nonsurgical areas.
To evaluate the effect of rhBMP-2 in aging individuals, a group
of six Macaca animals over 20 years of age received the same type
of mandibular resection followed by BMP grafting with functional
stimulation by mastication on root form implants placed at 5 months after
BMP implantation. The entire mandible regenerated as in the younger
group of animals; therefore, age did not appear to be a factor in
the reparative process. Thus, the number of stem cells supposedly
reduced with increasing age did not appear to affect the overall
result of BMP-induced bone regeneration. Additionally, in applying
the inductor material to younger monkeys (1-1 years of age), the
rhBMP-2 was placed in simulated bilateral cleft palate defects.
On one side, the rhBMP-2 was placed with use of the collagen sponge
carrier. The autogenous graft most frequently used at present for
regeneration of the osseous defects of maxillary clefts is iliac
crest particulate cancellous bone. As a control graft on the contralateral
side, therefore, autogenous particulate bone and marrow was placed.
At the end of 3 months, the cleft side receiving the BMP-2 showed
complete osseous restoration of the simulated cleft. The autogenously grafted
side exhibited bone repair but incomplete regeneration of the bone
defect at the early (3-months postoperative) stage of healing.
Conclusions and Clinical Relevance: The results
of these three subhuman primate defect studies—(a) mandibular
resection defects in middle-aged Macaca fascicularis animals, (b)
mandibular resection defects in Macaca fascicularis animals over
20 years of age, and (c) simulated bilateral clefts in Macaca mulatta
animals 1 years of age (comparable with a 5-year-old child)—were
very encouraging. Histomorphometric analysis in all of these investigations
indicated that the use of rhBMP-2 in bone repair without the use
of bone grafting materials will offer a new method of osseous reconstruction
in clinical facial bone defects.