Animal studies of application of rhBMP-2 in maxillofacial reconstruction.

A pilot study in adult male Macaca fascicularis (rhesus) monkeys was undertaken to observe the effect of two dose ranges of recombinant human BMP-2 on bone regeneration following bilateral hemimandibulectomies. The mandibulectomies consisted of 2.2 centimeter resections through the entire thickness of the mandible with the remaining bone segments maintained in a distracted position by orthopaedic mesh (TiMesh). In three animals, the dose range on one mandibulectomy site in each animal was 0.8 mg BMP-2 per cc with the contralateral defect receiving 0.2 mg of the rhBMP-2. The carrier was a collagen I sponge (Helistat). These animals were sacrificed at five months postoperatively. In an additional four animals, a dose of 0.4 mg per cc was used on one site with a particulate autogenous graft of cortical cancellous bone used as a control on the contralateral defect. After four months, the reconstructed areas were re-exposed and implanted with root-form Steri-oss implants (Steri-Oss). These implants were brought into occlusion at the end of an additional four month period and are being evaluated for a period of 6 months of function. In all seven animals, the alveolar ridges were regenerated completely with restoration of contour and cortical bone. In the three animals euthanized at five months, histomorphmeic analysis revealed excellent calcified bone matrix to marrow spaces ratios. The result of this work indicates that recombinant human BMP-2 can bring about osseous regeneration of critical sized hemimandibulectomy defects in rhesus monkeys.

The restoration of resected mandibles in children without the use of bone grafts.

Following resection of the mandible for various types of neoplastic disease, six patients between the ages of 5 and 14 were followed for a period of 8 to 12 years after osseous surgical reconstructive surgery. It was found in children of this age group that a surgical technique may be employed which will effect complete bone regeneration without the use of bone graft materials. All six of the patients spontaneously regenerated large segments of the mandible from full-body ostectomy to hemimandibulectomy defects. The surgical procedure involves the use of a titanium mesh implant between the ostectomized bone fragments to maintain the surrounding soft tissues in a distracted position. It is found that if the soft tissues of the growing child are surgically prepared using the described technique, a new periosteum and bone will be formed along the titanium mesh implant. The titanium mesh may be removed at a later date or, depending on its method of placement, may be allowed to remain as the child grows, regenerating additional bone structure. It was found that in only one case was additional grafting necessary to obtain osseous union between the spontaneously regenerated mandibular bone and the host-bone ostectomized fragments. The technique is advocated for bone restoration in cases of large osseous discontinuity defects of the mandible in children.

Advanced imaging of osseous maxillary clefts.

A computed tomographic (CT) technique to establish precise two-dimensional (2-D) and three-dimensional (3-D) images of the osseous defects of cleft palates is presented and illustrated by two case studies. Prospective soft tissue algorithms and bone detail imaging was made possible by a retrospective program, a specific software program and vertical reformatting technique leading to 3-D image reconstruction. The two cases illustrate the flexibility of the CT program in accurately providing morphometric and bone density data on the location and size of the osseous defects involved in the cleft. Not every cleft palate patient is a candidate for the procedures outlined; however, the diagnosis of and treatment planning for patients presenting with bilateral or extensive osseous clefting can be more accurate.

Application of bone morphogenetic proteins in the treatment of clinical oral and maxillofacial osseous defects.

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 1/2 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 1/2 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.

Mandibular fracture after endosseous implant placement in conjunction with inferior alveolar nerve transposition: a patient treatment report.

A patient with a severely atrophic right posterior mandible had three endosseous implants placed in conjunction with transposition of the inferior alveolar nerve. Three weeks following implant placement surgery, the patient experienced a spontaneous fracture of the mandible involving the two anterior implants. The two implants were removed, and the fracture was treated with open reduction and fixation with titanium mesh. The fracture healed, and the posterior implant integrated. This report suggests that the buccolingual and superior-inferior position of the mandibular canal can increase the possibility of mandibular fracture by increasing the size of the buccal cortical plate that is removed to expose the nerve during surgery.

Titanium mesh and particulate cancellous bone and marrow grafts to augment the maxillary alveolar ridge.

A detailed explanation of a surgical technique for grafting of deficient maxillary alveolar ridges is presented. In addition, a technical modification, for use where a fibrous hypermobile soft tissue ridge exists over the deficient maxilla is outlined. Results to date have been excellent as has been the follow-up (12-48 months); continued used of this technique and its modification is encouraged.

Healing potential of osteotomies of the nasal sinus in the dog.

UNLABELLED: Maxillary sinus osteotomy is indicated for transantral surgical approaches to palatal roots of maxillary teeth. There are no reports on the healing potential of such defects. OBJECTIVES: To determine by histologic examination, the reparative process of the nasal cavity of dogs after small and large perforations with and without a resorbable collagen membrane. STUDY DESIGN: Five mm and 6 x 12 mm diameter osteotomies were created through the maxilla of 12 beagle dogs. Resorbable collagen membranes were placed over defects on six dogs. After 5 months, sections of the defects were histologically evaluated. RESULTS: Examination revealed partial osseous healing with presence of central areas of fibrous scar tissue in all samples. Defects covered with the resorbable collagen membranes showed no improvement in osseous regeneration. CONCLUSION: Based on our results, defects (regardless of their size) tend to repair with limited bony covering and fibrous scar. Furthermore, resorbable collagen membranes do not improve osseous repair.

Lingual mandibular bone concavity.

The lingual mandibular bone concavity is not pathognomonic but is a radiographic bone entity. The origin of the entity and the histologic picture of the contents found within the concavity are probably related to the size and growth of the structures located in the submandibular space and the contiguous area. This accounted for the presence of normal submandibular space tissue contents in this patient and in nine of the ten patients whose conditions are reviewed in the literature. The question of whether a surgical exploration is indicated should be decided in terms of each individual case by the oral surgeon. However, only by performing a surgical exploration and submitting the tissue contents for a histopathologic examination can an accurate diagnosis be made. The general practitioner of dentistry should be aware of this bone entity and be prepared to discuss the condition with the patient and to refer the patient for exploration of the area if appropriate.

Advances in subperiosteal implant reconstruction.

Recent advances in subperiosteal implant surgery of the mandible and maxilla are described in terms of changes in implant design, use of particulate autogenous marrow cancellous bone in conjunction with subperiosteal implant to structurally rebuild marked deficient mandibles at the time the implant is placed, and the of computerized tomography to develop a three-dimensional model for the construction of implant framework, eliminating the direct bone impression surgery. The latter procedure has revolutionized the use of subperiosteal implants. These techniques are outlined, and areas of future research in use of implants in structurally deficient areas are described.

An evaluation of bone induction delivery materials in conjunction with root-form implant placement.

The success of bone-inductive cytokines in surgical alveolar defects is greatly dependent upon the ability of carrier materials to effectively deliver the inductive protein to the surgical site. An evaluation of three types of carrier materials was undertaken in six monkeys using an osseous defect of 2.0 cm that was produced by partial resection of the maxilla and mandible and placement of titanium implants in each alveolar quadrant. After 5 months, abutments were placed on the implants, which were allowed to function for an additional 5 months. Intravital labeling with tetracycline was used to evaluate the late healing remodeling processes. The carriers were evaluated by studying (1) the amount of surface osseointegration on the root-form implants; (2) the bone density as related to trabecular pattern and cortex formation; and (3) the quantitative and qualitative thickness of the alveolar bone buccolingually at the implanted sites. Of the three materials, the calcium carbonate coral (BioCoral) produced a decreased amount of bone regeneration in comparison with both the poly(methylethyl methacrylate) material (HTR) and the porous bone mineral (Bio-Oss). Both the HTR and Bio-Oss with rhBMP-2 produced excellent thickness of the repaired alveolar ridge. All three materials produced the same amount of osseointegration with the titanium implant surfaces. Good bone quality, as reflected in thickening of the trabecular bone patterns, was seen with both Bio-Oss and HTR. While all three of these carrier materials appeared to produce good osseointegration with the titanium implants, BioCoral did not effect a quantitative or qualitative restoration of the alveolar bone comparable to that following the use of either HTR or Bio-Oss with rhBMP-2.

A feasibility study evaluating rhBMP-2/absorbable collagen sponge for maxillary sinus floor augmentation.

This 16-week open-label study assessed the safety and technical feasibility of implanting human recombinant bone morphogenetic protein-2 delivered on an absorbable collagen sponge (rhBMP-2/ACS) for two-stage maxillary floor sinus augmentation. This first use of rhBMP-2/ACS in human clinical maxillary sinus floor augmentation included 12 patients with inadequate bone height in the posterior maxilla. The total delivered dose of rhBMP-2 implanted varied from 1.77 to 3.40 mg per patient. The rhBMP-2/ACS device was easily handled. Significant bone growth was documented by computerized tomographic scans in all evaluable patients (11/12). The overall mean height response for the maxillary sinus floor augmentation was 8.51 mm (95% confidence interval 6.07 to 10.95). There were no serious or unexpected immunologic or adverse effects and no clinically significant changes in complete blood counts, blood chemistries, or urinalysis results. The most frequent adverse effects were facial edema, oral erythema, pain, and rhinitis. Eleven patients have received dental implants and follow-up examinations are still being conducted. Histologic examinations of core bone biopsies obtained at the time of dental implant placement confirmed the quality of the bone induced by rhBMP-2/ACS. These results tend to indicate that rhBMP-2/ACS may provide an acceptable alternative to traditional bone grafts and bone substitutes for maxillary sinus floor augmentation procedures in humans.

Trauma to the oral cavity.

Sports events, particularly those in which mouth protectors are not commonly used, can be associated with injuries to the oral structures. While the incidence of sports-related orofacial injuries is not as high as for other traumatic events, the incidence could be reduced further by increased use of mouth and face protection. When injuries occur, quick action by primary health care providers can significantly improve the final outcome of the definitive treatment. Also important is appropriate follow-up evaluation and care since the effect of trauma on teeth is not always immediately apparent. Destructive resorption, unnecessary tooth loss, and possible alveolar infections may be prevented by referral to appropriate health care providers for evaluation following the initial urgent care of trauma patients.

Analysis of performance of root-form endosseous implants placed in the maxillary sinus.

To evaluate the long-term effect on metal-bone interface of the perforation of the maxillary antral floor by root-form titanium implants, a study was undertaken in five mature Macaca fascicularis monkeys. One root-form titanium implant was placed bilaterally in the maxillary sinus perforating the sinus 5 mm and a second implant was placed completely in bone tissue. The protruding implant in the right antrum was grafted with autogenous cancellous bone and porous bone mineral (Bio-Oss) and the contralateral antral implant protruding in the antrum was left without grafting. The bilateral implants were used to support "free-standing" fixed prostheses, which were in full function for 14 months, during which time there was excellent clinical function and no mobility of the implants. Histomorphometric analysis of specimens revealed that there was no difference in the trabecular pattern or the amount of calcified matrix vs. marrow vascular spaces along the titanium implant interface. New reparative bone partially restored the osseous surface along the implant on the ungrafted side. Implants in the grafted antrum demonstrated bone regeneration over the implant surface ranging from 2 cm to complete regeneration. Histomorphometric analysis revealed the peri-implant bone to contain some particles of the Bio-Oss, although most of the implant bone interface exhibited only vital bone and marrow vascular spaces. The study indicates that the protrusion of implants maximally into the sinus floor does not necessarily require a bone graft to produce functional abutments for fixed prostheses and that implants can function well with 5 mm of protrusion into the antrum with excellent bone-metal interface.

Early treatment of facial trauma.

Early local care of maxillofacial trauma involves identification and diagnosis of the injuries and early consultation with the appropriate specialists (ie, plastic surgeon, ophthalmologist, otolaryngologist, oral and maxillofacial surgeon). Treatment of the injuries should proceed from the inside mucosal surface toward the cutaneous surface of the face, after occlusal patterns have been established and preliminary fixation of maxillary and mandibular fractures has been effected. Closure of through-and-through lacerations from the inside out and establishment of the mandible as a stable plane against which the remainder of the face may be oriented (the "inside out and bottom up" approach) provide an excellent basis for later definitive rehabilitation.

Lateral expansion of the mandible in the baboon. Following osteotomy at the symphysis.

The mandibles of three baboons are expanded laterally by surgical osteotomy at the symphysis, followed by different regimes of stabilization and orthodontic movement.