The loss of multiple teeth or trauma to the anterior maxilla often results in a deficient ridge width for prosthetic tooth rehabilitation. This study evaluated the use of titanium mesh and recombinant human bone morphogenetic protein 2 (rhBMP-2) for the repair of major bone defects in the alveolar bone. Five patients were enrolled in the study; these patients required implant replacements for two contiguous missing teeth in the anterior maxilla, which lacked sufficient bone. Residual ridges were augmented with rhBMP-2 and titanium mesh to direct the geometry of the newly formed bone. Seven months later, a bone biopsy specimen was removed from the implantation site before osteotomy and insertion of dental implants. Cone beam computed tomography (CBCT) scans were obtained preoperatively, postoperatively (baseline), and 48 months after implantation to evaluate implant healing. All dental implants were placed in the grafted sites without the need for further bone augmentation. The most frequent adverse effects were facial oedema and oral erythema. Biopsy specimens were used to evaluate bone quality. CBCT scans provided a prediction of alveolar restoration and long-term success. The combination of rhBMP-2 and titanium mesh provided effective augmentation of the atrophic anterior maxilla prior to implant placement.
In 1965, Urist et al. demonstrated that bone morphogenetic proteins (BMPs) extracted from bovine bone are able to induce ectopic bone formation subcutaneously in rats. These results suggested the potential use of BMPs to induce bone regeneration and dental implant osseointegration. A subfamily of the transforming growth factor beta (TGF-β) superfamily, BMPs mediate signalling pathways that affect cell proliferation, cell differentiation, and extracellular matrix formation. In particular, recombinant human BMP-2 (rhBMP-2) has been shown to stimulate adult mesenchymal stem cells to induce clinically relevant bone formation.
Since 2002, the US Food and Drug Administration (FDA) has approved the use of absorbable collagen sponge (ACS) as a carrier for rhBMP-2 in lumbar fusion and long bone fracture repairs. In 2007, rhBMP-2 was used for alveolar ridge and maxillary sinus augmentation. Relevant bone formation for various skeletal defects, including those of the craniofacial complex, has been observed in the presence of rhBMP-2 in clinical studies. However, only a few reports have evaluated the use of rhBMP-2 or other BMP family members in conjunction with dental implants in the aesthetic zone. Therefore, the objective of this prospective case series study was to evaluate the clinical and histological effects of rhBMP-2 alveolar bone augmentation in the rehabilitation of the severely resorbed anterior maxilla with osseointegration implants.
Materials and methods
Selection of patients
This prospective case series study was conducted in accordance with the STROBE guidelines for observational studies and the Declaration of Helsinki. The study was approved by the local ethics committee.
Five consecutive patients (one male, four females; mean age 49.4 ± 20.8 years) who were referred to the authors’ institution in 2009 for implant therapy in the anterior region were considered for inclusion in the study. Patients were included if they had trauma- or pathology-induced alveolar bone defects in all three dimensions in the anterior region ( Fig. 1 ), an absence of two contiguous teeth, and were in good general health at the time of surgery. Patients were excluded if they met any of the following criteria: (1) endodontic treatment required for a tooth adjacent to the evaluated site, (2) smoking habit of >10 cigarettes a day, (3) parafunctional habits, (4) pregnancy, (5) known hypersensitivity to rhBMP-2, bovine type I collagen, or any other component of the Infuse bone graft kit, (6) active or suspected malignancy, and (7) undergoing treatment for malignancy.
Patients received 2 g of amoxicillin 1 h before surgery. They were instructed to wash their mouths with a 0.12% chlorhexidine solution for 30 s immediately before surgery. All reconstructive surgeries, implant placements, and prosthetic restorations were completed by the same professional (SR).
Briefly, local anaesthesia consisting of 2% lidocaine (1:50,000 epinephrine) was administered. An incision was made along the ridge through the keratinized gingiva in the alveolar crest, and a lateral releasing incision was made at the base on both sides. A mucoperiosteal flap was reflected to expose the atrophic ridge completely. Future implant sites were planned. The site for insertion of a 0.2-mm-thick titanium mesh for graft coverage was assessed. The lateral borders of the mesh were to be extended slightly beyond the desired area of augmentation to contact the residual ridge. The concave region below the mesh would be the site for the rhBMP-2-containing ACS. The cortex of the crest was perforated multiple times to produce bleeding at various sites ( Fig. 2 ), while pilot holes for fixation screws were prepared for the titanium mesh.
An Infuse bone graft kit (Medtronic) was used to repair each defect. The collagen sponge included in the kit was saturated evenly with 0.7 ml of 1.5 mg/ml rhBMP-2 for 15 min, in accordance with the manufacturer’s instructions. The titanium mesh was then applied to cover the rhBMP-2-containing collagen sponge ( Figs. 3 and 4 ). The periosteum of the buccal flap was released to allow tension-free coronal advancement of the flap, wound closure, and suturing. The flaps were closed with 4–0 Vicryl (Ethicon) interrupted and horizontal mattress sutures.
All patients were prescribed oral antibiotics, including 500 mg of amoxicillin (or 1 g clindamycin in the case of allergy), and 100 mg of the non-steroidal anti-inflammatory agent nimesulide for seven consecutive days after the reconstruction procedure. Postoperative instructions included the maintenance of a liquid/soft diet and use of 0.12% chlorhexidine mouthwash until the sutures were removed between 10 and 15 days after the reconstruction.
Seven months after the reconstruction, implants were placed (without the need for additional augmentation procedures) and the insertion torque was evaluated. Briefly, after the administration of local anaesthesia, a full mucoperiosteal flap was raised to expose the titanium mesh, which was cut with a diamond disc. The buccal portion was maintained to protect the newly formed bone ( Fig. 5 ). A bone biopsy specimen (2.2 mm in diameter) was harvested from the previously augmented area using a bone trephine drill. This site was also the location of the implant osteotomy. Osteotomies were prepared according to the manufacturer’s drilling sequence and dental implant placement guidelines (Nobel Biocare Replace) ( Fig. 6 ).
The bone density was determined on the basis of the Lekholm and Zarb index (D1 to D4), and the bone density at each site was recorded clinically for the surgeon. The Lekholm and Zarb index consists of a density scale that ranges from 1 (densest bone) to 4 (least dense bone). Soft tissue augmentation procedures were performed at each surgery stage. Cone beam computed tomography (CBCT) scans, study plaster models, and clinical photographs were used for the planning of rehabilitation of all selected patients. After a 6-month healing period, the implants were uncovered for placement of an unsplit cemented prosthetic restoration on a custom zirconia abutment. A single experienced prosthodontist performed all of the prosthetic procedures.
All patients were evaluated every 6 months during a 48-month follow-up period. Every follow-up visit included a clinical examination of implant mobility, occlusion, and hygiene conditions. Peri-apical radiographs were obtained at every visit. CBCT and clinical photographs were also obtained at the last follow-up visit.
One previously calibrated researcher (BSSM), who was not involved in the treatment steps, performed all evaluations of the soft tissue and implant crown aesthetics. The state of soft tissue aesthetics was evaluated with the Jemt index. Two clinical standardized oral photographs were obtained 24 h after definitive crown delivery and at the last follow-up visit (48 months). These photographs included at least one adjacent tooth on each side, and were obtained under the same lighting conditions with similar framing.
All CBCT scans were acquired with the same system (i-CAT 3D Imaging System, i-CAT Vision Software; Imaging Sciences International) through the soft tissue CBCT technique. The maxilla was scanned preoperatively and at 48 months postoperatively. Sagittal sections (1.0 mm in thickness) were obtained as CBCT reconstructions.
A previously trained examiner (BSSM) assessed all CBCT images independently. For the measurements, the most central sagittal sections of the titanium mesh (preoperative CBCT) and of each implant (postoperative CBCT) were selected. The examiner measured the distance from the lingual border to the buccal bone ridge border using the Image Tool software package. Measurements were performed at a minimum of 2-week intervals. Means and standard deviations (SDs) were calculated for each reference measurement. The examiner recorded the second set of measurements while blinded to the first set, in order to evaluate the reliability of the recordings.
Biopsy specimens were fixed in 10% neutral buffered formalin, dehydrated in ethanol, embedded in paraffin, and sectioned (4 μm). These sections were stained with haematoxylin and eosin. A descriptive histological analysis was performed with a standard light microscope by an experienced examiner. This analysis included observations of new bone formation and resorption, woven and lamellar bone, cortex formation, seroma formation, fibrovascular tissue and marrow, and inflammatory responses. The cell and tissue morphologies were also identified.
Five patients were treated with rhBMP-2 and titanium mesh. All patients achieved successful regeneration of their alveolar defects. All regeneration sites exhibited swelling and mild erythema of the healing soft tissue. However, the recovery period for each patient was largely uneventful. All patients progressed to implant placement and final prosthetic reconstruction. No exposure of the mesh was observed during the healing process, and none of the implant sites required further bone augmentation ( Fig. 7 ). Table 1 shows the bone gain, bone quality, insertion torque, and implant size for all patients. After 6 months of healing, all of the implants achieved primary stability, although the bone quality of the regenerated tissue was rated as soft (D4) for all of the sites.