|89th Annual Meeting Abstracts
Improving the Success Rate of Gingivoperiosteoplasty in Cleft Lip Alveolus and Palate: Pre-clinical Investigation of Novel Therapies
Edward H. Davidson, MA MBBS, Phuong D. Nguyen, MD, Denis Knobel, MD, Steven M. Sultan, BA, Parag Butala, MD, James L. Crawford, BS, Pradip R. Shetye, MDS MOrthRCS DDS, Hitesh Kapadia, DDS PhD, Barry H. Grayson, DDS, Court B. Cutting, MD, Stephen M. Warren, MD.
New York University, New York, NY, USA.
Presurgical infant orthopedics followed by gingivoperiosteoplasty (GPP) has decreased the need for alveolar bone grafting in patients with unilateral clefts of the lip, alveolus, and palate (UCLP) by 41-73%. However, the effectiveness of this procedure has not yet been described in bilateral clefts of the lip, alveolus and palate. This study seeks to first determine the success rate of avoiding secondary alveolar bone grafts in the bilateral cleft lip and palate patient (BCLP) using nasoalveolar molding and GPP. Furthermore, whilst several groups have advocated novel therapies such as BMP2 to improve the success of GPP, these have been isolated case reports or series without appropriate controls. We offer the first pre-clinical investigation of such novel therapies in a rat GPP model.
Patients with BCLP who presented to our institution from 1988 - 1998 and underwent presurgical infant orthopaedics and bilateral GPP were included. Clinical examination, panoramic and periapical radiographs, and/or dental CT scans were used to assess alveolar bone formation. Additionally, a 7x4x3-mm complete alveolar defect was surgically created in sixty 8-week old Sprague-Dawley rats. Four scaffolds were tested within the defect: absorbable collagen sponge (ACS), ACS+BMP-2, hydroxyapatite-tricalcium phosphate (HA-TCP), HA-TCP+BMP-2, and no scaffold as control. Animals were sacrificed at post-operative weeks 4, 8, and 12. New bone was assessed morphometrically (micro-CT) and histologically.
In total, 27 patients were identified. While 16 of 27 patients (59%) required unilateral alveolar bone grafting, no patient required bilateral bone grafting. 11 of 27 patients (41%) had enough alveolar bone stock bilaterally in order to avoid bone grafting.
Morphometric analysis of treated animals demonstrated that the ACS group had 50±6%, 79±9%, and 69±7% bone formation at 4, 8 and 12 weeks, respectively. The ACS+BMP group had 49±2% and 71±6%, and 66±7% bone formation, respectively. HA-TCP displayed 69±12% bone growth at 4 weeks and plateaued to 86±3% (p<0.05) at 8 weeks and 87±14% at 12 weeks, while adding BMP yielded 55±15%, 91±3% (p<0.05) and 90±1% (p<0.05) at 12 weeks. Gomori trichrome staining showed increased new bone formation within the defect in both ACS and HA-TCP groups compared to negative control at all time points (p<0.05), though the addition of BMP did not produce significantly more bone formation. Early time points (4 weeks) displayed activated osteoblasts, osteoprogenitor cells, and nascent bone along leading edges of bone spicules, within an inflammatory milieu within the intercalary gap. Later time points (8 and 12 weeks) showed a denser population of fibroblasts arrayed in an organized fashion as well as maturing bone from woven bone to lamellar bone.
Success rates of primary GPP are comparable for patients with unilateral and bilateral clefts and highlight the need for novel therapies to improve outcomes and avoid the morbidity of secondary bone grafting procedures. Our preclinical study supports the use of biomimetic hydroxyapatite tricalcium scaffolds over collagen scaffolds and demonstrated no further benefit with addition of BMP-2.