EXPERIMENTAL Establishment of a Critical-Sized Alveolar Defect in the Rat: A Model for Human Gingivoperiosteoplasty Phuong D. Nguyen, M.D. Clarence D. Lin, M.A. Alexander C. Allori, M.D., M.P.H. John L. Ricci, Ph.D. Pierre B. Saadeh, M.D. Stephen M. Warren, M.D. New York, N.Y. Background: Despite technical advancement, treatment of congenital alveolar clefts has remained controversial. Currently, primary alveolar cleft repair (i.e., gingivoperi- osteoplasty) has a 41 to 73 percent success rate. However, the remaining patients have persistent alveolar bone defects requiring secondary grafting procedures. Morbidity of secondary procedures includes pain, graft resorption, extrusion or infection, and graft or tooth loss. The authors present a novel rat alveolar defect model designed to facilitate investigation of therapeutics aimed at improving bone formation following primary alveolar cleft repair in humans. Methods: Sixteen 8-week-old Sprague-Dawley rats underwent creation of a 7  4  3-mm complete alveolar defect from the maxillary incisors to the zygomatic arch. Four animals were humanely killed at each of the following time points: 0, 4, 8, and 12 weeks. Morphometric analysis of the alveolar defect was determined by means of micro- computed tomography and histology. Results: Micro-computed tomography demonstrated that new bone filled 43  5.6 percent of the alveolar defect at 4 weeks, 53  8.3 percent at 8 weeks, and 48  3.5 percent at 12 weeks. Histologically, at 4 weeks, proliferating fibroblasts and polymor- phonuclear cells were scattered throughout the disorganized collagen in the intercalary gap. By 8 weeks, nascent woven bone spicules extended from the edges of the defect. At 12 weeks, the woven spicules had remodeled, with scant additional bone deposition. Conclusion: This model creates a critical-size alveolar defect that is similar in size and location to human alveolar defects and is suitable for studying proposed therapeutics. (Plast. Reconstr. Surg. 123: 817, 2009.) C left lip, with or without palate, remains the most prevalent congenital craniofacial anomaly, seen in one in 700 live births. 1 Although treatment of the cleft lip– cleft palate is becoming standardized, treatment of the alveolar cleft remains controversial. 2 Alveolar clefts may result in delayed dental eruption, tooth loss, and/or collapse of alveolar segments. To promote bony healing within these defects, Skoog de- veloped a periosteoplasty technique, serving to create a periosteal tunnel between cleft alveolar segments. 3 The advent of the first preoperative orthodontic alve- olar molding, described by McNeil 4 and later modified by Millard and Latham, 5 decreased the alveolar gap to permit gingivoperiosteoplasty at the time of the lip repair. Santiago et al., however, demonstrated that gin- givoperiosteoplasty produces satisfactory alveolar bone regeneration in only 60 percent of patients. 6 Additional studies have reported success rates of 41 to 73 percent. 7,8 In the patients for whom gingivoperiosteo- plasty was unsuccessful, a persistent alveolar gap re- mains. Currently, surgeons typically treat this gap with autologous bone graft from the iliac crest when the patient is 7 to 9 years of age. 9 Unfortunately, bone grafting requires a second operation and may be com- plicated by donor-site morbidity (including short- and long-term pain and sensory disturbances), infection, graft resorption, failed tooth eruption, or tooth loss. 2 To date, there is no accurate, reproducible, and cost-effective animal model with which to test technical modifications or therapeutic strategies designed to improve bone formation following gingivoperiosteoplasty. A rat midline palatal de- From the Institute of Reconstructive Plastic Surgery, New York University School of Medicine, and the Department of Bioma- terials and Biomimetics, New York University College of Dentistry. Received for publication June 4, 2008; accepted September 23, 2008. Copyright ©2009 by the American Society of Plastic Surgeons DOI: 10.1097/PRS.0b013e31819ba2f4 Disclosure: None of the authors has any financial interests to disclose. www.PRSJournal.com 817