Construction of a Pig Alveolar Cleft Model in Imitation of Cleft Lip and Palate Congenital Deformity

Alveolar cleft repair is a key step in multiple disciplinary treatment for patients with cleft lip/and palate. Although autologous bone grafting has been used worldwide over the past half century, alternative advanced techniques, such as the use of bone substitutes and guided tissue regeneration, have shown their great potentials and have been recommended by a growing number of physicians and surgeons. The employment of new therapeutic approaches and devices in clinical routine requires tremendous experimental efforts and appropriate animal models with similar sizes and sites of deformity to that of human both anatomically and physiologically. The aim of this study is to develop a juvenile porcine model with surgically created alveolar clefts imitating congenital alveolar cleft in the cleft lip and palate. Alveolar defects between second incisor and canine were surgically created in two miniature pigs (unilateral cleft in P1 and P2); bilateral alveolar defects were surgically created between first and third incisor in one miniature pig (P3) using piezo surgery. Pigs were sacrificed (P1 at 1 month after the surgery and P2 at 3 months postoperatively) and the evaluation of defects were performed by assessing result from the computed tomography (CT) scan and histopathological examination. Postoperative CT scan results showed that the size of the defect remained the same, whereas the edge of the defect became irregular 3 months after the surgery. In all pig subjects, histopathological examination found no sign of osteogenesis in the area of defect, indicating that our surgical procedure was successful in establishing porcine models for alveolar cleft in congenital cleft lip and palate. In conclusion, we developed alveolar cleft in porcine models to mimic the size, site, and environment of congenital alveolar cleft in cleft lip and palate. The novel animal model can be employed in pilot studies for the purpose of optimizing the current surgical treatment techniques as well as developing new treatment procedures and test the bone substitute materials. The bilateral model can be applied in further control studies. IMPACT STATEMENT: Cancellous iliac bone graft was the most popular surgical technique as well as the gold standard to reconstruct alveolar cleft. Nevertheless, several disadvantages exist regarding the additional surgical field of donor side and delayed age of alveolar bone grafting. Bone tissue-engineered strategy offers a promising alternative to address the gap in the current limitation of autologous bone to treat the growing craniofacial skeleton. Among different species of laboratory animals, porcine is suitable for oral and maxillofacial bone and implant-related research, where alveolar defect can be surgically developed simulating the size and site of alveolar cleft occurring together with cleft lip and palate. In this proposal, a reproducible porcine model of alveolar bone defect imitating congenital alveolar cleft during craniofacial growing stage is successfully constructed that will show great potential application in the field of tissue engineering and regenerative medicine. The model for bilateral alveolar cleft can be potentially applied in a controlled study in future.