Effects Of Sodium Phenytoin Poly (Lactide-co-glycolide) Microspheres Poloxamer 407 Gel On Periodontal Wound Healing In Fenestration Defects Of Rats

Objective: To investigate the effects of sodium phenytoin poly (lactide-co-glycolide) microspheres Poloxamer 407 gel (PHT-PLGA-MG) on periodontal wound healing in fenestration defects of rats, and provide an in vivo basis for the development of new PHT formulation for local drug delivery.Methods: PHT-PLGA-MG and PLGA-MG were developed by School of Pharmacy, Shandong University after routine test. Following surgery to create a bony window on the buccal aspects of mandibular molar roots, 48 male Wistar rats were randomly divided into three groups, treated with PHT-PLGA-MG, PLGA-MG and nothing respectively. In each group, animals were randomly sacrificed after 2 or 4 weeks and then the mandibles were processed for histological examination. Histometric measurements were performed with Image-Pro-Express system. The percentage of new bone area, new bone width, new bone height was compared among groups at different time stage. Data were processed by t-test following test for homogeneity of variances using SAS 9.0 statistical package.Results: 2 weeks: Partial regeneration of new alveolar bone, new periodontal ligament and new cementum was observed mainly in the apical area of the defects. In the control group the newly formed bone was meshy, triangle-shaped with bone cells. There was periodontal ligament between root surface and new bone. In PHT-PLGA-MG group, new bone was strip-shaped and scattering in the whole defect; infiltration of inflammatory cells was observed. In PLGA-MG group dense fibrous connective tissues occupied most of the defects with scare bone regeneration. New cellular cementum was seen on the surface of the old cementum. 4 weeks: The adequate width of regenerative periodontal ligament was observed along the total length, and almost complete alveolar bone reconstruction could be found in all three groups. In the region with new cementum, regular Sharpey's fibers attached from the cementum and inserted to the nearby new bone, while periodontal connective tissue was arranged loosely and disorderly on the root surface without cementum regeneration. Gingival epithelial cells and fibrous connective tissue in PHT-PLGA-MG group were normal and similar with those in the other two groups.In either 2 or 4 weeks, the new alveolar bone on the denuded root surfaces in PHT-PLGA-MG group was significantly greater than that in PLGA-MG group (P<0.05). There was no statistical difference between PHT-PLGA-MG group and the control group, although the control group had more bone regeneration (P>0.05).Conclusions: PHT-PLGA-MG may serve as a novel therapeutic strategy for periodontal bone regeneration without obvious side effect of gingival overgrowth in our in vivo study.