(680a) Treating Periodontal Disease through Recruitment of Regulatory Lymphocytes

Periodontal disease is characterized by destructive inflammation of the periodontium (gingival tissue, alveolar bone and periodontal ligament) and is considered the most pressing oral health concern today, affecting over 78 million Americans. Several invasive bacteria species are thought to trigger the inflammatory immune reaction that is responsible for both soft and hard tissue destruction. Current periodontal disease therapies focus on the elimination of these invasive bacteria through surgical procedures known as scaling and root planing, and in severe cases the use of local antibiotics. These therapies are costly and patients often undergo multiple treatments as a result of reoccurring periodontal lesions. Recent literature indicates that though bacteria insult initiates the disease, symptoms are perpetuated by an imbalanced immune response. Furthermore, recent data suggests that periodontal disease severity can be characterized by the presence or absence of a subset of lymphocytes that mediate immunological tolerance and homeostasis. We hypothesize that recruiting regulatory lymphocytes into periodontal lesions may not only decrease the symptoms of the disease, but also restore immunological homeostasis and promote regeneration. To this end, we have engineered poly(lactic-co-glycolic acid) (PLGA) controlled release microparticles using a double emulsion procedure to encapsulate and sustain a biological gradient of regulatory lymphocyte chemokine (CCL-22). In a murine model of periodontitis, we observed recruitment of regulatory T cells and amelioration of disease symptoms upon treatment with our microparticle formulation. These results support our hypothesis and suggest treating the underlying immune dysfunction may lead to more efficacious, long lasting and cost effective solutions for periodontal disease.