Wada, Keisuke
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Publication Animal Models to Study Host-Bacteria Interactions Involved in Periodontitis(2012-01-01) Graves, Dana T; Kang, Jun; Wada, Keisuke; Andriankaja, Oelisoa; Rossa, CarlosAnimal models have distinct advantages because they can mimic cellular complexities that occur in humans in vivo and are often more accurate than in vitro studies that take place on plastic surfaces with limited numbers of cell types present. Furthermore, cause and effect relationships can be established by applying inhibitors or activators or through the use of genetically modified animals. Such gain or loss of function studies are often difficult to achieve in human clinical studies, particularly in obtaining target tissue due to important ethical considerations. Animal models in periodontal disease are particularly important at this point in the development of the scientific basis for understanding the predominant pathological processes. Periodontal disease can be broken down into discrete steps, each of which may be studied separately depending upon the animal model. These steps involve the development of a pathogenic biofilm, invasion of connective tissue by bacteria or their products, induction of a destructive host response in connective tissue and limitation of are pair process that follows tissue breakdown. Animal studies can test hypotheses related to each of these steps, and should be evaluated by their capacity to test a specific hypothesis rather than recapitulating all aspects of periodontal disease. Thus, each of the models described below can be adapted to test discrete components of the pathological process of periodontal disease, but not necessarily all of them.Publication Locally Delivered Salicylic Acid From a Poly(anhydride-ester): Impact on Diabetic Bone Regeneration(2013-10-10) Wada, Keisuke; Yu, Weling; Elaziz, Mohamad; Barakat, Sandrine; Ouimet, Michelle A; Rosario-Meléndez, Roselin; Fiorellini, Joseph P; Graves, Dana T; Uhrich, Kathryn EDiabetes mellitus (DM) involves metabolic changes that can impair bone repair, including a prolonged inflammatory response. A salicylic acid-based poly(anhydride-ester) (SA-PAE) provides controlled and sustained release of salicylic acid (SA) that locally resolves inflammation. This study investigates the effect of polymer-controlled SA release on bone regeneration in diabetic rats where enhanced inflammation is expected. Fifty-six Sprague–Dawley rats were randomly assigned to two groups: diabetic group induced by streptozotocin (STZ) injection or normoglycemic controls injected with citrate buffer alone. Three weeks after hyperglycemia development or vehicle injection, 5 mm critical sized defects were created at the rat mandibular angle and treated with SA-PAE/bone graft mixture or bone graft alone. Rats were euthanized 4 and 12 weeks after surgery, then bone fill percentage in the defect region was assessed by micro-computed tomography (CT) and histomorphometry. It was observed that bone fill increased significantly at 4 and 12 weeks in SA-PAE/bone graft-treated diabetic rats compared to diabetic rats receiving bone graft alone. Accelerated bone formation in normoglycemic rats caused by SA-PAE/bone graft treatment was observed at 4 weeks but not at 12 weeks. This study shows that treatment with SA-PAE enhances bone regeneration in diabetic rats and accelerates bone regeneration in normoglycemic animals.