Purpose: The purpose of this study was to examine the local tissue reactions associated with 3 different poly(lactic-co-glycolic acid) (PLGA) prototype membranes and to compare them to the reactions associated with commercially available resorbable membranes in rats. Methods: Seven different membranes—3 synthetic PLGA prototypes (T1, T2, and T3) and 4 commercially available membranes (a PLGA membrane, a poly[lactic acid] membrane, a native collagen membrane, and a cross-linked collagen membrane)—were randomly inserted into 6 unconnected subcutaneous pouches in the backs of 42 rats. The animals were sacrificed at 4, 13, and 26 weeks. Descriptive histologic and histomorphometric assessments were performed to evaluate membrane degradation, visibility, tissue integration, tissue ingrowth, neovascularization, encapsulation, and inflammation. Means and standard deviations were calculated. Results: The histological analysis revealed complete integration and tissue ingrowth of PLGA prototype T1 at 26 weeks. In contrast, the T2 and T3 prototypes displayed slight to moderate integration and tissue ingrowth regardless of time point. The degradation patterns of the 3 synthetic prototypes were similar at 4 and 13 weeks, but differed at 26 weeks. T1 showed marked degradation at 26 weeks, whereas T2 and T3 displayed moderate degradation.Inflammatory cells were present in all 3 prototype membranes at all time points, and these membranes did not meaningfully differ from commercially available membranes with regard to the extent of inflammatory cell infiltration. Conclusions The 3 PLGA prototypes, particularly T1, induced favorable tissue integration, exhibited a similar degradation rate to native collagen membranes, and elicited a similar inflammatory response to commercially available non–cross-linked resorbable membranes.The intensity of inflammation associated with degradable dental membranes appears to relate to their degradation kinetics, irrespective of their material composition.

Periodontal disease is associated with chronic oxidative stress and inflammation. Caffeic acid phenethyl ester (CAPE), which is a potent inducer of heme oxygenase 1 (HO1), is a central active component of propolis, and the application of propolis improves periodontal status in diabetic patients. Here, primary murine macrophages were exposed to CAPE. Target gene expression was assessed by whole-genome microarray, RT-PCR and Western blotting. The antioxidative and anti-inflammatory activities of CAPE were examined by exposure of the cells to hydrogen peroxide, saliva and periodontal pathogens. The involvement of HO1 was investigated with the HO1 inhibitor tin protoporphyrin (SnPP) and knockout mice for Nrf2, which is a transcription factor for detoxifying enzymes. CAPE increased HO1 and other heat shock proteins in murine macrophages. A p38 MAPK inhibitor and Nrf2 knockout attenuated CAPE-induced HO1 expression in macrophages. CAPE exerted strong antioxidative activity. Additionally, CAPE reduced the inflammatory response to saliva and periodontal pathogens. Blocking HO1 decreased the antioxidative activity and attenuated the anti-inflammatory activity of CAPE. In conclusion, CAPE exerted its antioxidative effects through the Nrf2-mediated HO1 pathway and its anti-inflammatory effects through NF-κB inhibition. However, preclinical models evaluating the use of CAPE in periodontal inflammation are necessary in future studies.
Animals ; Caffeic Acids ; pharmacology ; Heme Oxygenase-1 ; genetics ; metabolism ; Humans ; Inflammation ; drug therapy ; Mice ; NF-kappa B ; antagonists & inhibitors ; genetics ; metabolism ; Oxidative Stress ; drug effects ; Phenylethyl Alcohol ; analogs & derivatives ; pharmacology