Antiproliferative effect of topic hyaluronic acid gel. Study in gingival biopsies of patients with periodontal disease.

Hyaluronic acid (HA) is the most abundant glycosaminoglycan of high molecular weight in the extracellular matrix of soft periodontal tissues. Our group recently demonstrated an HA-induced reduction in lymphoplasmocyte inflammatory infiltrate in periodontal disease. The objective of this study was to determine the effect of an HA gel of high molecular weight on cell proliferation, inflammation, and different periodontal lesion parameters. A double-blind clinical trial was conducted on the effect of an HA gel on cell proliferation in gingival biopsies from 28 patients with periodontal disease. A split-mouth design was used, randomly applying the gel to one quadrant and a placebo to the contralateral one. A gingival biopsy was taken for histopathological and immunohistochemical study, in order to determine the expression of cell proliferation antigen Ki-67 and to evaluate the inflammatory infiltrate. HA gel treatment induced a significant reduction in the proliferation index of the gingival epithelium, with 276 (range 234-317) Ki-67-positive cells per mm2 in treated samples versus 514 (range 158-876) per mm2 in controls (Mann-Whitney U test, p<0.003). In 13 patients, the number of Ki-67-positive fibroblastic cells was reduced by the treatment, whereas in 6 patients no differences were found (global difference, p=0.12). In 10 patients, Ki-67-positive cells were decreased in chronic inflammatory infiltrate present in the lamina propria, whereas in 6 patients no differences were found (global difference, p=0.054). We conclude that high molecular-weight HA gel reduces cell proliferation in epithelial cells such as fibroblasts and lymphocytes, abates the inflammatory process, and improves the periodontal lesion in patients with chronic periodontitis.