BIOCOMPATIBILITY OF POTENTIAL WOUND MANAGEMENT PRODUCTS - HYDROGEN-PEROXIDE GENERATION BY FUNGAL CHITIN CHITOSANS AND THEIR EFFECTS ON THE PROLIFERATION OF MURINE L929 FIBROBLASTS IN CULTURE/

Agaricus bisporus, Fusarium graminearum, Phycomyces blakesleeanus, unb leached and bleached, Rhizomucor miehei, and Rhizopus oryzae were exam ined as sources of fungal chitin/chitosan. The nitrogen content of the alkali-treated mycelia/sporangiophores obtained after optimization of culture conditions, and of similarly treated A. bisporus stipes, was 2.87, 1.29, 6.27, 6.50, 4.80, and 4.95% w/w, respectively, which relat es to an estimated chitin content of 42, 19, 91, 94, 70, and 72%, resp ectively. The hydrogen peroxide (H2O2)-generating ability of the treat ed fungal materials after 8 h at pH 7.4 and 37 degrees C decreased in the order X. oryzae > P. blakesleeanus unbleached approximate to X. mi ehi > F. graminearum > A. bisporus > P. blakesleeanus bleached. This d id not correlate with estimated chitin content. The effect of these fu ngal materials on the rate of proliferation of murine L929 fibroblasts in culture also was examined. Both pro-and antiproliferant effects we re observed. Significant (P < .05) proproliferant effects were observe d on day 6 with R. miehei, R. oryzae, and P. blakesleeanus (unbleached and bleached) at 0.01% w/v. The greatest antiproliferant effect was o bserved with X. oryzae at 0.05% w/v on day 6 (-63% relative to the con trol, P < .05; cell viability, 95%). fn contrast, A. bisporus failed t o affect cell yield significantly at either 0.01 or 0.05% w/v. Additio n of catalase to cultures containing X. oryzae or X. miehei at 0.05% w /v failed to abolish the antiproliferant effect on day 3, instead prod ucing a small but significant (P < .05) increase in the effect. Catala se also failed to affect significantly the antiproliferant effect of F , graminearum at 0.05% w/v, but did abolish the proproliferant effect of P. blakesleeanus (unbleached and bleached) on day 3. Overall, our r esults suggest that the H2O2 being generated by the fungal materials m odulates cell proliferation but that this effect is superimposed upon a H2O2-independent antiproliferant effect manifesting itself at the hi gher concentrations of fungal material. The antiproliferant effect was not attributable to Ca2+, Mg-(2+), or Fe2+ depletion although chelati on of Fe2+ did correlate with H2O2-generating ability. Only P, blakesl eeanus appears to lack this antiproliferant activity while retaining H 2O2-generating activity. These results may aid the selection of fungal chitin/chitosan for further evaluation as a potential wound managemen t material. (C) 1998 John Wiley & Sons, Inc.