The effect of chitin and chitosan on the proliferation of human skin fibroblasts and keratinocytes in vitro

The effects of chitin [(1 -->4)-2-acetamido-2-deoxy-beta -D-glucan] and its partially deacetylated derivatives, chitosans, on the proliferation of hum an dermal fibroblasts and keratinocytes were examined in vitro. Chitosans w ith relatively high degrees of deacetylation strongly stimulated fibroblast proliferation while samples with lower levels of deacetylation showed less activity. Fraction, CL313A, a shorter chain length, 89% deacetylated chito san chloride was further evaluated using cultures of fibroblasts derived fr om a range of human donors. Some fibroblast cultures produced a positive mi togenic response to CL313A treatment with proliferation rates being increas ed by approximately 50% over the control level at an initial concentration of 50 mug/ml, whilst others showed no stimulation of proliferation or even a slight inhibition (<10%). The stimulatory effect on fibroblast proliferat ion required the presence of serum in the culture medium suggesting that th e chitosan may be interacting with growth factors present in the serum and potentiating their effect. In contrast to the stimulatory effects on fibrob lasts, fraction CL313A inhibited human keratinocyte mitogenesis with up to 40% inhibition of proliferation being observed at 50 <mu>g/ml. In general h ighly deacetylated chitosans were more active than those with a lower degre e of deacetylation. These data demonstrate that highly deacetylated chitosa ns can modulate human skin cell mitogenesis in vitro. Analysis of their eff ects on cells in culture may be useful as a screen for their potential acti vity in vivo as wound healing agents, although in the case of fibroblasts i t is important to select appropriate strains of cells for use in the screen . (C) 2001 Elsevier Science Ltd. All rights reserved.