The effect of heparin ionically linked to chitosan on the stimulation of re-epithelialisation of full thickness wounds in human skin was investigated in an in vitro model. After seven days of incubation, heparin-chitosan gel stimulated 9/10 of the full thickness wounds to re-epithelialise compared with only 3/10 of the wounds that were covered with chitosan gel or membrane, and none of the wounds incubated without gel or membrane or with heparin solution alone. Both dermal and epidermal cells were viable after the incubation time. Furthermore, the stimulatory effect of the heparin-chitosan complexes depended on the concentration of heparin in the complex. We hypothesise that these effects are caused by stabilisation and activation of growth factors that bind to immobilised heparin.

Locally produced growth factors are of great importance in wound healing in human skin. Wound fluid from chronic wounds contains low concentrations of growth factors possibly because of rapid degradation as a result of the high concentration of proteases. Many growth factors involved in wound healing bind to heparin and are thereby stabilised and activated. We have recently shown that heparin in combination with chitosan stimulates re-epithelialisation in an in vitro model of human wound healing. In the present study we investigated the effects of a chitosan-heparin membrane on wound healing in 10 split-thickness graft donor sites in human skin. The chitosan-heparin membrane stimulated healing of the donor sites both when judged macroscopically in a blinded fashion and when biopsy specimens from the treated and untreated parts of the wound were investigated microscopically. We hypothesise that the beneficial effects of the chitosan-heparin membrane result from slow release of heparin into the wound area which protects locally produced growth factors. The result is increased stabilisation and concentration of growth factors in the wound area, which stimulate healing. We believe that these results may be important in the treatment of wounds that are reluctant to heal.