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.

No abstract

Radiotherapy as a risk factor for free flap failure has been widely debated. The purpose of this study was to investigate vascular complications in free flap surgery at a center advocating preoperative radiotherapy. On the basis of previous experimental studies, we also aimed to investigate temporal aspects of vascular complications in both arteries and veins. Furthermore, we aimed to study the effect of tissue plasminogen activator (tPA), because irradiated microvascular recipient vessels are associated with impaired fibrinolysis.A retrospective review was conducted for 344 consecutive head and neck microvascular reconstructions. Radiotherapy was administered previously in 283 (82%) of the cases, median dose 64 Gy. Flap outcome, vascular complications, and salvage attempts were identified, along with time elapsed from completed radiotherapy, described as early (<6 weeks), delayed (6-15 weeks) and late (>15 weeks) reconstructions.Total flap loss was more common in irradiated cases (P = 0.035), among which flap failure increased with time elapsed from the last radiotherapy session to surgery (P = 0.021). Among 30 registered vascular complications, venous thrombosis was the most common type and increased in delayed, compared to early, reconstructions (P = 0.012). Increased salvage rates were observed when tPA was administered intraoperatively (P = 0.015).The present study indicates that previous radiotherapy is a risk factor for head and neck free flap failure, especially in delayed reconstructions. This may be linked to previous findings of impaired fibrinolysis in irradiated microvascular recipient veins, which is further supported by the beneficial effect of tPA during salvage surgery. We emphasize the importance of early reconstruction after radiotherapy and suggest that there is a role for fibrinolytic agents during free flap salvage surgery in previously irradiated subjects.

Oral administration of high dosages of the dithiocarbamate pesticides maneb and mancozeb was teratogenic in rats but not in mice. The malformations, severe limb and craniofacial defects, were pronounced after maneb treatment but less so after mancozeb and propineb, zinc-containing compounds. The teratogenic effect of maneb was progressively reduced by simultaneously administering increasing amounts of zinc acetate. The mechanism of the teratogenic effect may involve the compounds being chelating agents, trapping zinc required for many important enzyme systems.

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.