IN-VITRO AND IN-VIVO BIOCOMPATIBILITY OF DEXTRAN DIALDEHYDE CROSS-LINKED GELATIN HYDROGEL FILMS

The biosafety of a new hydrogel wound dressing material consisting of dextran dialdehyde cross-linked gelatin was evaluated (i) in vitro in cultures of dermal fibroblasts, epidermal keratinocytes, and endotheli al cells, three cell types which play a major role in the process of c utaneous wound healing, and (ii) in vivo by subcutaneous implantation studies in mice. The cytotoxicities of this hydrogel, two semi-occlusi ve polyurethane dressings (Tegaderm and OpSite), and a hydrocolloid dr essing (DuoDERM) were compared by measuring cell survival with the tet razolium salt reduction (MTT) assay after incubations of the wound dre ssing samples for up to 6 d, in the presence of-but not in direct cont act with-the cells. In vitro, the degree of cytotoxicity of the new hy drogel was greater in keratinocyte cultures than in fibroblast and end othelial cell cultures, and increased upon longer incubation time. In keratinocyte cultures, the semi-occlusive polyurethane dressings, the hydrocolloid, and the hydrogel dressings induced low, high and accepta ble degrees of cytotoxicity, respectively. The toxicity of the isolate d hydrogel components was assessed in Balb MK keratinocyte cultures. I n these cells, epidermal growth-factor-stimulated thymidine incorporat ion into DNA was higher in the presence of gelatin. By contrast, conce ntrations of dextran dialdehyde as low as 0.002% were found to signifi cantly decrease thymidine incorporation (P < 0.01). Subcutaneous impla ntation studies in mice showed that in vivo the hydrogel was biocompat ible since the foreign body reaction seen around the implanted hydroge l samples was moderate and became minimal upon increasing implantation time. These results indicate that dextran dialdehyde cross-linked gel atin hydrogels have an appropriate biocompatibility. (C) 1998 Publishe d by Elsevier Science Ltd. All rights reserved.