The purpose of this study was to investigate cross-linking of (damaged) collagen by tannic acid, with a view to reconsider its use as a possible therapeutical agent in the treatment of burn wounds. Because of contradictory reports in the literature, and increased purity of tannic acid, this method has again become valuable for re-evaluation. A laboratory study using dermal sheep collagen was conducted to analyse the influence of several metal ions on collagen cross-linking with tannic acid. The tannic acid concentration vs degree of cross-linking, tannic acid uptake and release, influence of the addition of metal ions, and the rate of degradation of treated collagen were established. We have shown that tannic acid mediated collagen cross-linking in a concentration-dependent manner. Cross-linking was influenced by the presence of metal ions: Fe3+ and Ag+ were shown to exert a stimulatory effect on the degree of cross-linking by a 2% tannic acid solution, whereas Zn2+ had an inhibitory effect Ce3+ Ca2+ and Na+ did not influence the degree of cross-linking. The degree of cross-linking was proportional to the uptake of tannic acid, which variod between 6 and 35 wt%. Reversibility of cross-linking was established. Tannic acid-treated dermal sheep collagen showed a slow degradation rate relative to differently cross-linked collagen materials when subjected to collagenase or pancreatic proteolytic enzymes. The results of this study suggest that tannic acid could have a function in vivo in burn treatment by binding burn toxins and inhibiting degradation of the (remaining) dermal matrix, and allows combination with metal ions as antimicrobials. Optimal cross-linking was obtained using a 2 wt% tannic acid solution; combination with Ce3+ as a potential antimicrobial agent is possible without diminishing cross-linking.