Background To minimize the inflammatory reaction and improve healing, a new modifieddermal substitute composed of an atelocollagen, chondroitin-6-sulfate, and amnioticmembrane (AM) was applied to full-thickness skin defects in a pig. Atelocollagen was extractedfrom bovine skin, and two modified dermal substitutes were generated according to the crosslinkingtype.Methods The AM-collagen dermal substitutes were characterized and compared withcurrently used dermal substitutes in a pig skin defect model. There were five experimentalgroups: dehydrothermal (DHT) cross-linking atelocollagen with the AM on the top (AM-DHT),DHT and chemical cross-linking atelocollagen with the AM on the top (AM-DHT/chemical),Terudermis, Integra, and AlloDerm. After 3×3 cm full-thickness skin defects on the back ofa pig were created, each dermal substitutes dermal substitutes was randomly grafted on thedefects. Two weeks after grafting, autologous partial-thickness skin was over-grafted on theneodermis. The take rate of the dermal substitutes, skin, and histological sections were allassessed at 1, 2, and 4 weeks postoperatively.Results More rapid healing and a higher take rate were evident in the AM-DHT and Terudermisgroups. Histological examination revealed fewer inflammatory cells and more fibroblasthyperplasia in these two groups. Four weeks after surgery, the amount of newly formedcollagen was significantly more appropriate in the AM-DHT group.Conclusions These observations provide supporting evidence that a newly developed amnioticcollagendermal substitute may inhibit inflammatory reactions and promote wound healing.