Collagen sponge (CS) reconstituted from purified bovine skin collagen in the presence of a tanning agent, was studied as a dressing material in third degree burn models in pigs and as cartilage-bone substitute in various animal models. We found that tanning with glutaraldehyde induces adverse cytotoxic effects, while tanning with diisocyanate is biologically acceptable. As burn dressing, CS showed several advantages over materials such as pig skin, polyurethane foam, xeroform. As cartilage substitute, CS promotes the adequate replacement of articular cartilage in knee joint of dogs. We demonstrated that diisocyanate tanned CS is faster seeded by fibrogenic cells than CS tanned with glutaraldehyde. In three models of bone defect (humerus in rabbits, spine fusion in dogs and mastoid cavity obliteration in guinea pigs) CS promoted fibrotic replacement of the tissue defect.