Methods for sealing an orifice in tissue in the body of a living animal using an adhesive formed by reacting an oxidized polysaccharide with a poly(hydroxylic) compound derivatized with acetoacetate groups in the presence of a base catalyst are disclosed. Methods for using the adhesive for medical and veterinary applications such as topical wound closure and surgical procedures, such as intestinal anastomosis, vascular anastomosis, tissue repair, and ophthalmic procedures and drug delivery are described.