Disclosed are tissue sealants that include whole blood and an effective amount of an exogenous protein cross-linker to cross-link the whole blood. Also disclosed are methods for forming a tissue sealant. Such methods include, providing whole blood and mixing the whole blood with an effective amount of an exogenous protein cross-linker to cross-link the whole blood into an adherent mass, thereby forming the tissue sealant. The disclosed tissue sealants can be used for any application, for example to achieve hemostasis, bond tissue of a subject and/or or seal a fluid or gas leak in a tissue of a subject.