Pre-polymers for use as tissue sealants and adhesives, and methods of making and using thereof are provided. The pre-polymers have flow characteristics such that they can be applied through a syringe or catheter but are sufficiently viscous to remain in place at the site of application and not run off the tissue. The pre-polymers are also sufficiently hydrophobic to resist washout by bodily fluids. The pre-polymers are stable in bodily fluids; that is the pre-polymer does not spontaneously crosslink in bodily fluids absent the presence of an intentionally applied stimulus to initiate crosslinking. Upon crosslinking, the adhesive exhibits significant adhesive strength in the presence of blood and other bodily fluids. The adhesive is sufficiently elastic that it is able to resist movement of the underlying tissue. The adhesive can provide a hemostatic seal. The adhesive is biodegradable and biocompatible, causing minimal inflammatory response.