Tissue fusion is a complex, poorly understood process which bonds collagenous tissues together using heat and pressure. The goal of this study is to elucidate the role of hydration in bond efficacy. Hydration of porcine splenic arteries (n=30) was varied by pre-fusion treatments: 24-48 hour immersion in isotonic, hypotonic, or hypertonic baths. Treated arteries were fused in several locations using Conmed's Altrus thermal fusion device and the bursting pressure was then measured for each fused segment. Artery sections were then weighed before and after lyophilization, to quantify water content. Histology (HE, EVG staining) enabled visualization of the bonding interface. Bursting pressure was significantly greater (p=4.17 E-ll) for the hypotonic group (607.6 ± 83.2mmHg), while no significant difference existed between the isotonic (332.6 ± 44.7mmHg) and hypertonic (348.7 ± 44.0mmHg) treatment groups. Total water content varied (p=8.80 E-24) from low water content in the hypertonic samples (72.5% weight ± 0.9), to high water content in the hypotonic samples (83.1% weight ± 1.9), while the isotonic samples contained 78.8% weight ± 1.1. Strength differences between the treated vessels imply that bound water driven from the tissue during fusion may reveal available collagen crosslinking sites to facilitate bond formation during the fusion process. Thus when the tissue contains greater bound water volumes, more crosslinking sites may become available during fusion, leading to a stronger bond. This study provides an important step towards understanding the chemistry underlying tissue fusion and the mechanics of tissue fusion as a function of bound water within the tissue.