Background: Endoscopic reconstruction of skull base defects remains a challenge. Laser tissue welding (LTW) is a technique in which a laser-activated solder is used to create instantaneous repairs of skull base defects with burst strengths far exceeding intracranial pressure (ICP). This study was designed to define the thermal and inflammatory profile of a novel polysaccharide soldering gel, to assess the burst strength of the repair, and to determine the time required for solder resorption. Methods: A prospective study was performed in rabbit and mouse models. Ten dorsal rabbit maxillary sinusotomies were laser welded and burst pressure thresholds were compared with control wounds on postoperative days (PODs) 0 and 5. All welds were examined histologically on PODs 0, 5, and 45 for thermal injury, inflammation, and degree of solder resorption. In mice, dura was exposed and laser welding was performed (n = 2). Results were compared histologically with dura exposed to laser energy alone (n = 2) on POD 7. Results: The burst pressures of the rabbit LTW group were significantly higher than control on PODs 0 (135.0 mmHg and SD = 5.8 versus 8.0 mmHg and SD = 0.5; n = 4) and 5 (155.4 mmHg and SD = 2.9 versus 41.7 mmHg and SD = 7.3; n = 4; p < 0.05). No significant thermal or inflammatory effect was found in any of the rabbit or mouse welds. Complete solder resorption was noted by POD 45. Conclusion: LTW using a polysaccharide gel is capable of creating mucosal repairs capable of withstanding over four times normal ICP without additional grafting materials. These repairs increase in strength over time, have no thermal or inflammatory sequelae, and establish complete solder resorption within 45 days. [ABSTRACT FROM AUTHOR]