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Background: Liquid solder laser-assisted vascular welding using biocompatible polymeric scaffolds (ssLAVW) is a novel technique for vascular anastomoses. Although ssLAVW has pronounced advantages over conventional suturing, drawbacks include low welding strength and extensive thermal damage. Aim: To determine optimal ssLAVW parameters for maximum welding strength and minimal thermal damage. Methods: Substudy 1 compared breaking strength (BS) of aortic strips welded with electrospun poly( -caprolactone) (PCL) or poly(lactic-co-glycolic acid) (PLGA) scaffold, 670-nm laser, 50-s single-spot continuous lasing (SSCL), and semi-solid solder (48% bovine serum albumin (BSA)/0.5% methylene blue (MB)/3% hydroxypropylmethylcellulose (HPMC)). Substudy 2 compared the semi-solid solder to 48% BSA/0.5% MB/0.38% genipin and 48% BSA/0.5% MB/3% HPMC/0.38% genipin solder. Substudy 3 compared SSCL to single-spot pulsed lasing (SSPL). Results: PCL-ssLAVW yielded an acute BS of 248.0 ± 54.0 N/cm 2 and remained stable up to 7d of hydration. PLGA-ssLAVW obtained higher acute BS (408.6 ± 78.8 N/cm 2 ) but revealed structural defects and a BS of 109.4 ± 42.6 N/cm 2 after 14 d of hydration. The addition of HPMC and genipin improved the 14-d BS of PLGA-sLAVW (223.9 ± 19.1 N/cm 2 ). Thermal damage was reduced with SSPL compared with SSCL. Keywords:non-invasive vascular surgery cohesive and adhesive bonding coaptation albumin solder polycaprolactone poly(lactic-co-glycolic acid) biomaterial scaffold Conclusions: PCL-ssLAVW yielded lower but more stable welds than PLGA-ssLAVW. The addition of HPMC and genipin to the solder increased the post-hydration BS of PLGA-ssLAVW. SSPL regimen reduced thermal damage. PLGA-ssLAVW using 48% BSA/0.5% MB/3% HPMC/0.38% genipin solder and SSPL constitutes the most optimal welding modality. Relevance for patients: Surgical patients requiring vascular anastomoses may benefit from the advantages that ssLAVW potentially offers over conventional sutures (gold standard). These include no needle trauma and remnant suture materials in the patient, reduction of foreign body reaction, immediate liquid-tight sealing, and the possibility of a faster and easier procedure for minimally invasive and endoscopic anastomotic techniques. D. R. Pabittei et al.