While often life-saving, surgical resectioning of diseased tissues puts patients at risk for post-operative complications. Sutures and staples are well-accepted and routinely used to reconnect tissues, however, their mechanical mismatch with biological soft tissue and invasiveness contribute to wound healing complications, infections, and post-operative fluid leakage. In principle, laser tissue soldering offers an attractive, minimally-invasive alternative for seamless soft tissue fusion. However, despite encouraging experimental observations, including accelerated healing and lowered infection risk, critical issues related to temperature monitoring and control during soldering and associated complications have prevented their clinical exploitation to date. Here, intelligent laser tissue soldering (iSoldering) with integrated nanothermometry is introduced as a promising yet unexplored approach to overcome the critical shortcomings of laser tissue soldering. It demonstrates that adding thermoplasmonic and nanothermometry nanoparticles to proteinaceous solders enables heat confinement and non-invasive temperature monitoring and control, offering a route to high-performance, leak-tight tissue sealing even at deep tissue sites. The resulting tissue seals exhibit excellent mechanical properties and resistance to chemically-aggressive digestive fluids, including gastrointestinal juice. The iSolder can be readily cut and shaped by surgeons to optimally fit the tissue defect and can even be applied using infrared light from a medically approved light source, hence fulfilling key prerequisites for application in the operating theatre. Overall, iSoldering enables reproducible and well-controlled high-performance tissue sealing, offering new prospects for its clinical exploitation in diverse fields ranging from cardiovascular to visceral and plastic surgery.

Biomedical Center Faculty of Medicine in Pilsen Charles University 32300 Pilsen Czech Republic

Department of Surgery Faculty of Medicine in Pilsen Charles University 32300 Pilsen Czech Republic

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Centre of Preclinical Research 20122 Milan Italy

Nanoparticle Systems Engineering Laboratory Institute of Energy and Process Engineering ETH Zurich 8092 Zurich Switzerland

Particles Biology Interactions Laboratory Department of Materials Meet Life Swiss Federal Laboratories for Materials Science and Technology 9014 St Gallen Switzerland

Swiss HPB and Transplant Center University Hospital Zurich 8091 Zurich Switzerland

Transplantation Center Digestive Disease and Surgery Institute and Department of Immunity and Inflammation Lerner Research Institute Cleveland Clinic 44106 OH Cleveland United States

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Robotic Laser Tissue Soldering for Atraumatic Soft Tissue Fusion Guided by Fluorescent Nanothermometry