Anastomosis is a critical surgical procedure for reconnecting the tissue ends. Despite progress in surgical techniques, complications such as leaks and strictures still pose serious health risks. Most traditional approaches primarily focus on tissue alignment and perfusion. However, they often overlook the influence of mechanical cues on healing process. In this review, we introduce the concept of mechanomedicine that is a new field for integration of biomechanics and mechanobiology to guide cellular responses and tissue regeneration during anastomosis. We summarize the mechanical characteristics of different anastomotic techniques, including the type and level of mechanical forces generated at the repair site. In addition, we explore how these mechanical cues affect signaling pathways, such as Piezo1, TRPV4, and YAP/TAZ that are essential for hemostasis, inflammation, and tissue regeneration during the anastomotic healing process. By evaluating conventional and emerging anastomotic techniques, we reveal how distinct mechanical cues influence clinical outcomes. Finally, we highlight the potential of artificial intelligence and robotic systems that may help to optimize the mechanical microenvironment, predict complications, and personalize treatments. This review will establishe a novel mechanomedicine-driven framework for anastomosis, aiming to utilize biomechanics and mechanobiology for enhancing surgical precision and improving patient outcomes.
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