Programmable Hydrogels for Surgical Interface Control: Function-Based Design, DNA-Based Molecular Modules, and Translational Evaluation.

Surgical procedures create dynamic interfaces between tissues, fluids, gases, and applied materials. Failure to control these interfaces can cause leakage, postoperative adhesion, scar tethering, poor tissue integration, maladaptive host responses, or loss of mechanical support. Hydrogels are attractive surgical materials because their hydrated polymer networks can be engineered for wet-tissue conformity, adhesion, transport, degradation, mechanical compatibility, and local biological activity. However, many hydrogel systems are still evaluated by polymer chemistry, stimulus type, or isolated physicochemical properties rather than by the operative function required at a defined surgical boundary. This narrative review proposes a function-based framework for designing and evaluating programmable hydrogels in surgical-interface control. Four principal functions-sealing, separation, protection, and integration/reinforcement-are linked to dominant failure modes, design priorities, endpoints, and comparator requirements. Hemostatic and other biological activities are treated as primary clinical claims or adjunct programs when they support these interface functions. Responsiveness is distinguished from clinically meaningful programmability using five operational criteria: input relevance, encoded transition, baseline and off-target stability, interface-level output, and matched-control comparison. DNA-based hydrogels are discussed as molecular modules for recognition, assembly, crosslinking, degradation, actuation, and release, mainly within mechanically robust hybrid systems. This framework emphasizes time-resolved, function-specific evaluation under procedure-relevant conditions.