Smart DNA hydrogels for post-surgical hemostasis and tumor recurrence prevention: bridging bioengineering and clinical translation

Post-surgical complications, particularly hemorrhage and tumor recurrence, remain leading drivers of morbidity, extended hospitalization, and healthcare burden. Hemorrhage poses an immediate, life-threatening risk, while tumor recurrence undermines long-term survival and quality of life. Current hemostatic agents—while effective in providing rapid local clot formation—are constrained by poor tissue adherence, mechanical fragility, and limited durability, often necessitating re-intervention. Similarly, conventional adjuvant strategies (e.g., systemic chemotherapy or radiotherapy) fail to achieve adequate drug concentrations at the surgical bed, exposing patients to systemic toxicity while leaving behind residual disease that seeds recurrence. This dual clinical challenge underscores a critical unmet need for multifunctional, localized, and adaptive post-surgical interventions. Programmable DNA hydrogels have recently emerged as next-generation biomaterials uniquely suited to address this gap. Built from sequence-specific DNA motifs that self-assemble into three-dimensional networks, these hydrogels combine biocompatibility and biodegradability with tunable mechanical strength and stimuli-responsive release. Crucially, they can be engineered to carry pro-coagulant agents for immediate hemostasis while simultaneously delivering chemotherapeutics, immunomodulators, or targeted nanoparticles to suppress residual tumor growth. Beyond drug delivery, hybrid DNA hydrogel systems can integrate biosensing elements and smart, patient-specific responsiveness, enabling precision post-operative care. This review provides a clinician-focused overview of DNA hydrogels in surgical oncology. We emphasize their dual-function potential—rapid hemostasis and recurrence prevention—while outlining mechanistic underpinnings, preclinical evidence, and translational pathways. By bridging bioengineering, biomaterials science, and oncology, we propose DNA hydrogels as a roadmap toward next-generation, adaptive therapeutics that redefine post-surgical management. Dual-function therapeutic potential: DNA hydrogels simultaneously promote rapid post-surgical hemostasis and prevent tumor recurrence. Programmable, stimuli-responsive platform: Sequence-specific DNA motifs allow precise spatial and temporal release of chemotherapeutics, immunomodulators, and pro-coagulant factors. Targeted post-operative intervention: Functionalization with ligands, aptamers, or antibodies ensures selective accumulation at surgical sites and residual tumor niches. Integration of bioengineering and biomaterials: Hybrid DNA-polymer and DNA-nanoparticle systems enhance mechanical robustness, drug loading, and site-specific efficacy. Real-time monitoring and adaptive therapy: Biosensor integration enables dynamic assessment of hemostatic progression and residual tumor activity, facilitating precision post-operative care. Translational relevance: DNA hydrogels provide a next-generation platform for patient-specific, multifunctional post-surgical therapeutics, bridging regenerative medicine and oncology.