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.