Inflammation-Responsive Hydrogels in Perioperative Pain and Wound Management: Design Strategies and Emerging Potential

Surgical procedures trigger dynamic inflammatory responses that influence postoperative pain, wound healing, and long-term outcomes. Conventional therapies rely on the systemic delivery of anti-inflammatory and analgesic agents, which often lack spatiotemporal precision and carry significant side effects. Inflammation-responsive hydrogels offer a promising alternative by enabling localized, stimulus-adaptive drug release aligned with the evolving biochemical milieu of surgical wounds. These smart biomaterials respond to endogenous triggers, such as reactive oxygen species, acidic pH, and proteolytic enzymes, allowing precise modulation of inflammation and tissue repair. This narrative review outlines the pathophysiological features of perioperative inflammation and the design principles of responsive hydrogel systems, including pH-, reactive oxygen species-, enzyme-sensitive, and multi-stimuli platforms. We evaluated the integration of key payloads, NSAIDs, corticosteroids, α₂-adrenergic agonists, and biologics, highlighting their therapeutic synergy and translational relevance. Preclinical studies across soft tissue, orthopedic, thoracic, and abdominal models have demonstrated the efficacy of these systems in modulating immune responses, reducing pain, and enhancing regeneration. Despite these encouraging results, challenges remain, including trigger fidelity, surgical compatibility, and regulatory readiness. Future advances in biosensor integration, logic-based design, and artificial intelligence-guided formulation may accelerate clinical translation. Inflammation-responsive hydrogels represent a transformative strategy for precise perioperative care.