Responsive to revolutionary: thermoresponsive hydrogels pioneering drug delivery and tissue engineering

• Thermoresponsive hydrogels facilitate minimal-invasive and temperature-stimulated sol–gel transitions through in situ gelation under physiological conditions • Polymer chemistry and molecular design support LCST/UCST behavior, mechanical strength, degradation, and drug release kinetics. • Thermogels enable controlled, localized, and sustained delivery of small molecules, proteins, and nucleic acids across various routes. • Thermoresponsive hydrogels function as dynamic scaffolds supporting cell encapsulation, tissue regeneration, and wound healing. • Recent advances highlight translational opportunities and challenges in clinical adoption of thermogelling biomaterials. Thermoresponsive hydrogels are emerging biomaterials in drug delivery and tissue engineering, which respond to temperature changes, enabling controlled drug release and scaffold functionality. This review summarizes thermoresponsive hydrogels from their fundamental principles to transformative applications in biomedical science. These hydrogels exhibit reversible sol–gel transitions at physiological temperatures, enabling minimally invasive delivery and targeted action, and making them suitable for injectable drug depots, intelligent wound dressings, and 3D cell culture platforms. The article examines the molecular structures and polymeric compositions, from poly(N-isopropylacrylamide)-based systems to natural-synthetic hybrids, influencing their thermal sensitivity, mechanical strength, and biocompatibility. Special attention is directed to the design techniques that influence critical solution temperatures, degradation kinetics, and cargo-loading efficiency. In drug delivery, they provide a sustained, responsive release profile for small molecules, proteins, and nucleic acids, with potential for cancer treatment, pain alleviation, and regenerative medicine. In tissue engineering, they function as scaffolds that replicate extracellular matrix characteristics, promote cell growth, and respond to physiological signals, enabling applications in cartilage repair, neuronal regeneration, and stem cell encapsulation. This article highlights the significance of thermoresponsive hydrogels in transforming biomedical frameworks by integrating contemporary advancements and prospective trajectories, ranging from responsive platforms to innovative instruments for precision treatments.