Diabetic wound healing represents a crucial and complex subject in clinical medicine, because of its physiological mechanism and pathological state, the conventional treatment methods are often limited. In recent years, multifunctional hydrogels have emerged as a focal point in the research field regarding the healing of diabetic wounds. This is attributed to their outstanding biocompatibility, the capacity for controlling drug release, and the traits of facilitating cell migration and proliferation. This paper reviews the fundamental materials, modification strategies for functionality, the principles underlying drug release, and the latest application advancements of multifunctional hydrogels in the context of facilitating the healing process of diabetic wounds. By introducing bioactive molecules and utilizing 3D bioprinting technology, researchers continue to optimize the properties of hydrogels to adapt to various wound conditions, which demonstrates great promise in the use of wound dressings. Taking the microenvironment of diabetic wounds into consideration, strategies for antibacterial, anti-inflammatory, immunomodulatory, antioxidant, and pro-angiogenic effects are integrated with multifunctional hydrogels. This paper systematically analyzes the existing challenges and explores the future research directions, and emphasizes the potential of multifunctional hydrogels in improving wound healing of diabetes and their clinical application prospects.

As a novel drug delivery system responsive to environmental stimuli (temperature, pH, ionic strength, etc). nasal in situ gels undergo phase transition to provide breakthrough solutions for precision and long-term management of nasal disorders through the integration of targeted therapy and sustained-release technology. Following nasal administration, the liquid formulation rapidly transforms into a semi-solid gel depot on the mucosal surface, significantly prolonging drug residence time and reducing drug loss due to mucociliary clearance. This process enhances local drug concentration and therapeutic persistence. Incorporating mucoadhesive technology and controlled-release drug-loading systems, this platform enables precise delivery of anti-inflammatory, antihistaminic, and immunomodulatory agents to lesion sites. It effectively mitigates systemic side effects (e.g. drowsiness, hepatic/renal burden) associated with conventional dosage forms while reinforcing nasal mucosal barrier repair. Clinical studies confirm its superior efficacy and safety profile in conditions requiring long-term therapy, including allergic rhinitis, sinusitis, and central nervous system disorders. Its mild gelation properties enhance patient tolerance, and single/every-other-day dosing regimens significantly improve compliance. Further optimization of release kinetics through multi-level drug-loading techniques (e.g. composite nanoparticles) demonstrates potential in gene therapy and vaccine delivery. This review systematically examines material design strategies, drug release mechanisms, clinical advancements, and translational challenges, with focused analysis on the impact of gelation kinetics on delivery efficiency, bottlenecks in scaled-up production. The work aims to provide theoretical foundations for optimized design and clinical translation while exploring future prospects for multifaceted applications in the era of precision medicine.

Modulating inflammation within the tumor microenvironment (TME) has emerged as a crucial avenue in contemporary cancer therapy. However, the intricate signaling networks, mechanical heterogeneity, spatiotemporal drug gradients, and poor immune cell infiltration continue to hinder the effectiveness of conventional therapeutic strategies. Hydrogels, with tunable physicochemical properties and versatile biological functions, offer a promising platform for addressing these challenges. This review first unpacks the inflammatory pathways active in the TME and then provides a structured overview of hydrogel classifications and material characteristics. From there, it discusses how mechanotransduction pathways (e.g., YAP/TAZ, Piezo1, FAK) and chemical signaling frameworks shape the interaction between hydrogels and the TME. In addition, the article highlights hydrogels’ translational potential by outlining their roles in inflammation-associated biomarker detection, precision drug delivery systems, and in vivo compatibility evaluations. Recent advances in dynamic covalent hydrogels, DNA-based hydrogels, living hydrogels, and stimuli-responsive systems are critically reviewed to clarify the field’s technological direction. Their integration with immunotherapy is particularly promising but raises concerns about long-term biosafety, degradation product toxicity, and immune compatibility. Despite their considerable promise for precisely modulating TME inflammation, hydrogels face persistent challenges that must be addressed to enable clinical potential. Overcoming these hurdles will require sustained multidisciplinary efforts. We further propose a stage-aware immunomodulatory framework, in which programmable hydrogels can coordinate mechanical, metabolic, and immune regulation according to the evolving biological state of the TME. Here, stage-aware does not imply a universal temporal hierarchy of TME remodeling, but rather refers to adaptive coordination of multiple regulatory modules according to tumor-specific biological states. This concept moves beyond single-pathway modulation and aligns with the emerging paradigm of “adaptive immunotherapy” that dynamically responds to TME evolution.