Optimizing delivery of specialized pro-resolving mediators for oral inflammation via smart hydrogels and biomaterials.

Chronic oral inflammatory diseases such as pulpitis, periodontitis, and peri-implantitis pose significant clinical challenges, often resulting in irreversible tissue loss despite the application of current therapies. Specialized pro-resolving mediators (SPMs) offer a novel therapeutic paradigm by actively promoting the resolution of inflammation and tissue regeneration without compromising host defense. However, the clinical translation of SPMs is hindered by their rapid degradation, low bioavailability, and poor localization to inflamed tissues. Smart biomaterial-based delivery systems, particularly stimuli-responsive hydrogels, have emerged as promising platforms to overcome these barriers. These systems enable controlled, localized, and environment-triggered release of SPMs, enhancing their stability and therapeutic efficacy. Preclinical studies in models of oral inflammation demonstrate that hydrogel-mediated SPM delivery not only resolves inflammation but also preserves tissue structure and promotes regeneration. Future strategies will focus on optimizing dosing protocols, ensuring long-term bioactivity, and addressing regulatory and manufacturing challenges to enable clinical adoption. By enhancing the delivery and sustained bioactivity of SPMs, biomaterial-based strategies have the potential to fundamentally transform the management of oral inflammatory diseases and advance regenerative dental therapies.