Abstract
Stroke remains a leading cause of disability worldwide, underscoring the urgent need for novel and innovative therapeutic strategies to enhance neuroprotection, support regeneration, and improve functional recovery. Previous research has shown that phytochemicals such as curcumin, tannic acid, gallic acid, ginsenosides, resveratrol, and isorhamnetin display extensive neuroprotective properties, including antioxidant, anti-inflammatory, and anti-apoptotic effects. These natural compounds could also promote neurogenesis, angiogenesis, and the preservation of the blood-brain barrier. Despite their promising bioactivities, clinical application is often limited by poor solubility, bioavailability, and suboptimal pharmacokinetics. Hydrogels offer a promising solution by encapsulating and controlling the gradual release of these phytochemicals directly at the site of injury. Recent advancements in hydrogel formulations, constructed from biopolymers and functionalized using nanotechnological approaches, could significantly improve the solubility, stability, and targeted delivery of phytochemicals. Controlled release profiles from pH-sensitive and environment-responsive hydrogels could ensure that the compounds' therapeutic effects are optimally timed with individual and critical stages of post-stroke repair. Moreover, hydrogel scaffolds with tailored material properties and biocompatibility can create a favorable microenvironment, reducing secondary inflammation, enhancing tissue regeneration, and potentially improving functional and cognitive outcomes following stroke. This review explores the potential of integrating phytochemicals within hydrogel-based delivery systems specifically designed for post-stroke recovery. The design and synthesis of biocompatible, biodegradable hydrogels functionalized especially with phytochemicals and their applications are also discussed. Lastly, we emphasize the need for additional robust and translatable preclinical studies.