Pomegranate Polyphenol-Derived Injectable Therapeutic Hydrogels to Enhance Neuronal Regeneration

Drug delivery for the treatment of neurological disorders has long been considered complex due to difficulties in ensuring the drug targeting on a specific site of the damaged neural tissues and its prolonged release. A syringe-injectable polymeric hydrogel with mechanical moduli matching those of brain tissues can provide a solution to deliver the drugs to the specific region through intracranial injections in a minimally invasive manner. In this study, an injectable therapeutic hydrogel with antioxidant pomegranate polyphenols, punicalagin, is reported for efficient neuronal repair. The hydrogels composed of tyramine-functionalized hyaluronic acid and collagen crosslinked by enzymatic reactions have great injectability with high shape fidelity and effectively encapsulate the polyphenol therapeutics. Furthermore, the punicalagin continuously released from the hydrogels over several days could enhance the growth and differentiation of the neurons. Our findings for efficacy of the polyphenol therapeutic-encapsulated injectable hydrogels on neuronal regeneration would be promising for designing a new type of antioxidative biomaterials in brain disorder therapy.