(78e) Grafted Poly(N-isopropylacrylamide) on Hyaluronic Acid As an Injectable Hydrogel for Localized Mitochondria Delivery

Mitochondria transplantation (MT) presents a promising approach for treating diseases associated with mitochondrial dysfunction, including neurodegenerative diseases, metabolic disorders, and conditions requiring tissue regeneration like spinal cord injuries (SCI). The ability to augment or replace damaged mitochondria with functional ones offers a novel therapeutic pathway, potentially circumventing the limitations of traditional treatments that merely alleviate symptoms without addressing underlying cellular energetics and dysfunction. Nonetheless, challenges such as maintaining mitochondrial viability in adverse environments and ensuring efficient cellular uptake hinder its efficacy. Our research addresses these obstacles by investigating the potential of Poly(N-isopropylacrylamide) grafted onto Hyaluronic Acid (HA-PNIPAm) hydrogels as a novel delivery system for MT therapeutics. PNIPAm is known for its exceptional lower critical solution temperature (LCST) that is close to human body temperature. On the other hand, HA is recognized for its unique biocompatibility and anti-inflammatory properties, existing in many parts of biological systems across the human body including central nervous system. This combination of co-polymer constitutes an ideal pairing to facilitate sustained and controlled mitochondrial delivery. We synthesized various compositions of grafted hydrogels, evaluating its phase transition and gelation properties using ultraviolet-visible spectroscopy and dynamic scanning calorimetry. Hydrogel erosion and mitochondrial release over time were studied using a closed system drug dissolution module and a fluorescence microplate reader. Lastly, seahorse assay was used to study released mitochondria respiration and viability after incubation in HA-PNIPAm hydrogel.