2024 AIChE Annual Meeting

Optimization of Hyaluronic Acid-Pnipaam Co-Polymers for Mitochondrial Transplantation

Organelle transplantation is a biomedical technique that involves the transfer of healthy organelles, such as mitochondria, from donor cells to damaged or dysfunctional recipient cells. This approach aims to restore cellular function by replacing impaired organelles with fully functional ones. Mitochondrial transplantation is an emerging treatment to serve as a therapy for mitochondrial dysfunction diseases such as secondary spinal cord injury. One of the key limitations of this therapy is the lack of localization of exogenous mitochondria to the intended site of action. This study investigates the synthesis and optimization of poly(N-isopropylacrylamide) grafted hyaluronic acid (HA-pNiPAAm) hydrogels for mitochondrial delivery as a therapeutic treatment for secondary spinal cord injury. The primary objective is to optimize and enhance reaction conditions and yields while reducing synthesis times. Reaction kinetics and dialysis purification were evaluated using amine detection assays. Along with this, a library of HA-pNiPAAm hydrogels were synthesized, with varying HA molecular weights, pNiPAAm molecular weights, and grafting percentages, using the refined protocol. The hydrogels were characterized for their lower critical solution temperature (LCST), viscosity, and gelling properties using ultraviolet-visible spectroscopy and viscometry. This comprehensive characterization aims at identifying the optimal hydrogel formulation for efficient mitochondrial delivery. The results provide valuable insights into the hydrogel properties that most improve mitochondrial delivery, laying the groundwork for future in vivo studies and clinical applications.