Degalactosylated xyloglucan hydrogels as a delivery strategy for neural cells mitochondrial transplantation

Abstract

Mitochondria are essential for ATP production, metabolism regulation, and cellular homeostasis. Their dysfunction is implicated in neurodegenerative diseases, yet no targeted mitochondrial therapies currently exist. Mitochondrial transplantation (MT) has emerged as a promising strategy to restore bioenergetics, reduce oxidative stress, and enhance neuronal survival. However, challenges such as extracellular oxidative stress and inefficient mitochondrial delivery limit its clinical potential. This study explores a novel MT approach utilizing a degalactosylated xyloglucan (dXG) hydrogel to encapsulate mitochondria, ensuring protection and controlled release. The hydrogel shields mitochondria from oxidative stress, preserving their functionality, and facilitating sustained local delivery. Rheological analysis confirms the hydrogel stability and mechanical support, while in vitro experiments demonstrate improved mitochondrial viability and cellular uptake. By enhancing mitochondrial retention and function at the target site, this hydrogel-based strategy offers a potential breakthrough for neurodegenerative disease treatment.