Mitochondria embedded in degalactosylated xyloglucan hydrogels to improve mitochondrial transplantation

Abstract

Mitochondria are the major source of intracellular adenosine triphosphate (ATP) and play an essential role in a plethora of physiological functions, including regulating metabolism and maintaining cellular homeostasis. Mitochondrial dysfunction is associated with the onset of several cardiovascular diseases and, although several approaches currently exist to counteract it, no treatment using mitochondria as a therapeutic target exists to date. Recently, mitochondrial transplantation (MT) has been identified as a potential therapy that leads to increased ATP production, reduced oxidative stress, and improved bioenergetics. MT involves the replacement of damaged mitochondria, following injury or diseases.

With MT, mitochondria must survive an inhospitable extracellular environment often characterized by oxidizing agents due to pathological and/or inflammatory conditions. Furthermore, only a small percentage of the injected mitochondria reaches the target site due to dispersion throughout the body.

In this work, an MT strategy involving degalactosylated xyloglucan hydrogel encapsulating mitochondria, to overcome MT problems and improve its efficiency, is illustrated for the treatment of cardiovascular damage. The presence of the hydrogel presents the following advantages: improves the health of mitochondria; plays a protective role towards mitochondria from the extracellular environment and oxidative stress; allows for sustained release of viable mitochondria and local transfer into host cells.