# Adipose-Derived Stem Cell Membrane-Coated Mitochondria Restore Tendon Stromal Cell Function Through Metabolic Reprogramming and Promote Achilles Tendon Healing

## TL;DR

This study shows that using mitochondria coated with stem cell membranes can improve healing in Achilles tendon injuries by restoring cell function.

## Contribution

The novel use of ADSC membrane-coated mitochondria to target and correct mitochondrial dysfunction in tendon stromal cells is introduced.

## Key findings

- Mito-NPs enhanced oxidative phosphorylation and metabolic homeostasis in inflammatory tendon stromal cells.
- Mito-NPs@HG improved gait function and histological repair in rat Achilles tendon injuries.
- Treatment reduced inflammation and enhanced collagen organization in damaged tendons.

## Abstract

Achilles tendon rupture often leads to poor functional recovery due to limited self-healing, with mitochondrial dysfunction in tendon stromal cells (TSCs) being a key factor in disease progression. Here, we developed adipose-derived stromal cell (ADSC) membrane-coated mitochondria (Mito-NPs) to target this dysfunction and evaluate their therapeutic potential for tendon repair. Mito-NPs exhibited uniform size, stable surface charge, and effective membrane coating. In lipopolysaccharide-induced inflammatory TSCs, Mito-NPs enhanced oxidative phosphorylation, improved mitochondrial metabolic homeostasis, and reshaped gene expression profiles to normalize TSC functional phenotypes, including inflammation, migration, and collagen synthesis. When encapsulated in a reactive oxygen species (ROS)-responsive hydrogel (Mito-NPs@HG) and implanted into rat Achilles tendon injuries, Mito-NPs@HG improved gait function, decreased local inflammation, and promoted histological repair of damaged tendons by enhancing collagen organization and reducing inflammation. Our findings demonstrate that ADSC membrane-coated mitochondria effectively rescue TSC dysfunction and facilitate tendon regeneration, providing a promising translational strategy for treating tendon injuries.