# A Conjugation Delivery System of Macrophages and Platelet Pharmacytes Promotes Regeneration After Spinal Cord Injury

## TL;DR

A new system using platelets and macrophages to deliver mitochondria and genes helps repair spinal cord injuries by restoring cell function.

## Contribution

A novel macrophage–platelet conjugation system co-delivers mitochondria and PPARγ-encoding nanoparticles to enhance efferocytosis and tissue repair.

## Key findings

- Platelets transfer mitochondria to macrophages under stress, restoring efferocytosis.
- The M-P-NPs@PPARγ system increases ATP production and lipid homeostasis in macrophages.
- The system promotes neural regeneration and motor recovery in spinal cord injury models.

## Abstract

Mitochondrial dysfunction occurs in macrophages with efferocytosis defects, which hinders recovery from tissue injury. Targeting intercellular mitochondrial transfer is a promising therapy for augmenting cellular therapy. Here, this work elucidates the stress resistance capabilities of mitochondria in anucleate platelets and shows that platelets transfer mitochondria to macrophages under cellular stress, which restores impaired efferocytosis. This work devises a delivery system in which platelets are loaded with cationic polymers (NPs) for PPARγ overexpression and conjugated to macrophages (M‐P‐NPs@PPARγ). In this system, activated platelets induce mitochondrial transfer and release NPs into macrophages, increasing ATP production and maintaining lipid homeostasis. As a proof‐of‐concept, in representative efferocytosis‐deficit central nervous system disease spinal cord injury model, impaired efferocytosis is reversed by M‐P‐NP@PPARγ, resulting in neural regeneration and remyelination and ultimately promoting motor function recovery. In summary, this work has developed a strategy combining mitochondria and gene delivery to restore macrophage efferocytosis postinjury by regulating energy and lipid metabolism.

A macrophage–platelet conjugation system (M‐P‐NPs@PPARγ) targets injure tissue to co‐deliver platelet mitochondria and PPARγ‐encoding NPs. This strategy boosts the macrophage energy supply and restores lipid homeostasis, leading to synergistically enhanced efferocytosis and tissue repair