# The Composite Antiadhesion Barrier Facilitated Fibroblast Autophagy Activation for Tendon Repair

## TL;DR

This study introduces a new three-layer barrier that prevents tendon adhesion by boosting fibroblast autophagy through IL-37 delivery.

## Contribution

A novel composite barrier with on-demand IL-37 delivery to activate autophagy and prevent tendon adhesion is developed.

## Key findings

- The composite barrier significantly inhibits fibroblast proliferation and collagen synthesis.
- IL-37 delivery via the barrier promotes scarless repair in a rat Achilles tendon model.
- The barrier effectively suppresses peritendinous adhesion formation.

## Abstract

While dysregulated autophagy is implicated in fibrotic processes in various organs, its specific role in peritendinous fibrosis and tendon adhesion formation remains to be elucidated. This study hypothesizes that autophagy exerts a protective effect, inhibiting adhesion formation following tendon injury. Furthermore, it is proposed that interleukin‐37 (IL‐37) can be a potential therapeutic target for preventing tendon adhesions through autophagy activation. Therefore, an innovative three‐layer composite antiadhesion barrier (pDNA@E–H–E′) equipped with on‐demand and unidirectional delivery strategy of bioactive plasmid DNA (pDNA) for IL‐37 overexpression is designed. The novel finding of the fibroblast's autophagy activity as a protective factor in tendon adhesion highlights the encapsulation of IL‐37‐encoding pDNA nanocomposites in barrier for reaching supreme antiadhesion efficacy. Moreover, the reactive‐oxygen‐species‐responsive and releasing‐direction‐guided pDNA@E–H–E′ membranes afford wonderful inhibition of fibroblast proliferation, fibroblast‐to‐myofibroblast differentiation, and collagen synthesis by enhancing autophagy. Further in a rat Achilles tendon adhesion model, pDNA@E–H–E′ membranes also significantly suppress peritendinous adhesion formation on the repaired sites and promote the scarless repair of Achilles tendon with optimum efficiency. In all, this study provides a promising approach for preventing tendon adhesion by employing a composite barrier with on‐demand and unidirectional delivery strategy.

Synthesis of an innovative three‐layer composite antiadhesion barrier (plasmid DNA@E–H–E′) is schematically illustrated, highlighting its reactive‐oxygen‐species‐responsive, unidirectional interleukin‐37 delivery to enhance fibroblast autophagy, thereby effectively preventing tendon adhesion and promoting scarless tendon repair.