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ROS-Responsive Spatiotemporal Delivery System Targeting Tendon-Bone Interface for Rotator Cuff Repair.

Ziqi Huo1, Zeyu Wang1, Zhuxuan Zhang2

  • 1Department of Sports Medicine, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, P.R. China.

ACS Applied Materials & Interfaces
|March 3, 2026
PubMed
Summary

This study introduces CMMKT, a novel nanomedicine that coordinates inflammation control and fibrocartilage regeneration for tendon-bone interface healing. CMMKT promotes cell repair and enhances tissue strength after rotator cuff injury.

Keywords:
BiomaterialsMagnesiumOxidative stressRotator cuff repairTendon−bone interface

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Tissue Engineering

Background:

  • Rotator cuff injuries involve persistent inflammation and poor fibrocartilage regeneration at the tendon-bone interface (TBI).
  • Current treatments struggle to address both inflammation and regeneration simultaneously for effective TBI healing.

Purpose of the Study:

  • To develop and evaluate a spatiotemporally coordinated therapeutic strategy for TBI repair.
  • To investigate the efficacy of a multifunctional nanomedicine (CMMKT) in controlling inflammation and promoting fibrocartilage regeneration.

Main Methods:

  • Development of CMMKT, a nanomedicine using ROS-responsive polymers for controlled release of Mg2+ and kartogenin (KGN), coated with fibrochondrocyte cell membranes.
  • In vitro assessment of CMMKT on bone marrow mesenchymal stem cells (BMSCs) under inflammatory conditions.
  • In vivo evaluation of CMMKT in a rat rotator cuff tear model, including transcriptomic and metabolomic analyses.

Main Results:

  • CMMKT enhanced BMSC migration, proliferation, and differentiation while inhibiting apoptosis and promoting M2 macrophage polarization.
  • In vivo, CMMKT facilitated immunomodulation, restored fibrochondrocyte-specific matrix deposition, and improved collagen maturity and biomechanical strength.
  • Transcriptomic and metabolomic data revealed suppressed oxidative stress and activated anabolic pathways in fibrocartilage.

Conclusions:

  • The CMMKT nanomedicine effectively integrates inflammatory microenvironment reprogramming with targeted fibrocartilage regeneration.
  • This spatiotemporal coordination strategy shows significant promise for advancing tendon-bone interface repair in rotator cuff injuries.