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

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.