Harnessing Gradient Topography and Dual-Mode Bioactive Delivery via Bone-Adhesive Exosome Mimetics for Rotator Cuff...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Orthopedic Surgery

Background:

• Rotator cuff repair failure stems from the lack of a native tendon-to-bone enthesis transition.
• Current repair methods struggle to replicate this complex interface, leading to poor healing outcomes.

Purpose of the Study:

• To engineer an enthesis-mimetic scaffold with dual gradients for enhanced tendon-to-bone healing.
• To integrate structural and compositional cues for spatially programmed tissue regeneration.

Main Methods:

• Developed a dual-gradient scaffold using modified electrospinning for fiber orientation control.
• Incorporated graded hydroxyapatite mineralization and quercetin-loaded, alendronate-conjugated exosome mimetics (EMQ^A).
• Utilized bioorthogonal chemistry and alendronate-hydroxyapatite affinity for controlled EMQ^A immobilization.

Main Results:

• In vitro studies showed region-selective cell lineage responses (osteogenic vs. chondrogenic/tenogenic).
• Preclinical rotator cuff repair models demonstrated improved mineralized tissue formation and interface remodeling.
• The scaffold promoted reduced lipid deposition and superior mechanical performance post-repair.

Conclusions:

• The developed dual-gradient scaffold successfully recreates an enthesis-like microenvironment.
• This scalable strategy enhances tendon-to-bone healing by integrating structural gradients and bioactive delivery.
• The findings offer a promising approach for improving rotator cuff repair efficacy.