A Mechanoresponsive Drug‐Releasing Silk Balloon Catheter for Inflation‐Triggered Biophysical and Biochemical Treatment of Cardiovascular Plaque

Drug-coated balloon catheters are widely used to dilate narrowed arteries and deliver therapeutic agents to atherosclerotic plaques; however, uncontrolled passive drug leakage during catheter navigation remains a challenge. Herein, we developed a mechanoresponsive drug-releasing silk balloon catheter that actively releases drugs upon balloon inflation while minimizing passive drug leakage. To this end, we designed a molecular template that induces densely packed hydrophobic domains within the silk fibroin network. These domains enable strong binding and mechanoresponsive release of hydrophobic therapeutics. The biochemical effects of mechanoresponsive therapeutic release in human umbilical vein endothelial cells and foam cells support its potential for the treatment of cardiovascular plaques. Furthermore, the densely packed structure enhanced strength, toughness, and elasticity, enabling inflation up to 15 atm without bursting. Moreover, it exhibited excellent fatigue resistance and rapid elastic deflation, demonstrating physical compatibility with balloon catheter applications. In addition, a drug loss test showed that the silk balloon catheter exhibited 2,355-fold lower drug loss than a commercial drug-coated balloon. Finally, the silk balloon catheter achieved up to 49% dilation of the ex vivo porcine coronary artery while simultaneously exhibiting mechanoresponsive drug delivery. The proposed mechanoresponsive drug-releasing silk balloon catheter enables active and localized drug delivery during angioplasty.