A Piezoelectric and Suture‐Free Cardiac Patch Assembled by all FDA‐approved Materials Achieves a Minimally Invasive Gene Therapy

Abstract Balancing biosafety with multifunctionality remains a critical challenge in biopatch development, impeding clinical translation. This study introduces a minimally invasive myocardial patch fabricated entirely from FDA‐approved components, integrating piezoelectric property and a sustained release of miRNA agomir. Briefly, the piezoelectric small intestinal submucosa (SIS) serves as the matrix for the in situ growth of β‐cyclodextrin metal‐organic framework (β‐CD‐MOF). Cholesterol‐modified miR‐210 Agomir is efficiently loaded into cyclodextrin cavities through host‐guest interactions. Flexibility and water‐triggered adhesion properties, bestowed by a poly (sodium thioctate) (PST) coating on the rim, allow the dry SIS‐Patch to fold into a catheter‐deliverable tube for minimally invasive implantation. In rat myocardial infarction models, the Ago‐Patch achieved sustained miR‐210 Agomir release, effectively downregulating target gene expression. Simultaneously, the piezoelectric SIS converts mechanical energy in vivo into electrical pulses, activating related signaling pathway. Synergistic gene‐electrical therapy improved cardiac function, increasing ejection fraction by 14.0% and fractional shortening by 10.4%, while attenuating left ventricular remodeling and fibrosis. The Ago‐Patch's dual‐action mechanism offers a safe, multifunctional solution for cardiac repair.