A personalized, 3D printed, biopolymeric elastic support device for the mitigation of post-MI cardiac remodelling: multi-omics, echocardiographic and hemodynamic evaluation from small and large animal models

Introduction: Myocardial infarction (MI) leads to adverse remodelling and ventricular dilation, culminating in heart failure (HF), a leading cause of mortality and morbidity despite therapeutic advances. We developed a personalized, 3D-printed, biopolymer-based Elastic Cardiac Support Device (CARD) tailored to individual cardiac anatomy and physiology. CARD applies gentle epicardial pressure, reducing wall stress and mechanotransduction, thereby minimizing myocardial remodelling. This study assessed the mechanical, hemodynamic, and molecular effects of CARD in rat and swine MI models.

Methods: MI was induced via left anterior descending artery (LAD) ligation in rats and swine. CARD devices were 3D-printed based on echocardiography (rats) and CT imaging (swine). Animals were randomized into LAD-only or LAD+CARD groups (rats: LAD, n=4; LAD+CARD, n=6; swine: LAD, n=5; LAD+CARD, n=5) and followed for 28 days. Echocardiography, proteomics, and metabolomics analyses were performed in rats. Swine underwent echocardiography and Swan-Ganz catheterization to assess remodelling and hemodynamics.

Result: LAD ligation reduced ejection fraction (EF) in rats and fractional shortening in swine. Changes in parameters of diastolic function such as E/E’ was more stable in the LAD+CARD group in rats but similar across swine groups. CARD significantly prevented the change in left ventricular diastolic diameter (LVEDD delta) in both rats (LAD: 1.06 ± 1.053 cm ;LAD+CARD 0.217 ± 0.844 cm, p < 0.05) and swine (LAD = 1.1 ± 0.4261 cm; LAD+CARD = 0.4080± 0.3666cm, p <0.05). Proteomics in rats revealed changes in fibrosis and remodelling pathways, including Serum Amyloid P-Component and MFAP4, while metabolomics indicated recovery pathways involving mitochondrial function, the TCA cycle, and nitrogen metabolism (Fig.1). In swine, CARD reduced right atrial preload, diastolic right ventricular pressure, and left ventricular end-diastolic pressure, with excellent anatomical compatibility via 3D printing (Fig.2).

Conclusion: CARD reduced adverse cardiac remodelling, triggered distinct proteomic and metabolic recovery pathways and improved hemodynamic in MI animal model.