In the near term, the field of tissue engineering aims to produce artificial tissue structures that can support cells and integrate with native tissue when implanted into an injury, promoting regeneration that would not otherwise have taken place. In the longer term, the goal is to produce entirely artificial, fully functional organs - but first things first. Producing large sections of pseudo-tissue that can reliably promote regeneration is still a work in progress, with many projects at varying stages of development. As this paper makes clear, the fine details involved in sufficiently replicating tissue structural properties can be a challenge.
Myocardial Infarction (MI) occurs when blood flow to the heart is restricted, causing cardiomyocyte death, scar tissue formation, and myocardial remodeling. These changes reduce the heart's efficiency, increasing the mechanical load on surrounding tissue and causing the infarcted region to thin. In severe cases, this leads to myocardial rupture, which requires immediate surgical intervention. Here, cardiac patches made from biological (bovine pericardium), synthetic materials (polytetrafluoroethylene or polyester fiber) are implanted to stabilize the heart. However, these materials do not degrade, contract, or integrate into the myocardium. Furthermore, these patches undergo undesirable biological interactions such as calcification, thrombosis, and inflammation. These drawbacks hinder the application of cardiac patches in pediatric patients, impairing long-term recovery and safety in many cases.
An ideal cardiac patch would be implantable, easy to handle surgically and provide short-term mechanical support while promoting biological regeneration of the damaged myocardium. Such a patch would fully integrate with native tissue, degrade in a controlled manner, and avoid triggering an immune response or other adverse effect. Tissue-engineered cardiac patches, or engineered heart tissues (EHTs), offer a potential solution to these challenges. Previous research has shown that large, clinically relevant cardiac tissues can be fabricated and engrafted onto animal hearts, where they maintain their structural and electrical properties, undergo vascularization, and improve cardiac function. However, tissue-engineered cardiac patches are primarily applied to the epicardial surface of the heart, and few examples of intraventricular implantation exist.
In this work, we developed an implantable, intraventricular cardiac patch by reinforcing EHTs with 3D-printed polycaprolactone (PCL) materials. A key challenge in designing intraventricular cardiac patches is balancing the biological compatibility of soft materials with the mechanical robustness required for implantation. To address this, we utilized volumetric 3D printing (VP) to fabricate a porous PCL metamaterial that could be infiltrated with a cell-laden hydrogel and provide tunable mechanical properties that match the myocardium. We combined our metamaterial with a hydrogel-infiltrated melt-electrowritten (MEW) mesh, which reduces permeability and enables patch implantation via suturing. This multi-material design enabled the patch to be implanted in an acute large animal trial, where it withstood intraventricular pressure, prevented bleeding, and enabled hemodynamic restabilization (partial restoration of blood pressure and heart rate), demonstrating its potential for myocardial defect repair.
Link: https://doi.org/10.1002/adma.202504765
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