Melt electrowritten medium chain length polyhydroxyalkanoate cardiac patches for Post-MI cardiac regeneration
Year: 2025
Type: article
Abstract: Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) hold promise in averting the development of heart failure with reduced ejection fraction (HFrEF) following myocardial infarction (MI) by potentially regenerating the infarcted myocardium and restoring left ventricular contractility. However, challenges remain regarding the structural and functional maturation states of these cells, as well as their retention and integration into the myocardium. Here, we developed a novel three-dimensional cardiac patch and evaluated its potential to instigate cardiac regeneration. For the first time, melt electrowriting (MEW) was utilised to fabricate reproducible, structurally anisotropic, and handleable scaffolds from high molecular weight, medium chain-length polyhydroxyalkanoates (MCL-PHAs). These MEW-PHA scaffolds maintained hPSC-CMs, facilitating their rapid structural maturation and functional improvement in vitro. Different combinations of hPSC-derived cardiovascular cells were seeded onto the MEW-PHA scaffolds and stacked to create synchronously beating, multi-scaffold cardiac patches. These were well-accepted in a murine MI model without capsule formation. Notably, cardiac patches containing hPSC-derived cardiac microvascular-like endothelial cells (hPSC-CMVECs) initiated vascular regeneration within the infarcted myocardium. This novel advancement enabled the reproducible fabrication of high molecular weight MCL-PHA-based MEW cardiac patches that matured hPSC-CMs and promoted vascular regeneration, offering potential for future improvement in post-MI cardiac function through enhanced hPSC-CM retention.
Source: Materials Today Bio
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,400
Funders: Foundation for Cardiovascular Research, Whitaker International Program, Wellcome Trust, British Heart Foundation, Academy of Finland, Vetenskapsrådet, Sydäntutkimussäätiö, Emberi Eroforrások Minisztériuma, Sigrid Juséliuksen Säätiö, UK Regenerative Medicine Platform, Medical Research Council, Engineering and Physical Sciences Research Council, Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, British Heart Foundation Centre of Regenerative Medicine
Awards: G1295621590, G1542225194, Tracking hydrogel therapeutics using quantitative whole-body imaging, G2431946445, G263283853, Multi-spectral in vivo optical imaging system, G2970348276, G298428782, G3426299250, G3431256986, G3631400605, G3673498540, New drug targets and small molecules for promoting cardiac regeneration, Multi-spectral in vivo optical imaging system, G4465225751, SEE MORE MAKE MORE: Secondary Electron Energy Measurement Optimisation for Reliable Manufacturing of Key Materials, G4861171967, Highly Mucoadhesive Sustainable Patches for Effective Treatment of Oral Lichen Planus, Next generation multifunctional biomaterials for the infarcted heart, Sustainable manufacture of biodegradable film packaging from recalcitrant waste streams, G6481023684, Research Excellence (renewal), BHF Centre of Regenerative Medicine (renewal), G7270720874, Image-guided cardiac regeneration: visible biomaterials functionalised to enhance stem cell-mediated repair and improve cardiac function, Acellular / Smart Materials - 3D Architecture: UK RMP Hub, G852333781, G8820281899
OpenAlex ID: W4413805149