Modular assembly of thick multifunctional cardiac patches

Abstract

In cardiac tissue engineering cells are seeded within porous biomaterial scaffolds to create functional cardiac patches. Here, we report on a bottom-up approach to assemble a modular tissue consisting of multiple layers with distinct structures and functions. Albumin electrospun fiber scaffolds were laser-patterned to create microgrooves for engineering aligned cardiac tissues exhibiting anisotropic electrical signal propagation. Microchannels were patterned within the scaffolds and seeded with endothelial cells to form closed lumens. Moreover, cage-like structures were patterned within the scaffolds and accommodated poly(lactic-co-glycolic acid) (PLGA) microparticulate systems that controlled the release of VEGF, which promotes vascularization, or dexamethasone, an anti-inflammatory agent. The structure, morphology, and function of each layer were characterized, and the tissue layers were grown separately in their optimal conditions. Before transplantation the tissue and microparticulate layers were integrated by an ECM-based biological glue to form thick 3D cardiac patches. Finally, the patches were transplanted in rats, and their vascularization was assessed. Because of the simple modularity of this approach, we believe that it could be used in the future to assemble other multicellular, thick, 3D, functional tissues.

3D bioprinting for cardiovascular regeneration and pharmacology

“…Microfabrication-based patterning techniques (such as surface topography, micromolding/microchannels, microcontact printing, sacrificial template methods, high temperature molding, and laser patterned electrospinning), have been developed in some pioneering studies to confine colony geometry, regulate cell morphology and functions, and support high-throughput analysis [2]. However, these 2D culture systems lack the full architecture and functionality of 3D human tissues and organs [2,139,142,144]. Alternatively, 3D bioprinting not only can accomplish this anisotropy in 3D architecture, but also cells can be directly encapsulated into the constructs to form cellularized tissue.…”

Nano‐ and Microfabrication for Engineering Native‐Like Muscle Tissues

“…In spite of the effects of constructing prevascularized muscle tissues using CMs and vessel‐forming ECs, challenges still remain due to the distinct requirements of different cells. To address this issue, Fleischer et al developed a modular assembly strategy where myocytes and ECs were cultured and matured separately and then integrated before implantation. VEGF was encapsulated in PLGA particles for a prolonged release and promotion of vascularization.…”

Engineering tissue‐specific blood vessels

“…(a) Bone perivascular niche‐on‐a‐chip schematic displaying formation, usage, and flow direction . (b) Schematic depicting the construction of a thick cardiac patch . (c) Neural construct displaying endothelial cells aligning with glial cells .…”

“…Fleischer et al have made a self‐organized model utilizing an electrospinning technique to create albumin fiber scaffolds with each layer having one of three structures (Figure b). After being electrospun, each layer is laser patterned to have either grooves, microtunnels and cages, or cages alone.…”