Ron Feiner

Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, free-standing electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on-demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

Nanoengineering gold particle composite fibers for cardiac tissue engineering

Gold nanostructures can be incorporated into macroporous scaffolds to increase the matrix conductivity and enhance the electrical signal transfer between cardiac cells. Here we report a simple approach for fabricating 3-dimensional (3D) gold nanoparticle (NP)-based fibrous scaffolds, for engineering functional cardiac tissues generating a strong contraction force. A polycaprolactone-gelatin mixture was electrospun to obtain fibrous scaffolds with an average fiber diameter of 250 nm. In a facile method, gold NPs were evaporated on the surface of the fibers, creating nanocomposites with a nominal gold thickness of 2, 4, and 14 nm. Compared to pristine scaffolds, cardiac cells seeded on the nano-gold scaffolds assembled into more elongated and aligned tissues. The gold NPs on the fibers were able to maintain the ratio of cardiomyocytes to fibroblasts in the culture, to encourage the growth of cardiomyocytes with significantly higher aspect ratio, and promote massive cardiac sarcomeric actinin expression. Finally, engineering cardiac tissues within gold NP-based scaffolds exhibited significantly higher contraction amplitudes and rates, as compared to scaffolds without gold. We envision that cardiac tissues engineered within these gold NP scaffolds can be used to improve the function of the infarcted heart.

Composite biomaterial scaffolds for cardiac tissue engineering

Coronary heart diseases result from the blockage of one of the coronary arteries, which nourishes the heart muscle. This process leads to ischaemia of a segment of the heart and death of the contractile tissue. As cardiac tissue is unable to regenerate itself, heart function is impaired. Tissue engineering (TE) is a field of science that integrates knowledge from biology, materials sciences, engineering and medicine to develop artificial, functional tissue constructs to replace defected tissues. In cardiac TE, contracting cells are seeded within supporting biomaterial scaffolds that provide them with the essential microenvironment for functional tissue assembly. Various strategies and methods for fabricating these scaffolds have been proposed and tested in the last decade, some of which combine multiple elements that altogether contribute to the formation of an improved functional tissue. This review summarises the unique properties of various composite biomaterial scaffolds and highlights their advantages over other pristine scaffolds for engineering functional three-dimensional cardiac patches.

Modular assembly of thick multifunctional cardiac patches

Significance Heart disease is the primary cause of death in the United States. Cardiac tissue engineering has evolved with the goal of creating heart patches to treat end-stage patients. Here, we report on a bottom-up approach to assemble a modular cardiac patch that consists of various tissue layers, each performing a different function. One layer was designed to accommodate cardiac cells and promote their organization into a contracting tissue. Another layer enables the organization of endothelial cells into blood vessels, and layers with microparticulate systems enable the controlled release of different biofactors affecting the engineered tissue or the host. We have shown that the patch can be assembled from its building blocks just before transplantation and can perform in the body. 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.

Cutting-edge platforms in cardiac tissue engineering

As cardiac disease takes a higher toll with each passing year, the need for new therapies to deal with the scarcity in heart donors becomes ever more pressing. Cardiac tissue engineering holds the promise of creating functional replacement tissues to repair heart tissue damage. In an attempt to bridge the gap between the lab and clinical realization, the field has made major strides. In this review, we will discuss state of the art technologies such as layer-by-layer assembly, bioprinting and bionic tissue engineering, all developed to overcome some of the major hurdles faced in the field.

Cardiac tissue engineering: from matrix design to the engineering of bionic hearts.

The field of cardiac tissue engineering aims at replacing the scar tissue created after a patient has suffered from a myocardial infarction. Various technologies have been developed toward fabricating a functional engineered tissue that closely resembles that of the native heart. While the field continues to grow and techniques for better tissue fabrication continue to emerge, several hurdles still remain to be overcome. In this review we will focus on several key advances and recent technologies developed in the field, including biomimicking the natural extracellular matrix structure and enhancing the transfer of the electrical signal. We will also discuss recent developments in the engineering of bionic cardiac tissues which integrate the fields of tissue engineering and electronics to monitor and control tissue performance.

Multifunctional degradable electronic scaffolds for cardiac tissue engineering

ABSTRACT The capability to on‐line sense tissue function, provide stimulation to control contractility and efficiently release drugs within an engineered tissue microenvironment may enhance tissue assembly and improve the therapeutic outcome of implanted engineered tissues. To endow cardiac patches with such capabilities we developed elastic, biodegradable, electronic scaffolds. The scaffolds were composed of electrospun albumin fibers that served as both a substrate and a passivation layer for evaporated gold electrodes. Cardiomyocytes seeded onto the electronic scaffolds organized into a functional cardiac tissue and their function was recorded on‐line. Furthermore, the electronic scaffolds enabled to actuate the engineered tissue to control its function and trigger the release of drugs. Post implantation, these electronic scaffolds degraded, leading to the dissociation of the inorganic material from within the scaffold. Such technology can be built upon to create a variety of degradable devices for tissue engineering of various tissues, as well as pristine cell‐free devices with electronic components for short‐term in vivo use.