A three-dimensional hybrid pacemaker electrode seamlessly integrates into engineered, functional human cardiac tissue in vitro

Abstract

Pacemaker systems are an essential tool for the treatment of cardiovascular diseases. However, the immune system’s natural response to a foreign body results in the encapsulation of a pacemaker electrode and an impaired energy efficiency by increasing the excitation threshold. The integration of the electrode into the tissue is affected by implant properties such as size, mechanical flexibility, shape, and dimensionality. Three-dimensional, tissue-like electrode scaffolds render an alternative to currently used planar metal electrodes. Based on a modified electrospinning process and a high temperature treatment, a conductive, porous fiber scaffold was fabricated. The electrical and immunological properties of this 3D electrode were compared to 2D TiN electrodes. An increased surface of the fiber electrode compared to the planar 2D electrode, showed an enhanced electrical performance. Moreover, the migration of cells into the 3D construct was observed and a lower inflammatory response was induced. After early and late in vivo host response evaluation subcutaneously, the 3D fiber scaffold showed no adverse foreign body response. By embedding the 3D fiber scaffold in human cardiomyocytes, a tissue-electrode hybrid was generated that facilitates a high regenerative capacity and a low risk of fibrosis. This hybrid was implanted onto a spontaneously beating, tissue-engineered human cardiac patch to investigate if a seamless electronic-tissue interface is generated. The fusion of this hybrid electrode with a cardiac patch resulted in a mechanical stable and electrical excitable unit. Thereby, the feasibility of a seamless tissue-electrode interface was proven.

Improvement of the Electronic—Neuronal Interface by Natural Deposition of ECM

“…The second disadvantage of dense carbon nanofiber scaffolds is their poor flexibility. By generating pores within the scaffold, the flexibility was enhanced in previous works [ 9 , 14 ]. Thereby, NaCl particles were positioned as porogens, which also vanished during the carbonization, between the fibers during the spinning process.…”

“…Therefore, new strategies focus on shielding the electrodes surface with more tissue-like materials in order to prevent the direct electrode-tissue contact yet allowing electrical transmission. Examples are to enclose the electrode in the living target tissue like published for cardiac applications [ 9 ] or to develop synthetic neuronal compatible hydrogels as electrode coatings [ 10 ]. Moreover, coatings of extra cellular matrix improve the immunological compatibility to neuronal tissue [ 11 , 12 ]; however, the natural composition and structure cannot be generated artificially without much effort and thereby cannot completely shield against the immune system.…”

Biopolymer‐Based Coatings: Promising Strategies to Improve the Biocompatibility and Functionality of Materials Used in Biomedical Engineering

“…Other applications, however, might require properties of the coating which go beyond the ability to control binding and unbinding. Examples include—but are not limited to—controlling/maintaining the conductivity of the coated object, e.g., for pacemakers [ 89 ] or neural electrodes, [ 90 ] or its transparency, e.g., for endoscopes. [ 91 ] In the following, we will discuss four different categories of functional coatings that either aim at creating lubricious or antifouling surfaces, promote cellular adhesion, act as a drug delivery system or work as a biosensor, and we give examples of applications for which these coatings have and can be used.…”

ROR1-CAR T cells are effective against lung and breast cancer in advanced microphysiologic 3D tumor models

“…The BioVaSc was originally designed for the generation of artificial normal human tissues in regenerative medicine. Several normal human tissues, including trachea, myocardium, liver, skin, intestine, and kidney, have been generated on this platform (12,(35)(36)(37)(38)(39)(40). Accordingly, we believe that there is a potential for assessing safety and tissue cross-reactivity of CAR T cells in 3D normal tissue models.…”