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.
Abstract:Current implantable electrodes facilitate only a low cellular infiltration impairing the long-term integration into the host's tissue. To accomplish a seamless electronic-tissue interface, conductive three-dimensional (3D) scaffolds were generated by carbonization of electro-spun fiber meshes. When introducing NaCl particles as porogens, tailored tissue-like electrodes were generated. Characterization of the porous 3D fiber electrodes demonstrated improved material and electrical characteristics compared to standard carbon fiber meshes or flat gold surfaces. The feasibility of the porous 3D electrodes was assessed by cell culture experiments, confirming the migration of cells into the electrode and the formation of contracting cardiomyocyte clusters. Finally, a complex cardiac co-culture system proved the integration of the tissue into the 3D electrode in long-term culture of 7 weeks. These results strengthen the development of tissue-like 3D scaffolds as alternative to two-dimensional (2D) electrodes. The main challenge in the development of implantable electrodes is to improve the currently limited long-term tissue integration that induces adverse effects such as the encapsulation of the implant [1], [2]. This drawback is caused by differences in elasticity between the host tissue and the electrode, an insufficient electrode flexibility to follow tissue deformation as well as surface properties impairing the infiltration of the electrode with cells [3], [4]. Therefore, concepts for the generation of flexible electrodes were developed, consisting of microscopic conducting paths embedded in flexible silicone or SU-8 photoresist [5], [6]. However, the infiltration of cells in the electrodes is still limited, although Bryers et al. [7] showed that the presence of interconnected pores, which facilitate cell infiltration in an implant, significantly reduces the foreign body reaction. Thus, an improved approach may be a seamless 3D tissue-electronic interface composed of conductive nanofibers that are embedded in the tissue. A common method for the fabrication of 3D nanofiber scaffolds is electrospinning, producing meshes in the regime of extracellular matrix fibers [8]. For example, by spinning polyacrylonitrile (PAN) with a subsequent carbonization, highly conductive nanofiber scaffolds with biocompatible properties were generated [9]. Disadvantage of electro-spun scaffolds is the small mesh size that impairs cell infiltration of the scaffold. The generation of electro-spun porous scaffolds by introducing porogens like sugar or NaCl into a non-conductive nanofiber scaffold during the spinning process has already been reported by different groups [10], [11]. Although the highly flexible polymer fibers demonstrated the infiltration of high cell numbers, the obtained pores were susceptible to collapse. Moreover, these porous polymer scaffolds are not applicable as electrodes due to their insulating properties. In our study, we fabricated conductive porous fiber scaffolds. Therefore, we combined conductive nan...
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