Flexible tissue-like electrode as a seamless tissue-electronic interface

Abstract

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...

Fully Synthetic 3D Fibrous Scaffolds for Stromal Tissues—Replacement of Animal‐Derived Scaffold Materials Demonstrated by Multilayered Skin

“…Electrospinning of Highly Porous Polymer Fiber Scaffolds: The modified electrospinning process for the generation of 3D electro-spun scaffolds was adapted from a previously developed protocol. [34] A 12% (m/v) solution of polyamide 6 (Sigma-Aldrich, 181 110) or polycaprolactone (Sigma-Aldrich, 440 744) in 1,1,1,3,3,3-hexafluoro-2-propanol (Sigma-Aldrich, 105 228) was spun on a custom-made coaxial electro spinner system. [71] The distance and voltage was set to 15 cm and 7-9 kV (DC; positive voltage), respectively.…”

“…[33] In our study, we improved the previous efforts to generate highly porous electrospun fiber scaffolds. We adapted a previously presented technique for the generation of defined 3D porous carbon fiber scaffolds [34,35] to polymeric materials, whose mechanical properties are more similar to native stromal tissue and dramatically increased the porosity in the scaffold to address the defined requirements. To present the suitability of the developed highly porous electrospun fibrous scaffolds as stromal scaffolds, dermal tissues were generated and extended with a functional epidermis as well as a hypodermis.…”

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

“…The generation of pores inside the nanofiber electrode highly increased the nanofiber scaffolds' flexibility, as the thereby enlarged fiber distance enhanced their freedom of movement and thereby reduced the development of tension peaks during bending of the electrode scaffold. Compared to previous publications [9,14] the reduction of the particular porogen size reduced the delamination probability and improved the electrodes' cohesion. By adding a second porogen in the form of nanoscaled electrospun fibers, homogeniously distributed wide mesh openings are ensured.…”

“…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.…”

“…The nano fibrous electrode approach reduced the average elasticity, which is hardly possible for metal-based electrodes. Additionally, the generated pores in the nanofiber electrode provided the electrode a high flexibility [ 14 ]. In the second step, fibroblasts were seeded on the carbon fiber electrodes to synthesize ECM proteins.…”