Establishment of a New Device for Electrical Stimulation of Non-Degenerative Cartilage Cells In Vitro

Abstract

In cell-based therapies for cartilage lesions, the main problem is still the formation of fibrous cartilage, caused by underlying de-differentiation processes ex vivo. Biophysical stimulation is a promising approach to optimize cell-based procedures and to adapt them more closely to physiological conditions. The occurrence of mechano-electrical transduction phenomena within cartilage tissue is physiological and based on streaming and diffusion potentials. The application of exogenous electric fields can be used to mimic endogenous fields and, thus, support the differentiation of chondrocytes in vitro. For this purpose, we have developed a new device for electrical stimulation of chondrocytes, which operates on the basis of capacitive coupling of alternating electric fields. The reusable and sterilizable stimulation device allows the simultaneous use of 12 cavities with independently applicable fields using only one main supply. The first parameter settings for the stimulation of human non-degenerative chondrocytes, seeded on collagen type I elastin-based scaffolds, were derived from numerical electric field simulations. Our first results suggest that applied alternating electric fields induce chondrogenic re-differentiation at the gene and especially at the protein level of human de-differentiated chondrocytes in a frequency-dependent manner. In future studies, further parameter optimizations will be performed to improve the differentiation capacity of human cartilage cells.

Membrane Remodeling of Human-Engineered Cardiac Tissue by Chronic Electric Stimulation

“…Therefore, the contribution from the intense physical training during electrical pacing is small. As previously reported, the ES on non-excitable cells can increase the activity of ion channels and trigger a variety of intracellular signaling pathways and affect various cellular responses, including migration, alignment, proliferation, and differentiation . ES might also trigger the expression of mechanoreceptors (mediation of force transmission) and improve calcium handling .…”

Contributions of deep learning to automated numerical modelling of the interaction of electric fields and cartilage tissue based on 3D images

“…In future research, the numerical models of electrical stimulation can be coupled to impedance measurements to enable a so-called ‘digital twin’ ( Zimmermann et al, 2021 ). The then-available accurate description of the electric fields the cells are exposed to can be expected to explain, which electrical stimulation protocol should be used as currently various waveforms, frequencies and amplitudes are considered ( Vaca-González et al, 2017 ; Krueger et al, 2021 ; Zhou et al, 2023 ). Additionally, more data to improve the presented workflow will be generated.…”

“…As a result, osteoarthritis has been a significant contributor to the global burden of disease ( Nelson, 2018 ). Electrical stimuli are being studied as a potential means of enhancing proliferation, differentiation, and cell activity in cartilaginous tissue regeneration ( Brighton et al, 2008 ; Vaca-González et al, 2017 ; Krueger et al, 2021 ). Despite experimental progress, a deep understanding of the effect of electrical stimulation on cartilage is still lacking.…”

Some Electrical Stimulation Methods for Articular Cartilage Regeneration

“…Krueger et al have created a device that, once programmed, can function as an automated ES system [19]. It was primarily composed of software, a control and signaling module as well as a sample carrier (cell chamber) with electrodes.…”

“…In addition, this electrode design may simulate the distribution of physiological EFs in cartilage tissue, since the distribution of cartilage matrix components is likewise heterogeneous. Initial findings by Krueger et al indicate that the applied EFs result in a frequency-dependent decrease in collagen type I protein production in human dedifferentiated chondrocytes [19]. To better comprehend the signaling pathways involved in cartilage regeneration in response to ES, more research was done.…”