Differential effect of electrical stimuli on a 3D bioprinted model of inflamed skin

Electrostimulation is the object of the study of a variety of clinical approaches, ranging from bioelectronic medicine where the aim is to elicit the activity of the autonomic nervous system (ANS), to electroacupuncture with the general objective to restore homeostasis, to transcutaneous electrical nerve stimulation (TENS) to control pain and degeneration, to name a few. Among the numerous obstacles preventing from a clear adoption or rejection of these approaches in mainstream clinical practice, is the difficulty in standardizing experimental systems for testing and validation. Consequently, indications on the appropriate magnitude of an effective stimulus (duration, frequency, intensity) remain unclear. To approach this issue we present preliminary results on the differential molecular activity elicited in a 3D bioprinted construct containing fibroblasts and keratinocytes in a collagen matrix, by two diverse types of electrical stimulation (direct and alternate current). Two conditions, physiology and inflammation induced by TNF? perfusion were tested with anelectrobiomedical device. The system mimics a simplified model of skin, the largest and most accessible of our organs, in inflamed or physiological states, treated by electrostimulation. The bioprinted sample is constructed to yield an appropriate number of cell enabling high-throughput screens. We report here our preliminary results on RNA-seq differential expression comparing direct and alternate current stimuli, with a focus on wound healing and inflammation as part of the greater inflammatory pathway. Our construct offer reproducibility of the experience, and direct comparison among potentially numerous conditions and types of stimulation. Our preliminary results shows that electrostimulation offers differential elicitation of biological functions. In particular, direct and alternate current provoke differential activation of proliferation and development associated functions.