A Bioreactor for Controlled Electrical and Mechanical Stimulation of Developing Scaffold-Free Constructs

Abstract

Bioreactors are commonly used to apply biophysically-relevant stimulations to tissue-engineered constructs in order to explore how these stimuli influence tissue development, healing, and homeostasis, and they offer great flexibility because key features of the stimuli (e.g., duty cycle, frequency, amplitude, duration) can be controlled to elicit a desired cellular response. However, most bioreactors that apply mechanical and electrical stimulations do so to a scaffold after the construct has developed, preventing study of the influence these stimuli have on early construct development. To enable such exploration, there is a need for a bioreactor that allows the direct application of mechanical and electrical stimulation to constructs as they develop. Herein, we develop and calibrate a bioreactor, based on our previously established modified Flexcell system, to deliver precise mechanical and electrical stimulation, either independently or in combination, to developing scaffold-free tissue constructs. Linear calibration curves were established, then used to apply precise dynamic mechanical and electrical stimulations, over a range of physiologically relevant strains and voltages respectively. Following calibration, applied mechanical and electrical stimulations were not statistically different from their desired target values, and were consistent whether delivered independently or in combination. Concurrent delivery of mechanical and electrical stimulation resulted in a negligible change in mechanical (< 2%) and electrical (<1%) values, compared to their independently-delivered values. With this calibrated bioreactor, we can apply precise, controlled, reproducible mechanical and electrical stimulations, alone or in combination, to scaffold-free, tissue engineered constructs as they develop.

Current Concepts and Methods in Tissue Interface Scaffold Fabrication

“…In this set up, a laser is focused on the energy absorbing layer, leading to a vapor bubble that provides pressure to dispense bioink droplets ( Figure 2 C) [ 81 ]. Following printing using any of these methods, the construct is commonly placed in a bioreactor to optimize cell proliferation, tissue remodeling, and maturation prior to implantation [ 96 , 97 ].…”

Fixation method of a single muscle fiber by magnetic force for stretching, transportation, and evaluation of mechanical properties

“…As the result, a hole-structure occurs on the muscle tissue, and the fixation becomes loose [6]. Some researchers recognized this issue, and they used collagen sponge embedded with cells as anchors for fixing muscle fibers [9]. In this way, the connection between the fixing part and muscle fibers was enhanced by the interaction between cells in the sponge and cells in the muscle fibers.…”