Cell‐Traction‐Triggered On‐Demand Electrical Stimulation for Neuron‐Like Differentiation

Abstract

support for cells but also provides a train of biochemical and biophysical cues to regulate cell behaviors and trigger tissue functions. [2] An in-depth understanding of the evolution of cell microenvironment over time and modeling of this dynamic microenvironment are essential for tissue regeneration. Biomimetic materials with time-modulated properties, that is, 4D biomimetic materials, have drawn increasing attention due to their bionic nature. Triggered by external stimuli (e.g., temperature, light, electricity, and magnetic field), 4D biomimetic materials exhibit specific changes of their own characteristics, such as mechanical property, hydrophobic/hydrophilic property, redox state, and conformation of surface ligands, to build a dynamic cell microenvironment. [3] However, most existing 4D bionic systems need external stimuli, which is inconvenient for patients, and may limit their clinical transformation. Recently, researchers found that there is a bi-directional interaction between cells and ECM. [4] Specifically, cells do not merely respond passively to biochemical and biophysical signals that are delivered to them. [5] Instead, many cells actively alter their surrounding environment to suit their needs, including soluble factor secretion and matrix deposition, degradation, and reorganization. [6] Among them, the mechanical interaction between cells and substrates has been widely studied, mainly focusing on the regulation of cell adhesion and behavior by stiffness of the substrate, as well as the reorganization of the substrate morphology by cell traction. [7] However, the dynamic interactions between cells and substrates at different stages are rarely studied. Moreover, how this dynamic process directs cells behaviors remains relatively unexplored.In this work, we fabricated a piezoelectric fibrous network with mechanical stiffness similar to that of collagen and applied this network to elucidate the dynamic mechanical interaction between cells and substrates. Mature focal adhesion (FA) is one of the necessary conditions for cell-substrate bi-directional mechanical perception. Thus, the whole process involves two distinct stages: i) "slippage". Before the formation of mature FAs, cells and substrate do not perceive each other's mechanical behaviors, thereby cell activity causes relative slippage of the cells to the substrate without causing nanofiber deformation (Video S1, Supporting Information); and ii) "traction". After the formation of mature FAs, the intracellular biophysical Electromechanical interaction of cells and extracellular matrix are ubiquitous in biological systems. Understanding the fundamentals of this interaction and feedback is critical to design next-generation electroactive tissue engineering scaffold. Herein, based on elaborately modulating the dynamic mechanical forces in cell microenvironment, the design of a smart piezoelectric scaffold with suitable stiffness analogous to that of collagen for on-demand electrical stimulation is reported. Specifically, it generated a piezoele...

Electrical Stimulation Enabled via Electrospun Piezoelectric Polymeric Nanofibers for Tissue Regeneration

“…Electrical cue from nanofibers can be sufficient to mediate the cell fate owing to the transmembrane potential for most cells ranging from -10 mV to -90 mV [79]. In addition, this ES with cell traction as a loop feedback signal can stimulate the cell accordingly, thereby avoiding the unfavorable effect of early electrical stimulation on cell spreading and adhesion [56]. Thus, cell traction is an ideal source of mechanical loading on piezoelectric polymeric nanofibers as a result of no external energy consumption and bidirectional electromechanical feedback.…”

“…In addition, external stimuli, such as ultrasound [48][49][50] and magnetic fields [51][52][53][54][55], are capable of controllably activating the piezoelectric material in a wireless and noninvasive manner. In particular, fibrous piezoelectric polymers with a nanostructure are sensitive enough to achieve significant deformation through subtle stress caused by cell traction, thus generating considerable electrical signal for cell activity modulation [56]. Moreover, the nanofibrous web can mimic the biological function and microstructure of the collagen fibers (a natural piezoelectric material in ECM), acting as a medium of bioelectric signal transmission and communication between cells [57].…”

Electromechanical Nanogenerators for Cell Modulation

“…It could also generate piezopotential up to millivolts through cell inherent force, thereby providing in situ electrostimulation for the adherent cells. Liu et al prepared nanofibers with a suitable stiffness that was analogous to that of collagen using electrospinning technology [92]. Interestingly, the obvious mechanical deformation of the nanofibers was only observed after cell adhesion and mature focal adhesion formation (Figure 10h,i).…”

Mechanical Sensors for Cardiovascular Monitoring: From Battery-Powered to Self-Powered

“…Self-powered capability is of great significance for future intelligent implants [ 57 , 58 , 59 , 60 ], and battery-free sensing of physiological signals in artificial blood vessels may be an ideal application. Li et al developed an electric field-assisted 3D printing technique for fabricating in situ polarized ferroelectric artificial arteries ( Figure 5 A), providing battery-free real-time blood pressure sensing and occlusion monitoring capabilities [ 57 ].…”