During natural tissue regeneration, tissue microenvironment and stem cell niche including cell–cell interaction, soluble factors, and extracellular matrix (ECM) provide a train of biochemical and biophysical cues for modulation of cell behaviors and tissue functions. Design of functional biomaterials to mimic the tissue/cell microenvironment have great potentials for tissue regeneration applications. Recently, electroactive biomaterials have drawn increasing attentions not only as scaffolds for cell adhesion and structural support, but also as modulators to regulate cell/tissue behaviors and function, especially for electrically excitable cells and tissues. More importantly, electrostimulation can further modulate a myriad of biological processes, from cell cycle, migration, proliferation and differentiation to neural conduction, muscle contraction, embryogenesis, and tissue regeneration. In this review, endogenous bioelectricity and piezoelectricity are introduced. Then, design rationale of electroactive biomaterials is discussed for imitating dynamic cell microenvironment, as well as their mediated electrostimulation and the applying pathways. Recent advances in electroactive biomaterials are systematically overviewed for modulation of stem cell fate and tissue regeneration, mainly including nerve regeneration, bone tissue engineering, and cardiac tissue engineering. Finally, the significance for simulating the native tissue microenvironment is emphasized and the open challenges and future perspectives of electroactive biomaterials are concluded.

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Ultrasound (US)-triggered sonodynamic therapy (SDT) based on semiconductor nanomaterials has attracted considerable attention for cancer therapy. However, most inorganic sonosensitizers suffer from low efficiency due to the rapid recombination of electron–hole pairs. Herein, the Cu2–x O–BaTiO3 piezoelectric heterostructure was fabricated as a sonosensitizer and chemodynamic agent, simultaneously, for improving reactive oxygen species (ROS) generation and cancer therapeutic outcome. Under US irradiation, the Cu2–x O–BaTiO3 heterojunction with a piezotronic effect exhibits high-performance singlet oxygen (1O2) and hydroxyl radical (•OH) generation to enhance SDT. Moreover, it possesses Fenton-like reaction activity to convert endogenous H2O2 into •OH for chemodynamic therapy (CDT). The integration of SDT and CDT substantially boosts ROS generation and cellular mitochondria damage, and the in vitro and in vivo results demonstrate high cytotoxicity and tumor inhibition on murine refractory breast cancer. This work realizes improvement in cancer therapy using piezoelectric heterostructures with piezotronic effects.

Owing to their self‐renewal and differentiation ability, stem cells are conducive for repairing injured tissues, making them a promising source of seed cells for tissue engineering. The extracellular microenvironment (ECM) is under dynamic mechanical control, which is closely related to stem cell behaviors. During the design and fabrication of biomaterials for regenerative medicine, the physiochemical properties of the natural ECM should be closely mimicked, which can reinforce stem cell lineage choice and tissue engineering. By reproducing the biophysical stimulations that stem cells may experience in vivo, many studies have highlighted the key role of biophysical cues in regulation of cell fate. Optimization of biophysical factors leads to desirable stem cell functions, which can maximize the effectiveness of regenerative treatment. In this review, the main biophysical cues of biomaterials, including stiffness, topography, mechanical force, and external physical fields are summarized, and their individual and synergistic influence on stem cell behavior is discussed. Subsequently, the current progress in tissue regeneration using biomaterials is presented, which directs the design and fabrication of functional biomaterial. The mechanisms via which biophysical cues activate cellular responses are also analyzed. Finally, the challenges in basic research as well as for clinical translation in this field are discussed.

Improving output performance of triboelectric nanogenerators (TENGs) is crucial for expanding their applications in smart devices, especially for flexible and wearable bioelectronics. In this study, we design and fabricate a flexible, stretchable, and highly transparent TENG based on an unsymmetrical PAM/BTO composite film, made of polyacrylamide (PAM) hydrogel and BaTiO 3 nanocubes (BTO NCs, BTO), and the TENG performance can be tailored by adjusting the amount and distribution location of BTO. The stretchable hydrogel electrode could bear over 8 times stretching. By changing the content and distribution location of BTO in the unsymmetrical hydrogel film, the output of the fabricated TENGs could be improved, acting as pressure sensors with high sensitivity to distinguish a spectrum of forces (0.25−6 N) at the low frequency. The mechanism of the enhanced output performance of the PAM/BTO composite hydrogel-based TENG is discussed in detail. By integrating piezoresistive, piezoelectric, and triboelectric effects, the optimized TENG and piezoresistive sensors are used as multimodal biomechanical sensors for detecting the motions of human bodies, pressure, and curvature with high sensitivity.

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...

Electrospinning (e‐spin) technique has emerged as a versatile and feasible pathway for constructing diverse polymeric fabric structures, which show potential applications in many biological and biomedical fields. Owing to the advantages of adjustable mechanics, designable structures, versatile surface multi‐functionalization, and biomimetic capability to natural tissue, remarkable progress has been made in flexible bioelectronics and tissue engineering for the sensing and therapeutic purposes. In this perspective, we review recent works on design of the hierarchically structured e‐spin fibers, as well as, the fabrication strategies from one‐dimensional individual fiber (1D) to three‐dimensional (3D) fiber arrangements adaptive to specific applications. Then, we focus on the most cutting‐edge progress of their applications in flexible bioelectronics and tissue engineering. Finally, we propose future challenges and perspectives for promoting electrospun fiber‐based products toward industrialized, intelligent, multifunctional, and safe applications.

The production of reactive oxygen species (ROS) to elicit lethal cellular oxidative damage is an attractive pathway to kill cancer, but it is still hindered by the low ROS production...