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Orthopedic implant failures, primarily attributed to aseptic loosening and implant site infections, pose significant challenges to patient recovery and lead to revision surgeries. Combining piezoelectric materials with ionic liquids as interfaces for orthopedic implants presents an innovative approach to addressing both issues simultaneously. In this study, films of poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) incorporated with 1-ethyl-3-methylimidazolium hydrogen sulfate ([Emim][HSO4]) ionic liquid were developed. These films exhibited strong antibacterial properties, effectively reducing biofilm formation, thereby addressing implant-related infections. Furthermore, stem cell-based differentiation assays exposed the potential of the composite materials to induce osteogenesis. Interestingly, our findings also revealed the upregulation of calcium channel expression as a result of electromechanical stimulation, pointing to a mechanistic basis for the observed biological effects. This work highlights the potential of piezoelectric materials with ionic liquids to improve the longevity and biocompatibility of orthopedic implants. Offering dual-functionality for infection prevention and bone integration, these advancements hold significant potential for advancing orthopedic implant technologies and improving patient outcomes.

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Development of piezoelectric biomaterials with high piezoelectric performance, while possessing excellent flexibility, biocompatibility, and biodegradability still remains a great challenge. Herein, a flexible, biocompatible and biodegradable piezoelectric ß-glycine-alginate-glycerol (Gly-Alg-Glycerol) film with excellent in vitro and in vivo sensing performance was developed. Remarkably, a single, monolithic ß-glycine spherulite, instead of more commonly observed multiple spherulites, was formed in alginate matrix, thereby resulting in outstanding piezoelectric property, including high piezoelectric constant (7.2 pC/N) and high piezoelectric sensitivity (1.97 mV/kPa). The Gly-Alg-Glycerol film exhibited superior flexibility, enabling complex shape-shifting, e.g. origami pigeon, 40% tensile strain, and repeated bending and folding deformation without fracture. In vitro, the flexible Gly-Alg-Glycerol film sensor could detect subtle pulse signal, sound wave and recognize shear stress applied from different directions. In addition, we have demonstrated that the Gly-Alg-Glycerol film sensor sealed by polylactic acid and beeswax could serve as an in vivo sensor to monitor physiological pressure signals such as heartbeat, respiration and muscle movement. Finally, the Gly-Alg-Glycerol film possessed good biocompatibility, supporting the attachment and proliferation of rat mesenchymal stromal cells, and biodegradability, thereby showing great potential as biodegradable piezoelectric biomaterials for biomedical sensing applications.

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Since neurons were first cultured outside a living organism more than a century ago, a number of experimental techniques for their in vitro maintenance have been developed. These methods have been further adapted and refined to study specific neurobiological processes under controlled experimental conditions. Despite their limitations, the simplicity and visual accessibility of 2D cultures have enabled the study of the effects of trophic factors, adhesion molecules, and biophysical stimuli on neuron function and morphology. Nevertheless, the impact of fundamental properties of the surfaces to which neurons adhere when cultured in vitro has not been sufficiently considered. Here, we used an electroactive polymer with different electric poling states leading to different surface charges to evaluate the impact of the net electric surface charge on the behavior of primary neurons. Average negative and positive surface charges promote increased metabolic activity and enhance the maturation of primary neurons, demonstrating the relevance of considering the composition and electric charge of the culture surfaces. These findings further pave the way for the development of novel therapeutic strategies for the regeneration of neural tissues, particularly based on dynamic surface charge variation that can be induced in the electroactive films through mechanical solicitation.

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Poly-L-lactide (PLLA) offers a unique possibility for processing into biocompatible, biodegradable, and implantable piezoelectric structures. With such properties, PLLA has potential to be used as an advanced tool for mimicking biophysical processes that naturally occur during the self-repair of wounds and damaged tissues, including electrostimulated regeneration. The piezoelectricity of PLLA strongly depends on the possibility of controlling its crystallinity and molecular orientation. Here, it is shown that modifying PLLA with a small amount (1 wt%) of crystalline filler particles with a high aspect ratio, which act as nucleating agents during drawing-induced crystallization, promotes the formation of highly crystalline and oriented PLLA structures. This increases their piezoelectricity, and the filler-modified PLLA films provide a 20-fold larger voltage output than nonmodified PLLA during ultrasound (US)-assisted activation. With 99% PLLA content, the ability of the films to produce reactive oxygen species (ROS) and increase the local temperature during interactions with US is shown to be very low. US-assisted piezostimulation of adherent cells directly attach to their surface (such as skin keratinocytes), stimulate cytoskeleton formation, and as a result cells elongate and orient themselves in a specific direction that align with the direction of PLLA film drawing and PLLA dipole orientation.

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Biomaterials with spontaneous piezoelectric property are highly emerging in recent times for the generation of electricity from mechanical energy sources that are amply available in nature. In this context, pyroelectricity, an integral property of piezoelectric materials, might be an interesting tool in harvesting thermal energy from the fluctuations of temperature. On the other hand, respiration and heart pulse are the significant human vital signs that can be used for early detection and prevention of cardiorespiratory diseases. Here, we report an all-three-dimensional (3D)-printed pyro-piezoelectric nanogenerator (Py-PNG) based on the most abundant and completely biodegradable biopolymer on earth, i.e., cellulose nanocrystal (CNC) for hybrid (mechanical as well as thermal) energy harvesting, and interestingly, the NG could be used as an e-skin sensor for application in self-powered noninvasive cardiorespiratory monitoring for personal healthcare. Notably, the CNC-based device will be biocompatible and economically advantageous due to its biomaterial-based supremacy and huge availability. This is an original approach with 3D geometrical advancement in designing a NG/sensor, where the unique all-3D-printed manner is adopted, and certainly, it has promising potential in reducing the number of processing steps to required equipment during the multilayer fabrication. The all-3D-printed NG/sensor shows outstanding mechano-thermal energy harvesting performance along with sensitivity and is capable of accurate detection of heart pulse as well as respiration, whenever and whichever required without the need of any battery or an external power supply. In addition, we have also extended its application in demonstrating a smart mask-based breath monitoring system. Thus, the real-time cardiorespiratory monitoring provides notable and fascinating information in medical diagnosis, stepping toward biomedical device development and human-machine interface.

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Insufficient angiogenesis frequently occurs after the implantation of orthopedic materials, which greatly increases the risk of bone defect reconstruction failure. Therefore, the development of bone implant with improved angiogenic properties is of great importance. Mimicking the extracellular matrix clues provides a more direct and effective strategy to modulate angiogenesis. Herein, inspired by the bioelectrical characteristics of the bone microenvironment, a piezoelectric bioactive glasses composite (P-KNN/BG) based on the incorporation of polarized potassium sodium niobate is constructed, which could effectively promote angiogenesis. It is found that P-KNN/BG has exceptional wireless electrical stimulation performance and sustained active ions release. In vitro cell experiments reveal that P-KNN/BG enhances endothelial cell adhesion, migration, and differentiation via activating the eNOS/NO signaling pathway, which might be contributed to cell membrane hyperpolarization induced by wireless electrical stimulation increase the influx of active ions into the cells. In vivo chick chorioallantoic membrane experiment demonstrates that P-KNN/BG shows excellent pro-angiogenic capacity and biocompatibility. This work broadens the current understanding of bioactive materials with bionic electrical properties, which brings new insights into the clinical treatment of bone defect repair.

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There is increasing evidence that chondrocytes within articular cartilage are affected by endogenous force-related electrical potentials. Furthermore, electrical stimulation (ES) promotes the proliferation of chondrocytes and the synthesis of extracellular matrix (ECM) molecules, which accelerate the healing of cartilage defects. These findings suggest the potential application of ES in cartilage repair. In this review, we summarize the pathogenesis of articular cartilage injuries and the current clinical strategies for the treatment of articular cartilage injuries. We then focus on the application of ES in the repair of articular cartilage in vivo. The ES-induced chondrogenic differentiation of mesenchymal stem cells (MSCs) and its potential regulatory mechanism are discussed in detail. In addition, we discuss the potential of applying piezoelectric materials in the process of constructing engineering articular cartilage, highlighting the important advances in the unique field of tissue engineering.

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The present work reports on a new approach based on electroactive microenvironments to mitigate skeletal muscle cancer. For that, piezoelectric films based on poly(vinylidene fluoride) have been applied to evaluate the influence of mechano- and/or electrical stimuli on rhabdomyosarcoma (RMS) proliferation. Human embryonal rhabdomyosarcoma (RD) cells were cultured on PVDF pristine films with different surface charge (non-poled, poled+ and poled-) and magnetic composites (10% and 20% Fe3O4, and 20% CFO filler content) to allow magneto-mechanical and magnetoelectrical stimulation films. Electrospun PVDF pristine (oriented and randomly) and magnetic (10% Fe3O4) fiber mats were also evaluated to take into consideration the morphology effect on cell response. It was found that the mechanical stimuli enhance RMS proliferation whereas the mechano-electrical decreases it. It was also verified that the RD cells proliferate better on randomly oriented fibers, whereas myoblast cells do it better in oriented ones. The obtained results confirm that electroactive microenvironments can be used to develop novel and effective approaches to deal with RMS cancer, that can be extrapolated to others cancer types.

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Dental caries and traumatic injuries to teeth may cause irreversible inflammation and eventual death of the dental pulp. Nevertheless, predictably, repair and regeneration of the dentin-pulp complex remain a formidable challenge. In recent years, smart multifunctional materials with antimicrobial, anti-inflammatory, and pro-regenerative properties have emerged as promising approaches to meet this critical clinical need. As a unique class of smart materials, piezoelectric materials have an unprecedented advantage over other stimuli-responsive materials due to their inherent capability to generate electric charges, which have been shown to facilitate both antimicrobial action and tissue regeneration. Nonetheless, studies on piezoelectric biomaterials in the repair and regeneration of the dentin-pulp complex remain limited. In this review, we summarize the biomedical applications of piezoelectric biomaterials in dental applications and elucidate the underlying molecular mechanisms contributing to the biological effect of piezoelectricity. Moreover, we highlight how this state-of-the-art can be further exploited in the future for dental tissue engineering.

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Severe peripheral nervous system injuries currently hold limited therapeutic solutions. Existing clinical techniques such as autografts, allografts, and newer nerve guidance conduits have shown variable outcomes in functional recovery, adverse immune responses, and in some cases low or minimal availability. This can be attributed in part to the lack of chemical, physical, and electrical cues directing both nerve guidance and regeneration. To address this pressing clinical issue, electrospun nanofibers and microfibers composed of piezoelectric polyvinylidene flouride-triflouroethylene (PVDF-TrFE) have been introduced as an alternative template for tissue engineered biomaterials, specifically as it pertains to their relevance in soft tissue and nerve repair. Here, biocompatible scaffolds of PVDF-TrFE are fabricated and their ability to generate an electrical response to mechanical deformations and produce a suitable regenerative microenvironment is examined. It is determined that 20% (w/v) PVDF-TrFE in (6:4) dimethyl formamide (DMF):acetone solvent maintains a desirable piezoelectric coefficient and the proper physical and electrical characteristics for tissue regeneration. Further, it is concluded that scaffolds of varying thickness promoted the adhesion and alignment of Schwann cells and fibroblasts. This work offers a prelude to further advancements in nanofibrous technology and a promising outlook for alternative, autologous remedies to peripheral nerve damage.

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This Special Issue highlights the recent developments and future directions of virus-based nanomaterials and nanostructures in energy and biomedical applications. The virus-based biomimetic materials formulated using innovative ideas presented herein are characterized for the applications of biosensors and nanocarriers. The research contributions and trends based on virus-based materials, covering energy-harvesting devices to tissue regeneration over the last two decades, are described and discussed.

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Current bioelectronics are facing a paradigm shift from old-fashioned unrecyclable materials to green and degradable functional materials with desired biocompatibility. As an essential electromechanical coupling component in many bioelectronics, new piezoelectric materials are being developed with biodegradability, as well as desired mechanical and electromechanical properties for the next generation implantable and wearable bioelectronics. In this review, we provide an overview of the major advancements in biodegradable piezoelectric materials. Different natural (such as peptide, amino acids, proteins, cellulose, chitin, silk, collagen, and M13 phage) and synthetic piezoelectric materials (such as polylactic acid) are discussed to reveal the underlying electromechanical coupling mechanism at the molecular level, together with typical approaches to the alignment of orientation and polarization to boost their electromechanical performance. Meanwhile, in vivo and in vitro degradation manners of those piezoelectric materials are summarized and compared. Representative developments of typical electronic prototypes leveraging these materials are also discussed. At last, challenges toward practical applications are pointed out together with potential research opportunities that might be critical in this new materials research area.

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The aim of engineering of biomaterials is to fabricate implantable biocompatible scaffold that would accelerate regeneration of the tissue and ideally protect the wound against biodevice-related infections, which may cause prolonged inflammation and biomaterial failure. To obtain antimicrobial and highly biocompatible scaffolds promoting cell adhesion and growth, materials scientists are still searching for novel modifications of biomaterials. This review presents current trends in the field of engineering of biomaterials concerning application of various modifications and biophysical stimulation of scaffolds to obtain implants allowing for fast regeneration process of bone and cartilage as well as providing long-lasting antimicrobial protection at the site of injury. The article describes metal ion and plasma modifications of biomaterials as well as post-surgery external stimulations of implants with ultrasound and magnetic field, providing accelerated regeneration process. Finally, the review summarizes recent findings concerning the use of piezoelectric biomaterials in regenerative medicine.

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