To address limitations in current approaches for treating large peripheral nerve defects, the presented study evaluated the feasibility of functional material-mediated physical stimuli on peripheral nerve regeneration. Electrospun piezoelectric poly(vinylidene fluoride-trifluoroethylene) nanofibers were utilized to deliver mechanical actuation-activated electrical stimulation to nerve cells/tissues in a non-invasive manner. Using morphologically and piezoelectrically optimized nanofibers for neurite extension and Schwann cell maturation based on in vitro experiments, piezoelectric nerve conduits were synthesized and implanted in a rat sciatic nerve transection model to bridge a critical-sized sciatic nerve defect (15 mm). A therapeutic shockwave system was utilized to periodically activate the piezoelectric effect of the implanted nerve conduit on demand. The piezoelectric nerve conduit-mediated mechano-electrical stimulation (MES) induced enhanced peripheral nerve regeneration, resulting in full axon reconnection with myelin regeneration from the proximal to the distal ends over the critical-sized nerve gap. In comparison, a control group, in which the implanted piezoelectric conduits were not activated in vivo, failed to exhibit such nerve regeneration. In addition, at both proximal and distal ends of the implanted conduits, a decreased number of damaged myelination (ovoids), an increased number of myelinated nerves, and a larger axonal diameter were observed under the MES condition as compared to the control condition. Furthermore, unlike the control group, the MES condition exhibited a superior functional nerve recovery, assessed by walking track analysis and polarization-sensitive optical coherence tomography, demonstrating the significant potential of the piezoelectric conduit-based physical stimulation approach for the treatment of peripheral nerve injury.

Polymeric biomaterials exhibit excellent physicochemical characteristics as a scaffold for cell and tissue engineering applications. Chemical modification of the polymers has been the primary mode of functionalization to enhance biocompatibility and regulate cellular behaviors such as cell adhesion, proliferation, differentiation, and maturation. Due to the complexity of the in vivo cellular microenvironments, however, chemical functionalization alone is usually insufficient to develop functionally mature cells/tissues. Therefore, the multifunctional polymeric scaffolds that enable electrical, mechanical, and/or magnetic stimulation to the cells, have gained research interest in the past decade. Such multifunctional scaffolds are often combined with exogenous stimuli to further enhance the tissue and cell behaviors by dynamically controlling the microenvironments of the cells. Significantly improved cell proliferation and differentiation, as well as tissue functionalities, are frequently observed by applying extrinsic physical stimuli on functional polymeric scaffold systems. In this regard, the present paper discusses the current state-of-the-art functionalized polymeric scaffolds, with an emphasis on electrospun fibers, that modulate the physical cell niche to direct cellular behaviors and subsequent functional tissue development. We will also highlight the incorporation of the extrinsic stimuli to augment or activate the functionalized polymeric scaffold system to dynamically stimulate the cells.

Article Piezocatalytic ZnS: Mn2+ Nanocrystals for Enhanced Organic Dye Degradation Zhongxiang Wang 1, Elizaveta Tiukalova 2, Youyi Tai 3, Miaofang Chi 2, Jin Nam 3,* and Yadong Yin 1,* 1 Department of Chemistry, University of California, Riverside, CA 92521, USA 2 Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA 3 Department of Bioengineering, University of California, Riverside, CA 92521, USA * Correspondence: jnam@engr.ucr.edu (J.N.); yadong.yin@ucr.edu (Y.Y.) Received: 15 October 2024; Revised: 20 November 2024; Accepted: 21 November 2024; Published: 22 November 2024 Piezocatalysis, an emerging approach that harnesses mechanical energy to drive chemical reactions, has garnered significant attention due to its potential applications in diverse fields, particularly in environmental remediation. Its broader application, however, is often hindered by the low efficiency of existing piezocatalytic materials. Here, we report the synthesis of Mn2+-doped ZnS nanocrystals with improved piezoelectric properties using an emulsion-based colloidal assembly technique. Through well-controlled Mn2+ doping, these nanocrystals demonstrate high piezocatalytic activity for degrading organic dyes under ultrasonic vibration. The optimal performance is achieved with 3% Mn2+ doping, outperforming many existing piezocatalysts. Mechanistic studies reveal the generation of reactive oxygen species as the primary driving force for degradation. Notably, pre-excitation with UV light further boosts the piezocatalytic efficiency of these metal ion-doped ZnS nanocrystals by filling electron trap states, leading to improved overall performance. This research paves the way for developing high-performance piezocatalysts, expanding the potential of piezocatalysis for a wide range of applications.

The intricate interplay between biochemical and physical cues dictates pluripotent stem cell (PSC) differentiation to form various tissues. While biochemical modulation has been extensively studied, the role of biophysical microenvironments in early lineage commitment remains elusive. Here, we introduce a novel 3D cell culture system combining electrospun nanofibers with microfabricated polydimethylsiloxane (PDMS) patterns. This system enables the controlled formation of semispherical human induced pluripotent stem cell (hiPSC) colonies, facilitating the investigation of local mechanical stem cell niches on mechano-responsive signaling and lineage specification. Our system unveiled spatially organized RhoA activity coupled with actin-myosin cable formation, suggesting mechano-dependent hiPSC behaviors. Nodal network analysis of RNA-seq data revealed RhoA downstream regulation of YAP signaling, DNA histone modifications, and patterned germ layer specification. Notably, altering colony morphology through controlled PDMS microwell shaping effectively modulated the spatial distribution of mechano-sensitive mediators and subsequent differentiation. This study provides a cell culture platform to decipher the role of biophysical cues in early embryogenesis, offering valuable insights for material design in tissue engineering and regenerative medicine applications.

Leadless intracardiac pacemakers (LIP) are a technological breakthrough that offer tremendous benefits to patients, including minimally invasive delivery, improved quality of life, and reduced financial burden. However, limited by its size and capacity, the battery component becomes a major roadblock to further advancing LIP technology toward lifelong, maintenance-free implants without the need for device retrieval or replacement. Here, we present an integrated, nanogenerator-powered LIP with a clinically compatible architecture. The LIP is solely powered by a double-oscillatory triboelectric nanogenerator (TENG) that is capable of generating a volumetric power density of 276.6 μW cc ⁻¹ driven by heartbeats. The miniaturized TENG can also fit within the battery compartment of a commercial Medtronic Micra LIP, allowing standard femoral-venous delivery by commercial catheters. When implanted in the heart of a swine model, the device delivers stable, rate-responsive electrical energy in vivo, which reliably supports the cardiac pacing function for heart rates control at physiological levels through harvested energy. Long-term intracardiac implantation further confirmed secure fixation, unaffected cardiac function and minimal tissue reaction of the fully integrated device. This development suggests a clinically compatible path toward self-sustainable intracardiac electronic systems.