Electrical stimulation has shown promise in clinical studies to treat nerve injuries. This work is aimed to create an aligned bioelectronic construct that can be used to bridge a nerve gap, directly interfacing with the damaged nerve tissue to provide growth support. The conductive three-dimensional bioelectronic scaffolds described herein are composite materials, comprised of conductive polypyrrole (PPy) nanoparticles embedded in an aligned collagen hydrogel. The bioelectronic constructs are seeded with dorsal root ganglion derived primary rat neurons and electrically stimulated in vitro. The PPy loaded constructs support a 1.7-fold increase in neurite length in comparison to control collagen constructs. Furthermore, upon electrical stimulation of the PPy-collagen construct, a 1.8-fold increase in neurite length is shown. This work illustrates the potential of bioelectronic constructs in neural tissue engineering and lays the groundwork for the development of novel bioelectronic materials for neural interfacing applications.

Herein, fullerenol (Ful), a highly water-soluble derivative of C fullerene with demonstrated antioxidant activity, is incorporated into calcium phosphate cements (CPCs) to enhance their osteogenic ability. CPCs with added carboxymethyl cellulose/gelatin (CMC/Gel) are doped with biocompatible Ful particles at concentrations of 0.02, 0.04, and 0.1 wt v% and evaluated for Ful-mediated mechanical performance, antioxidant activity, and in vitro cellular osteogenesis. CMC/gel cements with the highest Ful concentration decrease setting times due to increased hydrogen bonding from Ful's hydroxyl groups. In vitro studies of reactive oxygen species (ROS) scavenging with CMC/gel cements demonstrate potent antioxidant activity with Ful incorporation and cement scavenging capacity is highest for 0.02 and 0.04 wt v% Ful. In vitro cytotoxicity studies reveal that 0.02 and 0.04 wt v% Ful cements also protect cellular viability. Finally, increase of alkaline phosphatase (ALP) activity and expression of runt-related transcription factor 2 (Runx2) in MC3T3-E1 pre-osteoblast cells treated with low-dose Ful cements demonstrate Ful-mediated osteogenic differentiation. These results strongly indicate that the osteogenic abilities of Ful-loaded cements are correlated with their antioxidant activity levels. Overall, this study demonstrates exciting potential of Fullerenol as an antioxidant and proosteogenic additive for improving the performance of calcium phosphate cements in bone reconstruction procedures.

Conventional energy sources are continuously depleting, and the world is actively seeking new green and efficient energy solutions. Enormous amounts of acoustic energy are dissipated daily, but the low intensity and limited efficiency of current harvesting techniques are preventing its adoption as a ubiquitous method of power generation. Herein, a strategic solution to increase acoustic energy harvesting efficiency using a specially designed metamaterial is implemented. A scalable transmissive labyrinthine acoustic metamaterial (LAM) is designed, developed, and employed to maximize ultrasound (40 kHz) capture over its large surface area (>27 k mm), which is focused onto a piezoelectric film (78.6 mm), thus magnifying incident sound pressure by 13.6 times. Three different piezoelectric films - two commercial and one lab-made nanocomposite film are tested with LAM in the acoustic energy harvesting system. An extraordinary voltage gain of 157-173% and a maximum power gain of 272% using the LAM compared to the case without the LAM are achieved. Multipoint focusing using holographic techniques, showcasing acoustic patterning to allow on-demand simultaneous harvesting in separate locations, is demonstrated. Our versatile approach for high-intensity acoustic energy harvesting opens future opportunities to exploit sound energy as a resource to contribute toward global sustainability.

Chronic wound biofilm infections represent a major clinical challenge which results in a substantial burden to patients and healthcare systems. Treatment with topical antibiotics is oftentimes ineffective as a result of antibiotic-resistant microorganisms and biofilm-specific antibiotic tolerance. Use of biocides such as hypochlorous acid (HOCl) has gained increasing attention due to the lack of known resistance mechanisms. We designed an HOCl-generating electrochemical bandage (e-bandage) that delivers HOCl continuously at low concentrations targeting infected wound beds in a similar manner to adhesive antimicrobial wound dressings. We developed a battery-operated wearable potentiostat that controls the e-bandage electrodes at potentials suitable for HOCl generation. We demonstrated that e-bandage treatment was tunable by changing the applied potential. HOCl generation on electrode surfaces was verified using microelectrodes. The developed e-bandage showed time-dependent responses against and biofilms, reducing viable cells to non-detectable levels within 6 and 12 hours of treatment, respectively. The developed e-bandage should be further evaluated as an alternative to topical antibiotics to treat wound biofilm infections.

Polymeric microneedles fabricated via two-photon polymerization (2PP) lithography enable safe medical access to the inner ear. Herein, the material class for 2PP-lithography-based microneedles is expanded by pyrolyzing 2PP-fabricated polymeric microneedles, resulting in glassy carbon microneedles. During pyrolysis the microneedles shrink up to 81% while maintaining their complex shape when the exposed surface-area-to-volume ratio (SVR) is 0.025 < SVR < 0.04, for the temperature history protocol used herein. The derived glassy carbon is confirmed with energy-dispersive X-ray spectroscopy and Raman spectroscopy. The pyrolyzed glassy carbon has Young's modulus 9.0 GPa. As a brittle material, the strength is stochastic. Using the two-parameter Weibull distribution, the glassy carbon has Weibull modulus of 3.1 and characteristic strength of 710 MPa. The viscoelastic response has characteristic time scale of about 10000 s. In vitro experiments demonstrate that the glassy carbon microneedles introduce controlled perforations across the guinea pig round window membrane (RWM) from the middle ear space into the inner ear, without damaging the microneedle. The resultant controlled perforation of RWM is known to enhance diffusion of therapeutics across the RWM in a predictable fashion. Hence, the glassy carbon microneedles can be deployed for mediating inner ear delivery.

Advances in additive manufacturing techniques have enabled the development of micro-architectured materials displaying a combination of low-density and lightweight structures with high specific strength and toughness. The mechanical performance of micro-architectured materials can be assessed using standard techniques; however, when studying low- and ultralow density micro-architectured materials, standard characterization techniques can be subject to experimental artifacts. Additionally, quantitative assessment and comparisons of microarchitectures with distinct lattice patterns is not always straightforward. Cancellous bone is a natural, ultralow density (porosity often exceeding 90%), irregular, cellular solid that has been thoroughly characterized in terms of micro-architecture and mechanical performance over the past 30 years. However, most the literature on cancellous bone mechanical properties and micro-structure-function relationships is in the medical literature and is not immediately accessible to materials designers. Here we provide a brief review of state-of-the-art approaches for characterizing the micro-architecture and mechanical performance of ultralow density cancellous bone, including methods of addressing experimental artifacts during mechanical characterization of ultralow density cellular solids, methods of quantifying microarchitecture, and currently understood structure-function relationships.

The 3D printing of nasopharyngeal swabs during the COVID-19 pandemic presents a central case of how to efficiently address a break in the global supply chain of medical equipment. Herein a comprehensive study of swab design considerations for mass production by stereolithography is presented. The retention and comfort performance of a range of novel designs of 3D-printed swabs are compared with the standard flocked-head swab used in clinical environments. Sample retention of the 3D swab is governed by the volume, porosity density, and void fraction of the head as well as by the pore geometry. 3D-printed swabs outperform conventional flock-head swabs in terms of sample retention. It is argued that mechanically functional designs of the swab head, such as corkscrew-shaped heads and negative Poisson ratio heads, maximize sample retention and improve patient comfort. In addition, available designs of swab shafts for an optimized sample collection procedure are characterized. The study is conducted in vitro, using artificial mucus, covering the full range of human mucus viscosities in a 3D-printed model of a nasal cavity. The work sets the path for the resilient supply of widespread sterile testing equipment as a rapid response to the current and future pandemics.

Enhancement in the capabilities of additive manufacturing (AM) methods has led to development of many high-value components for aerospace, automotive and medical fields. Security concerns, such as (a) a predominantly cloud based process chain of AM may be breached and stolen files can be used for unauthorized reproduction of parts and (b) legitimately acquired parts can be reverse engineered, need to be addressed for this field to protect intellectual property and deter counterfeiting or unauthorized production. In the present work, a method of embedding an identification code inside the parts manufactured by AM methods is presented, which takes advantage of the layer-by-layer manufacturing process. The code is obfuscated by segmenting it into a specific number of parts, which are distributed throughout a large number of printed layers. In this case, viewing the code only from a specific direction is provides the correct visualization. A further obfuscation scheme is demonstrated that embeds multiple identification codes in the interpenetrating format. Only a specific set of processing conditions can lead to printing of the authentic code inside the part correctly. Numerous other conditions lead to printing of wrong code inside the part, which will lead to positive identification of counterfeit or unauthorized parts. Securing the AM process chain can help in accelerating the industrial applications of this versatile method.

A facile method for the preparation of large, microporous, drug-loaded particles is presented. High shear bollus injections of silk with cross-linker and drug colloids into super-cooled hexane were utilized to trigger phase separation of silk droplets, followed by immediate freezing at -60°C. A subsequent -20°C freeze-thaw of the frozen droplets resulted in self-assembly (crystallization) of the silk. The silk particles developed an internal interconnected microporous morphology with 0.1-10 µm in diameter pores. The silk particles ranged in diameter from 100 to 1,300 µm, with particle mean diameter and polydispersity controlled by the starting concentration of the cross-linking agent and silk, the rheology of the reaction mixture, and the injection pressure (80 - 300kPa). Cryogranulation provided a one-step process to produce microporous meso-scale silk particles with encapsulated drugs, such as doxorubicin chloride (DoxR), tobramycin sulfate (TS), kanamycin sulfate (KS) or gentamicin sulfate (GS). Almost 100% drug encapsulation efficiency was achieved in the process, and subsequent release profiles depended on the starting concentration of both the drug, silk, and pH of the elution medium. Kirby-Bauer tests and bioluminescent imaging confirmed the retention of anti-bacterial potency of the antibiotics pre-encapsulated in the cryo-particles, and macroparticles cytocompatibility towards human fibroblast and kidney cells.

Application of 3D printed structures via stereolithography (SLA) is limited by imprecise dimensional control and inferior mechanical properties. These challenges is attributed to poor understanding ofpolymerization behavior during the printing process and inadequate post-processing methods. The former via a modified version of Jacob's working curve equation that incorporates the resin's sub-linear response to irradiation intensity is addressed by the authors. This new model provides a more accurate approach to select 3D printing parameters given a desired z-resolution and conversion profile along the depth of the printed part. The authors use this improved model to motivate a novel material design that can be post-processed to be indistinguishable from the polymer at 100% conversion. This approach employs a dual initiating system in which photo-initiated printing is followed by a thermal post-cure to achieve uniform conversion. The authors show that this approach enables fast printing times (10 s per layer), exceptional horizontal resolution (1-10 microns), precise control over vertical resolution, and decreased surface corrugations on a 10's of microns scale. The techniques described herein use an acrylate-based SLA resin, but the approach can be extended to other monomer systems to simultaneously achieve predictable properties and dimensions that are critical for application of additive manufacturing in load-bearing applications.

Graphene foam (GF), a 3-dimensional derivative of graphene, has received much attention recently for applications in tissue engineering due to its unique mechanical, electrical, and thermal properties. Although GF is an appealing material for cartilage tissue engineering, the mechanical properties of GF - tissue composites under dynamic compressive loads have not yet been reported. The objective of this study was to measure the elastic and viscoelastic properties of GF and GF-tissue composites under unconfined compression when quasi-static and dynamic loads are applied at strain magnitudes below 20%. The mechanical tests demonstrate a 46% increase in the elastic modulus and a 29% increase in the equilibrium modulus after 28-days of cell culture as compared to GF soaked in tissue culture medium for 24h. There was no significant difference in the amount of stress relaxation, however, the phase shift demonstrated a significant increase between pure GF and GF that had been soaked in tissue culture medium for 24h. Furthermore, we have shown that ATDC5 chondrocyte progenitor cells are viable on graphene foam and have identified the cellular contribution to the mechanical strength and viscoelastic properties of GF - tissue composites, with important implications for cartilage tissue engineering.

Zirconium-based alloys are used in water-cooled nuclear reactors for both nuclear fuel cladding and structural components. Under this harsh environment, the main factor limiting the service life of zirconium cladding, and hence fuel burn-up efficiency, is water corrosion. This oxidation process has recently been linked to the presence of a sub-oxide phase with well-defined composition but unknown structure at the metal-oxide interface. In this paper, the combination of first-principles materials modeling and high-resolution electron microscopy is used to identify the structure of this sub-oxide phase, bringing us a step closer to developing strategies to mitigate aqueous oxidation in Zr alloys and prolong the operational lifetime of commercial fuel cladding alloys.

This article describes the establishment, over a period of ten years or so, of a multi-user, institution-wide facility for the characterization of materials and devices at the nano-scale. Emphasis is placed on the type of equipment that we have found to be most useful for our users, and the business strategy that maintains its operations. A central component of our facility is an aberration-corrected environmental transmission electron microscope and its application is summarized in the studies of plasmon energies of silver nanoparticles, the band gap of PbS quantum dots, atomic site occupancy near grain boundaries in yttria stabilized zirconia, the lithiation of silicon nanoparticles, in situ observations on carbon nanotube oxidation and the electron tomography of varicella zoster virus nucleocapsids.

We present in situ transmission electron microscope tensile tests on focused ion beam fabricated single and multiple slip oriented Cu tensile samples with thicknesses in the range of 100-200 nm. Both crystal orientations fail by localized shear. While failure occurs after a few percent plastic strain and limited hardening in the single slip case, the multiple slip samples exhibit extended homogenous deformation and necking due to the activation of multiple dislocation sources in conjunction with significant hardening. The hardening behavior at 1% plastic strain is even more pronounced compared to compression samples of the same orientation due to the absence of sample taper and the interface to the compression platen. Moreover, we show for the first time that the strain rate sensitivity of such FIB prepared samples is an order of magnitude higher than that of bulk Cu.

We report a method for modulating the physicochemical properties of surfaces that is based on the reactive layer-by-layer fabrication of covalently crosslinked thin films using azlactone-functionalized copolymers. We demonstrate that copolymers containing different molar ratios of methylmethacrylate (MMA) and 2-vinyl-4,4-dimethylazlactone (VDMA) can be alternately deposited with poly(ethyleneimine) to assemble covalently crosslinked thin films. Characterization using ellipsometry demonstrates that, in general, film growth and thickness decrease as the content of reactive, azlactone functionality in the copolymer used to assemble the film decreases. Reflective infrared spectroscopy experiments demonstrate that films fabricated from MMA:VDMA copolymers contain residual azlactone functionality and that these reactive groups can be exploited to modify film-coated surfaces. Fabricating films from MMA:VDMA copolymers containing different compositions permitted modulation of the density of reactive groups within the films and, thus, the extent to which the films are functionalized by exposure to small molecule amines. For example, functionalization of MMA:VDMA copolymer films with the small molecule D-glucamine resulted in films with water contact angles that varied with the composition of the copolymer used to fabricate the film (e.g., as the azlactone content in the film increased, glucamine-modified films became more hydrophilic). We demonstrate further that treatment of copolymer-containing films with glucamine resulted in changes in the numbers of mammalian cells that grow on the surfaces of the films. Our results suggest the basis of methods that could be used to modulate or tune the density of chemical and biological functionality presented on surfaces of interest in a variety of fundamental and applied contexts.

The use of microneedles for transdermal drug delivery is limited due to the risk of infection associated with formation of channels through the stratum corneum layer of the epidermis. The risk of infection associated with use of microneedles may be reduced by imparting these devices with antimicrobial properties. In this study, a photopolymerization-micromolding technique was used to fabricate microneedle arrays from a photosensitive material containing polyethylene glycol 600 diacrylate, gentamicin sulfate, and a photoinitiator. Scanning electron microscopy indicated that the photopolymerization-micromolding process produced microneedle arrays that exhibited good microneedle-to-microneedle uniformity. An agar plating assay revealed that microneedles fabricated with polyethylene glycol 600 diacrylate containing 2 mg mL(-1) gentamicin sulfate inhibited growth of Staphylococcus aureus bacteria. Scanning electron microscopy revealed no platelet aggregation on the surfaces of platelet rich plasma-exposed undoped polyethylene glycol 600 diacrylate microneedles and gentamicin-doped polyethylene glycol 600 diacrylate microneedles. These efforts will enable wider adoption of microneedles for transdermal delivery of pharmacologic agents.