Search

Phenylalanine ammonia-lyase (PAL) has gained attention in recent years for the treatment of phenylketonuria (PKU), a genetic disorder that affects ~1 in 15,000 individuals globally. However, the enzyme is easily degraded by proteases, unstable at room temperature, and is currently administered in PKU patients as daily subcutaneous injections. We report here the stabilization of the PAL from Anabaena variabilis, which is currently used to formulate pegvaliase, through incorporation in a silk fibroin matrix. The combination with silk stabilizes PAL at 37 °C. In addition, in vitro studies showed that inclusion in a silk matrix preserves the biological activity of the enzyme in simulated intestinal fluid, which will enable oral administration of PAL to treat PKU.

The use of saliva as a diagnostic biofluid has been increasing in recent years, thanks to the identification and validation of new biomarkers and improvements in test accuracy, sensitivity, and precision that enable the development of new noninvasive and cost-effective devices. However, the lack of standardized methods for sample collection, treatment, and storage contribute to the overall variability and lack of reproducibility across analytical evaluations. Furthermore, the instability of salivary biomarkers after sample collection hinders their translation into commercially available technologies for noninvasive monitoring of saliva in home settings. The present review aims to highlight the status of research on the challenges of collecting and using diagnostic salivary samples, emphasizing the methodologies used to preserve relevant proteins, hormones, genomic, and transcriptomic biomarkers during sample handling and analysis.

Biomaterial implants for the sustained delivery of therapeutics can be utilized to deliver drugs at near-constant rates over extended time frames to provide an alternative to daily oral medications. The biomaterials used to construct these systems, however, are often not bioresorbable and thus require a secondary surgery for removal from the body, and fabrication of these systems may require the use of harsh chemical solvents. To address these shortcomings, a fabrication process was developed to generate biodegradable drug reservoir systems from regenerated silk fibroin protein solution (23% w/v). The tubular systems, with an inner diameter of 2.0 mm and wall thickness < 250µm, were developed using an all-aqueous solution-gel-solid phase transition curing process. Two different clinically-relevant therapeutics were released at near-constant rates for 30 days (> 100µg/day). The protein secondary structure of the devices consisted of 40% crystalline beta sheet. Mechanically, radial compression (1mm/min) of unloaded systems demonstrated Young’s moduli similar to cancellous (spongy) bone (100 to 250 MPa) and the systems showed good recovery under cyclic compression (to 17.5% strain). The devices could be generated in complex shapes (e.g., hollow cylinders) via an additive molding process, offering the potential for drug delivery but also for broader applications in tissue engineering and diagnostics.

Electrically tunable metadevices can add novel functionalities to electronic and electromagnetic systems such as antennas and cloaking technologies. However, current microwave metadevices are based on materials that require sophisticated and expensive fabrication processes, and are not compatible with large-area and high-throughput deposition techniques on flexible platforms. Here we report reconfigurable microwave resonators that are electrically tuned by organic electrochemical transistors. The devices are fabricated via inkjet printing onto polyimide substrates using commercial metal nanoparticle and conducting polymer inks. By applying electrostatic gating to the polymer—a mixed ion–electron conductor—we show that the amplitude and frequency of different microwave resonant structures, including individual magnetic and electric split-ring resonators as well as a metasurface, can be modulated in the sub-5-GHz range. Electrically tunable metamaterial-inspired devices in the microwave range can be created by using resonators that are integrated with organic electrochemical transistors and are entirely fabricated via inkjet-printed onto polyimide substrates.

Cephalopods camouflage abilities arise from highly specialized chromatic elements in their skin, chromatophores, iridophores, and leucophores, that enable them to display complex and rapidly changing color patterns. Despite the extensive study of these chromatic elements in squid and cuttlefish, full characterization of their individual optical response is still elusive in the Octopus species. We present here detailed multispectral analysis and mapping of the Octopus bimaculoides skin that allows to precisely identify the spatial distribution of the animal’s pigmented and structural elements. The mutual interaction of chromatophores and iridophores is also characterized both in terms of spectral response and spatial localization. The spectral information obtained through this analysis helps to understand the complexity and behavior of these natural tissues while continuing to serve as an inspiration for the fabrication of advanced, chromatically adaptable materials.

Phenylalanine ammonia-lyase (PAL) has gained attention in recent years for the treatment of phenylketonuria (PKU), a genetic disorder that affects ∼1 in 15,000 individuals globally. However, the enzyme is easily degraded by proteases, unstable at room temperature, and is currently administered in PKU patients as daily subcutaneous injections. We report here the stabilization of the PAL from Anabaena variabilis, which is currently used to formulate pegvaliase, through incorporation in a silk fibroin matrix. The combination with silk stabilizes PAL at 37 °C. In addition, in vitro studies showed that inclusion in a silk matrix preserves the biological activity of the enzyme in simulated intestinal fluid, enabling the oral administration of pegvaliase for the treatment of PKU.

Optical devices have been traditionally fabricated using materials whose chemical and physical properties are finely tuned to perform a specific, single, and often static function, whereby devices’ variability is achieved by design changes. Due to the integration of optical systems in multifunctional platforms, there is an increasing need for intrinsic dynamic behavior, such as devices built with materials whose optical response can be programmed to change by leveraging the material’s variability. Here, regenerated silk fibroin is presented as an enabler of devices with active optical response due to the protein’s intrinsic properties. Silk’s abilities to controllably change conformation, reversibly swell and shrink, and degrade in a programmable way affect the form and the response of the optical structure in which it is molded. Representative silk-based devices whose behavior depends on the silk variability are presented and discussed with a particular focus on structures that display reconfigurable, reversibly tunable and physically transient optical responses. Finally, new research directions are envisioned for silk-based optical materials and devices.

Bioinspired actuators with stimuli-responsive and deformable properties are being pursued in fields such as artificial tissues, medical devices and diagnostics, and intelligent biosensors. These applications require that actuator systems have biocompatibility, controlled deformability, biodegradability, mechanical durability, and stable reversibility. Herein, we report a bionic actuator system consisting of stimuli-responsive genetically engineered silk–elastin-like protein (SELP) hydrogels and wood-derived cellulose nanofibers (CNFs), which respond to temperature and ionic strength underwater by ecofriendly methods. Programmed site-selective actuation can be predicted and folded into three-dimensional (3D) origami-like shapes. The reversible deformation performance of the SELP/CNF actuators was quantified, and complex spatial transformations of multilayer actuators were demonstrated, including a biomimetic flower design with selective petal movements. Such actuators consisting entirely of biocompatible and biodegradable materials will offer an option toward constructing stimuli-responsive systems for in vivo biomedicine soft robotics and bionic research.

Natural systems displaying optical properties have for long been an inspiration for new classes of optical constructs. Using the same families of materials employed by Nature in combination with their directed assembly allows access to n-dimensions of control to, ultimately, generate optical systems with multiple coexisting functions. This review provides an overview of lab-made optical systems made of protein and polysaccharide-derived materials found in naturally occurring optical systems. Recent advances in optical biomimicry and bioinspired, polyfunctional optical structures are presented, addressing attributes such as sensing, edible devices, biologically activity, and resorbable optical formats.

Recently, we have reported the preparation of a silk fibroin-supported Palladium catalyst (Pd/SF) and its use in the Suzuki-Miyaura cross-coupling of aryl iodides. Since its synthetic applicability and structural features are still far from being fully explored, a deeper investigation is reported here. Pd/SF is tested as a catalyst for the Suzuki-Miyaura and Ullmann coupling reactions of aryl chlorides, in HO/EtOH solvent mixture under atmospheric conditions. Starting from the analysis of the products of the Pd/SF promoted Ullmann reactions of poly-haloarenes, we can hypothesize the existence of catalytic pockets where monoatomic palladium species can form stable complexes with SF. To shed light on this hypothesis, Pd/SF is characterized by Wide-Angle X-ray Scattering (WAXS) analysis, which supports the supposition of catalytic pockets. Finally, using a computational model developed by Molecular Mechanic Energy Minimization we have estimated the dimension of the catalytic pocket of Pd/SF (about 15 Å), in good agreement with the experimental results.

Implantable electronics hold enormous clinical potential for diagnosis and treatment of neurodegenerative and cardiac diseases and abnormalities. Transient devices are attractive alternatives to conventional silicon electrodes, as they can provide short-term electrical stimulation/recording followed by complete device degradation, mitigating the need for removal surgeries. Packaging transient metals is inherently challenging as they degrade upon contact with aqueous conditions. Development of new transient metal packaging strategies is a critical step toward transient device development. In this fundamental work, a solvent-free compression molding approach to encapsulate magnesium, a resorbable metal, in silk fibroin protein is reported. Silk fibroin was selected because of its processing versatility, desirable mechanical properties, compatibility with biological environments, and controllable degradation behavior in aqueous environments. The silk/magnesium composites were fabricated via compression molding, followed by water annealing to modify the secondary structure of the silk protein matrix to tune physical properties. Transient composite properties as a function of water annealing time are presented, which elucidate synergies between silk physical properties and degradation kinetics of the encapsulated magnesium, information useful in the design of multifunctional, transient metal-based constructs.

Deformable Mirrors (DMs) have wide applications ranging from astronomical imaging to laser communications and vision science. However, they often require bulky multi-channel cables for delivering high power to their drive actuators. A low powered DM which is driven in a contactless fashion could provide a possible alternative to this problem.Here, we present a photo-magnetically actuated deformable mirror (PMADM) concept which is actuated in a contactless fashion by a permanent magnet and low power laser heating source. This paper presents the laboratory demonstration of prototype optical surface quality, magnetic control of focus, and COMSOL simulations of its precise photo-control. The PMADM prototype is made of a magnetic composite (polydimethylsiloxane [PDMS] + ferromagnetic $\text{CrO}_\text{2}$) and an optical-quality substrate layer and is 30.48 mm $\times$ 30.48 mm $\times$ 175 $\mu$ m in dimension with an optical pupil diameter of 8 mm. It deforms to 5.76 $\mu$ m when subjected to a 0.12 T magnetic flux density and relaxes to 3.76 $\mu$ m when illuminated by a 50 mW laser. A maximum stroke of 8.78 $\mu$ m before failure is also estimated considering a 3x safety factor. This works also includes simulation of astigmatism generation with the PMADM, a first step in demonstrating control of higher order modes. A fully developed PMADM can have potential application for wavefront corrections in vacuum and space environments., Comment: 19 pages, 18 figures

Embolization is a catheter-based minimally invasive procedure that deliberately occludes diseased blood vessels for treatment purposes. We report a novel silk based embolic material (SEM) that was developed and optimized to provide tandem integration of both embolization and the delivery of therapeutics. Natural silk was processed into fibroin proteins of varying lengths and combined with charged nanoclay particles to allow visibility and injectability using clinical catheters as small as 600 microns in diameter at lengths >100 cm. SEMs loaded with fluorochrome labeled bovine albumin and Nivolumab, which is among the most used immunotherapy drugs world-wide, demonstrated a sustained release profile in vitro over 28 days. In a porcine renal survival model, SEMs with labeled albumin and Nivolumab successfully embolized porcine arteries without recanalization and led to the delivery of both albumin and Nivolumab into the interstitial space of the renal cortex. Mechanistically, we show that tissue delivery is most optimal when the internal elastic membrane of the embolized artery is disrupted. SEM is a potential next-generation multifunctional embolic agent that can achieve embolization and deliver a wide range of therapeutics to treat vascular diseases including tumors. This article is protected by copyright. All rights reserved.

Bioinspired Biomaterials A silk cocoon is nestled within a mussel shell. Taking inspiration from the adhesive property of mussels and the assembly properties of silk materials new, water‐based, eco‐friendly glues with exceptional underwater adhesion performance can be formulated. More details can be found in article number 2004786 by Gianluca M. Farinola, Fiorenzo G. Omenetto, and co‐workers. [Image: see text]

In recent decades, increasing research interest has shifted from traditional rigid skeleton robotics to flexible, shape-programmable, environmentally adaptive and stimuli-responsive “soft robotics”. Within this discipline, soft-robots capable of untethered and/or remote-controlled operation are of particular interest given their utility for actuation in complex situations with larger range of mobility and higher degrees of freedom. The use of new materials and the development of advanced fabrication techniques enable better performance and expand the utility of such soft actuators, moving them towards real-world applications. This review outlines some recent advances in untethered soft robotics and actuators to illustrate the promise of these applications at the interface of material science and device engineering.

Nanoscale field-effect transistors (FETs) represent a unique platform for real time, label-free transduction of biochemical signals with unprecedented sensitivity and spatiotemporal resolution, yet their translation toward practical biomedical applications remains challenging. Herein, we demonstrate the potential to overcome several key limitations of traditional FET sensors by exploiting bioactive hydrogels as the gate material. Spatially defined photopolymerization is utilized to achieve selective patterning of polyethylene glycol on top of individual graphene FET devices, through which multiple biospecific receptors can be independently encapsulated into the hydrogel gate. The hydrogel-mediated integration of penicillinase was demonstrated to effectively catalyze enzymatic reaction in the confined microenvironment, enabling real time, label-free detection of penicillin down to 0.2 mM. Multiplexed functionalization with penicillinase and acetylcholinesterase has been demonstrated to achieve highly specific sensing. In addition, the microenvironment created by the hydrogel gate has been shown to significantly reduce the nonspecific binding of nontarget molecules to graphene channels as well as preserve the encapsulated enzyme activity for at least one week, in comparison to free enzymes showing significant signal loss within one day. This general approach presents a new biointegration strategy and facilitates multiplex detection of bioanalytes on the same platform, which could underwrite new advances in healthcare research.

Oral health monitoring is highly desired, especially for in home use, however, current methods are not sensitive enough and technically convoluted for this purpose. This paper presents incorporation of bioactive materials and colorimetric chemical sensors into routinely used oral appliances transforming them into bioresponsive, conformable interfaces. Specifically, endodontic paper points and dental floss can be functionalized to locally sense and monitor pH variations within the oral cavity via color changes. Moreover, edible colorimetric indicators are developed and used to make sensing, edible devices in the form factor of candies that can dynamically and visually respond to acidity changes in saliva. These interfaces would enable early detection of caries (e.g., using dental floss and paper points) providing low‐cost point of care devices that respond in real‐time by detecting pH variations in biological fluids thus bringing monitoring to home settings ., pH‐responsive biomaterial‐based formulations based on fruit can be tuned to convert inert interfaces such as dental floss and highly absorbent paper points into devices for real‐time localized chemical mapping of the oral cavity. These can be extended to mouth‐conformable interfaces to acquire information on the health status of the user and for the design of point of care diagnostic devices.

Microneedles represent an exciting departure from the existing parenteral injection paradigm for drug delivery, particularly for the administration of vaccines. While the benefit of delivering vaccine antigens to immunocompetent tissue in the skin has been established, there have been varying degrees of success using microneedles to do so. Here, we investigate the use of silk fibroin protein to produce microneedles and evaluate their ability to deliver vaccines against influenza, Clostridium difficile, and Shigella. Fibroin protein from the silkworm Bombyx mori possesses suitable properties for use in a microneedle system, including all-aqueous processing, mechanical strength in dried formats, biocompatibility, and the ability to temperature stabilize biomacromolecules. As such, this biomaterial combines the processing and biocompatibility advantages of a dissolving microneedle system with the product stability and mechanical strength of coated insoluble microneedles. Through successful vaccination of mic...

The development of functional biomaterials for tissue engineering and medical applications has received increasing attention. While it has been known for decades that dityrosine bonds are a key component to many biopolymer materials in native tissues, only recently have these motifs been exploited in the development of new biomaterials. Here, we first review the importance of tyrosine–tyrosine chemical bonds in the assembly and mechanical properties of natural materials. Next, we discuss the chemistries available for cross-linking via tyrosine bonds and how these interactions have been applied to biomaterials. The goal of this Review is to highlight dityrosine bonding in biomaterial development, the reactions used to form them, and their utility in cross-linking native and chemically substituted phenolic side chains, as an underutilized tool in the de novo development of biomaterials.

Silk protein-based hydrogel materials suitable for hosting living microalgae due to the biocompatibility and ambient conditions gelation were developed. The silk was selected due to its robust mechanical properties, safe and compatible utility, green sourcing, and versatile materials formation. Through a series of assessments the mechanics and gelation kinetics of the hydrogel materials were optimized for three-dimensional (3D) printing. Silk hydrogel structures containing a marine microalgal strain, Platymonas sp. were printed and these structures supported cell proliferation for at least 4 weeks and consistent photosynthetic activity for more than 90 days, the limits of the study time frame. This long-term cell viability and function suggest that these systems may be suitable for a broad range of applications, such as oxygen replenishment and carbon dioxide reduction toward a green, healthier indoor environment.

Regenerated silk fibroin, a biopolymer derived from silkworm cocoons, is a versatile material that has been widely explored for a number of applications (e.g., drug delivery, tissue repair, biocompatible electronics substrates, and optics) due to its attractive biochemical properties and processability. Here, we report on the free-form printing of silk-based, 3D microstructures through multiphoton lithography. Utilizing multiphoton lithography in conjunction with specific photoinitiator chemistry and postprint cross-linking, a number of microarchitectures were achieved including self-supporting fibroin arches. Further, the straightforward production of high fidelity and biofunctional protein architectures was enabled through the printing of aqueous fibroin/immunoglobulin solutions.

3D printing is an additive manufacturing (AM) technique that has quickly disrupted traditional design and manufacturing strategies. New structures can be manufactured that could not be fabricated using other methods. These new capabilities are considered by many to hallmark a historic shift representative of a new industrial revolution. Exciting utilities of this evolving technology are the fields of biomedical engineering and translational medicine, particularly in applying three-dimensional (3D) printing toward enabling on-demand fabrication of customized tissue scaffolds and medical device geometries. AM techniques are promising a future where on-demand production of patient-specific living tissues is a reality. In this review, we cover the rapid evolution and widespread concepts of a bio-"ink" and bioprinted devices and tissues from the past two decades as well as review the various additive manufacturing methods that have been used toward 3D bioprinting of cells and scaffolds with a special look at the benefits and practical considerations for each method. Despite being a young technology, the evolution and impact of AM in the fields of tissue engineering and regenerative medicine has progressed rapidly. We finish the review by looking toward the future of bioprinting and identify some of the current bottlenecks facing the blossoming industry.

Silk fibroin from the Bombyx mori caterpillar has been processed into many material forms, with potential applications in areas ranging from optoelectronics to tissue engineering. As a hydrogel, silk fibroin has been engineered as a substrate for the regeneration of soft tissues where hydration and mechanical compatibility are necessary. Current fabrication of silk fibroin hydrogels produces microstructured materials that lack transparency and limits the ability to fully exploit the hydrogel form. Transparency is the main characteristic of some human tissues (e.g., cornea) where silk fibroin in the film format has shown potential as scaffolding material, however, lacking the necessary hydration and successful attachment of cells without biochemical functionalization. Additionally, detection using light is an important method to translate information for instruction, sensing, and visualization of biological entities and light sensitive molecules. Here, we introduce a method for the fabrication of transpare...

High resolution bioimaging is not only critical to the study of cellular structures and processes but it also has important applications in drug delivery and therapeutics. Fluorescent nanodiamonds (NDs) are excellent candidates for long-term bioimaging and tracking of biological structures at the nanoscale. Encapsulating NDs in natural biopolymers like silk fibroin (SF) widens their biomedical applications. Here we report the synthesis, structural and optical characterization of ND incorporated SF nanospheres. The photoluminescence from optical defects within the NDs is found to increase when encapsulated in the SF spheres. The encapsulated NDs are applied in vitro to investigate the intracellular mobility compared to bare NDs. The diffusion rate of encapsulated NDs is shown to improve due to SF coating. These ND-SF spheres are envisioned as highly suitable candidates for bioinjectable imaging and drug release carriers for targeted drug delivery applications.

Made available in DSpace on 2021-06-25T10:22:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-02-07 In optical biosensing, silk fibroin (SF) appears as a promising alternative where other materials, such as paper, find limitations. Besides its excellent optical properties and unmet capacity to stabilize biomacromolecules, SF in test strips exhibits additional functions,i.e.capillary pumping activity of 1.5 mm s−1, capacity to filter blood cells thanks to its small, but tuneable, porosity and enhanced biosensing sensitivity. The bulk functionalization of SF with the enzymes glucose oxidase and peroxidase and the mediator ABTS produces colourless and transparent SF films that respond to blood glucose increasing 2.5 times the sensitivity of conventional ABTS-based assays. This enhanced sensitivity results from the formation of SF-ABTS complexes, where SF becomes part of the bioassay. Additionally, SF films triple the durability of most stable cellulose-based sensors. Although demonstrated for glucose, SF microfluidic test strips may incorporate other optical bioassays,e.g.immunoassays, with the aim of transferring them from central laboratories to the place of patient's care. Instituto de Microelectrónica de Barcelona (IMB-CNM CSIC) São Carlos Institute of Physics University of São Paulo Departament de Química Universitat Autònoma de Barcelona Bellaterra (Barcelona) Instituto Murciano de Investigación y Desarrollo Agrario y Alimentario (IMIDA) Institute of Chemistry São Paulo State University (UNESP) Silklab Department of Biomedical Engineering Tufts University Department of Electrical and Computer Engineering Tufts University Department of Physics Tufts University Laboratory for Living Devices Tufts University Institute of Chemistry São Paulo State University (UNESP)

Structurally colored materials, which rely on the interaction between visible light and nanostructures, produce brilliant color displays through fine control of light interference, diffraction, scattering, or absorption. Rationally combining different color-selective functions into a single form offers a powerful strategy to create programmable optical functions which are otherwise difficult, if not impossible to obtain. By leveraging structural protein templates, specifically silk fibroin, nanostructured materials that combine plasmonic and photonic crystal paradigms are shown here. This confluence of function enables directional, tunable, and multiple co-located optical responses derived from the interplay between surface plasmon resonance and photonic bandgap effects. Several demonstrations are shown with programmable coloration at varying viewing sides, angle, and by solvent infiltration, opening avenues for smart displays and multi-mode information encoding applications.

Artificial microcilia structures have shown potential to incorporate actuators in various applications such as microfluidic devices and biomimetic microrobots. Among the multiple possibilities to achieve cilia actuation, magnetic fields present an opportunity given their quick response and wireless operation, despite the difficulty in achieving localized actuation because of their continuous distribution. In this work, a high-aspect-ratio (>8), elastomeric, magnetically responsive microcilia array is presented that allows for wireless, localized actuation through the combined use of light and magnetic fields. The microcilia array can move in response to an external magnetic field and can be locally actuated by targeted illumination of specific areas. The periodic pattern of the microcilia also diffracts light with varying diffraction efficiency as a function of the applied magnetic field, showing potential for wirelessly controlled adaptive optical elements.

Current methods to produce silk films include casting and spin coating. Here we introduce a new method for the fabrication of silk films: electrogelation. Through use of a closed-loop anode, films with high surface smoothness and optical transparency are produced. Bending the electrode loop allows films with three-dimensional topologies to be formed, possessing thicknesses capable of descending into the submicron thin film regime.

Wearable interfaces are central to multiple healthcare and wellness strategies encompassing diet and nutrition, personalized health monitoring, and performance optimization. Specifically, the advent of flexible electronic formats coupled with microfluidic interfaces has resulted in sophisticated conformal devices for biofluid sampling and quantification. Here, a complementary approach is presented to wearable sensing by using a large-scale, conformal, distributed format that relies on the use of biomaterial-based inks to print and stabilize deterministic patterns of biochemical reporters with high resolution. Colorimetric devices can vary in size and a sensing T-shirt based on a colorimetric pattern is developed to illustrate the utility that such formats can add to the wearable interface space. Image analysis allows parameter variation to be tracked in real-time, yielding a map-like format of distributed biophysical response.

Photoactive materials hold great promise for a variety of applications. We present a finite element model of light-controlled flexible magnetic composite structure composed of 33.3% Chromium dioxide (CrO2) and 66.7% Polydimethylsiloxane (PDMS) by weight. The structure has a dimension of 8 mm x 2 mm x 100 um and has been previously experimentally studied. Due to the low Curie temperature, the structure acts as an actuator, shows significant deflection under the external magnetic field and relaxation due to laser heating. Thermal and magnetic deflection analysis has been performed using the FEM model. The simulation results show a maximum structural deflection of 6.08 mm (76% of the length of the structure) when subjected to 30 mT magnetic flux density and 160 mW laser power at 303 K (room temperature). We will present the results of the simulation model and comparison to experimental data reproducing the previously observed motion of the (CrO2+PDMS). This model will enable future fracture and fatigue analysis as well as extension to new photoactive geometries., Comment: 12 pages, 10 figures, published in Proceedings Volume 11477, Molecular and Nano Machines III; 1147704 (2020), Event: SPIE Organic Photonics + Electronics, 2020, Online Only