Stretchable and Heat‐Resistant Protein‐Based Electronic Skin for Human Thermoregulation

Silk protein is one of the a promising materials for on‐skin and implantable electronic devices due to its biodegradability and biocompatibility. However, its intrinsic brittleness as well as poor thermal stability limits its applications. In this work, robust and heat‐resistant silk fibroin composite membranes (SFCMs) are synthesized by mesoscopic doping of regenerated silk fibroin (SF) via the strong interactions between SF and polyurethane. Surprisingly, the obtained SFCMs can endure the tensile test (>200%) and thermal treatment (up to 160 °C). Attributed to these advantages, traditional micromachining techniques, such as inkjet printing, can be carried out to print flexible circuits on such protein substrate. Based on this, Ag nanofibers (NFs) and Pt NFs networks are successfully constructed on both sides of the SFCMs to function as heaters and temperature sensors, respectively. Furthermore, the integrated protein‐based electronic skin (PBES) exhibits high thermal stability and temperature sensitivity (0.205% °C^?1). Heating and temperature distribution detection are realized by array‐type PBES, contributing to potential applications in dredging of the blood vessel for alleviating arthritis. This PBES is also inflammation‐free and air‐permeable so that it can directly be laminated onto human skin for long‐term thermal management.     

A Natural Silk Fibroin Protein‐Based Transparent Bio‐Memristor

The recent discovery of nanoelectronics memristor devices has opened up a new wave of enthusiasm and optimism in revolutionizing electronic circuit design, marking the beginning of new era for the advancement of neuromorphic, high‐density logic and memory applications. Here a highly non‐linear dynamic response of a bio‐memristor is demonstrated using natural silk cocoon fibroin protein of silkworm, Bombyx mori. A film that is transparent across most of the visible spectrum is obtained with the electronic‐grade silk fibroin aqueous solution of ca. 2% (wt/v). Bipolar memristive switching is demonstrated; the switching mechanism is confirmed to be the filamentary switching as observed by probing local conduction behavior at nanoscale using scanning tunneling microscopy. The memristive transition is elucidated by a physical model based on the carrier trapping or detrapping in silk fibroin films and this appears to be due to oxidation and reduction procedures, as evidenced from cyclic voltammetry measurements. Hence, silk fibroin protein could be used as a biomaterial for bio‐memristor devices for applications in advanced bio‐inspired very large scale integration circuit design as well as in biologically inspired synapse links for energy‐efficient neuromorphic computing.     

A Room‐Temperature High‐Conductivity Metal Printing Paradigm with Visible‐Light Projection Lithography

Fabricating electronic devices require integrating metallic conductors and polymeric insulators in complex structures. Current metal‐patterning methods such as evaporation and laser sintering require vacuum, multistep processes, and high temperature during sintering or postannealing to achieve desirable electrical conductivity, which damages low‐temperature polymer substrates. Here reports a facile ecofriendly room‐temperature metal printing paradigm using visible‐light projection lithography. With a particle‐free reactive silver ink, photoinduced redox reaction occurs to form metallic silver within designed illuminated regions through a digital mask on substrate with insignificant temperature change (<4 °C). The patterns exhibit remarkably high conductivity achievable at room temperature (2.4 × 10⁷ S m^?1, ≈40% of bulk silver conductivity) after simple room‐temperature chemical annealing for 1–2 s. The finest silver trace produced reaches 15 µm. Neither extra thermal energy input nor physical mask is required for the entire fabrication process. Metal patterns were printed on various substrates, including polyethylene terephthalate, polydimethylsiloxane, polyimide, Scotch tape, print paper, Si wafer, glass coverslip, and polystyrene. By changing inks, this paradigm can be extended to print various metals and metal–polymer hybrid structures. This method greatly simplifies the metal‐patterning process and expands printability and substrate materials, showing huge potential in fabricating microelectronics with one system.     

Control of the Electronic Properties of Thermosensitive Poly(N‐isopropylacrylamide) and Au‐Nano‐particle/Poly(N‐isopropylacrylamide) Composite Hydrogels upon Phase Transition

The electrical resistances of poly(N‐isopropylacrylamide), poly‐(NIPA), upon thermal phase transition between the swollen hydrogel (20 °C) and solid (40 °C) states are analyzed by Faradaic impedance spectroscopy, chronopotentiometry, and cyclic voltammetry. The incorporation of Au‐nanoparticles into the poly‐(NIPA) by a thermal “breathing‐in” process, reduces the electron transfer resistance in the solid composite material.     

Direct‐Write Assembly of Microperiodic Silk Fibroin Scaffolds for Tissue Engineering Applications

Three–dimensional, microperiodic scaffolds of regenerated silk fibroin have been fabricated for tissue engineering by direct ink writing. The ink, which consisted of silk fibroin solution from the Bombyx mori silkworm, was deposited in a layer‐by‐layer fashion through a fine nozzle to produce a 3D array of silk fibers of diameter 5 µm. The extruded fibers crystallized when deposited into a methanol‐rich reservoir, retaining a pore structure necessary for media transport. The rheological properties of the silk fibroin solutions were investigated and the crystallized silk fibers were characterized for structure and mechanical properties by infrared spectroscopy and nanoindentation, respectively. The scaffolds supported human bone marrow‐derived mesenchymal stem cell (hMSC) adhesion, and growth. Cells cultured under chondrogenic conditions on these scaffolds supported enhanced chondrogenic differentiation based on increased glucosaminoglycan production compared to standard pellet culture. Our results suggest that 3D silk fibroin scaffolds may find potential application as tissue engineering constructs due to the precise control of their scaffold architecture and their biocompatibility.     

Fabrication of Silk Microneedles for Controlled‐Release Drug Delivery

Microneedles are emerging as a minimally invasive drug delivery alternative to hypodermic needles. Current material systems utilized in microneedles impose constraints hindering the further development of this technology. In particular, it is difficult to preserve sensitive biochemical compounds (such as pharmaceuticals) during processing in a single microneedle system and subsequently achieve their controlled release. A possible solution involves fabricating microneedles systems from the biomaterial silk fibroin. Silk fibroin combines excellent mechanical properties, biocompatibility, biodegradability, benign processing conditions, and the ability to preserve and maintain the activity of biological compounds entrained in its material matrix. The degradation rate of silk fibroin and the diffusion rate of the entrained molecules can be controlled simply by adjusting post‐processing conditions. This combination of properties makes silk an ideal choice to improve on existing issues associated with other microneedle‐based drug delivery system. In this study, a fabrication method to produce silk biopolymer microstructures with the high aspect ratios and mechanical properties required to manufacture microneedle systems is reported. Room temperature and aqueous‐based micromolding allows for the bulk loading of these microneedles with labile drugs. The drug release rate is decreased 5.6‐fold by adjusting the post‐processing conditions of the microneedles, mainly by controlling the silk protein secondary structure. The release kinetics are quantified in an in vitro collagen hydrogel model, which allows tracking of the model drug. Antibiotic loaded silk microneedles are manufactured and used to demonstrate a 10‐fold reduction of bacterial density after their application. The processing strategies developed in this study can be expanded to other silk‐based structural formats for drug delivery and biologicals storage applications.     

Biocompatible Electromechanical Actuators Composed of Silk‐Conducting Polymer Composites

Single‐component, metal‐free, biocompatible, electromechanical actuator devices are fabricated using a composite material composed of silk fibroin and poly(pyrrole) (PPy). Chemical modification techniques are developed to produce free‐standing films with a bilayer‐type structure, with unmodified silk on one side and an interpenetrating network (IPN) of silk and PPy on the other. The IPN formed between the silk and PPy prohibits delamination, resulting in a durable and fully biocompatible device. The electrochemical stability of these materials is investigated through cyclic voltammetry, and redox sensitivity to the presence of different anions is noted. Free‐end bending actuation performance and force generation within silk‐PPy composite films during oxidation and reduction in a biologically relevant environment are investigated in detail. These silk–PPy composites are stable to repeated actuation, and are able to generate forces comparable with natural muscle (>0.1 MPa), making them ideal candidates for interfacing with biological tissues.     

Programmable Arrays of “Micro‐Bubble” Constructs via Self‐Encapsulation

The fabrication of ordered arrays of self‐encapsulated “micro‐bubble” material constructs based on the capillary‐driven collapse of flexible silk fibroin sheets during propagation of the diffusion front of the encapsulated material is demonstrated. The individual micro‐bubbles of different shapes are composed of a sacrificial material encapsulated within the ultrathin silk coating, which covers and seals the inner material during dissolution of supporting layer. The array of microscopic rectangular multi‐layer silk sheets on supporting polymer layers can be selectively dissolved along the edges to initiate their self‐encapsulation. The resulting micro‐bubble morphology, shape, and arrangements can be readily pre‐programmed by controlling the geometry of the silk sheets, such as thickness, dimension, and aspect ratio. These micro‐bubble constructs can be utilized for encapsulation of various materials as well as nanoparticles in a single or multi compartmental manner. These biocompatible and biodegradable micro‐bubble constructs present a promising platform for one‐shot spatial and controllable loading and locking material arrays with addressable abilities.     

Silk as a Multifunctional Biomaterial Substrate for Reduced Glial Scarring around Brain‐Penetrating Electrodes

The reliability of chronic, brain‐penetrating electrodes must be improved for these ‐neural recording technologies to be viable in widespread clinical applications. One approach to improving electrode reliability is to reduce the foreign body response at the probe‐tissue interface. In this work, silk fibroin is investigated as a candidate material for fabricating mechanically dynamic neural probes with enhanced biocompatibility compared to traditional electrode materials. Silk coatings are applied to flexible cortical electrodes to produce devices that transition from stiff to flexible upon hydration. Theoretical modeling and in vitro testing show that the silk coatings impart mechanical properties sufficient for the electrodes to penetrate brain tissue. Further, it is demonstrated that silk coatings may reduce some markers of gliosis in an in vitro model and that silk can encapsulate and release the gliosis‐modifying enzyme chondroitinase ABC. This work establishes a basis for future in vivo studies of silk‐based brain‐penetrating electrodes, as well as the use of silk materials for other applications in the central nervous system where gliosis must be controlled.     

Multiple Structural Coloring of Silk‐Fibroin Photonic Crystals and Humidity‐Responsive Color Sensing

In the biological world, numerous creatures such as butterflies, insects, and birds have exploited photonic structures to produce bicolor reflections with important biofunctions in addition to unique brilliant structural coloration. Although the mimicking of bistructural color reflection is possible, the fabrication involves a process of combined layer deposition techniques, which is complicated and less flexible. Here, a bistructural color mimicking, based on silk fibroin, is reported using a simple and inexpensive self‐assembly method. Silk‐fibroin inverse opals with different spectral positions of bistructural color reflection (i.e., ultraviolet and visible peaks, ultraviolet and near infrared peaks, and visible and near infrared peaks) are obtained by simply controlling their lattice constants. Furthermore, the inline and continuous tuning of the peak positions of bistructural color reflection can be achieved by the humidity‐induced cyclic contraction of silk fibroin. The potential applications of silk‐fibroin photonic structures in eco‐dying and multifunctional silk fabrics are also demonstrated.     

Silk Fibroin‐Regulated Crystallization of Calcium Carbonate

Mollusk shell is one of the best studied of all calcium carbonate biominerals. Its silk‐like binder‐matrix protein plays a pivotal role during the formation of aragonite crystals in the nacre sheets. Here, we provide novel experimental insights into the interaction of mineral and protein compounds using a model system of reconstituted Bombyx mori silk fibroin solutions serving as templates for the crystallization of calcium carbonate (CaCO₃). We observed that the inherent (self‐assembling) aggregation process of silk fibroin molecules affected both the morphology and crystallographic polymorph of CaCO₃ aggregates. This combination fostered the growth of a novel, rice‐grain‐shaped protein/mineral hybrid with a hollow structure with an aragonite polymorph formed after ripening. Our observations suggest new hypotheses about the role of silk‐like protein in the natural biomineralization process, but it may also serve to shed light on the formation process of those ‘ersatz’ hybrids regulated by artificially selected structural proteins.     

A Facile Sol–Gel Strategy for the Synthesis of Rod‐Shaped Nanocrystalline High‐Surface‐Area Lanthanum Phosphate Powders and Nanocoatings

Synthesis of rod‐shaped nanocrystalline lanthanum phosphate with an average length of 40 nm even after calcination at 400 °C has been realized through a room‐temperature aqueous sol–gel process. The sol is characterized by particle‐size, zeta‐potential, and viscosity measurements. Gelation of the sol is induced by ammonia. The lanthanum phosphate phase‐formation process is followed by thermal, Fourier‐transform IR, and X‐ray diffraction analysis. Transmission electron microscopy shows that the sol and gel particles have a rod‐shaped morphology and comparable particle sizes. Using the Scherrer equation a crystallite size of 11 nm is obtained for the gel powder calcined at 400 °C and Brunauer–Emmett–Teller (BET) nitrogen‐adsorption analysis showed a high specific surface area of 100 m² g^–1. Ammonia temperature‐programmed desorption measurements show that the density of Lewis acid sites is four times higher than ever reported in the case of lanthanum phosphates. The catalytic activity of the above sample is demonstrated by using it as a Lewis‐acid catalyst in an acetal‐formation reaction with a very good yield of 85 %. The sol is used to develop nanocoatings on a glass surface and the morphology of the coatings is investigated using atomic force microscopy and scanning electron microscopy. The microstructure of the coating confirmed the rod‐shaped nature of the sol particles. The coating was uniform with a thickness of about 55 nm.     

High‐Strength,Durable All‐Silk Fibroin Hydrogels with Versatile Processability toward Multifunctional Applications

Hydrogels are the focus of extensive research due to their potential use in fields including biomedical, pharmaceutical, biosensors, and cosmetics. However, the general weak mechanical properties of hydrogels limit their utility. Here, pristine silk fibroin (SF) hydrogels with excellent mechanical properties are generated via a binary‐solvent‐induced conformation transition (BSICT) strategy. In this method, the conformational transition of SF is regulated by moderate binary solvent diffusion and SF/solvent interactions. β‐sheet formation serves as the physical crosslinks that connect disparate protein chains to form continuous 3D hydrogel networks, avoiding complex chemical and/or physical treatments. The Young's modulus of these new BSICT–SF hydrogels can reach up to 6.5 ± 0.2 MPa, tens to hundreds of times higher than that of conventional hydrogels (0.01–0.1 MPa). These new materials fill the “empty soft materials' space” in the elastic modulus/strain Ashby plot. More remarkably, the BSICT–SF hydrogels can be processed into different constructions through different polymer and/or metal‐based processing techniques, such as molding, laser cutting, and machining. Thus, these new hydrogel systems exhibit potential utility in many biomedical and engineering fields.     

Construction of White‐Light‐Emitting Silk Protein Hybrid Films by Molecular Recognized Assembly among Hierarchical Structures

The fabrication of bio‐hybrid functional films is demonstrated by applying a materials assembly technique. Based on the hierarchical structures of silk fibroin materials, functional molecular/materials, i.e., quantum dots (QDs), can be fixed to amino acid groups in silk fibroin films. It follows that white‐light‐emitting QD silk hybrid films are obtained by hydrogen bond molecular recognition to the –COO^– groups functionalized to blue luminescent ZnSe (5.2 nm) and yellow luminescent CdTe (4.1 nm) QDs in a molar ratio of 30:1 of ZnSe to CdTe QDs. Simultaneously, a systematic blue shift in the emission peak is observed from the QD solution to QDs silk fibroin films. The significant blue shift hints the appearance of the strong interaction between QDs and silk fibroins, which causes strong white‐light‐emitting uniform silk films. The molecular recognized interactions are confirmed by high resolution transmission electron microscopy, field scanning electron microscope, and attenuated total internal reflectance Fourier transform infrared spectroscopy. The QD silk films show unique advantages, including simple preparation, tunable white‐light emission, easy manipulation, and low fabrication costs, which make it a promising candidate for multicomponent optodevices.     

Ambipolar Conductive 2,7‐Carbazole Derivatives for Electroluminescent Devices

A series of 2,7‐disubstituted carbazole (2,7‐carb) derivatives incorporating arylamines at the 2 and 7 positions are synthesized via palladium‐catalyzed C–N or C–C bond formation. These compounds possess glass transition temperatures ranging from 87 to 217 °C and exhibit good thermal stabilities, with thermal decomposition temperatures ranging from 388 to 480 °C. They are fluorescent and emit in the purple‐blue to orange region. Two types of organic light emitting diodes (OLEDs) were constructed from these compounds: (I) indium tin oxide (ITO)/2,7‐carb (40 nm)/1,3,5‐tris(N‐phenylbenzimidazol‐2‐yl)benzene (TPBI, 40 nm)/Mg:Ag; and (II) ITO/2,7‐carb (40 nm)/tris(8‐hydroxyquinoline) aluminum (Alq₃, 40 nm)/Mg:Ag. In type I devices, the 2,7‐disubstituted carbazoles function as both hole‐transporting and emitting material. In type II devices, light is emitted from either the 2,7‐disubstituted carbazole layer or Alq₃. The devices appear to have a better performance compared to devices fabricated with their 3,6‐disubstituted carbazole congeners. Some of the new compounds exhibit ambipolar conductive behavior, with hole and electron mobilities up to 10^–4 cm² V^–1 s^–1.     

Polyarylene Networks via Bergman Cyclopolymerization of Bis‐ortho‐diynyl Arenes

Bis‐ortho‐diynylarene (BODA) monomers, prepared from common bisphenols in three high yielding steps, undergo free‐radical‐mediated thermal polymerization via an initial Bergman cyclo‐rearrangement. Polymerization is carried out at 210 °C in solution or neat with large pre‐vitrification melt windows (4–5 h) to form branched oligomers containing reactive pendant and terminal aryldiynes. Melt‐ and solution‐processable oligomers with weight‐average molecular weight M_w = 3000–24 000 g mol^–1 can be coated as a thin film or molded using soft lithography techniques. Subsequent curing to 450 °C affords network polymers with no detectable glass transition temperatures below 400 °C and thermal stability ranging from 0.5–1.5 % h^–1 isothermal weight loss measured at 450 °C under nitrogen. Heating to 900–1000 °C gives semiconductive glassy carbon in high yield. BODA monomer synthesis, network characterization and kinetics, processability, thin‐film photoluminescence, and thermal properties are described.     

Silk Fibroin–Substrate Interactions at Heterogeneous Nanocomposite Interfaces

Silk fibroin adsorption at the heterogeneous hydrophobic–hydrophilic surface of graphene oxide (GO) with different degrees of oxidation is addressed experimentally and theoretically. Samples are prepared using various spin‐assisted deposition conditions relevant to assembly of laminated nanocomposites from graphene‐based components, and compared with silicon dioxide (SiO₂) as a benchmark substrate. Secondary structure of silk backbones changes as a function of silk fibroin concentration, substrate chemical composition, and deposition dynamics are assessed and compared with molecular dynamic simulations. It is observed that protofibrils form at low concentrations while variance in the deposition speed has little effect on silk secondary structure and morphology. However, balance of nonbonded interactions between electrostatic and van der Waals contributions can lead to silk secondary structure retention on the GO surface. Molecular dynamics simulations of silk fibroin at different surfaces show that strong van der Waals interactions play a pivotal role in losing and disrupting secondary structure on graphene and SiO₂ surfaces. Fine tuning silk fibroin structure on heterogeneous graphene‐based surfaces paves the way toward development of biomolecular reinforcement for biopolymer–graphene laminated nanocomposites.     

Microneedle‐Array Patch Fabricated with Enzyme‐Free Polymeric Components Capable of On‐Demand Insulin Delivery

Achieving persistent glycemic control in a painless and convenient way is the ultimate goal of diabetes management. Herein, an “enzyme‐free” polymeric microneedle (MN)‐array patch composed of a boronate‐containing hydrogel semi‐interpenetrated by biocompatible silk fibroin is developed. Consistent with the previous reports, the presence of the boronate‐hydrogel allows for glucose‐responsive diffusion‐control of insulin, while the crystalline fibroin component serves as a matrix‐stiffener to validate skin penetration. Remarkably, this “enzyme‐free” smart artificial on‐skin pancreas prototype remains stable for at least 2 months in an aqueous environment. Furthermore, it establishes sustained as well as acute glucose‐responsive insulin delivery, and is to the authors' knowledge, the first successful material design addressing such two technical challenges at once on an MN format. This long‐acting, on‐demand insulin delivery technology may offer a candidate for a next‐generation diabetes therapy that is remarkably stable, safe, economically efficient, and capable of providing both acute‐ and continuous glycemic control in a manner minimally dependent on patient compliance.     

Water‐Stable Silk Films with Reduced β‐Sheet Content

Silk fibers have outstanding mechanical properties. These fibers are insoluble in organic solvents and water, are biocompatible, and exhibit slow biodegradation in vitro and in vivo due to the hydrophobic nature of the protein and the presence of a high content of β‐sheet structure. Regenerated silk fibroin can be processed into a variety of materials normally stabilized by the induction of β‐sheet formation through the use of solvents or by physical stretching. To extend the biomaterial utility of silk proteins, options to form water‐stable silk‐based materials with reduced β‐sheet formation would be desirable. To address this need for more rapidly degradable silk biomaterials, we report the preparation of water‐stable films from regenerated silk fibroin solutions, with reduced β‐sheet content. The keys to this process are the preparation of concentrated (8 % by weight) aqueous solutions of fibroin and a subsequent water‐based annealing procedure. These new materials degrade more rapidly due to the reduced β‐sheet content, as determined in vitro via enzymatic hydrolysis, yet support human adult stem‐cell expansion in vitro in a similar or improved fashion to the crystallized proteins in film form. These new silk‐based materials extend the range of biomaterial properties that can be generated from this unique family of proteins.     

Charge‐Tunable Autoclaved Silk‐Tropoelastin Protein Alloys That Control Neuron Cell Responses

Tunable protein composites are important for constructing extracellular matrix mimics of human nerve tissues with control of charge, structural, and mechanical properties. Molecular interaction mechanisms between silk fibroin protein and recombinant human tropoelastin, based on charge, are utilized to generate a new group of multifunctional protein alloys with different net charges. These new biomaterials are then utilized as a biomaterial platform to control neuron cell response. With a +38 net charge in water, tropoelastin molecules provide extraordinary elasticity and selective interactions with cell surface integrins. In contrast, negatively charged silk fibroin protein (net charge ?36) provides remarkable toughness and stiffness with morphologic stability in material formats via autoclaving‐induced beta‐sheet crystal physical crosslinks. The combination of these properties in alloy format extends the versatility of both structural proteins, providing a new biocompatible, biodegradable, and charge‐tunable biomaterial platform for neural repair. The data point to these protein alloys as an alternative to commonly used charged synthetic polymers, particularly with regard to the versatility of material formats (e.g., gels, sponges, films, fibers). The results also provide a practical example of physically designed protein materials with control of net charge to direct biological outcomes, in this case for neuronal tissue engineering.