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A variety of artificial silk spinning approaches are attempted to mimic the natural spinning process found in silkworms and spiders, yet instantaneous silk fiber formation with hierarchical structure under physiological and ambient conditions without post‐treatment procedures remains unaddressed. Here, this work reports a new strategy to fabricate silk protein‐based aerosols and silk fibers instantaneously in situ using a spray device, avoiding complicated and costly advanced manufacturing techniques. The key to success is the instantaneous conformational transition of silk fibroin from random coil to β‐sheet right before spraying by mixing silk and polyethylene glycol (PEG) solutions in the spray device, allowing aerosols and silk fibers to be sprayed, with further control achieved via the molecular weight of silk. The spinning process of the spray device is based on the use of green solvents, that is, all steps of instant conformational transition of silk fibroin are carried out in aqueous conditions or with buffers at ambient conditions, in combination with shear and elongational flow caused by the hydraulic pressure generated in the spray container. The system supports a portable and user‐friendly system that could be used for drug delivery carriers, wound coating materials, and rapid silk fiber conformal coatings on surfaces. [ABSTRACT FROM AUTHOR]

Objective: Tracheomalacia is characterized by weakness of the tracheal wall resulting in dynamic airway collapse during respiration; severe cases often require surgical intervention. Off-label external splinting with degradable implants has been reported in humans; however, there remains a need to develop splints with tunable mechanical properties and degradation profiles for the pediatric population. The objective of this pilot study is to assess the safety and efficacy of silk fibroin-based splints in a clinically relevant preclinical model of tracheomalacia.Methods: Silk splints were evaluated in a surgically induced model of severe tracheomalacia in N = 3 New Zealand white rabbits for 17, 24, and 31 days. An image-based assay was developed to quantify the dynamic change in airway area during spontaneous respiration, and histopathology was used to study the surrounding tissue response.Results: The average change in area in the native trachea was 23% during spontaneous respiration; surgically induced tracheomalacia resulted in a significant increase to 86% (P < 0.001). The average change in airway area after splint placement was reduced at all terminal time points (17, 24, and 31 days postimplantation), indicating a clinical improvement, and was not statistically different than the native trachea. Histopathology showed a localized inflammatory reaction characterized by neutrophils, eosinophils, and mononuclear cells, with early signs suggestive of fibrosis at the splint and tissue interface.Conclusion: This pilot study indicates that silk fibroin splints are well tolerated and efficacious in a rabbit model of severe tracheomalacia, with marked reduction in airway collapse following implantation and good tolerability over the studied time course.Level Of Evidence: NA Laryngoscope, 129:2189-2194, 2019. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

The production of structural and functional materials with enhanced mechanical properties through the integration of soft and hard components is a common approach to Nature's material design. However, directly mimicking these optimized design routes in the lab for practical applications remains challenging. For example, graphene and silk are two materials with complementary mechanical properties that feature ultrahigh stiffness and toughness, respectively. Yet, no simple and controllable approach is developed to homogeneously integrate these two components into functional composites, mainly due to the hydrophobicity and chemical inertness of graphene. In this study, well-dispersed and highly stable graphene/silk fibroin (SF) suspension systems are developed, which are suitable for processing to fabricate polymorphic materials, such as films, fibers, and coatings. The obtained graphene/SF nanocomposites maintain the electronic advantages of graphene, and they also allow tailorable mechanical performance to form including ultrahigh stretchable (with a strain to failure to 611 ± 85%), or high strength (339 MPa) and high stiffness (7.4 GPa) material systems. More remarkably, the electrical resistances of these graphene/SF materials are sensitive to material deformation, body movement, as well as humidity and chemical environmental changes. These unique features promise their utility as wearable sensors, smart textiles, intelligent skins, and human-machine interfaces. [ABSTRACT FROM AUTHOR]

Heart failure is the leading cause of death in the United States and rapidly becoming the leading cause of death worldwide. While pharmacological treatments can reduce progression to heart failure following myocardial infarction, there still exists a need for new therapies that promote better healing postinjury for a more functional cardiac repair and methods to understand how the changes to tissue mechanical properties influence cell phenotype and function following injury. To address this need, we have optimized a silk-based hydrogel platform containing cardiac tissue-derived extracellular matrix (cECM). These silk-cECM hydrogels have tunable mechanical properties, as well as rate-controllable hydrogel stiffening over time. In vitro, silk-cECM scaffolds led to enhanced cardiac fibroblast (CF) cell growth and viability with culture time. cECM incorporation improved expression of integrin an focal adhesion proteins, suggesting that CFs were able to interact with the cECM in the hydrogel. Subcutaneous injection of silk hydrogels in rats demonstrated that addition of the cECM led to endogenous cell infiltration and promoted endothelial cell ingrowth after 4 weeks in vivo. This naturally derived silk fibroin platform is applicable to the development of more physiologically relevant constructs that replicate healthy and diseased tissue in vitro and has the potential to be used as an injectable therapeutic for cardiac repair. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3058-3072, 2016. [ABSTRACT FROM AUTHOR]

In recent years, the use of biopolymers as interface materials between inorganic electronics and biological tissues has increased, which has necessitated the integration of micro- and nanofabrication techniques with these unconventional materials. This combination has led to devices with intriguing operational characteristics such as so-called 'transient' bioresorbable devices. Here, a method is investigated which leverages the thermal reflow characteristics of non-beta-sheet crystallized silk fibroin protein films to transfer print electronic components onto bioresorbable silk substrates. This is accomplished by applying heat and pressure to the interface of the silk and fabricated components, leading to reflow of the silk and transfer of the components from a silicon carrier wafer onto silk. We demonstrate application of this for both traditional (Au) and highly labile transient metals (Mg), over large areas with single micrometer resolution, all while retaining functionality of the transferred components. Additionally, it is shown how control over the reflow characteristics of silk through the process parameters can lead to both water-stable and water-soluble device outcomes and retain the efficacy of entrained biological dopants within the silk substrate matrix. Through these means, this method has the potential to improve the number of fabrication options for devices at the biotic/abiotic interface. [ABSTRACT FROM AUTHOR]

Recent use of biopolymers as interface materials between planar, inorganic electronics and biological tissues has required the adaptation of micro- and nanofabrication techniques for use with these nontraditional materials. In this work, a method which builds on this principle for spatial control of adhesion in multilayer silk fibroin laminates is investigated. This is accomplished through the addition of a spatially patterned amorphous silk adhesive layer in between the films to be adhered, before thermally processing them with heat (120 °C) and pressure (80 Psi) according to established procedures. A one-step method for rapid, high-throughput fabrication is demonstrated, which establishes a strong (1100 kPa) bond between the layers independent of the initial processing conditions of the films. The adhesive layers can be patterned using existing silk fabrication techniques, allowing for the assembly of complex geometries including bilayers and microbubbles. Additionally, the utility of this method is demonstrated for potential applications in drug delivery and transient electronics. This approach provides a versatile method for construction of complex multilayer structures in silk, which with future work may ultimately improve the utility of this material as a bridge between high technology and the biomedical sciences. [ABSTRACT FROM AUTHOR]

Silk solvent casting, electrospinning, and electrogelation techniques were used to create a biodegradable, biocompatible silk fibroin dural substitute. The all-silk system was designed and produced to improve on currently available materials, grafts and tissue sealants used for dural closure in neurosurgery. The silk biomaterial was successfully fabricated as a dual layer adhesive system designed to seal durotomies while also functioning as a dural regeneration scaffold. The mechanical characteristics, biocompatibility, biodegradability, and hydrodynamic sealing capability of the material were evaluated. Results showed that the biomaterial was biocompatible with neural cells and fibroblasts, had mechanical properties mimicking the natural dura, was biodegradable with controllable degradation, and was able to seal against a hydrodynamic pressure of 205 mmHg, which greatly exceeds the maximum cerebrospinal fluid pressure seen in both cranial and spinal dural closures of 50 mmHg. Based on its design and experimental results, the adhesive silk dual layer composite biomaterial shows potential as a sutureless dural repair system that would improve on current dural closure techniques. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 485-494, 2015. [ABSTRACT FROM AUTHOR]

Neural engineering provides promise for cell therapy by integrating the host brain with brain-machine-interface technologies in order to externally modulate functions. Long-term interfaces with the host brain remain a critical challenge due to insufficient graft cell survivability and loss of brain electrode sensitivity over time. Here, integrated neuron-electrode interfaces are developed on thin flexible and transparent silk films as brain implants. Mechanical properties and surface topography of silk films are optimized to promote cell survival and alignment of primary rat cortical cells. Compartmentalized neural cultures and co-patterned electrode arrays are incorporated on the silk films with built-in wire connections. Electrical stimulation via electrodes embedded in the films activated surrounding neurons to produce evoked calcium responses. In mice brains, silk film implants show conformal contact capable of modulating host brain cells with minimal inflammatory response and stable indwelling for weeks. The approach of combining cell therapy and brain electrodes could provide sustained functional interfaces with ex vivo control with spatial precision. [ABSTRACT FROM AUTHOR]

ABSTRACT Microencapsulation is becoming increasingly important in the food, cosmetics, and medicinal industries due to its potential for stabilization and delivery of volatile and delicate compounds. Novel food-safe techniques for encapsulating oil in silk biomaterials using emulsion-based processes that exploit silk's unique properties (including amphiphilicity, biocompatibility, aqueous and ambient processing, and tunable physical crosslinking behavior) are described. The sonication-induced self-assembly of silk previously applied to hydrogel fabrication replaced the use of the thermal or chemical suspension crosslinking traditionally used to stabilize the aqueous protein phase in emulsions. Stable, physically crosslinked silk micro- and macro-particles loaded with oil or water-soluble dye were produced by aliquoting sonicated silk solutions into an oil bath. Oil micro-droplets emulsified in aqueous silk solutions did not impede the self-assembly of silk into films or hydrogel networks. In O/W/O emulsions, particle morphology and silk permeability to a model lipophilic dye in the interior phase were controllable via processing. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014, 131, 39990. [ABSTRACT FROM AUTHOR]

The utilization of silk fibroin protein (SFP) in the field of biomaterials and tissue engineering plays an important role due to its promising mechanical, biological, and processing properties. In the present study, SFP solutions were exposed to ultrasound sonication to assess impact on molecular weight (Mw), sol-gel transition behavior, and physico-chemical properties. The Mw of SFP was significantly reduced with sonication, determined by sodium dodecyl sulfate polyacrylamide gels (SDS-PAGE) gel electrophoresis. Sol-gel transitions were observed as SFP assembled to form a reversible SFP gel network at different concentrations and sonication time with the formation of a β-sheet-rich conformation in the gel state. The conformational changes and morphological properties were correlated over a range of SFP concentrations by circular dichroism (CD), UV spectroscopy, swelling and attenuated total reflectance fourier transformed infrared spectroscopy (ATR-FTIR). [ABSTRACT FROM AUTHOR]

Effective treatment of infections in avascular and necrotic tissues can be challenging due to limited penetration into the target tissue and systemic toxicities. Controlled-release polymer implants have the potential to achieve the high local concentrations needed while also minimizing systemic exposure. Silk biomaterials possess unique characteristics for antibiotic delivery, including biocompatibility, tunable biodegradation, stabilizing effects, water-based processing, and diverse material formats. The functional release of antibiotics spanning a range of chemical properties from different material formats of silk (films, microspheres, hydrogels, coatings) is reported. The release of penicillin and ampicillin from bulk-loaded silk films, drug-loaded silk microspheres suspended in silk hydrogels and bulk-loaded silk hydrogels is investigated and the in vivo efficacy of the ampicillin-releasing silk hydrogels is demonstrated in a murine infected-wound model. Silk sponges with nanofilm coatings are loaded with gentamicin and cefazolin, and release is sustained for 5 and 3 days, respectively. The capability of silk antibiotic carriers to sequester, stabilize, and then release bioactive antibiotics represents a major advantage over implants and pumps based on liquid drug reservoirs, where instability at room or body temperature is limiting. The present studies demonstrate that silk biomaterials represent a novel, customizable antibiotic platform for focal delivery of antibiotics using a range of material formats (injectable to implantable). [ABSTRACT FROM AUTHOR]

Release data for several dyes from untreated, water-annealed, and methanol-treated silk films are collected and modeled. Through modeling, Fickian diffusion is identified as the major release mechanism. Estimated diffusivities are compared with dye properties to characterize parameter-property relationships. FTIR-ATR spectra of the silk films confirm an increase in the crystalline beta-sheet content within the silk films for methanol-treated and water-annealed films. An aqueous binding study is completed and shows weak binding of three dyes to the silk films. The Langmuir equation is fit to each of the binding curves and compared. The rate of diffusion from silk films is highly impacted by the molecular structure, water solubility, and molecular charge of the releasing solute and the matrix crystallinity. [ABSTRACT FROM AUTHOR]

Fabricating electrode materials with superior electrochemical performance remains a challenge. Here, a simple but effective strategy for the formation of metal oxide nanomaterials with superior performance has been developed. Silk protein nanofibers adhered on reduced graphene oxide (rGO) sheets are used as templates to regulate the formation of nanostructured iron oxide composites, achieving porous nanorod structures that could not be attained in control experiments. These porous nanorods demonstrate superior electrochemical performance as electrodes with retention of a capacity of 1495 mAh g−1 after 180 cycles at 0.2 C and a rate capability of 900 mAh g−1 at 2 C discharge rate. These new rGO/silk composite templates provide a more controllable environment for Fe2O3 fabrication, resulting in improved nanostructures and superior electrical performance. The strategy developed here should also be more broadly applicable in the design of metal oxide nanomaterials with specialized structures and useful performance. [ABSTRACT FROM AUTHOR]