Degradable Elastomeric Silk Biomaterial for Flexible Bioelectronics.

The integration of degradable and biomimetic approaches in material and device development can facilitate the next generation of sustainable (bio) electronics. The use of functional degradable materials presents exciting opportunities for applications in healthcare, soft robotics, energy, and electronics. These include conformability to curved surfaces, matching of stiffness of tissue, and the ability to withstand mechanical deformations. Nature-derived materials such as silk fibroin (SF) provide excellent biocompatibility, resorbability, and tunable properties toward such goals. However, fibroin alone lacks the required mechanical properties and durability for processing in biointegrated electronics and dry conditions. To overcome these limitations, we report on an elastomeric photocurable composite of silk fibroin and poly(dimethylsiloxane) (PDMS). Photofibroin (containing methacryl functionalities) is doped with photoPDMS (methacryloxypropyl-terminated poly(dimethylsiloxane)) to form an elastomeric photofibroin (ePF) composite. The elastomeric silk is photocurable, allowing for microfabrication using UV photolithography. It is suitable for circuits, strain-sensing devices, and biointegrated systems. The ePF exhibits flexibility in both wet and dry conditions, enhanced mechanical strength and long-term durability, and optical transparency. It is stable at high temperatures, compatible with electronic materials, and cytocompatible while being enzymatically degradable. This work therefore highlights a path toward combining natural and synthetic materials to achieve versatile properties and demonstrates the potential of silk fibroin composites in (bio) electronics, encapsulation, and packaging.

Tunable Light-Actuated Interpenetrating Networks of Silk Fibroin and Gelatin for Tissue Engineering and Flexible Biodevices.

Soft materials with tunable properties are valuable for applications such as tissue engineering, electronic skins, and human-machine interfaces. Materials that are nature-derived offer additional advantages such as biocompatibility, biodegradability, low-cost sourcing, and sustainability. However, these materials often have contrasting properties that limit their use. For example, silk fibroin (SF) has high mechanical strength but lacks processability and cell-adhesive domains. Gelatin, derived from collagen, has excellent biological properties, but is fragile and lacks stability. To overcome these limitations, composites of gelatin and SF have been explored. However, mechanically robust self-supported matrices and electrochemically active or micropatterned substrates were not demonstrated. In this study, we present a composite of photopolymerizable SF and photogelatin, termed photofibrogel (PFG). By incorporating photoreactive properties in both SF and gelatin, control over material properties can be achieved. The PFG composite can be easily and rapidly formed into free-standing, high-resolution architectures with tunable properties. By optimizing the ratio of SF to gelatin, properties such as swelling, mechanical behavior, enzymatic degradation, and patternability are tailored. The PFG composite allows for macroscale and microscale patterning without significant swelling, enabling the fabrication of structures using photolithography and laser cutting techniques. PFG can be patterned with electrically conductive materials, making it suitable for cell guidance and stimulation. The versatility, mechanical robustness, bioactivity, and electrochemical properties of PFG are shown for skeletal muscle tissue engineering using C2C12 cells as a model. Overall, such composite biomaterials with tunable properties have broad potential in flexible bioelectronics, wound healing, regenerative medicine, and food systems.

Deep-Learning-Based Digitization of Protein-Self-Assembly to Print Biodegradable Physically Unclonable Labels for Device Security.

The increasingly pervasive problem of counterfeiting affects both individuals and industry. In particular, public health and medical fields face threats to device authenticity and patient privacy, especially in the post-pandemic era. Physical unclonable functions (PUFs) present a modern solution using counterfeit-proof security labels to securely authenticate and identify physical objects. PUFs harness innately entropic information generators to create a unique fingerprint for an authentication protocol. This paper proposes a facile protein self-assembly process as an entropy generator for a unique biological PUF. The posited image digitization process applies a deep learning model to extract a feature vector from the self-assembly image. This is then binarized and debiased to produce a cryptographic key. The NIST SP 800-22 Statistical Test Suite was used to evaluate the randomness of the generated keys, which proved sufficiently stochastic. To facilitate deployment on physical objects, the PUF images were printed on flexible silk-fibroin-based biodegradable labels using functional protein bioinks. Images from the labels were captured using a cellphone camera and referenced against the source image for error rate comparison. The deep-learning-based biological PUF has potential as a low-cost, scalable, highly randomized strategy for anti-counterfeiting technology.

Sericin coated thin polymeric films reduce keratinocyte proliferation via the mTOR pathway and epidermal inflammation through IL17 signaling in psoriasis rat model.

Therapeutic treatment forms can play significant roles in resolving psoriatic plaques or promoting wound repair in psoriatic skin. Considering the biocompatibility, mechanical strength, flexibility, and adhesive properties of silk fibroin sheets/films, it is useful to combine them with anti-psoriatic agents and healing stimulants, notably silk sericin. Here, we evaluate the curative properties of sericin-coated thin polymeric films (ScF) fabricated from silk fibroin, using an imiquimod-induced psoriasis rat model. The film biocompatibility and psoriatic wound improvement capacity was assessed. A proteomics study was performed to understand the disease resolving mechanisms. Skin-implantation study exhibited the non-irritation property of ScF films, which alleviate eczema histopathology. Immunohistochemical and gene expression revealed the depletion of ß-defensin, caspase-3 and -9, TNF-α, CCL-20, IL-1ß, IL-17, TGF-ß, and Wnt expressions and S100a14 mRNA level. The proteomics study suggested that ScF diminish keratinocyte proliferation via the mTOR pathway by downregulating mTOR protein, corresponding to the modulation of TNF-α, Wnt, and IL-1ß levels, leading to the enhancement of anti-inflammatory environment by IL-17 downregulation. Hematology data demonstrated the safety of using these biomaterials, which provide a potential therapeutic-option for psoriasis treatment due to desirable effects, especially anti-proliferation and anti-inflammation, functioning via the mTOR pathway and control of IL-17 signaling.

Templated Synthesis of 2D Polyimide Covalent Organic Framework for Rechargeable Sodium-Ion Batteries.

Covalent organic frameworks (COFs) hold great promise for electrochemical energy storage because of their high surface area, readily accessible redox-active sites, and environment-friendly chemical composition. In this study, the synthesis of a redox-active pyrene-containing polyimide COF (PICOF-1) by linker exchange using an imine-linked COF as a template is reported and its performance in sodium-ion batteries (SIBs) is demonstrated. The reported synthetic route based on linker exchange mitigates the challenges typically encountered with crystallizing chemically stable polyimide COFs from typical condensation reactions; thus, facilitating their rapid synthesis and purification. Using this approach, PICOF-1 exhibits high crystallinity with very low refinement parameters RP and RWP of 0.415% and 0.326%, respectively. PICOF-1 has a high Brunauer-Emmette-Teller (BET) surface area of 924 m2  g-1 and well-defined one-dimentional (1D) channels of 2.46 × 1.90 nm, which enable fast ion transport and charge transfer, reaching a capacity at 0.1 C of almost nearly as its theoretical capacity and maintaining 99% Coulombic efficiency over 175 cycles at 0.3 C. The study demonstrates that imine-linked COFs are effective templates for integrating carbonyl-rich polyimide moieties into high-surface COFs to advance electrochemical energy storage applications.

Stretchable and Electroactive Crosslinked Gelatin for Biodevice and Cell Culture Applications.

Biomimetic substrates that incorporate functionality such as electroactivity and mechanical flexibility, find utility in a variety of biomedical applications. Toward these uses, nature-derived materials such as gelatin offer inherent biocompatibility and sustainable sourcing. However, issues such as high swelling, poor mechanical properties, and lack of stability at biological temperatures limit their use. The enzymatic crosslinking of gelatin via microbial transglutaminase (mTG) yields flexible and robust large area substrates that are stable under physiological conditions. Here, we demonstrate the fabrication and characterization of strong, stretchable, conductive mTG crosslinked gelatin thin films. Incorporation of the conductive polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate in the gel matrix with a bioinspired polydopamine surface coating is used to enable conductivity with enhanced mechanical properties such as extensibility and flexibility, in comparison to plain gelatin or crosslinked gelatin films. The electroconductive substrates are conducive to cell growth, supporting myoblast cell adhesion, viability, and proliferation and could find use in creating active cell culture systems incorporating electrical stimulation. The substrates are responsive to motion such as stretching and bending while being extremely handleable and elastic, making them useful for applications such as electronic skin and flexible bioelectronics. Overall, this work presents facile, yet effective development of bioinspired conductive composites as substrates for bio-integrated devices and functional tissue engineering.

Use of hormone-specific antibody probes for differential labeling of contributor cell populations in trace DNA mixtures.

A significant proportion of casework analyzed by forensic science laboratories is often "touch" or trace forensic DNA evidence, which is deposited through physical contact and is comprised of sloughed epidermal cells. These samples can be challenging to analyze due to low DNA concentrations, frequent degradation, and the presence of cells from multiple individuals in the same sample. To address these challenges, we investigated a new approach for characterizing trace evidence prior to DNA profiling that labels epidermal cells with antibody probes targeting hormone molecules testosterone and dihydrotestosterone (DHT). The goal was to test whether cell populations derived from separate individuals showed different binding efficiencies to hormone probes and, thus, could be used to detect the presence of multiple cell populations. Additionally, we investigated whether antibody probes could be used to isolate contributor cell populations from an epidermal cell mixture and facilitate deconvolution of mixed DNA profiles recovered from touch/trace evidence. Results showed that cell populations from some individuals could differentiated in trace samples based on fluorescence histograms following probe labeling. However, certain pairs of contributors showed largely or completely overlapping histogram profiles and could not be resolved. Preliminary efforts to separate cell populations that could be differentiated with hormone probes with fluorescence-activated cell sorting (FACS) coupled to DNA profiling and probabilistic modeling indicated that it is possible to enrich contributor cell populations from touch/trace samples and produce more probative DNA profiles compared to the original mixture sample. The variability in labeling, differentiation, and physical separation of cell populations may be impacted by similarities in biochemical profiles across some contributors as well as imbalance of contributor DNA quantities in certain mixtures as is typical in casework involving touch/trace evidence. Ultimately, screening and separation of trace DNA samples with this approach may be presumptive and constrained by sample-specific parameters of the original mixture.

Flexible Sensing Systems for Cancer Diagnostics.

Practical screening tools and ultrasensitive technologies can play pivotal roles in precision cancer profiling for early diagnosis at asymptomatic stages, as well as for monitoring prognosis, risk stratification, and disease recurrence. While a number of sensors and diagnostic tools continue to be developed for ultrasensitive detection and off-site analysis, there has been an increasing interest in point-of-care devices, particularly those that are mechanically flexible and potentially wearable by the patient. In this chapter, we present a critical insight into the integrated engineering approaches involved in such flexible systems. We consider various aspects in the design of flexible devices, the biomarkers of interest, and the different transduction mechanisms by which mechanically flexible devices can be used in the area of cancer monitoring. We then discuss the different types of flexible biosensing platforms that have been developed to date, including wearables on skin and on clothing, and exhaled breath and implantable sensors. Finally, we discuss the design challenges and future outlook in the development of flexible platforms that can provide comprehensive cancer biomarker panels for patients and clinicians.

Kirigami-Inspired Biodesign for Applications in Healthcare.

Mechanically flexible and conformable materials and integrated devices have found diverse applications in personalized healthcare as diagnostics and therapeutics, tissue engineering and regenerative medicine constructs, surgical tools, secure systems, and assistive technologies. In order to impart optimal mechanical properties to the (bio)materials used in these applications, various strategies have been explored-from composites to structural engineering. In recent years, geometric cuts inspired by the art of paper-cutting, referred to as kirigami, have provided innovative opportunities for conferring precise mechanical properties via material removal. Kirigami-based approaches have been used for device design in areas ranging from soft bioelectronics to energy storage. In this review, the principles of kirigami-inspired engineering specifically for biomedical applications are discussed. Factors pertinent to their design, including cut geometry, materials, and fabrication, and the effect these parameters have on their properties and configurations are covered. Examples of kirigami designs in healthcare are presented, such as, various form factors of sensors (on skin, wearable), implantable devices, therapeutics, surgical procedures, and cellular scaffolds for regenerative medicine. Finally, the challenges and future scope for the successful translation of these biodesign concepts to broader deployment are discussed.

Synthesis of pH and Glucose Responsive Silk Fibroin Hydrogels.

Silk fibroin (SF) has attracted much attention due to its high, tunable mechanical strength and excellent biocompatibility. Imparting the ability to respond to external stimuli can further enhance its scope of application. In order to imbue stimuli-responsive behavior in silk fibroin, we propose a new conjugated material, namely cationic SF (CSF) obtained by chemical modification of silk fibroin with ε-Poly-(L-lysine) (ε-PLL). This pH-responsive CSF hydrogel was prepared by enzymatic crosslinking using horseradish peroxidase and H2O2. Zeta potential measurements and SDS-PAGE gel electrophoresis show successful synthesis, with an increase in isoelectric point from 4.1 to 8.6. Fourier transform infrared (FTIR) and X-ray diffraction (XRD) results show that the modification does not affect the crystalline structure of SF. Most importantly, the synthesized CSF hydrogel has an excellent pH response. At 10 wt.% ε-PLL, a significant change in swelling with pH is observed. We further demonstrate that the hydrogel can be glucose-responsive by the addition of glucose oxidase (GOx). At high glucose concentration (400 mg/dL), the swelling of CSF/GOx hydrogel is as high as 345 ± 16%, while swelling in 200 mg/dL, 100 mg/dL and 0 mg/dL glucose solutions is 237 ± 12%, 163 ± 12% and 98 ± 15%, respectively. This shows the responsive swelling of CSF/GOx hydrogels to glucose, thus providing sufficient conditions for rapid drug release. Together with the versatility and biological properties of fibroin, such stimuli-responsive silk hydrogels have great potential in intelligent drug delivery, as soft matter substrates for enzymatic reactions and in other biomedical applications.

Micropatterned Silk-Fibroin/Eumelanin Composite Films for Bioelectronic Applications.

There has been growing interest in the use of natural bionanomaterials and nanostructured systems for diverse biomedical applications. Such materials can confer unique functional properties as well as address concerns pertaining to sustainability in production. In this work, we propose the biofabrication of micropatterned silk fibroin/eumelanin composite thin films to be used in electroactive and bioactive applications in bioelectronics and biomedical engineering. Eumelanin is the most common form of melanin, naturally derived from the ink of cuttlefish, having antioxidant and electroactive properties. Another natural biomaterial, the protein silk fibroin, is modified with photoreactive chemical groups, which allows the formation of electroactive eumelanin thin films with different microstructures. The silk fibroin/eumelanin composites are fabricated to obtain thin films as well as electroactive microstructures using UV curing. Here, we report for the first time the preparation, characterization, and physical, electrochemical, and biological properties of these natural silk fibroin/eumelanin composite films. Higher concentrations of eumelanin incorporated into the films exhibit a higher charge storage capacity and good electroactivity even after 100 redox cycles. In addition, the microscale structure and the cellular activity of the fibroin/eumelanin films are assessed for understanding of the biological properties of the composite. The developed micropatterned fibroin/eumelanin films can be applied as natural electroactive substrates for bioapplications (e.g., bioelectronics, sensing, and theranostics) because of their biocompatible properties.

Atomic force microscopy as a biophysical tool for nanoscale forensic investigations.

The atomic force microscope (AFM) has found its way to the arsenal of tools available to the forensic practitioner for the analysis of samples at the nano and microscales. As a non-destructive probing tool that requires minimal sample preparation, the AFM is very attractive, particularly in the case of minimal or precious sample. To date, the use of the AFM has primarily been in the arena of imaging where it has been complementary to other microscopic examination tools. Forensic applications in the visual examination of evidence such as blood stains, questioned documents, and hair samples have been reported. While a number of reviews have focused on the use of AFM as an imaging tool for forensic analyses, here we not only discuss these works, but also point to a versatile enhancement in the capabilities of this nanoscale tool - namely its use for force spectroscopy. In this mode, the AFM can determine elastic moduli, adhesion forces, energy dissipation, and the interaction forces between cognate ligands, that can be spatially mapped to provide a unique spatial visualization of properties. Our goals in this review are to provide a context for this capability of the AFM, explain its workings, cover some exemplary works pertaining to forensic sciences, and present a critical analysis on the advantages and disadvantages of this modality. Equipped with this high-resolution tool, imaging and biophysical analysis by the AFM can provide a unique complement to other tools available to the researcher for the analysis and characterization of forensic evidence.

Technical note: Survey of extracellular and cell-pellet-associated DNA from 'touch'/trace samples.

The goal of this study was to characterize the reproducibility of extracellular and cell pellet associated DNA yields recovered from handled substrates. Results showed that extracellular DNA yields were extremely variable between contributors-ranging between 0 and >10ng-and tended to dwarf cell pellet yields, which varied between 0 and ∼230pg. DNA yields across multiple samples from the same contributor on different days showed similar levels of variability in both DNA fractions, indicating that extracellular DNA yield is largely influenced by extrinsic and/or environmental factors and is not a contributor-specific attribute. Microscopic surveys of cells from the pellet fraction as well as fingerprints from the same contributor samples were conducted following treatment with fluorescent DNA stain. Nearly all imaged cells exhibited diffuse fluorescence across the cell without discernable evidence of nuclei. This is consistent with the limited nature of DNA recovery from the pellet fraction and the prevalence of extracellular DNA in these samples.

Open source software tool for the automated detection and characterization of epithelial cells from trace biological samples.

This paper presents a strategy for an unsupervised workflow for identifying epithelial cells in microscopic images and characterizing their morphological and/or optical properties. The proposed method can be used on cells that have been stained with fluorescent dyes and imaged using conventional optical microscopes. The workflow was tested on cell populations that were imaged directly on touch/contact surfaces and stained with nucleic acid dyes to visualize genetic content. Our results show that this approach could be a useful strategy for characterizing differences in staining efficiency and/or morphological properties of individual cells or aggregate populations within a biological sample. Further, they can potentially reduce the laborious nature of microscopic analysis and increase throughput and reproducibility of similar studies.

Chitosan Stabilized Silver Nanoparticles for the Electrochemical Detection of Lipopolysaccharide: A Facile Biosensing Approach for Gram-Negative Bacteria.

Negatively charged lipopolysaccharide (LPS), a major endotoxin and component of the outer membrane of several Gram-negative bacteria, provides a useful biomarker for the indirect detection of these pathogens. For instance, Escherichia coli (E. coli) is a pathogenic bacterium that causes infections in almost all age groups, and has been implicated in food and water contamination. Current diagnostic and detection methods tend to be labor-intensive or expensive, necessitating the need for an easy, sensitive, rapid, and low-cost method. We report on the synthesis and use of positively charged chitosan stabilized silver nanoparticles (Chi-AgNPs) as a sensitive electrochemical nanobiosensor for the detection of LPS. Chi-AgNPs were synthesized through a facile, single step protocol, and characterized for size, charge, and morphology. Glassy carbon electrodes modified with Chi-AgNPs resulted in an enhancement of signal in the presence of both LPS and E. coli. Detection was accomplished over a large concentration range (several orders of magnitude) of 0.001-100 ng/mL and 10-107 CFU/mL. The biosensors can reliably detect LPS and E. coli at very low concentrations. Chi-AgNPs have potential as low cost, sensitive nanobiosensors for Gram-negative bacteria due to strong electrostatic interaction with LPS present in their outer membranes.

Biofunctional Silk Kirigami With Engineered Properties.

The fabrication of multifunctional materials that interface with living environments is a problem of great interest. A variety of structural design concepts have been integrated with functional materials to form biodevices and surfaces for health monitoring. In particular, approaches based on kirigami-inspired cuts can engineer flexibility in materials through the creation of patterned defects. Here, the fabrication of a biodegradable and biofunctional "silk kirigami" material is demonstrated. Mechanically flexible, free-standing, optically transparent, large-area biomaterial sheets with precisely defined and computationally designed microscale cuts can be formed using a single-step photolithographic process. Using modeling techniques, it is shown how cuts can generate remarkable "self-shielding" leading to engineered elastic behavior and deformation. As composites with conducting polymers, flexible, intrinsically electroactive sheets can be formed. Importantly, the silk kirigami sheets are biocompatible, can serve as substrates for cell culture, and be proteolytically resorbed. The unique properties of silk kirigami suggest a host of applications as transient, "green", functional biointerfaces, and flexible bioelectronics.

Nanoscale Phenotypic Textures of Yersinia pestis Across Environmentally-Relevant Matrices.

The persistence of bacterial pathogens within environmental matrices plays an important role in the epidemiology of diseases, as well as impacts biosurveillance strategies. However, the adaptation potentials, mechanisms for survival, and ecological interactions of pathogenic bacteria such as Yersinia pestis are largely uncharacterized owing to the difficulty of profiling their phenotypic signatures. In this report, we describe studies on Y. pestis organisms cultured within soil matrices, which are among the most important reservoirs for their propagation. Morphological (nanoscale) and phenotypic analysis are presented at the single cell level conducted using Atomic Force Microscopy (AFM), coupled with biochemical profiles of bulk populations using Fatty Acid Methyl Ester Profiling (FAME). These studies are facilitated by a novel, customizable, 3D printed diffusion chamber that allows for control of the external environment and easy harvesting of cells. The results show that incubation within soil matrices lead to reduction of cell size and an increase in surface hydrophobicity. FAME profiles indicate shifts in unsaturated fatty acid compositions, while other fatty acid components of the phospholipid membrane or surface lipids remained consistent across culturing conditions, suggesting that phenotypic shifts may be driven by non-lipid components of Y. pestis.

Nanoscale visualization of extracellular DNA on cell surfaces.

Nanoscale analysis of extracellular DNA (eDNA) that is present on the surface of cells in trace biological samples can provide insight into the understanding of DNA transfer through touch, and thereby, the role of eDNA is a biologically and forensically relevant phenomenon. While various bulk scale tools and DNA analysis can be used to quantitatively obtain this information, obtaining a three dimensional (3D) visualization of the eDNA can provide a unique look into the spatial and temporal dynamics at the cellular level. In this study, we show how atomic force microscopy (AFM) can be integrated with optical microscopy to visualize the distribution of surface associate eDNA at a single cell level. Using a nucleic acid fluorophore such as Diamond™ Dye, the surface eDNA can be observed and quantified using fluorescence microscopy. This informational channel can then be overlaid with surface topography and cellular elasticity to provide structural visualization. Finally, chemical force spectroscopy can be used to obtain the distribution of surface-associated eDNA on the cell surface at the molecular level. Such integrated techniques can enhance understanding of the biological role of eDNA, and can also be potentially valuable for investigating challenging trace samples, containing very few cells for various analyses.

Synthesis of chitosan coated metal organic frameworks (MOFs) for increasing vancomycin bactericidal potentials against resistant S. aureus strain.

Multiple drug resistant (MDR) has become a major issue in developing countries. MDR bacterial infections lead to significant increase in morbidity, mortality and cost of prolonged treatments. Therefore, designing of strategies for improving the antimicrobial potential of the therapeutic agents are highly required. Metal organic frameworks (MOFs) are highly tunable hybrid material, consist of metal ions linked together by organic bridging ligands have been used as an efficient drug delivery carrier because of their biodegradability, low toxicity and structure integrity upon loading and functionalizing process. Current study was based on the synthesis of chitosan coated MOFs with enhanced contact with S. aureus cell surface. Chitosan is deacetylated derivative of chitin and capable for non-bonding interaction with negatively charged bacterial cell leading to enhanced contact of MOFs with S. aureus. Chitosan coated MOFs were characterized with various techniques such as atomic force microscopy, scanning electron microscopy, DLS, FT-IR, TGA, DSC and Powder X-ray diffraction. They were also studied for their efficacy on resistant S. aureus, results revealed that Vancomycin bactericidal activity significantly increased upon loading in chitosan coated MOFs and caused increased inhibition of resistant S. aureus. AFM analysis of S. aureus strains clearly revealed complete distortion of morphology by treating with chitosan modified drug loaded MOFs. Findings of the current study suggest the potential of chitosan coated MOFs for reversing bacterial resistance against Vancomycin and provide new perspectives for improved antibiotic therapy of infections associated with MDR.

Silk Fibroin-Sheathed Conducting Polymer Wires as Organic Connectors for Biosensors.

Conductive polymers, owing to their tunable mechanical and electrochemical properties, are viable candidates to replace metallic components for the development of biosensors and bioelectronics. However, conducting fibers/wires fabricated from these intrinsically conductive and mechanically flexible polymers are typically produced without protective coatings for physiological environments. Providing sheathed conductive fibers/wires can open numerous opportunities for fully organic biodevices. In this work, we report on a facile method to fabricate core-sheath poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) PEDOT:PSS-silk fibroin conductive wires. The conductive wires are formed through a wet-spinning process, and then coated with an optically transparent, photocrosslinkable silk fibroin sheath for insulation and protection in a facile and scalable process. The sheathed fibers were evaluated for their mechanical and electrical characteristics and overall stability. These wires can serve as flexible connectors to an organic electrode biosensor. The entire, fully organic, biodegradable, and free-standing flexible biosensor demonstrated a high sensitivity and rapid response for the detection of ascorbic acid as a model analyte. The entire system can be proteolytically biodegraded in a few weeks. Such organic systems can therefore provide promising solutions to address challenges in transient devices and environmental sustainability.