Ultrathin silk nanofiber-carbon nanotube skin tattoos for wirelessly triggered and temperature feedbacked transdermal drug delivery.

Transdermal drug delivery has emerged as an alternative to conventional drug delivery systems as it enables painless and convenient drug administration. However, next-generation healthcare systems need to facilitate "on-demand" delivery operations and should be highly efficient to penetrate the physiological barriers in the skin. Here, we report an ultrathin dye-loaded epidermal tattoo (UDET) that allows wirelessly stimulated drug delivery with high efficiency. The UDET consists of an electrospun dye-loaded silk nanofiber mat and a covered carbon nanotube (CNT) layer. UDETs are conformally tattooed on pigskins and show stable operation under mechanical deformation. Biological fluorescence dyes such as vitamin B12, riboflavin, rhodamine B, and sodium fluorescein are applied as model drugs. Illuminating the UDET by a low-power light-emitting diode (< 34.5 mW/cm2) triggers transdermal drug delivery due to heat generation. The CNTs convert the absorbed light into heat, and then the dyes loaded on silk can be diffused through the epidermis. The CNT layer is electrically conductive and can detect the temperature by reading the resistance change (0.1917 Ω/°C). This indicates that the UDET can be used simultaneously to read temperature and deliver the loaded dye molecules, making it a promising on-demand drug delivery strategy for future medicine technology. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-024-00363-6.

Simulation of Cortical and Cancellous Bone to Accelerate Tissue Regeneration.

Different tissues have complex anisotropic structures to support biological functions. Mimicking these complex structures in vitro remains a challenge in biomaterials designs in support of tissue regeneration. Here, inspired by different types of silk nanofibers, a composite materials strategy was pursued towards this challenge. A combination of fabrication methods was utilized to achieve separate control of amorphous and beta-sheet rich silk nanofibers in the same solution. Aqueous solutions containing these two structural types of silk nanofibers were then simultaneously treated with an electric field and with ethylene glycol diglycidyl ether (EGDE). Under these conditions, the beta-sheet rich silk nanofibers in the mixture responded to the electric field while the amorphous nanofibers were active in the crosslinking process with the EGDE. As a result, cryogels with anisotropic structures were prepared, including mimics for cortical- and cancellous-like bone biomaterials as a complex osteoinductive niche. In vitro studies revealed that mechanical cues of the cryogels induced osteodifferentiation of stem cells while the anisotropy inside the cryogels influenced immune reactions of macrophages. These bioactive cryogels also stimulated improved bone regeneration in vivo through modulation of inflammation, angiogenesis and osteogenesis responses, suggesting an effective strategy to develop bioactive matrices with complex anisotropic structures beneficial to tissue regeneration.

Cartilage structure-inspired elastic silk nanofiber network hydrogel for stretchable and high-performance supercapacitors.

Flexible supercapacitors are an important portable energy storage but suffer from low capacitance, inability to stretch, etc. Therefore, flexible supercapacitors must achieve higher capacitance, energy density, and mechanical robustness to expand the applications. Herein, a hydrogel electrode with excellent mechanical strength was created by simulating the collagen fiber network and proteoglycan in cartilage using silk nanofiber (SNF) network and polyvinyl alcohol (PVA). The Young's modulus and breaking strength of the hydrogel electrode increased by 205 % and 91 % compared with PVA hydrogel owing to the enhanced effect of the bionic structure, respectively, which are 1.22 MPa and 1.3 MPa. The fracture energy and fatigue threshold reached 1813.5 J/m2 and 1585.2 J/m2, respectively. The SNF network effectively connected carbon nanotubes (CNTs) and polypyrrole (PPy) in series, affording a capacitance of 13.62 F/cm2 and energy density of 1.2098 mWh/cm2. This capacitance is the highest among currently reported PVA hydrogel capacitors, which can maintain >95.2 % after 3000 charge-discharge cycles. This capacitance Notably, the cartilage-like structure endowed the supercapacitor with high resilience; thus, the capacitance remained >92.1 % under 150 % deformation and >93.35 % after repeated stretching (3000 times), which was far superior to that of other PVA-based supercapacitors. Overall, this effective bionic strategy can endow supercapacitors with ultrahigh capacitance and effectively ensure the mechanical reliability of flexible supercapacitors, which will help expand the applications of supercapacitors.

CO2 fractional laser-assisted transdermal delivery of silk nanofiber carriers in a rabbit ear hypertrophic scar model.

Background: Hypertrophic scars are skin fibrotic diseases, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix. However, topical drug application for hypertrophic scars are unsatisfactory. The purpose of this study was to explore the permeability of silk nanofiber hydrogels (SNFs) loaded with rhodamine 6G (R6G) and rhodamine 110 (R110) mediated by CO2 fractional laser irradiation into hypertrophic scar tissues. Methods: In this work, R6G and R110 were chosen as hydrophilic and hydrophobic model molecules. They were loaded inside SNFs. In vivo rabbit ear hypertrophic scars were treated with CO2 fractional laser irradiation and then R6G/R110-laden SNFs were applied to the scars to evaluate their synergetic effect on drug penetration efficiency. Their permeability was quantified by fluorescence intensity and measured by confocal laser scanning microscopy on days 1, 3, 5 and 7. More specifically, the thermal coagulation zone (CZ) and its surrounding area (peri-CZ) caused by the thermal coagulation of the laser were discussed separately. Results: Our data indicated that the SNFs promoted the penetration of R6G but not that of R110 in the peri-CZ on day 1 when combined with laser irradiation. Interestingly, both R6G and R110 were abundant in the CZ and remained stable on days 1, 3 and 5. Moreover, rapid re-epithelialization hindered the long-term permeability of both drugs. Conclusion: Combining CO2 fractional laser irradiation with SNF drug delivery could improve the efficiency of hydrophilic drug delivery within 24 h before total re-epithelialization.

Fragile-Tough Mechanical Reversion of Silk Materials via Tuning Supramolecular Assembly.

Regenerated silk nanofibers are interesting as protein-based material building blocks due to their unique structure and biological origin. Here, a new strategy based on control of supramolecular assembly was developed to regulate interactions among silk nanofibers by changing the solvent, achieving tough mechanical features for silk films. Formic acid was used to replace water related to charge repulsion of silk nanofibers in solution, inducing interactions among the nanofibers. The films formed under these conditions had an elastic modulus of 3.4 ± 0.3 GPa, an ultimate tensile strength of 76.9 ± 1.6 MPa, and an elongation at break of 3.5 ± 0.1%, while the materials formed from aqueous solutions remained fragile. The mechanical performance of the formic acid-derived nanofiber films was further improved through post-stretching or via the addition of graphene. In addition, the silk nanofiber films could be functionalized with various bioactive ingredients such as curcumin. These new silk nanofiber films with a unique combination of mechanical properties and functions provide new biomaterials achieved using traditional solvents and processes through insight and control of their assembly mechanisms in solution.

Calcium sulfate bone cements with nanoscaled silk fibroin as inducer.

Both nanostructures and conformations of different protein/polysaccharide additives have critical influence on the performance of calcium sulfate (CS) bone cements. Silk fibroin (SF) as matrix and additives has been introduced to develop bone scaffolds and cements. Here, ß-sheet-rich SF nanofibers (SFF) was used to tune the solidification of CS, achieving better mechanical and biological properties. The ratio of SFF was adjusted to further optimize CS functions. Compared to that regulated with natural silk fibers (NSF) and SF solutions (SFS), the SFF-induced CS showed smaller size and more filament structures. Better mechanical properties were achieved, suggesting the superiority of the SFF as the solidifying solution to combine with α-calcium sulfate hemihydrate (α-CSH) at the same liquid/solid (L/S) ratio. Scanning electron microscope, X-ray diffraction, Fourier transform infrared spectroscopy, setting time, porosity, mechanical performance test, degradation performance test, and water resistance test were used to demonstrate the properties of this bone repair cement. Cell culture experiments in vitro was used to evaluate the biocompatibility of this composited material. In conclusion, the results demonstrated that nanofibers was a better form of SF in the modification of CSH cement. And the research conducted in this article on improving the mechanical and biological properties of CSH would supported the reference for later clinical experiments. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2611-2619, 2019.

Mass Production of Biocompatible Graphene Using Silk Nanofibers.

Mass production of high-quality graphene dispersions under mild conditions impacts the utility of the material for biomedical applications. Various proteins have been used to prepare graphene dispersions, rare sources, and expensive prices for these proteins restrict their large-scale utility for the production of graphene. Here, inexpensive silk proteins as an abundant resource in nature were used for graphene exfoliation. The silk proteins were assembled into hydrophobic nanofibers with negative charge, and then optimized for the production of graphene. Significantly higher concentrations (>8 mg mL-1) and yields (>30%) of graphene dispersions under ambient aqueous conditions were achieved compared with previous protein-assisted exfoliation systems. The exfoliated graphene exhibited excellent stability in water and fetal bovine serum solution, cytocompatibility, and conductivity, suggesting a promising future in biomedical and bioengineering applications.