Air-Spun Silk-Based Micro-/Nanofibers and Thin Films for Drug Delivery

Micro-/nanofibers have shown high promise as drug delivery vehicles due to their high porosity and surface-area-to-volume ratio. The current study utilizes air-spraying, a novel fiber fabrication technique, to create silk micro-/nanofibers without the need for a high voltage power source. Air-spraying was used to create silk fibrous mats embedded with several model drugs with high efficiency. In order to compare the effect of biomaterial geometry on the release of the model drugs, silk films were also created and characterized. Fourier-transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and a drug release study were performed on both fiber and film samples to study how the model drugs interact with the protein structure. FTIR analysis showed that while drugs could interact with the protein structure of porous silk fibers, they could not interact with the flat geometry of silk films. As a result, fibers could protect select model drugs from thermal degradation and slow their release from the fiber network with more control than the silk films. A trend was also revealed where hydrophobic drugs were better protected and had a slower release than hydrophilic drugs. The results suggest that the physical and chemical properties of drugs and protein-based biomaterials are important for creating drug delivery vehicles with tailored release profiles and that fibers provide better tunability than films do.

Silk films with nanotopography and extracellular proteins enhance corneal epithelial wound healing

Corneal wound healing depends on extracellular matrix (ECM) and topographical cues that modulate migration and proliferation of regenerating cells. In our study, silk films with either flat or nanotopography patterned parallel ridge widths of 2000, 1000, 800 nm surfaces were combined with ECMs which include collagen type I (collagen I), fibronectin, laminin, and Poly-d-Lysine to accelerate corneal wound healing. Silk films with 800 nm ridge width provided better cell spreading and wound recovery than other size topographies. Coating 800 nm patterned silk films with collagen I proves to optimally further increased mouse and rabbit corneal epithelial cells growth and wound recovery. This enhanced cellular response correlated with redistribution and increase in size and total amount of focal adhesion. Transcriptomics and signaling pathway analysis suggested that silk topography regulates cell behaviors via actin nucleation ARP-WASP complex pathway, which regulate filopodia formation. This mechanism was further explored and inhibition of Cdc42, a key protein in this pathway, delayed wound healing and decreased the length, density, and alignment of filopodia. Inhibition of Cdc42 in vivo resulted in delayed re-epithelization of injured corneas. We conclude that silk film nanotopography in combination with collagen I constitutes a better substrate for corneal wound repair than either nanotopography or ECM alone.

Nanoporous silk films with capillary action and size-exclusion capacity for sensitive glucose determination in whole blood

Nanoporous silk-fibroin films in test strips present capillary action and size-exclusion filtering capacity enabling quick optical biosensing in whole blood samples.

Development and characterization of silk films for burn wound healing

Purpose Wound healing is a dynamic process that relies on coordinated signaling molecules to succeed. Silk has proven to be a promising biomaterial for the development of a novel product. The purpose of the study is development of silk films, augmented functionality can be provided to silk by means of loading honey and recombinant human epidermal growth factor (rhEGF). Design/methodology/approach In this research work, the authors set out to explore possibilities of silk-based biomedical device development with particular attention to different fabrication strategies that can be leveraged for this purpose. They have produced a novel silk-based drug delivery material, in the form of silk films. Scanning electronic microscope was used to observe the morphology and the highly specific surface area. The structure was studied by Fourier-transform infrared spectroscopy. This methodology is accomplished using in vivo study data using Wister albonia rats. Findings The developed films also provided a significant higher healing rate in vivo, with well-formed epidermis with faster granulation tissue formation when compared to the controls. Biodegradable polymeric materials based on blending aqueous dispersions of natural polymer sodium alginate, Chitosan and rhEGF complex, which allow controlled antiseptic release, are presented. Originality/value These results suggest that silk-based controlled release of Chitosan-rhEGF may serve as a new therapy to accelerate healing of burn wounds.

Melatonin-induced osteogenesis with methanol-annealed silk materials

Melatonin, a hormone produced in the pineal gland, has been investigated for bone repair, remodeling, osteoporosis, as well as osseointegration of the implants. In this study, different concentrations of melatonin (0–2000-µM) were embedded into silk films annealed by methanol or water. Then, their capacity to differentiate human mesenchymal stem cells into osteoblasts was investigated for bone tissue regeneration. While methanol-annealed silk films have ~55% crystallinity, room-temperature water-annealed silk films have ~30% crystallinity by depending upon their different β-sheet contents. Melatonin-loaded silk films exhibited an initial burst release followed by a continuous release for up to 5 days, and the β-sheet content of silk films did not affect the release behavior of melatonin, an amphiphilic molecule. Moreover, human mesenchymal stem cells exhibited an increase in osteogenic markers such as alkaline phosphatase activity, osteocalcin, and runt-related transcription factor 2 expressions on the melatonin-loaded methanol-annealed silk films in both proliferation and osteogenic media. The bioactivity of the melatonin-modified silk films was further confirmed by the enhanced mineralization compared to silk films alone. This study demonstrated the feasibility of developing melatonin-loaded silk materials and the positive effect of releasing melatonin at micromolar concentrations on osteogenic differentiation of human mesenchymal stem cells cultured especially in osteogenic medium.