Silk fibroin catheter with stable bioinspired inner-surfaces for inhibition of bioadhesion.

Biofilm formation on indwelling medical devices such as catheters and ventilators due to the adhesion of bacteria poses significant challenges in healthcare. Surface modification with micro- and nano-structures offers a promising strategy to prevent bioadhesion and is safer than surface chemical modification approaches. Here, catheters were prepared using silk fibroin (SF) hydrogels and an infusion molding method, with the inner surface featuring a micropapillae structure inspired by lotus leaves (SF-CMP). After phenylethanol (PEA) fumigation treatment, the resulting catheters (SF-CMP PEA) displayed improved swelling resistance and mechanical properties compared to methanol-treated catheters (SF-CMP MeOH). PEA was more efficient than methanol in controlling the size, distribution, and content of silk crystalline ß-sheet blocks and thus the swelling and mechanical properties. Moreover, the micro-papillae structure on SF-CMP PEA remained stable over 35 days in solution, in contrast to SF-CMP MeOH, which lasted <7 days. SF-CMP PEA exhibited repellent effects against E. coli and S. aureusin vitro, and low cytotoxicity to the endothelial cells cultured on the unpatterned surface. Additionally, subcutaneous implantation studies showed reduced inflammation around the micropatterned samples compared to controls with a plain, unpatterned surface. The unique properties of SF-based materials, including tunable structures, biocompatibility, degradation, and drug-loading capability make them an attractive material for anti-bioadhesion in applications ranging from indwelling medical devices to tissue engineering scaffolds.

K-birnessite-MnO2/hollow mulberry-like carbon complexes with stabilized and superior rate performance for aqueous magnesium ion storage.

Manganese oxides are commonly employed as a cathode for magnesium ion storage in aqueous magnesium ion hybrid supercapacitors (MHS). However, sluggish reaction kinetics still hinders their practical application. Herein, we designed K-birnessite-MnO2 and electrostatically spun mulberry-like carbon composites (K-MnO2/HMCs) via an in situ growth technique. Benefiting from the 3D conductive carbon network substrate, the in situ fabricated K-MnO2 exhibits more active sites and provides more interfacial contact area between the electrode material and the electrolyte. This improvement enhances its conductivity, facilitating the rapid transfer of electrons, diffusion of ions, and redox reactions. As a result, K-MnO2/HMC-based MHS achieves a specific capacity of 168 mA h g-1 at 0.5 A g-1, simultaneously exhibiting a superior energy density of 111.1 W h kg-1 at a power density of 505 W kg-1. Furthermore, it demonstrates excellent high rate performance and a long cycling life for aqueous magnesium ion storage, offering new insights for MHS applications.

Facile synthesis of crumpled nitrogen-doped porous carbon nanosheets with ultrahigh surface area for high-performance supercapacitors.

Porous carbon nanosheets are currently considered excellent electrode materials for high-performance supercapacitors. However, their ease of agglomeration and stacking nature reduce the available surface area and limit the electrolyte ion diffusion and transport, thereby leading to low capacitance and poor rate capability. To solve these problems, we report an adenosine blowing and KOH activation combination strategy to prepare crumpled nitrogen-doped porous carbon nanosheets (CNPCNS), which exhibit much higher specific capacitance and rate capability compared to flat microporous carbon nanosheets. The method is simple and capable of one-step scalable production of CNPCNS with ultrathin crumpled nanosheets, ultrahigh specific surface area (SSA), microporous and mesoporous structure and high heteroatom content. The optimized CNPCNS-800 with a thickness of 1.59 nm has an ultrahigh SSA of 2756 m2 g-1, high mesoporosity of 62.9% and high heteroatom content (2.6 at% for N, 5.4 at% for O). Consequently, CNPCNS-800 presents an excellent capacitance, high rate capability and long cycling stability both in 6 M KOH and EMIMBF4. More importantly, the energy density of the CNPCNS-800-based supercapacitor in EMIMBF4 can reach up to 94.9 W h kg-1 at 875 W kg-1 and is still 61.2 W h kg-1 at 35 kW kg-1.

Upconversion nanoparticles anchored MnO2 nanosheets for luminescence "turn on" detecting hydrogen peroxide.

The sensitively and reliably detecting hydrogen peroxide (H2O2) is of significant for biology and environment protection fields. Herein, we reported a high sensitive H2O2 nanoprobe based on upconversion nanoparticles (UCNPs) anchored MnO2 nanosheets. In which, DNA modified NaYF4@NaYF4:Yb,Tm core-shell nanoparticles were anchored onto the MnO2 nanosheets surface via π-π stacking. Owing to the luminescence resonance energy transfer, the blue luminescence of UCNPs was effectively quenched by MnO2 nanosheets, then the luminescence could be restored by adding H2O2 for reducing MnO2 to Mn2+, and achieving a H2O2 concentration-dependent luminescence change, the detection limit could reach to 0.23 nM (S/N = 3). The proposed method could detect H2O2 in serum, lake water and real samples. Thus, a desired upconversion luminescence sensing strategy for detection H2O2 in life and environmental analysis was successfully constructed. It may be provide a potential tool in disease diagnosis and environmental monitoring fields.

Promotion of Wound Healing Using Nanoporous Silk Fibroin Sponges.

Wound dressings are important for wound repair. The morphology of the biomaterials used in these dressings, and in particular, the pore structure affects tissue regeneration by facilitating attachment and proliferation of cells due to the hierarchical multiscale, water absorbance, and nutrient transport. In the present study, silk fibroin (SF) sponges with walls containing nanopores (SFNS) were prepared from SF nanoparticles generated during the autoclaving of SF solutions, followed by leaching the SF nanoparticles from the freeze-dried sponges of SF. The nano/microporous structure, biofluid absorbance, and porosity of the SF sponges with and without nanopores were characterized. In vitro cell proliferation, in vivo biocompatibility, and wound healing were evaluated with the sponges. The results demonstrated that SFNS had significantly increased porosity and water permeability, as well as cell attachment and proliferation when compared with SF sponges without the nanopores (SFS). Wound dressings were assessed in a rat skin wound model, and SFNS was superior to SFS in accelerating wound healing, supported by vascularization, deposition of collagen, and increased epidermal thickness over 21 days. Hence, such a dressing material with a hierarchical multiscale pore structure could promote cell migration, vascularization, and tissue regeneration independently without adding any growth factor, which would offer a new strategy to design and engineer better-performed wound dressing.

Low-Density Silk Nanofibrous Aerogels: Fabrication and Applications in Air Filtration and Oil/Water Purification.

A method was developed to fabricate light, water-insoluble silk fibroin nanofibrous aerogels (SNFAs) through solvent welding of lyophilized silk nanofibrous 3D networks at the junction points while converting silk structures from random-coils to ß-sheets (water insoluble). Aromatic alcohols, especially phenethyl alcohol (PEA), supported robust solvent welding and the structural conversion of silk. PEA vapor treatment was a better approach than solvent infusion to retain volume, density, and mechanical strength of the SNFAs. The mechanical properties of highly orientated SNFAs were superior to randomly distributed fibers. The SNFAs had a low density (3.5 mg/cm3), high hydrophobicity (140.9°), and a porous surface morphology on the individual nanofibers, resulting in high efficiency and selectivity for absorbing particulate matter and oils. Compared with commonly used inorganic aerogels, the SNFAs developed in this study are biocompatible, easily functionalized, environmentally friendly, and low-cost and therefore have potential for air and water purification, biosensors, drug delivery, and tissue engineering.

Sustained Photosynthesis and Oxygen Generation of Microalgae-Embedded Silk Fibroin Hydrogels.

Microalgae immobilized in hydrogels offer advantages over those cultured in suspension culture in terms of carbon fixation and oxygen emission. However, alginate as a commonly used hydrogel for microalgal immobilization encounters problems with mechanical strength and stability. To address this limitation, silk fibroin (silk) hydrogels prepared by ultrasonication were utilized to host microalgae when mixed with the presonicated protein solution prior to its gelation. The gelation time, stability, and light transmission of these silk gels were evaluated, and a silk concentration of 4% w/v and a gel thickness of 1 mm provided mechanical strength and stability during algal culture in comparison to alginate hydrogels. Furthermore, silk hydrogels with algal cell densities of 7.6 × 105 and 7.8 × 107 cells/mL had better stability than those with a lower cell density (3.2 × 103 cells/mL), likely due to cell confinement and impact on proliferation. The silk hydrogels with microalgae at a high density generated 6.13 mg/L of oxygen continuously for 7 days. An oxygen-generating device was fabricated by coating the surface of a dialysis tube with a thin layer of the microalgae-embedded silk hydrogel, where the microalgal cells were nourished with culture medium prefilled in the dialysis tube. When suspended in a sealed flask filled with CO2 gas, the system continuously produced oxygen (151 mL) for at least 60 days, with an oxygen production efficiency 6 times that of microalgal suspension culture controls. This microalgae embedding and cultivation technique could have potential utility in air purification, tissue repair, and other applications due to the efficient and sustained generation of oxygen.

Control of octreotide release from silk fibroin microspheres.

Poly(d,l-lactide-co-glycolide) (PLGA) microspheres have been used as an injectable depot for prolonged release of octreotide (Sandostatin LAR®), a peptide drug for the treatment of acromegaly and gastrointestinal tumors. However, acylation and incomplete release of the encapsulated octreotide, as well as acidic degradation product-induced inflammation are the major challenges hampering widespread clinical applications of this delivery system. The purpose of this study was to develop a novel octreotide-delivering system utilizing naturally derived biodegradable material, silk fibroin (SF). Octreotide acetate was encapsulated in the SF microspheres with a high loading (8-10 wt%) using polyethylene glycol (PEG)-assisted emulsification method. The octreotide-SF microspheres exhibited a silk I structure (low crystallinity) and burst release in in vitro release studies. Ethanol treatment after microsphere formation significantly increased ß-sheet and silk II structure (high crystallinity) of the microspheres, significantly reducing the burst release and resulting in zero-order sustained release of octreotide over 102 days, and the data could be fit to the diffusion-driven release model. After the ethanol-treated microspheres were intramuscularly injected into rats at low (2 mg/kg) and high (8 mg/kg) octreotide doses, the plasma concentration of octreotide in the high dose group remained high (>50 pg/mL) at day 28 when compared to that of the control (pure drug at low dose) and low dose microsphere group. Interestingly, the plasma concentration for the high dose group at day 56 dramatically increased to >280 pg/mL observed at day 28. The low dose microsphere group showed a similar increase, but at a much lower level. The rebound octreotide level likely reflected degradation of the SF matrix which released tightly bound/trapped octreotide. Therefore, SF microspheres can deliver octreotide over a long period of time with release kinetics and the mechanism different from PLGA microsphere system.

Silk Fibroin-Based Fibrous Anal Fistula Plug with Drug Delivery Function.

The aim of this work is to develop a drug-loaded silk fibroin fibrous membrane (DSFM) that can be attached to the surface of an anal fistula plug to improve the treatment of Crohn's disease (CD). Curcumin (CUR) and 5-aminosalicylic acid (5-ASA)-loaded silk fibroin (SF) membranes are coaxially electrospun onto the surface of a braided silk filament plug. The membranes show a predominant structure of random coil and silk I conformation. The concentration of CUR/5-ASA (weight ratio of 1/1) in the SF solution is optimized to 0.4, 0.9, and 1.9 wt%. The morphologies, secondary structures, and in vitro drug release properties of the membranes are examined. Sectional images of fibers in the membranes show core-shell structures. The coaxial electrospinning process does not alter the chemical characteristics of the drugs. The dual-drugs encapsulated in the membranes are released in a steady and sustainable manner, and the cumulative release rate is improved by the increased drug loading. The membranes exhibit no cytotoxicity, thereafter increase the viability of human fibroblasts on the DSFMs. These SF membranes with core-shell structure and functional encapsulation of CUR and 5-ASA should be useful for further studies toward the treatment of CD.

A Biodegradable Stent with Surface Functionalization of Combined-Therapy Drugs for Colorectal Cancer.

In-stent restenosis caused by tumor ingrowth is a major problem for patients undergoing stent placement because conventional stents often lack sustainable antitumor capabilities. The aim of this work is to develop a silk fibroin (SF)-based nanofibrous membrane that is loaded with combined-therapy drugs by using electrospinning technologies, which is further coated on a polydioxanone (PDO) stent and used for the treatment of colorectal cancer (CRC). In order to improve treatment effectiveness, a combination of therapeutic drugs, i.e., curcumin (CUR) and 5-fluorouracil (5-FU), is dissolved into SF solution and then eletrospun onto the surface of the PDO stent. The morphology, secondary structure, and in vitro drug release profiles of the membranes are characterized. The antitumor efficacy is assessed in vitro and in vivo using a human CRC cell line and normal cells, and tumor-bearing nude mice. In vitro and in vivo studies on the nanofibrous memembrane-coating demonstrate improved antitumor effects for the CUR/5-FU dual drug system which can be attributed to cell cycle arrest in the S phase in association with induced apoptosis in tumor cells by blocking signal transducer and activator of transcription3 (Stat3) and nuclear factor kappa beta (NF-kB) signaling pathways, suggesting potential in the treatment of CRC in the future.

Effect of pH on polyethylene glycol (PEG)-induced silk microsphere formation for drug delivery.

The effects of changing solution pH in the range of 3.6-10.0 during a one-step silk microsphere preparation process, by mixing silk and polyethylene glycol (PEG), was assessed. The microspheres prepared at low pH (3.6) showed a more homogeneous size (1-3µm) and less porous texture than those prepared at neutral pH. High pH (10.0) inhibited microsphere formation, yielding small and inhomogeneous microspheres. Compared to neutral pH, low pH also increased the content of silk crystalline ß-sheet structure from approx. 30% to above 40%. As a result, the microspheres produced at low pH were more thermally stable as well as resistant to chemical (8M urea) and enzymatic (protease XIV) degradation when compared to microspheres prepared at neutral pH. Doxorubicin hydrochloride (DOX) and curcumin (CUR) were successfully loaded in silk microspheres via control of solution pH. The loading efficiency of DOX was approx. 95% at pH7.0 and approx. 60% for CUR at pH3.6, attributed to charge-charge interactions and hydrophobic interactions between the silk and drug molecules, respectively. When PBS, pH7.4, was used as a medium for release studies, the pH3.6 microspheres released both drugs more slowly than the pH7.0 microspheres, likely due to the high content of crystalline ß-sheet structure that enhanced drug-silk interactions as well as restricted drug molecule diffusion.