Antimicrobial peptide immobilization on catechol-functionalized PCL/alginate wet-spun fibers to combat surgical site infection.

Surgical site infection (SSI) caused by pathogenic bacteria leads to delayed wound healing and extended hospitalization. Inappropriate uses of antibiotics have caused a surge in SSI and common antibiotics are proving to be ineffective against SSI. Antimicrobial peptides (AMPs) can be a potential solution to prevent SSI because of their broad spectrum of antimicrobial activities. In this study, naturally sourced AMPs were studied along with microfibers, fabricated by a novel wet-spinning method using sodium alginate and polycaprolactone. Afterward, fibers were functionalized by the catechol groups of dopamine immobilizing nucleophilic AMPs on the surface. Conjugation between PCL and alginate resulted in fibers with smooth surfaces improving their mechanical strength via hydrogen bonds. Having an average diameter of 220 µm, the mechanical properties of the fiber complied with USP standards for suture size 3-0. Engineered microfibers were able to hinder the growth of Proteus spp., a pathogenic bacterium for at least 60 hours whereas antibiotic ceftazidime failed. When subjected to a linear incisional wound model study, accelerated healing was observed when the wound was closed using the engineered fiber compared to Vicryl. The microfibers promoted faster re-epithelialization compared to Vicryl proving their higher wound healing capacity.

Chitosan/starch based unoxidized tannic acid modified microparticles for rapid hemostasis with broad spectrum antibacterial activity.

The development of a rapid hemostat through a facile method with co-existing antibacterial activity and minimum erythrocyte lysis property stands as a major requirement in the field of hemostasis. Herein, a series of novel microparticle hemostats were synthesized using chitosan, different hydrothermally-treated starches, and cross-linked with tannic acid (TA) simultaneously in an unoxidized environment via ionotropic gelation method. Hemostats' comparative functional properties, such as adjustable antibacterial and erythrocyte compatibility upon various starch additions were evaluated. The in vivo hemostatic study revealed that the developed hemostats for mouse liver laceration and rat tail amputation had clotting times (13 s and 38 s, respectively) and blood loss (51 mg and 62 mg, respectively) similar to those of Celox™. The erythrocyte adhesion test suggested that erythrocyte distortion can be lowered by modifying the antibacterial hemostats with different starches. The broad-spectrum antibacterial efficacy of the hemostats remained intact against S. aureus (>90 %), E. coli (>80 %), and P. mirabilis bacteria upon starch modification. They also demonstrated high hemocompatibility (<3 % hemolysis ratio), moderate cell viability (>81 %), in vivo biodegradation, and angiogenesis indicating adequate biocompatibility and wound healing. The developed hemostats hold significant promise to be employed as rapid hemostatic agents for preventing major bleeding and bacterial infection in emergencies.

Self-assembled sodium alginate polymannuronate nanoparticles for synergistic treatment of ophthalmic infection and inflammation: Preparation optimization and in vitro/vivo evaluation.

Frequent administrations are often needed during the treatment of ocular diseases due to the low bioavailability of the existing eye drops owing to inadequate corneal penetration and rapid drug washout. Herein, sodium alginate polymannuronate (SA) nanocarriers were developed using ionic gelation method that can provide better bioavailability through mucoadhesivity and sustained drug release by binding to the ocular mucus layer. This study disproves the common belief that only the G block of SA participates in the crosslinking reaction during ionic gelation. Self-assembly capability due to the linear flexible structure of the M block, better biocompatibility than G block along with the feasibility of controlling physicochemical characteristics postulate a high potential for designing efficient ocular drug delivery systems. Initially, four crosslinkers of varied concentrations were investigated. Taguchi design of experiment revealed the statistically significant effect of the crosslinker type and concentration on the particle size and stability. The best combination was detected by analyzing the particle size and zeta potential values that showed the desired microstructural properties for ocular barrier penetration. The desired combination was SA-Ca-1 that had particle size within the optimal corneal penetration range, that is 10-200 nm (135 nm). The drug carriers demonstrated excellent entrapment efficiency (∼89 % for Ciprofloxacin and ∼96 % for Dexamethasone) along with a sustained and simultaneous release of dual drug for at least 2 days. The nanoparticles also showed biocompatibility (4 ± 0.6 % hemolysis) and high mucoadhesivity (73 ± 2 % for 0.25 g) which was validated by molecular docking analysis. The prepared formulation was able to reduce the scleral inflammation of the rabbit uveitis models significantly within 3 days. Thus, the eye drop showed remarkable potential for efficient drug delivery leading to faster recovery.

Xanthan and gum acacia modified olive oil based nanoemulsion as a controlled delivery vehicle for topical formulations.

In this study, olive oil nanoemulsion modified with xanthan gum and gum acacia was explored as a potential controlled topical delivery vehicle. Oil-in-water nanoemulsion formulated with optimized composition of olive oil, tween 80, and water was used as the drug carrier and further modified with gum. Effect of gum on nanoemulsion different physiochemical characteristics, stability, rheology, drug release and encapsulation efficiency were investigated. Results showed that developed nanoemulsion behaved as low viscosity Newtonian fluid and released 100 % drug within 6 h. Modification with xanthan and gum acacia had significantly improved formulation viscosity, drug encapsulation efficiency (>85 %) and controlled drug release up to 40 % with release pattern following Korsmeyer-Peppas model. Additionally, xanthan gum modified formulation exhibited shear thinning rheology by forming an extended network in the continuous phase, whereas gum acacia modified formulation behaved as Newtonian fluid at high shear rate (>200 s-1). Furthermore, xanthan gum modified formulations had improved zeta potential, stability, monodispersity, and hemocompatibility and showed high antibacterial activity against S. aureus than gum acacia modified formulations. These results indicate the higher potential of xanthan gum modified formulation as a topical delivery vehicle. Moreover, skin irritation test demonstrated the safety of developed formulations for topical application.

Preparation of different polymorphs of cellulose from different acid hydrolysis medium.

In this study, medical cotton was subjected to acid hydrolysis in sulfuric, hydrochloric and phosphoric acid medium to prepare cellulose nanocrystals (CNC) with different morphologies and polymorphism. Morphology of the prepared CNC samples revealed fiber shaped morphology for sulfuric and hydrochloric acid hydrolyzed samples, whereas, spherical shaped for phosphoric acid hydrolyzed samples. The size of the spherical shaped CNC decreased with the increase of hydrolysis time, from 853 nm for 12 h to 187 nm for 48 h. X-ray Diffraction analysis showed that hydrochloric acid hydrolyzed CNC is cellulose I (CI), phosphoric acid hydrolyzed CNC is cellulose II (CII) and sulfuric acid hydrolyzed CNC contain both CI and CII. The crystallinity of sulfuric and hydrochloric acid hydrolysis samples was 91%, whereas, the crystallinity of phosphoric acid hydrolysis samples was between 43 and 60% depending on hydrolysis time. Thermal properties were also affected by the hydrolysis medium. Thus cellulose nanocrystals were prepared with different morphologies and physical characteristics through a facile method.

pH-Activatable MnO-Based Fluorescence and Magnetic Resonance Bimodal Nanoprobe for Cancer Imaging.

Stimuli-responsive nanoprobes that combine both fluorescence and magnetic resonance imaging (MRI) are anticipated to be highly beneficial for tumor visualization with high imaging sensitivity. By employing an interfacial templating scheme, a pH-activatable fluorescence/MRI dual-modality imaging nanoprobe is successfully developed based on the coencapsulation of MnO nanoparticles and coumarin-545T inside a hybrid silica nanoshell. To promote cancer cell targeting with high-specificity, the nanoprobes are also conjugated with folic acid to establish a greater affinity for cancer cells that over-express folate receptors on their cell membrane. In the new nanosystem, MnO nanoparticles are shown to function as an efficient fluorescence quencher of coumarin-545T prior to cellular uptake. However, fluorescence recovery is achieved upon acidic dissolution of the MnO nanoparticles following receptor-mediated endocytosis into the low pH compartments of the cancer cells. Meanwhile, the Mn(2+) ions thus released are also shown to exert a strong T1 contrast enhancement in the cancer cells. Therefore, by demonstrating the dual-activatable MRI and fluorescence imaging in response to the low pH conditions, it is envisioned that these nanoprobes would have tremendous potential for emerging cancer-imaging modalities such as image-guided cancer therapy.

Silica-F127 nanohybrid-encapsulated manganese oxide nanoparticles for optimized T1 magnetic resonance relaxivity.

To properly engineer MnO nanoparticles (MONPs) of high r1 relaxivity, a nanohybrid coating consisting of silica and F127 (PEO106PPO70PEO106) is designed to encapsulate MONPs. Achieved by an interfacial templating scheme, the nanohybrid encapsulating layer is highly permeable and hydrophilic to allow for an optimal access of water molecules to the encapsulated manganese oxide core. Hence, the efficacy of MONPs as MRI contrast agents is significantly improved, as demonstrated by an enhancement of the MR signal measured with a pre-clinical 7.0 T MRI scanner. The nanohybrid encapsulation strategy also confers high colloidal stability to the hydrophobic MONPs by the surface decoration of PEO chains and a small overall diameter (<100 nm) of the PEO-SiO2 nanohybrid-encapsulated MONPs (PEOMSNs). The PEOMSNs are not susceptible to Mn-ion leaching, and their biocompatibility is affirmed by a low toxicity profile. Moreover, these hybrid nanocapsules exhibit a nano-rattle structure, which would favor the facile loading of various therapeutic reagents for theranostic applications.

Silicon nanoparticles encapsulated in hollow graphitized carbon nanofibers for lithium ion battery anodes.

Silicon (Si) is a promising material for lithium ion battery (LIB) anodes due to its high specific capacity. To overcome its shortcomings such as insulation property and large volume change during the charge-discharge process, a novel hybrid system, Si nanoparticles encapsulated in hollow graphitized carbon nanofibers, is studied. First, electrospun polyacrylonitrile (PAN)-Si hybrid nanofibers were obtained using water as the collector. The loose nanofiber lumps suspended in water have large inter-fiber distance, allowing in situ coating of a thin layer of polydopamine (PDA), the source for graphitized carbon, uniformly throughout the system. The designed morphology and structure were then realized by etching and calcination, and the morphology and structure were subsequently verified by various analytical techniques. Electrochemical measurements show that the resulting hollow hybrid nanofibers (C-PDA-Si NFs) exhibit much better cycling stability and rate capacity than conventional C/Si nanofibers derived by electrospinning of PAN-Si followed by calcination. For instance, the capacity of C-PDA-Si NFs is as high as 72.6% of the theoretical capacity after 50 cycles, and a high capacity of 500 mA h g(-1) can be delivered at a current density of 5 A g(-1). The significantly improved electrochemical properties of C-PDA-Si NFs are due to the excellent electrical conductivity of the carbonized PDA (C-PDA) shell that compensates for the insulation property of Si, the high electrochemical activity of C-PDA, which has a layered structure and is N-doped, the hollow nature of the nanofibers and small size of Si nanoparticles that ensure smooth insertion-extraction of lithium ions and more complete alloying with them, as well as the buffering effect of the remaining PAN-derived carbon around the Si nanoparticles, which stabilizes the structure.

Silica-shell cross-linked micelles encapsulating fluorescent conjugated polymers for targeted cellular imaging.

A bioinspired silification approach was successfully used to encapsulate fluorescent conjugated polymers inside silica-shell cross-linked polymeric micelles (CP-SSCL) in the highly benign synthesis environment of room temperature and near-neutral aqueous environment. Four different conjugated polymers were employed to demonstrate the versatility of the bioinspired silification, resulting in the formation of CP-SSCL with different emission wavelengths across the visible spectrum. The CP-SSCL are characterized by a large absorption coefficient and high quantum yield, indicating that they exhibit the required high fluorescence brightness for cellular imaging application. In addition, the CP-SSCL also exhibit a high colloidal stability and low cytotoxicity. The in vitro studies of using MDA-MB-231 breast cancer cells show that the CP-SSCL are successfully uptaken by the cancer cells and located at the cytoplasm of the cells. Furthermore, by conjugating folic acid on their surfaces, the uptake of CP-SSCL by MDA-MB-231 cells was enhanced significantly, suggesting their great potential for targeted imaging and early detection of cancer cells.

Carbon/SnO2/carbon core/shell/shell hybrid nanofibers: tailored nanostructure for the anode of lithium ion batteries with high reversibility and rate capacity.

A carbon/SnO(2)/carbon core/shell/shell hybrid nanofibrous mat was successfully prepared via single-spinneret electrospinning followed by carbonization and hydrothermal treatment. The morphology and structure of carbon/SnO(2)/carbon hybrid nanofibers were characterized by field-emission scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, wide-angle X-ray diffraction and X-ray photoelectron spectroscopy, and their electrochemical properties were studied as an anode in lithium ion batteries (LIBs). It is shown that the designed hybrid nanofibrous mat exhibits excellent electrochemical properties, including high reversible capacity with high columbic efficiency and impressive rate capacity. The greatly enhanced electrochemical performance is mainly due to the morphological stability and reduced diffusion resistance, which are induced by both the carbon core and deposited carbon skin. Furthermore, the embedded and de-aggregated SnO(2) nanoparticles in the carbon phase, which are less than 10 nm in size, provide large numbers of reaction sites for lithium ions and ensure complete alloying with them.

Intrinsically fluorescent carbon dots with tunable emission derived from hydrothermal treatment of glucose in the presence of monopotassium phosphate.

A facile method is developed to synthesize intrinsically fluorescent carbon dots by hydrothermal treatment of glucose in the presence of monopotassium phosphate. The fluorescence emission of the carbon dots thus produced is tunable by simply adjusting the concentration of monopotassium phosphate.

Silica nanocapsules of fluorescent conjugated polymers and superparamagnetic nanocrystals for dual-mode cellular imaging.

We describe here a facile and benign synthetic strategy to integrate the fluorescent behavior of conjugated polymers and superparamagnetic properties of iron oxide nanocrystals into silica nanocapsules, forming a new type of bifunctional magnetic fluorescent silica nanocapsule (BMFSN). The resultant BMFSNs are uniform, colloidally stable in aqueous medium, and exhibit the desired dual functionality of fluorescence and superparamagnetism in a single entity. Four conjugated polymers with different emissions were used to demonstrate the versatility of employing this class of fluorescent materials for the preparation of BMFSNs. The applicability of BMFSNs in cellular imaging was studied by incubating them with human liver cancer cells, the result of which demonstrated that the cells could be visualized by dual-mode fluorescence and magnetic resonance imaging. Furthermore, the superparamagnetic behavior of the BMFSNs was exploited for in vitro magnetic-guided delivery of the nanocapsules into the cancer cells, thereby highlighting their potential for targeting biomedical applications.

Biomimetic composite coating on rapid prototyped scaffolds for bone tissue engineering.

The objective of this present study was to improve the functional performance of rapid prototyped scaffolds for bone tissue engineering through biomimetic composite coating. Rapid prototyped poly(ε-caprolactone)/tri-calcium phosphate (PCL/TCP) scaffolds were fabricated using the screw extrusion system (SES). The fabricated PCL/TCP scaffolds were coated with a carbonated hydroxyapatite (CHA)-gelatin composite via biomimetic co-precipitation. The structure of the prepared CHA-gelatin composite coating was studied by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Compressive mechanical testing revealed that the coating process did not have any detrimental effect on the mechanical properties of the scaffolds. The cell-scaffold interaction was studied by culturing porcine bone marrow stromal cells (BMSCs) on the scaffolds and assessing the proliferation and bone-related gene and protein expression capabilities of the cells. Confocal laser microscopy and SEM images of the cell-scaffold constructs showed a uniformly distributed cell sheet and accumulation of extracellular matrix in the interior of CHA-gelatin composite-coated PCL/TCP scaffolds. The proliferation rate of BMSCs on CHA-gelatin composite-coated PCL/TCP scaffolds was about 2.3 and 1.7 times higher than that on PCL/TCP scaffolds and CHA-coated PCL/TCP scaffolds, respectively, by day 10. Furthermore, reverse transcription polymerase chain reaction and Western blot analysis revealed that CHA-gelatin composite-coated PCL/TCP scaffolds stimulate osteogenic differentiation of BMSCs the most, compared with PCL/TCP scaffolds and CHA-coated PCL/TCP scaffolds. These results demonstrate that CHA-gelatin composite-coated rapid prototyped PCL/TCP scaffolds are promising for bone tissue engineering.

A generic approach for preparing core-shell carbon-metal oxide nanofibers: morphological evolution and its mechanism.

Carbon-SnO(2) core-shell hybrid nanofibers were prepared via single-spinneret electrospinning and subsequent heat treatment. The Kirkendall effect during the heat treatment is found to be responsible for the formation of core-shell morphology. The route is proven to be generic for fabrication of carbon-metal oxide or carbon-metal core-shell nanofibers, and corresponding nanotubes.

Designing poly[(R)-3-hydroxybutyrate]-based polyurethane block copolymers for electrospun nanofiber scaffolds with improved mechanical properties and enhanced mineralization capability.

Efforts to mineralize electrospun hydrophobic polyester scaffold often require prior surface modification such as plasma or alkaline treatment, which may affect the mechanical integrity of the resultant scaffold. Here through rational design we developed a series of polyurethane block copolymers containing poly[(R)-3-hydroxybutyrate] (PHB) as hard segment and poly(ethylene glycol) (PEG) as soft segment that could be easily fabricated into mineralizable electrospun scaffold without the need of additional surface treatment. To ensure that the block copolymers do not swell excessively in water, PEG content in the polymers was kept below 50 wt %. To obtain good dry and hydrated state mechanical properties with limited PEG, low-molecular-weight PHB-diol with M(n) 1230 and 1790 were used in various molar feed ratios. The macromolecular characteristics of the block copolymers were confirmed by (1)H NMR spectroscopy, gel permeation chromatography (GPC), and thermal gravimetric analyses (TGA). With the incorporation of the hydrophilic PEG segments, the surface and bulk hydrophilicity of the block copolymers were significantly improved. Differential scanning calorimetry (DSC) revealed that the block copolymers had low PHB crystallinity and no PEG crystallinity. This was further confirmed by X-ray diffraction analyses (XRD) in both dry and hydrated states. With short PHB segments and soft PEG coupled together, the block copolymers were no longer brittle. Tensile measurements showed that the block copolymers with higher PEG content or shorter PHB segments were more ductile. Furthermore, their ductility was enhanced in hydrated states with one particular example showing increment in strain at break from 1090 to 1962%. The block copolymers were fabricated into an electrospun fibrous scaffold that was easily mineralized by simple incubation in simulated body fluid. The materials have good potential for bone regeneration application and may be extended to other applications by simply coating them with other biologically active substances.

Enhanced biomineralization in osteoblasts on a novel electrospun biocomposite nanofibrous substrate of hydroxyapatite/collagen/chitosan.

Electrospun chitosan (CTS)-based hydroxyapatite (HAp)/CTS biocomposite nanofibers for bone tissue engineering could afford a close biomimicry to the fibrous nanostructure and constituents of the hierarchically organized natural bone, but their biological performance is somewhat deficient compared with the HAp/collagen (Col) biocomposite system. This necessitates doping the electrospun HAp/CTS hybrid with the bioactive component of Col. We show herein that Col-doped HAp/CTS biocomposite (i.e., HAp/Col/CTS) containing 27.8 wt% HAp nanoparticles, 7.2 wt% Col, and 57.8 wt% CTS can be successfully electrospun into nanofibrous form through using small amount (7.2 wt%) of ultrahigh-molecular-weight poly(ethylene oxide) as the fiber-forming additive. Morphology, structure, composition, and mechanical properties of the electrospun HAp/Col/CTS scaffolds were examined by field emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy, and tensile tests, respectively. Human fetal osteoblasts on the nanofibrous HAp/Col/CTS scaffolds were cultured for up to 15 days to assess the cell-scaffold interaction and biomineralization effect. In comparison with different controls, significant increments in osteoblast proliferation, alkaline phosphatase expression, and mineral deposition were observed. Results obtained thus highlight that introduction of Col can significantly enhance the biological performance of osteoblasts on the CTS-based nanofibrous substrates and suggest that current electrospun HAp/Col/CTS biocomposite, as a highly biomimetic and bioactive nanofibrous structure, may be one of the most attractive candidates for various osteoregeneration-related applications.

Facile synthesis of hybrid silica nanocapsules by interfacial templating condensation and their application in fluorescence imaging.

A stable aqueous dispersion of hybrid silica nanocapsules encapsulating fluorescent conjugated polymers have been successfully synthesized via a facile and highly benign approach of templated condensation of silica precursors at the core-corona interface of PEO-based block copolymer micelles.

Effect of molecular orientation on mechanical property of single electrospun fiber of poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyvalerate].

Electrospun poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyvalerate] (PHBV) fibers were collected by using a counter electrode collector or a rotating disk collector. The molecular orientation and mechanical property of single PHBV fiber were studied. 2-D wide-angle X-ray diffraction and polarized Fourier transform infrared spectra of the macroscopically aligned fibers confirmed the orientation of polymer chains, with PHBV chains preferentially oriented along the fiber axis. The degree of orientation increased with increasing fiber take-up velocity. X-ray diffraction pattern also indicates the development of beta-form crystal in electrospun PHBV fibers collected at an angular velocity of 1500 rpm. The thermal behavior of electrospun PHBV fibers was studied using modulated differential scanning calorimetry. The tensile properties of single electrospun PHBV fibers were studied using a nanotensile tester. Our results indicate that electrospun PHBV fiber with a higher degree of molecular orientation exhibits a higher tensile modulus and strength but lower strain at break.

Improving hydrophilicity, mechanical properties and biocompatibility of poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyvalerate] through blending with poly[(R)-3-hydroxybutyrate]-alt-poly(ethylene oxide).

Natural source poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyvalerate] (PHBV) with a low hydroxyvalerate (HV) content ( approximately 8wt.%) was modified by blending it with poly[(R)-3-hydroxybutyrate]-alt-poly(ethylene oxide) (HE) alternating block copolymer. We hypothesized that the adjoining PHB segments could improve the miscibility of the poly(ethylene oxide) segments of HE with the PHBV matrix and therefore improve the physical properties of the PHBV/HE blends. A differential scanning calorimetry study revealed the improved miscibility of PEO segments of HE characterized by the interference of the crystallization of PHBV. The decrease in water contact angle and the increase in equilibrium water uptake of the PHBV/HE blends indicated that both the surface and bulk hydrophilicity of PHBV could be improved through blending HE. The mechanical properties of the hydrated PHBV/HE blends were assessed by measuring their tensile strength. In contrast to the hydrated natural source PHBV, which failed in a brittle manner, the hydrated PHBV/HE blends were ductile. Their strain at break increased with increasing HE content, reaching a maximum of 394% at an HE content of 15wt.%. The excellent integrity of the PHBV/HE blends in water is attributed to the strong affinity between the PHB segments of HE and the PHBV matrix. Platelet adhesion on the film surface of the PHBV/HE blends was investigated in vitro to evaluate their blood compatibility. The results demonstrated that the PHBV/HE blends effectively resisted the adhesion of platelets due to the anchored PEO segments from HE on the film surface.