Bikendra Maharjan

Three-dimensional cellulose sponge: Fabrication, characterization, biomimetic mineralization, and in vitro cell infiltration

In this study, cellulose based scaffolds were produced by electrospinning of cellulose acetate (CA) solution followed by its saponification with NaOH/ethanol system for 24h. The resulting nonwoven cellulose mat was treated with sodium borohydride (SB) solution. In situ hydrolysis of SB solution into the pores of the membrane produced hydrogen gas resulting a three-dimensional (3D) cellulose sponge. SEM images demonstrated an open porous and loosely packed fibrous mesh compared to the tightly packed single-layered structure of the conventional electrospun membrane. 3D cellulose sponge showed admirable ability to nucleate bioactive calcium phosphate (Ca-P) crystals in simulated body fluid (SBF) solution. SEM-EDX and X-ray diffraction studies revealed that the minerals deposited on the nanofibers have the nonstoichiometric composition similar to that of hydroxyapatite, the mineralized component of the bone. 3D cellulose sponge exhibited the better cell infiltration, spreading and proliferation compared to 2D cellulose mat. Therefore, a facile fabrication of 3D cellulose sponge with improved mineralization represents an innovative strategy for the bone tissue engineering applications.

Cellulose reinforced nylon-6 nanofibrous membrane: Fabrication strategies, physicochemical characterizations, wicking properties and biomimetic mineralization.

The aim of the present study is to develop a facile, efficient approach to reinforce nylon 6 (N6) nanofibers with cellulose chains as well as to study the effect that cellulose regeneration has on the physicochemical properties of the composite fibers. Here, a cellulose acetate (CA) solution (17wt%) was prepared in formic acid and was blended with N6 solution (20%, prepared in formic acid and acetic acid) in various proportions, and the blended solutions were then electrospun to produce hybrid N6/CA nanofibers. Cellulose was regenerated in-situ in the fiber via alkaline saponification of the CA content of the hybrid fiber, leading to cellulose-reinforced N6 (N6/CL) nanofibers. Electron microscopy studies suggest that the fiber diameter and hence pore size gradually decreases as the mass composition of CA increases in the electrospinning solution. Cellulose regeneration showed noticeable change in the polymorphic behavior of N6, as observed in the XRD and IR spectra. The strong interaction of the hydroxyl group of cellulose with amide group of N6, mainly via hydrogen bonding, has a pronounced effect on the polymorphic behavior of N6. The γ-phase was dominant in pristine N6 and N6/CA fibers while α- phase was dominant in the N6/CL fibers. The surface wettability, wicking properties, and the tensile stress were greatly improved for N6/CL fibers compared to the corresponding N6/CA hybrid fibers. Results of DSC/TGA revealed that N6/CL fibers were more thermally stable than pristine N6 and N6/CA nanofibers. Furthermore, regeneration of cellulose chain improved the ability to nucleate bioactive calcium phosphate crystals in a simulated body fluid solution.

In-situ synthesis of AgNPs in the natural/synthetic hybrid nanofibrous scaffolds: Fabrication, characterization and antimicrobial activities

Silver nanoparticles embedded within a nanofibrous polymer matrix have significant attention in recent years as an antimicrobial wound dressing materials. Herein, we have fabricated a novel Ag-polyurethane-zein hybrid nanofibrous scaffold for wound dressing applications. AgNPs were synthesized in-situ via reduction of silver nitrate in electrospinning solution. Varying mass composition of the components showed the pronounced effect on the morphology and physicochemical properties of the composite fibers. Field-Emission Scanning Electron Microscopy (FESEM) images revealed that PU and zein with mass ratio 2:1 produced the bead-free continuous and uniformly distributed nanofibers. Fourier-transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD) and Thermogravimetric Analysis (TGA) confirmed the well interaction between component polymers. Compared to the pristine PU nanofibers, composite fibers showed enhanced tensile strength, young׳s modulus and surface wettability. The antibacterial capacity of the nanofibrous membrane was evaluated against gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacterial strains via a zone of inhibition test, and the results showed high antibacterial performance for Ag incorporated composite mat. Experimental results of cell viability assay and microscopic imaging revealed that as-fabricated scaffolds have an excellent ability for fibroblast cell adhesion, proliferation and growth. Overall, as-fabricated antibacterial natural/synthetic composite scaffold can be a promising substrate for repairing skin defects.

pH/NIR-Responsive Polypyrrole-Functionalized Fibrous Localized Drug-Delivery Platform for Synergistic Cancer Therapy

Localized drug-delivery systems (LDDSs) are a promising approach for cancer treatment because they decrease systematic toxicity and enhance the therapeutic effect of the drugs via site-specific delivery of active compounds and possible gradual release. However, the development of LDDS with rationally controlled drug release and intelligent functionality holds great challenge. To this end, we have developed a tailorable fibrous site-specific drug-delivery platform functionalized with pH- and near-infrared (NIR)-responsive polypyrrole (PPy), with the aim of cancer treatment via a combination of photothermal ablation and chemotherapy. First, a paclitaxel (PTX)-loaded polycaprolactone (PCL) (PCL-PTX) mat was prepared by electrospinning and subsequently in situ membrane surface-functionalized with different concentrations of PPy. The obtained PPy-functionalized mats exhibited excellent photostability and heating property in response to NIR exposure. PPy-coated mats exhibited enhanced PTX release in a pH 5.5 environment compared to pH 7.4. Release was further accelerated in response to NIR under both conditions; however, superior release was observed at pH 5.5 compared to pH 7.4, indicating a dual stimuli-responsive (pH and NIR) drug-delivery platform. More importantly, the 808 nm NIR irradiation enabled markedly accelerated PTX release from PPy-coated PCL-PTX mats and slowed and sustained release following termination of laser irradiation, confirming representative stepwise drug-release properties. PPy-coated PCL-PTX mats presented significantly enhanced in vitro and in vivo anticancer efficacy under NIR irradiation compared to PPy-coated PCL-PTX mats not exposed to NIR or uncoated mats (PCL-PTX). This study has thus developed a promising fibrous site-specific drug-delivery platform with NIR- and pH-triggering that notably utilizes PPy as a dopant for synergistic photothermal chemotherapy.

A mussel inspired self-expandable tubular hydrogel with shape memory under NIR for potential biomedical applications

We engineered a novel shape memory polymer (SMP), a nanocomposite hydrogel containing polydopamine nanospheres (PDNs) as a self-expandable tubular hydrogel under near-infrared (NIR) irradiation. When NIR is applied to the nanocomposite hydrogel, the PDN nanoparticles absorb light, which is locally dissipated as heat to become the driving force for shape transition behavior. Since the fabricated PDN material has good mechanical properties, including rapid self-expandability and good biocompatibility, when developed with good heating properties under (NIR) irradiation, it might be useful for many biomedical applications such as the treatment of coronary artery disease.

Sacrificial template-based synthetic approach of polypyrrole hollow fibers for photothermal therapy

In the present work, polypyrrole hollow fibers (PPy-HFs) were fabricated by sacrificial removal of soft templates of electrospun polycaprolactone (PCL) fibers with polypyrrole (PPy) coating through chemical polymerization of pyrrole monomer. Different physicochemical properties of as-fabricated PPy-HFs were then studied by Field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), Fourier transform infra-red (FT-IR) spectroscopy, Differential scanning calorimetry/Thermogravimetric analysis (DSC/TGA), and X-ray photoelectron spectroscopy (XPS). The photothermal activity of PPy-HF was studied by irradiating 808-nm near infra-red (NIR) light under different power values with various concentrations of PPy-HFs dispersed in phosphate buffer solution (PBS, pH 7.4). These PPy-HFs exhibited enhanced photothermal performance compared with polypyrrole nanoparticles (PPy-NPs). Furthermore, these PPy-HFs showed photothermal effect that was laser-power- and concentration-dependent. The photothermal toxicity of the resulting nanofiber was evaluated using cell counting kit-8 (CCK-8) and live and dead cell assays. Results showed that these PPy-HFs were more effective in killing cancer cells under NIR irradiation. In contrast, hollow-fiber showed no cytotoxicity without NIR exposure. Among different nanofiber formulations, PPy-160 exhibited the highest photothermal toxicity. It could be explained by its enhanced photothermal performance compared to other specimens. The resulting PPy-HFs showed superior drug-loading capacity to PPy-NPs. This might be attributed to adequate binding of the drug into both luminal and abluminal hollow-fiber surfaces. Fabrication of this substrate type opens a promising new avenue for architectural design of biocompatible organic polymer for biomedical field.