Nano-Nets Covered Composite Nanofibers with Enhanced Biocompatibility and Mechanical Properties for Bone Tissue Engineering

Tiwari, Arjun Prasad,Joshi, Mahesh Kumar,Park, Chan Hee,Kim, Cheol Sang American Scientific Publishers 2018 Journal of nanoscience and nanotechnology Vol.18 No.1

<P>Enhancing the biocompatibility profiles including cell attachment, growth, and viability and mechanical properties of designed synthetic scaffolds have an essential role in tissue engineering applications. Polymer blending is one of the most effective methods for providing new anticipated biomaterials for tissue scaffolds. Here, the blend solution of the different mass weight ratio of polycaprolactone (PCL) to human serum albumin (HSA) was subjected to fabricate nanocomposite spider-web-like membranes using electrospinning process. The physicochemical aspects of fabricated membranes had been characterized by a different state of techniques like that of scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FT-IR), thermal gravimetric analysis (TGA), contact angle meter and universal testing machine. FE-SEM images revealed that all PCL/HSA mats were composed of interlinked nano-nets along with conventional electro-spun fibers while nano-nets were not found for pristine PCL mat. Moreover, composite membranes exhibited improved water absorbability, enhanced biodegradation compared to pristine PCL membrane and had much better mechanical properties (tensile strength increased by up to 3-fold, Young's modulus by 2-fold). The cell attachment and proliferation tests were carried by culturing Mc3T3-E1 (pre-osteoblasts) with the designated nanofibrous membranes. The hybrid nanofibers exhibited extraordinary support for the adhesion and proliferation of cells when compared to the pristine PCL membrane. These results indicate that the nano-nets supported PCL/HSA scaffolds can be promising for tissue engineering applications.</P>

Formation of lipophilic drug-loaded human serum albumin nanofibers with the aid of glutathione

Tiwari, Arjun Prasad,Joshi, Mahesh Kumar,Maharjan, Bikendra,Lee, Joshua,Park, Chan Hee,Kim, Cheol Sang Elsevier 2017 CHEMICAL ENGINEERING JOURNAL -LAUSANNE- Vol.313 No.-

<P><B>Abstract</B></P> <P>We report an efficient approach for the fabrication of hydrophobic drug-loaded human serum albumin nanofibers for the first time. The successful formation of nanofibers was found closely related to the glutathione (GSH) concentration, solution temperature, and heating time. As-fabricated nanofibers were characterized by electron microscopy, Fourier transform infrared spectroscopy (FTIR) and X-ray powder diffraction (XRD). The electron micrographs show that nanofibers have cylindrical morphology and diameters of 70–120nm and lengths of up to few micrometers with a smooth surface. GSH was found to contribute to the quicker unfolding of the HSA under high temperature (80–85°C) which resulted in the strong interaction with paclitaxel, leading to a morphological transformation from nanoparticles to nanofibers. In addition, the possible mechanisms of nanofiber formation have been discussed.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Hydrophobic drug (paclitaxel) loaded human serum albumin nanofiber is reported for the first time. </LI> <LI> Facile strategy to produce albumin fibers encapsulated with a hydrophobic drug. </LI> <LI> Glutathione concentration, solution temp, and heating time affected the nanofiber formation. </LI> <LI> Time-lapsed electron microscopy images confirmed three stages in fiber formation. </LI> <LI> Spherical particles evolved into cylindrical fibers in response to continuous heating. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

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

Tiwari, Arjun Prasad,Hwang, Tae In,Oh, Jung-Mi,Maharjan, Bikendra,Chun, Sungkun,Kim, Beom Su,Joshi, Mahesh Kumar,Park, Chan Hee,Kim, Cheol Sang American Chemical Society 2018 ACS APPLIED MATERIALS & INTERFACES Vol.10 No.24

<P>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.</P> [FIG OMISSION]</BR>

Heterogeneous electrospun polycaprolactone/polyethylene glycol membranes with improved wettability, biocompatibility, and mineralization

Tiwari, Arjun Prasad,Joshi, Mahesh Kumar,Lee, Joshua,Maharjan, Bikendra,Ko, Sung Won,Park, Chan Hee,Kim, Cheol Sang Elsevier 2017 Colloids and surfaces. A, Physicochemical and engi Vol.520 No.-

<P><B>Abstract</B></P> <P>Polycaprolactone (PCL) based electrospun membranes possess many favorable characteristics such as flexibility, high mechanical properties, and non-toxicity, all of which are required for tissue engineering applications. However, their hydrophobic nature and low biocompatibility limit their uses. To overcome these drawbacks, we propose highly biocompatible and hydrophilic heterogeneous scaffolds from a blend of PCL with polyethylene glycol (PEG) that is composed of nano-nets along with backbone/main fibers via an electro-spinning/netting (ESN) technique. Different scaffolds were fabricated by varying the mass composition of PCL to PEG and evaluated physicochemically and biologically. Scanning electron microscopy showed that the PCL/PEG membranes were of a bimodal structure consisting of backbone/main fibers (diameter range=350–600nm) and ultrathin nano-nets while the pure PCL mat was composed of only backbone fibers (diameter range=550–800nm). The nano-nets were composed of ultrathin nano-wires with an average diameter of 10–20nm, shaped in a hexagonal form. We have also prepared the PCL/PEG membranes without nano-nets and compared them to heterogeneous membranes in order to describe the effect of the nano-nets by well distinguishing the effect of PEG on tissue engineering applications such as wettability, biocompatibility, and biomineralization. The results showed that heterogeneous scaffolds exhibit enhanced wettability, mechanical stability, biocompatibility, and mineralization compared to pure PCL and PCL/PEG scaffolds without nano-nets, which confirmed that the nano-nets in the membranes had positive effects for tissue engineering applications. Findings from this study have revealed that the heterogeneous fibrous membrane could be useful in the design and tailoring of a suitable structure as a scaffold for bone tissue engineering.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Heterogeneous fibrous membrane was reported from PCL/PEG first time via electro-spinning/netting (ESN). </LI> <LI> Heterogeneous membrane was consisting of thicker/backbone fibers and ultrathin nano-nets. </LI> <LI> Hydrophilicity and mineralization were improved with incorporation of PEG into PCL fibers. </LI> <LI> Heterogeneous scaffolds showed better support for cell activities. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

An Implantable Fibrous Platform Modified with Multiple Stimuli-responsive Conjugated Polymer for Synergistic Cancer Therapy

Arjun Prasad Tiwari(티와리 아준 프리차스),김학용 한국고분자학회 2019 한국고분자학회 학술대회 연구논문 초록집 Vol.44 No.2

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

Joshi, Mahesh Kumar,Tiwari, Arjun Prasad,Maharjan, Bikendra,Won, Ko Sung,Kim, Han Joo,Park, Chan Hee,Kim, Cheol Sang Elsevier 2016 Carbohydrate polymers Vol.147 No.-

<P><B>Abstract</B></P> <P>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.</P> <P><B>Highlights</B></P> <P> <UL> <LI> N6/CL composite fibers were obtained via electrospinning and deacetylation. </LI> <LI> Fiber diameter and pore size controlled varying the composition of component polymers. </LI> <LI> N6/CL composite fiber were more thermally stable than pristine N6 and N6/CA fibers. </LI> <LI> Wicking rate was pronouncedly enhanced due to cellulose regeneration. </LI> <LI> Tensile properties and biomimetic mineralization were improved. </LI> </UL> </P>

A novel <i>in situ</i> deposition of hydroxyapatite nanoplates using anodization/hydrothermal process onto magnesium alloy surface towards third generation biomaterials

Mousa, Hamouda M.,Tiwari, Arjun Prasad,Kim, Jinwoo,Adhikari, Surya Prasad,Park, Chan Hee,Kim, Cheol Sang Elsevier 2016 Materials letters Vol.164 No.-

<P><B>Abstract</B></P> <P>Third-generation biomaterials aim to stimulate specific cellular responses at the molecular level, these materials characterized with a resorbable and bioactivity that help body heal once they have been implanted. Here, a biomimetic method was used to generate hydroxyapatite (HA) nanoplates on the surface of AZ31B Mg alloy via anodization in simulated body fluid (SBF), followed by a hydrothermal (HT) process. The resulting nanoplates were characterized using FE-SEM, XRD, and FT-IR, surface hydrophobicity, in addition, corrosion was assessed electrochemically. The excellent bioactivity of the treated samples compared with naked ones were confirmed <I>in vitro</I> with MC3T3-E1 osteoblastic cells with significant growth and proliferation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Anodization/HT process was performed on the AZ31B Mg alloy. </LI> <LI> HA nanoplates like shape structure was generated after HT process. </LI> <LI> An improved bioactivity and corrosion resistance of the alloy was resulted. </LI> <LI> The generated nanoplates was found to mimic that in natural bone. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

In Situ Generation of Cellulose Nanocrystals in Polycaprolactone Nanofibers: Effects on Crystallinity, Mechanical Strength, Biocompatibility, and Biomimetic Mineralization

Joshi, Mahesh Kumar,Tiwari, Arjun Prasad,Pant, Hem Raj,Shrestha, Bishnu Kumar,Kim, Han Joo,Park, Chan Hee,Kim, Cheol Sang American Chemical Society 2015 ACS APPLIED MATERIALS & INTERFACES Vol.7 No.35

<P>Post-electrospinning treatment is a facile process to improve the properties of electrospun nanofibers for various applications. This technique is commonly used when direct electrospinning is not a suitable option to fabricate a nonwoven membrane of the desired polymer in a preferred morphology. In this study, a representative natural-synthetic hybrid of cellulose acetate (CA) and polycaprolactone (PCL) in different ratios was fabricated using an electrospinning process, and CA in the hybrid fiber was transformed into cellulose (CL) by post-electrospinning treatment via alkaline saponification. Scanning electron microscopy was employed to study the effects of polymer composition and subsequent saponification on the morphology of the nanofibers. Increasing the PCL content in the PCL/CA blend solution caused a gradual decrease in viscosity, resulting in smoother and more uniform fibers. The saponification of fibers lead to pronounced changes in the physicochemical properties. The crystallinity of the PCL in the composite fiber was varied according to the composition of the component polymers. The water contact angle was considerably decreased (from 124° to less than 20°), and the mechanical properties were greatly enhanced (Young’s Modulus was improved by ≈20–30 fold, tensile strength by 3–4 fold, and tensile stress by ≈2–4 fold) compared to those of PCL and PCL/CA membranes. Regeneration of cellulose chains in the nanofibers increased the number of hydroxyl groups, which increased the hydrogen bonding, thereby improving the mechanical properties and wettability of the composite nanofibers. The improved wettability and presence of surface functional groups enhanced the ability to nucleate bioactive calcium phosphate crystals throughout the matrix when exposed to a simulated body fluid solution. Experimental results of cell viability assay, confocal microscopy, and scanning electron microscopy imaging showed that the fabricated nanofibrous membranes have excellent ability for MC3T3-E1 cell proliferation and growth. Given the versatility and widespread use of cellulose–synthetic hybrid systems in the construction of tissue-engineered scaffolds, this work provides a novel strategy to fabricate the biopolymer-based materials for applications in tissue engineering and regenerative medicine.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/aamick/2015/aamick.2015.7.issue-35/acsami.5b04682/production/images/medium/am-2015-04682d_0014.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/am5b04682'>ACS Electronic Supporting Info</A></P>

Thromboresistant semi-IPN hydrogel coating: Towards improvement of the hemocompatibility/biocompatibility of metallic stent implants

Obiweluozor, Francis O.,Tiwari, Arjun Prasad,Lee, Jun Hee,Batgerel, Tumurbaatar,Kim, Ju Yeon,Lee, Dohee,Park, Chan Hee,Kim, Cheol Sang Elsevier 2019 Materials science & engineering. C, Materials for Vol.99 No.-

<P><B>Abstract</B></P> <P>Here we developed a semi-interpenetrating network (IPN) hydrogel obtained by free radical polymerization to fabricate a coated stent with the aim of incorporating a natural topography present in the human body to improve biological activity. The method involves sandwiching a bare metal stent in the semi-IPN hydrogel via solution cast molding. The bio-functionality of the membrane could be tuned by incorporating Polydopamine into the matrix, and also the mechanical property was optimized by choosing an adequate concentration of acrylamide. The coating containing polydopamine hydrogel showed good mechanical stability under continuous flow condition, as demonstrated by crimping and deployment into a catheter without damage. Stent polymer bonding was enhanced via polydopamine incorporation in the matrix. The non-thrombogenicity of the coating containing hydrogel was confirmed through dynamic hemocompatibility studies in vitro. Vascular simulations, including other biomechanical performance, like durability testing, radial strength, and recoil, were demonstrated. The dopamine containing hydrogel membrane (DCHM) was found to promote cell material interaction due to the ability of the catechol to bind protein and induce HUVECs cytoplasmic spreading, proliferation, and migration, with reduced smooth muscle cell (SMCs) activity. SMCs inhibition correlated well with the amount of incorporated catechol in the matrix. Our results show that this material used as coated stent could be more effective in suppressing platelet aggregation with improved haemocompatibility/biocompatibility for faster re-endothelialization than bare metal stent (BMS).</P> <P><B>Highlights</B></P> <P> <UL> <LI> 2D modeling of hydrogel coated stent for improved hemodynamics in contrast to bare metal stent was proposed. </LI> <LI> Incorporating PU as a second network in the IPN hydrogel greatly improve the mechanical property. </LI> <LI> The fabricated membrane creates a stable coating that enable delivery via non-invasive approach (catheter). </LI> <LI> Incorporation of Polydopamine in the matrix enhance HUVECs viability/ proliferation and suppresses SMCs viability. </LI> </UL> </P>

Bio-inspired hybrid scaffold of zinc oxide-functionalized multi-wall carbon nanotubes reinforced polyurethane nanofibers for bone tissue engineering

Shrestha, Bishnu Kumar,Shrestha, Sita,Tiwari, Arjun Prasad,Kim, Jeong-In,Ko, Sung Won,Kim, Han-Joo,Park, Chan Hee,Kim, Cheol Sang Elsevier 2017 Materials & Design Vol.133 No.-

<P><B>Abstract</B></P> <P>In this study, we prepared nanotopographical polyurethane (PU)-based bioactive scaffolds that incorporated uniformly dispersed functionalized multi-wall carbon nanotubes (<I>f</I>MWCNTs) and zinc oxide (ZnO) nanoparticles (NPs) using an electrospinning technique. We found that well dispersed <I>f</I>MWCNTs along with ZnO NPs reinforced PU fibers demonstrated significant improvement in mechanical strength, hydrophilicity, thermal stability, electrical conductivity, degradability, biomineralization, and biocompatibility. Inspired by the exciting nature of biopolymeric composite (PU/ZnO-<I>f</I>MWCNTs) membranes, these hybrid scaffolds offer extensive interest to tissue engineering as a potential biomedical application. The specific bioactive properties and cell-biomaterial interaction of electrospun scaffold containing 0.2wt% ZnO with 0.4wt% <I>f</I>MWCNTs were found to demonstrate anti-bacterial activity and cytocompatibility. Furthermore, the highly charged density, large surface-to-volume ratio, and more functional groups in <I>f</I>MWCNTs integrated on the scaffolds promote osteogenic differentiation of pre-osteoblast (MC3T3-E1) cells. Therefore, the novel as-prepared multifunctional electrospun fibrous scaffold could suggest new avenues for exploration as promising osteoproductive and osteoinductive biomaterials that offer great benefit to bone tissue engineering.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Functionalized multi-wall carbon nanotubes (<I>f</I>MWCNTs) within nanofiber enhance the electrical conductivity of scaffolds. </LI> <LI> The <I>f</I>MWCNTs (0.4 wt%) in scaffolds show good antibacterial activity. </LI> <LI> Interaction of zinc oxide and <I>f</I>MWCNTs with simulated body fluid resulting nucleation of calcium phosphate. </LI> <LI> The bioscaffolds exhibit excellent platform for osteogenic differentiation of pre-osteoblastic cells. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>