Design and evaluation of acrylate polymeric carriers for fabrication of pH-sensitive microparticles.

Colon-targeted microparticles loaded with a model anti-inflammatory drug were fabricated using especially designed acrylic acid-butyl methacrylate copolymers. Microparticles were prepared by oil-in-oil solvent evaporation method using Span 80 as emulsifier. Microparticles were found to be spherical in shape, hemocompatible and anionic with zeta potential of -27.4 and -29.0 mV. Entrapment of drug in the microparticles was confirmed by Fourier transform infrared (FTIR) spectroscopy. However, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) revealed amorphous nature of microparticles due to the dilution effect of amorphous polymer. The microparticles released less than 5% drug at pH 1.2, while more than 90% of the drug load was released at pH 7.4. This suggested the colon targeting nature of the formulations. In experimentally developed colitis in Wistar rats, the microparticle formulation showed significant reduction (p < .05) in the disease activity score (disease symptoms), the colon-to-body weight ratio (tissue edema) and the myeloperoxidase, tumor necrosis factor (TNF)-α and interleukin (IL)-1ß activities.

Cytotoxic evaluation of hydroxyapatite-filled and silica/hydroxyapatite-filled acrylate-based restorative composite resins: An in vitro study.

STATEMENT OF PROBLEM: Although the physical and mechanical properties of hydroxyapatite-filled dental restorative composite resins have been examined, the biocompatibility of these materials has not been studied in detail. PURPOSE: The purpose of this in vitro study was to analyze the toxicity of acrylate-based restorative composite resins filled with hydroxyapatite and a silica/hydroxyapatite combination. MATERIAL AND METHODS: Five different restorative materials based on bisphenol A-glycidyl methacrylate (bis-GMA) and tri-ethylene glycol dimethacrylate (TEGDMA) were developed: unfilled (H0), hydroxyapatite-filled (H30, H50), and silica/hydroxyapatite-filled (SH30, SH50) composite resins. These were tested for in vitro cytotoxicity by using human bone marrow mesenchymal stromal cells. Surface morphology, elemental composition, and functional groups were determined by scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDX), and Fourier-transformed infrared spectroscopy (FTIR). The spectra normalization, baseline corrections, and peak integration were carried out by OPUS v4.0 software. RESULTS: Both in vitro cytotoxicity results and SEM analysis indicated that the composite resins developed were nontoxic and supported cell adherence. Elemental analysis with EDX revealed the presence of carbon, oxygen, calcium, silicon, and gold, while the presence of methacrylate, hydroxyl, and methylene functional groups was confirmed through FTIR analysis. CONCLUSIONS: The characterization and compatibility studies showed that these hydroxyapatite-filled and silica/hydroxyapatite-filled bis-GMA/TEGDMA-based restorative composite resins are nontoxic to human bone marrow mesenchymal stromal cells and show a favorable biologic response, making them potential biomaterials.

Culture & differentiation of mesenchymal stem cell into osteoblast on degradable biomedical composite scaffold: In vitro study.

BACKGROUND & OBJECTIVES: There is a significant bone tissue loss in patients from diseases and traumatic injury. The current autograft transplantation gold standard treatment has drawbacks, namely donor site morbidity and limited supply. The field of tissue engineering has emerged with a goal to provide alternative sources for transplantations to bridge this gap between the need and lack of bone graft. The aim of this study was to prepare biocomposite scaffolds based on chitosan (CHT), polycaprolactone (PCL) and hydroxyapatite (HAP) by freeze drying method and to assess the role of scaffolds in spatial organization, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro, in order to achieve bone graft substitutes with improved physical-chemical and biological properties. METHODS: Pure chitosan (100CHT) and composites (40CHT/HAP, 30CHT/HAP/PCL and 25CHT/HAP/PCL scaffolds containing 40, 30, 25 parts per hundred resin (phr) filler, respectively) in acetic acid were freeze dried and the porous foams were studied for physicochemical and in vitro biological properties. RESULTS: Scanning electron microscope (SEM) images of the scaffolds showed porous microstructure (20-300 µm) with uniform pore distribution in all compositions. Materials were tested under compressive load in wet condition (using phosphate buffered saline at pH 7.4). The in vitro studies showed that all the scaffold compositions supported mesenchymal stem cell attachment, proliferation and differentiation as visible from SEM images, [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay, alkaline phosphatase (ALP) assay and quantitative reverse transcription (qRT)-PCR. INTERPRETATION & CONCLUSIONS: Scaffold composition 25CHT/HAP/PCL showed better biomechanical and osteoinductive properties as evident by mechanical test and alkaline phosphatase activity and osteoblast specific gene expression studies. This study suggests that this novel degradable 3D composite may have great potential to be used as scaffold in bone tissue engineering.

Enhanced redifferentiation of chondrocytes on microperiodic silk/gelatin scaffolds: toward tailor-made tissue engineering.

Direct-write assembly allows rapid fabrication of complex three-dimensional (3D) architectures, such as scaffolds simulating anatomical shapes, avoiding the need for expensive lithographic masks. However, proper selection of polymeric ink composition and tailor-made viscoelastic properties are critically important for smooth deposition of ink and shape retention. Deposition of only silk solution leads to frequent clogging due to shear-induced ß-sheet crystallization, whereas optimized viscoelastic property of silk-gelatin blends facilitate the flow of these blends through microcapillary nozzles of varying diameter. This study demonstrates that induction of controlled changes in scaffold surface chemistry, by optimizing silk-gelatin ratio, can govern cell proliferation and maintenance of chondrocyte morphology. Microperiodic silk-gelatin scaffolds can influence postexpansion redifferentiation of goat chondrocytes by enhancing Sox-9 gene expression, aggregation, and driving cartilage matrix production, as evidenced by upregulation of collagen type II and aggrecan expression. The strategy for optimizing redifferentiation of chondrocytes can offer valuable consideration in scaffold-based cartilage repair strategies.

Soluplus--solubilized citrated camptothecin--a potential drug delivery strategy in colon cancer.

Camptothecin (CPT), a potent antitumor drug, exhibits poor aqueous solubility and rapid conversion from the pharmacologically active lactone form to inactive carboxylate form at physiological pH. Solid dispersion of CPT in Soluplus®, an amphiphilic polymeric solubilizer, was prepared to increase the aqueous solubility of CPT and the resultant solid dispersion along with citric acid was formulated as hard gelatin capsules that were subsequently coated with Eudragit S100 polymer for colonic delivery. FTIR spectrum of the solid dispersion confirmed the presence of CPT. PXRD and DSC revealed the semicrystalline nature of solid dispersion. The solubility of the drug was found to increase ~40 times in the presence of Soluplus and ~75 times in solid dispersion. The capsules showed no drug release in 0.01 N HCl but released 86.4% drug in lactone form in phosphate buffer (pH 7.4) and the result appears to be due to citric acid-induced lowering of pH of buffer from 7.4 to 6.0. Thus the presence of citric acid in the formulation led to stabilization of the drug in its pharmacologically active lactone form. Cytotoxicity studies conducted with the formulation of solid dispersion with citric acid, utilizing cell cytotoxicity test (MTT test) on Caco-2 cells, confirmed cytotoxic nature of the formulation.

Eudragit S-100 entrapped chitosan microspheres of valdecoxib for colon cancer.

COX-2 inhibitors have demonstrated beneficial effects in colorectal cancer. The purpose of this study was to prepare and evaluate the colon specific microspheres of COX-2 inhibitors using valdecoxib as a model drug. Mucoadhesive core microspheres were prepared using chitosan as polymer and entrapped within Eudragit S 100 for colon targeting. FTIR spectrum of selected, coated microspheres showed peaks of valdecoxib at 3377, 3250, 1334 and 1155 cm(-1). XRD showed amorphous character and DSC showed depressed broad endotherm of valdecoxib at 169.07 degrees C, which may be attributed to dilution effect by the amorphous polymer. The coated microspheres were spherical with an average size of 90 mum. Storage of the microspheres at 40 degrees C/75% relative humidity for 6 months indicated no significant drug degradation. The coated microspheres did neither release the drug in acidic pH of stomach (pH 1.2) nor in small intestinal pH between 5 to 6.8, and the release started at pH 7.4, indicting perfect colonic delivery. The coated microspheres pretreated with phosphate buffer pH 7.4 for 30 min, when applied to mucosal surface of freshly excised goat colon, showed good mucoadhesion. The drug release at pH 7.4 and good mucoadhesive property of the microspheres make the system ideal for colonic delivery.

Gelatin-polytrimethylene carbonate blend based electrospun tubular construct as a potential vascular biomaterial.

The present work details the fabrication of electrospun tubular scaffolds based on the biocompatible and unexploited blend of gelatin and polytrimethylene carbonate (PTMC) as a media (middle layer of blood vessel) equivalent for blood vessel regeneration. An attempt to resemble the media stimulated the selection of gelatin as a matrix (substitution for collagen) with the inclusion of the biodegradable elastomer PTMC (substitution for elastin). -The work highlights the variation of electrospinning parameters and its assiduous selection based on fiber diameter distribution and pore size distribution to obtain smooth microfibers and micropores which is reported for the first time for this blend. Electrospun conduits of gelatin-PTMC blend had fibers sized 6-8 µm and pores sized ~100-150 µm. Young's modulus of 0.40 ±â€¯0.045 MPa was observed, resembling the tunica media of the native artery (~0.5 MPa). An evaluation of the surface properties, topography, and mechanical properties validated its physical requirements for inclusion in a vascular graft. Preliminary biological tests confirmed its minimal in-vitro toxicity and in-vivo biocompatibility. MTT assay (indirect) elucidated cell viability above 70% with scaffold extract, considered to be non-toxic according to the EN ISO-10993-5/12 protocol. The in-vivo subcutaneous implantation in rat showed a marked reduction in macrophages within 15 days revealing its biocompatibility and its possibility for host integration. This comprehensive study presents for the first time the potential of microporous electrospun gelatin and PTMC blend based tubular construct as a potential biomaterial for vascular tissue engineering. The proposed media equivalent included in a bilayer or trilayer polymeric construct can be a promising off-shelf vascular graft.

Formulation, characterization and evaluation of rotavirus encapsulated PLA and PLGA particles for oral vaccination.

Polylactide (PLA) and polylactide-co-glycolide (PLGA) particles entrapping rotavirus (strain SA11) were formulated using a solvent evaporation technique. To minimize denaturation of viral antigen during the emulsification process, serum albumin was used as a stabilizer. Use of NaHCO(3) and sucrose during the primary emulsification step resulted in uniform stabilized particles entrapping rotavirus. Sonication during the primary emulsion and homogenization during the secondary emulsion process resulted in particles of sizes 2-8 microm, whereas nanoparticles were formed when sonication was used during both primary and secondary emulsion processes. Scanning electron and atomic force microscopy showed uniform pores and roughness throughout the polymer particle surface. Single dose oral immunization with 20 microg of antigen entrapped in PLA particles elicited improved and long-lasting IgA and IgG antibody titer in comparison to the soluble antigen. The study shows results illustrating the usefulness of polymeric microparticles as a potential oral delivery system for rotavirus vaccine.

Development of an orthosis for simultaneous three-dimensional correction of clubfoot deformity.

BACKGROUND: Clubfoot is a three-dimensional deformity of the foot in which the foot is twisted in three mutually perpendicular planes from the normal shape of the foot. Of the various treatment methods that are available to manage clubfoot, non-operative approaches are preferred. The conventional non-operative method of treatment is to apply a series of casts to the infant's clubfoot to gradually manipulate its position. However, prolonged use of casts can result in skin rash, skin dehydration and ulcers on the soft skin of an infant. Treatment using orthosis represents an alternative non-operative and convenient technique because an orthosis can be put on and taken off at any time. METHODS: In the present study, an orthosis was developed according to the rotation of three mutually perpendicular planes and was subsequently tested on five patients over the duration of one week. FINDINGS: In all five cases, the desired incremental correction to the clubfoot was achieved through the one week intervention with the orthosis. No form of rash, dehydration, ulcers, and so on were observed on the skin of any baby involved in the study during or following application of the orthosis. INTERPRETATION: By using the developed orthosis, partial correction of the clubfoot deformity was achieved over a short period of time. However the widespread use of this device for extended durations and with a larger number of patients will generate further evidence of the extent to which this orthosis can reliably treat clubfoot.

Gelatin - Oxidized carboxymethyl cellulose blend based tubular electrospun scaffold for vascular tissue engineering.

The present work deals with the fabrication of electrospun tubular scaffold based on in-situ crosslinked blend of gelatin - oxidized carboxymethyl cellulose (OCMC) for vascular tissue engineering. The flow behavior and spinability of the hydrogel despite the in-situ crosslinked gelatin chains evaluated by Raman spectroscopic studies and rheological studies was utilized for electrospinning. The study highlights the tunable pore size and fiber diameter of the nanofibers with the manipulation of electrospinning parameters. With a future perspective of vascular tissue engineering, the electrospinning parameters yielding smooth bead free fibers and maximum magnitude in pore size and fiber diameter as well their homogenous distribution were selected for the fabrication of tubular constructs which is rarely reported. The surface and mechanical properties were evaluated to validate its properties to the native vessel. Biocompatibility was studied in vitro with BALB/c 3T3 cells and in vivo after subcutaneous implantation in rats. MTT assay confirmed its no-toxicity and no abnormal foreign body reaction were observed by 7 and 15days after implantation. Crosslinking with biocompatible crosslinker OCMC has rendered insolubility to gelatin yet making it spinable for electrospinning to fabricate porous, nanofibrous vascular biomaterial.

Formation and characterization of three dimensional human hepatocyte cell line spheroids on chitosan matrix for in vitro tissue engineering applications.

Chitosan was used as a matrix to induce three-dimensional spheroids of HepG2 cells. Chitosan films were prepared and used for culturing Hep G2 cells. Attachment kinetics of the cells was studied on the chitosan films. The optimum seeding density of the Hep G2 cells, required for three-dimensional spheroid formation was determined and was found to be 5 x 10(4)/ml. The growth kinetics of Hep G2 cells was studied using (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) (MTT) assay, and morphology of the cells was studied through optical photographs taken at various days of culture. The liver cell functions of the spheroids were determined by measuring albumin and urea secretions. The results obtained from these studies have shown that the culture of Hep G2 cells on chitosan matrix taking appropriate seeding density resulted in the formation of three-dimensional spheroids and exhibited higher amount of albumin and urea synthesis compared to monolayer culture. These miniature "liver tissue like" models can be used for in vitro tissue engineering applications like preliminary evaluation of the toxicity of drugs and chemicals.

Extraction of metal ions using chemically modified silica gel covalently bonded with 4,4'-diaminodiphenylether and 4,4'-diaminodiphenylsulfone-salicylaldehyde Schiff bases.

Two new chelating materials (Si-DDE-o-HB, and Si-DDS-o-HB) were synthesized by modifying the activated silica gel phase with Schiff bases of 4,4'-diaminodiphenylether (DDE)/4,4'-diaminodiphenylsulfone (DDS) and o-hydroxybenzaldehyde (o-HB). The synthesized materials were characterized by FTIR and BET surface area measurement techniques. The extraction of metal ions such as Zn2+, Mn2+ and Cr3+ by the chelating material Si-DDE-o-HB was found to be higher than that by Si-DDS-o-HB. The order of metal sorption was found to be Zn2+ > Mn2+ > Cr3+. The correlation coefficients for Freundlich and Langmuir adsorption isotherms were compared for the sorption of Zn2+ onto the chelating material. The loading and elution of the metal ion solution was examined at optimum pH 7.5 and 0.5 cm3 min-1 flow rate of the solution using a column technique. The preconcentration factor for the elution of Zn2+ using dilute HNO3 was found to be 66.2 with a breakthrough volume of 15 cm3. The data obtained for the preconcentration of Zn2+ by the column technique suggested that the material Si-DDE-o-HB can find industrial applications.

Three-dimensional chitosan scaffold-based MCF-7 cell culture for the determination of the cytotoxicity of tamoxifen.

Three-dimensional (3D) culture of cancer cell lines has long been advocated as a better model of the malignant phenotype that is most closely related to tumorigenicity in vivo. Moreover, new drug development requires simple in vitro models that resemble the in vivo situation more in order to select active drugs against solid tumours and to decrease the use of experimental animals. A biodegradable, biocompatible and non-toxic polymer chitosan was employed for 3D culture of MCF-7 cell lines. Cells grown on chitosan scaffold produce more lactate from glucose in comparison to that secreted by cells grown on tissue culture plate, thus indicating the suitability of chitosan scaffold as an in vitro model resembling cancer tissue growth in vivo. Cytotoxic effect of tamoxifen at different concentrations was evaluated for MCF-7 breast cancer cell lines grown on tissue culture plate as well as on 3D chitosan scaffold. At a tamoxifen concentration of 10(-6) M, 50% reduction in cell growth was observed in tissue culture plate-grown cells where 15% reduction in cell growth was observed when cells were grown in chitosan scaffold. Higher tamoxifen concentrations were required to achieve comparable cytostatic action in 3D culture, supporting the fact that 3D culture is a better model for the cytotoxic evaluation of anticancer drugs in vitro. Carbohydrate metabolism of MCF-7 cells in terms of glucose utilization and lactate production in 3D and monolayer culture were unaffected by tamoxifen treatment. Cathepsin D activity, an autocrine growth factor in breast cancer cells was monitored in all experiments. In 3D culture, addition of tamoxifen promoted cathepsin D secretion but inhibited its uptake by cells. Growth of cells in 3D chitosan scaffold indicated that action of tamoxifen on estrogen positive cancer cells is also mediated through inhibition of cathepsin D uptake from the culture medium.

Design and development of a device to measure the deformities of clubfoot.

Clubfoot describes a range of foot abnormalities usually present at birth, in which the foot of a baby is twisted out of shape or position. In order to develop an effective treatment plan for clubfoot and/or assess the extent to which existing interventions are successful, medical practitioners need to be able to accurately measure the nature and extent of the deformity. This is typically performed using a goniometer. However, this device is only able to measure one dimension at a time. As such, a complete assessment of the condition of a foot can be extremely burdensome and time-consuming. This article describes a new device that can quickly and efficiently take several measurements on feet of various sizes and shapes. The use of this device was verified by measuring the deformities of real clubfeet. A silicone rubber clubfoot model was also used in this study to clearly illustrate the effectiveness with which the proposed device can measure the various deformities of clubfoot. It is envisaged that the use of this device will significantly reduce the time and effort orthopedists require to measure clubfoot deformities and develop and assess treatment plans.

Bioprintable, cell-laden silk fibroin-gelatin hydrogel supporting multilineage differentiation of stem cells for fabrication of three-dimensional tissue constructs.

Bioprinting has exciting prospects for printing three-dimensional (3-D) tissue constructs by delivering living cells with appropriate matrix materials. However, progress in this field is currently extremely slow due to limited choices of bioink for cell encapsulation and cytocompatible gelation mechanisms. Here we report the development of clinically relevant sized tissue analogs by 3-D bioprinting, delivering human nasal inferior turbinate tissue-derived mesenchymal progenitor cells encapsulated in silk fibroin-gelatin (SF-G) bioink. Gelation in this bioink was induced via in situ cytocompatible gelation mechanisms, namely enzymatic crosslinking by mushroom tyrosinase and physical crosslinking via sonication. Mechanistically, tyrosinases oxidize the accessible tyrosine residues of silk and/or gelatin into reactive o-quinone moieties that can either condense with each other or undergo nonenzymatic reactions with available amines of both silk and gelatin. Sonication alters the hydrophobic interaction and accelerates self-assembly of silk fibroin macromolecules to form ß-sheet crystals, which physically crosslink the hydrogel. However, sonication has no effect on the conformation of gelatin. The effect of optimized rheology, secondary conformations of silk-gelatin bioink, temporally controllable gelation strategies and printing parameters were assessed to achieve maximum cell viability and multilineage differentiation of the encapsulated human nasal inferior turbinate tissue-derived mesenchymal progenitor cells. This strategy offers a unique path forward in the direction of direct printing of spatially customized anatomical architecture in a patient-specific manner.

Synthesis, characterization, and blood compatibility of polyamidoamines copolymers.

This work reports the development of new non-thrombogenic polymers based on the linear polymers of polyamidoamines (PAAs), having heparin binding ability, obtained by polyaddition of secondary amines to N,N'-methylene bis-acrylamide. PAAs could not be used directly in the making of blood-contacting materials due to their poor mechanical strength. In order to overcome this lacuna, copolymers of amidoamine with methylmethacrylate (MMA) were prepared. Characterization studies indicated that the PAAs have been suitably incorporated into the MMA matrix. The relative hydrophilic nature of the synthesized copolymers was established from the measurement of water contact angle. The heparinized copolymers showed significant improvement in non-thrombogenic characteristics.

Synthesis of blood compatible polyamide block copolymers.

Blood compatibility of polyamides has been improved by introducing amido-amine groups in polymer backbone. Polyamide block-copolymer are synthesized by reacting amine end-capped polyamides with N,N'-methylene-bisacrylamide. Polyamide block-copolymers, thus produced found to have the ability of absorbing heparin. Heparinized polyamide block-copolymers have shown significant improvement in blood compatibility as evident from thrombus formation and hemolysis studies.

Release behaviour of drugs from tamarind seed polysaccharide tablets.

PURPOSE: This study examines the sustained release behaviour of both water-soluble (acetaminophen, caffeine, theophylline and salicylic acid) and water insoluble (indomethacin) drugs from tamarind seed polysaccharide isolated from tamarind kernel powder. It further investigates the effect of incorporation of diluents like microcrystalline cellulose and lactose on release of caffeine and partial cross-linking of the polysaccharide on release of acetaminophen. Applying exponential equation, the mechanism of release of soluble drugs was found to be anomalous. The insoluble drug showed near case II or zero order release mechanism. The rate of release was in the decreasing order of caffeine, acetaminophen, theophylline, salicylic acid and indomethacin. An increase in release kinetics of drug was observed on blending with diluents. However, the rate of release varied with type and amount of blend in the matrix. The mechanism of release due to effect of diluents was found to be anomalous. The rate of release of drug decreased on partial cross-linking and the mechanism of release was found to be super case II.

Strategies for replicating anatomical cartilaginous tissue gradient in engineered intervertebral disc.

A critical challenge in fabricating a load bearing tissue, such as an intervertebral disc, is to simulate cellular and matrix alignment and anisotropy, as well as a specific biochemical gradient. Towards this goal, multilamellar silk fibroin scaffolds having criss-cross fibrous orientation were developed, where silk fibers in inner layers were crosslinked with bioactive molecule chondroitin sulfate. Upon culturing goat articular chondrocytes under static and dynamic conditions, lamellar scaffold architecture guided alignment of cells and the newly synthesized extracellular matrix (ECM) along the silk fibers. The dynamic culture conditions further improved the cellular metabolic rate and ECM production. Further the synergistic effect of chemical composition of scaffold and hydrodynamic environment of bioreactor contributed in developing a tissue gradient within the constructs, with an inner region rich in collagen II, glycosaminoglycan (GAG), and stiffer in compression, whereas an outer region rich in collagen I and stiffer in tension. Therefore, a unique combination of chemical and physical parameters of engineered constructs and dynamic culture conditions provides a promising starting point to further improve the system towards replicating the anatomical structure, composition gradient, and function of intervertebral disc tissue.

Combined miRNA and mRNA signature identifies key molecular players and pathways involved in chikungunya virus infection in human cells.

Since its discovery, Chikungunya fever caused by a virus (CHIKV) has ravaged most of Africa and Southeast Asia. Despite there being more than a million reported cases in India alone and the seriousness of the disease in the chronic phase, a clear understanding of the disease pathogenesis and host response remains elusive. Here, we use microarray technology and quantitative PCR method to establish the complete miRNA, snoRNA and mRNA signature of host response upon CHIKV infection in human cell line infection model, HEK293T. The results were further validated in human primary cells (dermal fibroblasts). miRNA expression profiling revealed regulation of 152 miRNAs post CHIKV infection. An interesting overlap in miRNA signature was seen majorly with HCV, HPV and HIV1 virus. The microarray data further validated by qRT-PCR revealed induction of miR-744, miR-638, miR-503 and others among the top upregulated miRNAs. Notably, we found induction of snoRNAs belonging to C/D cluster including close paralogs of U3, U44, U76 and U78 snoRNAs. Genes were found to be differentially expressed along 3 major pathways; TGF-ß, endocytosis and the cell cycle pathways. qRT-PCR data confirmed strong induction of TGF-ß (SMAD6, JUN, SKIL) and endocytosis pathway (CXCR4, HSPA8, ADRB1) genes while downregulation of cell cycle genes (CDC27 and CDC23). Interestingly, use of TGF-ß inhibitor, SB-431542, increased CHIKV mediated cell death. Overall, this study aims at providing the first complete transcriptome signature of host response upon CHIKV infection to aid identification of possible biomarkers and therapeutic targets.