Publications by authors named "Jayesh Bellare"

114 Publications

"Viscotaxis"- directed migration of mesenchymal stem cells in response to loss modulus gradient.

Acta Biomater 2021 Aug 29. Epub 2021 Aug 29.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai, India. Electronic address:

Directed cell migration plays a crucial role in physiological and pathological conditions. One important mechanical cue, known to influence cell migration, is the gradient of substrate elastic modulus (E). However, the cellular microenvironment is viscoelastic and hence the elastic property alone is not sufficient to define its material characteristics. To bridge this gap, in this study, we investigated the influence of the gradient of viscous property of the substrate, as defined by loss modulus (G) on cell migration. We cultured human mesenchymal stem cells (hMSCs) on a collagen-coated polyacrylamide gel with constant storage modulus (G) but with a gradient in the loss modulus (G). We found hMSCs to migrate from high to low loss modulus. We have termed this form of directional cellular migration as "Viscotaxis". We hypothesize that the high loss modulus regime deforms more due to creep in the long timescale when subjected to cellular traction. Such differential deformation drives the observed Viscotaxis. To verify our hypothesis, we disrupted the actomyosin contractility with myosin inhibitor blebbistatin and ROCK inhibitor Y27632, and found the directional migration to disappear. Further, such time-dependent creep of the high loss material should lead to lower traction, shorter lifetime of the focal adhesions, and dynamic cell morphology, which was indeed found to be the case. Together, findings in this paper highlight the importance of considering the viscous modulus while preparing stiffness-based substrates for the field of tissue engineering. STATEMENT OF SIGNIFICANCE: While the effect of substrate elastic modulus has been investigated extensively in the context of cell biology, the role of substrate viscoelasticity is poorly understood. This omission is surprising as our body is not elastic, but viscoelastic. Hence, the role of viscoelasticity needs to be investigated at depth in various cellular contexts. One such important context is cell migration. Cell migration is important in morphogenesis, immune response, wound healing, and cancer, to name a few. While it is known that cells migrate when presented with a substrate with a rigidity gradient, cellular behavior in response to viscoelastic gradient has never been investigated. The findings of this paper not only reveal a completely novel cellular taxis or directed migration, it also improves our understanding of cell mechanics significantly.
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http://dx.doi.org/10.1016/j.actbio.2021.08.039DOI Listing
August 2021

Ethanol affects fibroblast behavior differentially at low and high doses: A comprehensive, dose-response evaluation.

Toxicol Rep 2021 18;8:1054-1066. Epub 2021 May 18.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra, 400076, India.

This study aims to develop a comprehensive understanding of effects of low and high doses of ethanol on cellular biochemistry and morphology. Here, fibroblast cells are exposed to ethanol of varied concentrations [0.005-10 % (v/v)] to investigate cellular activity, cytoskeletal organization, cellular stiffness, mitochondrial structure, and real-time behavior. Our results indicate a sharp difference in cellular behavior above and below 1 % ethanol concentration. A two-fold increase in MTT activity at low doses is observed, whereas at high doses it decreases. This increased activity at low doses does not involve cell proliferation changes or mitochondrial impairment, as seen at higher doses. Moreover, the study identifies different types of mitochondrial structure impairment at high doses. Morphologically, cells demonstrate a gradual change in cytoskeletal organization and an increase in cell stiffness with increase in doses. Cells exhibit adaptation to sub-toxic doses of ethanol, wherein recovery from ethanol-induced stress is a dose-dependent phenomenon. Cell survival at low doses and toxicity at higher doses are attributed to mild and strong oxidative stress, respectively. Overall, the study provides a comprehensive understanding of dose-dependent effects of ethanol, manifesting its biphasic or hormetic response, biochemically, at low doses and illustrating its toxicological effects at higher doses.
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http://dx.doi.org/10.1016/j.toxrep.2021.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296147PMC
May 2021

Physicochemical Variation in Nanogold-Based Ayurved Medicine Suvarna Bhasma Produced by Various Manufacturers Lead to Different In Vivo Bioaccumulation Profiles.

J Evid Based Integr Med 2021 Jan-Dec;26:2515690X211011064

Department of Chemical Engineering, 29491Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra, India.

(SB) is a gold particle-based medicine that is used in to treat tuberculosis, arthritis and nervous diseases. Traditionally, the preparation processes of SB do exist, but they are all long, tedious and involve several steps. Due to this, there is a possibility of bypassing the necessary processes or non-adherence to all steps or use of synthetic gold particles. Our aim is to characterize 5 commercial SB preparations from 5 different manufacturers. A comparative physicochemical, pharmacokinetic (PK) and bioaccumulation study was carried out on all the 5 SB preparations. The general appearance such as color and texture of these 5 samples were different from each other. The size, shape and gold concentration (from 32-98 wt%) varied among all the 5 SBs. The accumulation of ionic gold in zebrafish and gold concentration profiles in rat blood were found to be significantly different for all the 5 SBs. Non-compartmental PK model obtained from the concentration-time profile showed significant differences in various PK parameters such as peak concentration (C), half-life (t) and terminal elimination slope (λ) for all the 5 SB preparations. SB-B showed the highest C (8.55 μg/L), whereas SB-D showed the lowest C (4.66 μg/L). The dissolution of ionic gold from SBs in zebrafish tissue after the oral dose had a 5.5-fold difference between the highest and lowest ionic gold concentrations. All the 5 samples showed distinct physicochemical and biological properties. Based on characteristic microscopic morphology, it was found that 2 preparations among them were suspected of being manufactured by non-adherence to the mentioned references.
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http://dx.doi.org/10.1177/2515690X211011064DOI Listing
April 2021

Multiscale porosity in a 3D printed gellan-gelatin composite for bone tissue engineering.

Biomed Mater 2021 04 16;16(3). Epub 2021 Apr 16.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.

The aim of this work was to develop a complex-shaped gelatin-gellan composite scaffold with multiscale porosity using a combination of cryogenic 3D printing and lyophilization for bone tissue engineering. Cryogenic 3D printing was used to fabricate a low-concentration composite of complex-shaped macroporous gelatin-gellan structures with a pore size of 919 ± 89 µm. This was followed by lyophilization to introduce micropores of size 20-250 µm and nanometre-level surface functionalities, thus achieving a hierarchical porous structure. These multiscale porous scaffolds (GMu) were compared with two other types of scaffolds having only microporosity (GMi) and macroporosity (GMa) with regard to their physical andbiological properties. GMu scaffolds were found to be better than GMi and GMa in terms of swelling percentage, degradation rate, uniform pore distribution, cellular infiltration, attachment, proliferation, protein generation and mineralization. In conclusion, we have developed a controlled hierarchical bone-like structure, biomimicking natural bone, together with a reproducible process of manufacture by coupling soft hydrogel 3D printing with lyophilization. This enables the development of complex-shaped patient-specific 3D printed hydrogel scaffolds with enhanced performanceand great potential in the fields of tissue engineering, bioprinting and regenerative medicine.
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http://dx.doi.org/10.1088/1748-605X/abf1a7DOI Listing
April 2021

Viscoelastic substrate decouples cellular traction force from other related phenotypes.

Biochem Biophys Res Commun 2021 03 25;543:38-44. Epub 2021 Jan 25.

Department of Chemical Engineering, Indian Institute of Technology Bombay (IITB), Mumbai, 400076, India. Electronic address:

Survival and maintenance of normal physiological functions depends on continuous interaction of cells with its microenvironment. Cells sense the mechanical properties of underlying substrate by applying force and modulate their behaviour in response to the resistance offered by the substrate. Most of the studies addressing cell-substrate mechanical interactions have been carried out using elastic substrates. Since tissues within our body are viscoelastic in nature, here we explore the effect of substrate's viscoelasticity on various properties of mesenchymal stem cells. Here, we used two sets of polyacrylamide substrates having similar storage modulus (G' = 1.1-1.6 kPa) but different loss modulus (G" = 45 Pa and 300 Pa). We report that human mesenchymal stem cells spread more but apply less force on the viscoelastic substrate (substrate with higher loss modulus). We further investigated the effect of substrate viscoelasticity on the expression of other contractility-associated proteins such as focal adhesion (FA) proteins (Vinculin, Paxillin, Talin), cytoskeletal proteins (actin, mysion, intermediate filaments, and microtubules) and mechano-sensor protein Yes-Associated Protein (YAP). Our results show that substrate viscoelasticity decouples cellular traction from other known traction related phenotypes.
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http://dx.doi.org/10.1016/j.bbrc.2021.01.027DOI Listing
March 2021

Probing Kinetics and Mechanism of Formation of Mixed Metallic Nanoparticles in a Polymer Membrane by Galvanic Replacement between Two Immiscible Metals: Case Study of Nickel/Silver Nanoparticle Synthesis.

Langmuir 2021 Feb 26;37(5):1637-1650. Epub 2021 Jan 26.

Department of Chemical Engineering, IIT Bombay, Powai, Mumbai 400076, India.

Galvanic replacement between metals has received notable research interest for the synthesis of heterometallic nanostructures. The growth pattern of the nanostructures depends on several factors such as extent of lattice mismatch, adhesive interaction between the metals, cohesive forces of the individual metals, etc. Due to the difficulties in probing ultrafast kinetics of the galvanic replacement reaction and particle growth in solution, real-time mechanistic investigations are often limited. As a result, the growth mechanism of one metal on the surface of another metal at the nanoscale is poorly understood so far. In the present work, we could successfully probe the galvanic replacement of silver ions with nickel nanoparticles, stabilized in a polymer membrane, using two complementary methods, namely, small-angle X-ray scattering (SAXS) and radiolabeling, and the results are supported by density functional theory (DFT) computations. The silver-nickel system has been chosen for the present investigation because of the high degree of bulk immiscibility caused by the large lattice mismatch (15.9%) and the weak adhesive interaction, which makes it a perfect model system for immiscible metal pairs. Membrane, as a host medium, plays a crucial role in retarding the kinetics of atomic and particle rearrangements (nucleation and growth) due to slower mobility of the atoms (monomers) and particles within the polymer network. This allowed us to examine the real-time concentration of silver monomers during galvanic replacement of silver ions with nickel nanoparticles and evolution of Ni/Ag nanoparticles. From combined experiment and DFT computations, it has been demonstrated, for the first time to the best of our knowledge, that the majority of silver atoms, which are produced on the nickel nanoparticle surface by galvanic reactions, do not form traditional core-shell nanostructures with nickel and undergo a self-governing sequential nucleation and growth of silver nanoparticles via formation of intermediate prenucleation silver clusters, leading to the formation of mixed metallic nanoparticles in the membrane. The surface of NiNPs has a heterogeneous effect on the silver nucleation pathway, which is evident from the reduced critical free energy barrier of nucleation (Δ). The present work establishes an original mechanistic pathway based on a sequential nucleation model for formation of mixed metallic nanoparticles by the galvanic replacement route, which opens up future possibilities for size-controlled synthesis in mixed systems.
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http://dx.doi.org/10.1021/acs.langmuir.0c02311DOI Listing
February 2021

Adaptive mechanisms induced by sparingly soluble mercury sulfide (HgS) in zebrafish: Behavioural and proteomics analysis.

Chemosphere 2021 May 29;270:129438. Epub 2020 Dec 29.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, India; Wadhwani Research Centre for Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, India. Electronic address:

Mercury (Hg) causes great health concerns due to its extreme neurotoxicity. However, here we show that pretreatment of sparingly soluble mercury compound (HgS) could induce adaptive mechanisms in zebrafish, which can resist the neurotoxic effects of mercury chloride (HgCl). In this study, zebrafish were treated with HgS (in the form of 99% HgS arising from traditional Ayurvedic medicine Rasasindura (RS), chosen for its particle and crystallite sizes). This work was prompted by the traditional use of this form of HgS to treat nervous and immune-related diseases. Our investigation on zebrafish behaviour showed that RS pretreated fish group (RS-HG) was less severely affected by HgCl exposure, as compared to the RS non-treated (VC-HG) group. Further, biochemical tests showed that RS pretreatment prevents alteration of reactive oxygen species (ROS), acetylcholinesterase (AChE), and cortisol as compared to the VC-HG group. Proteomics and bioinformatics studies of zebrafish brain tissues suggested that Rasasindura (RS-HG group) protects alteration of various protein expression related to KEGG pathways, including citrate cycle (TCA cycle) and glutathione metabolism that are directly or indirectly linked to the oxidative stress, against HgCl induced neurotoxicity. We found that adaptive mechanisms were initiated by the initiation of response to stress (enrichment of GO:0006950 pathway), due to the accumulation of a small amount of ionic Hg (60 ± 10 ng/g) after 15 days of RS treatment. These adaptive mechanisms avoid further adverse neurotoxicity of HgCl. Thus, HgS (RS) pretreatment can induce protective effects in zebrafish.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129438DOI Listing
May 2021

Three Dimensional Quercetin-Functionalized Patterned Scaffold: Development, Characterization, and Assessment for Neural Tissue Engineering.

ACS Omega 2020 Sep 25;5(35):22325-22334. Epub 2020 Aug 25.

Wadhwani Research Centre for Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra 400076, India.

Regeneration of injured neuronal areas is a big challenge owing to the complex structure and function of the nervous system along with the limited regeneration capacity of neural cells. Recent reports show that patterned and functionalized scaffolds could control neural cell directional growth. In this study, aligned nanofibers (ANFs) were fabricated using a versatile and cost-effective approach, electrospinning, and further processed to make a patterned hybrid scaffold (HANF). The patterned scaffold had circular rings of ANFs reinforced in a biocompatible gellan-gelatin hydrogel matrix to provide adequate mechanical strength and contact guidance for adhesion and growth of neural cells . Quercetin was loaded into the nanofibrous scaffold to provide a functional agent that supported regeneration of neural cells. The reinforced ANFs enhanced the mechanical strength of the scaffold and provided a cylindrical nerve conduit structure to support neuronal cell growth. The influence of scaffold topology on cell behavior was assessed in cell culture conditions that revealed that the functionalized patterned scaffolds favored directed neurite cell growth/extension with favored cell culture morphology and showed no cytotoxicity toward neural cells. The results ultimately indicated that the fabricated scaffold has potential for guiding nerve tissue growth and can be used as nerve regeneration scaffolds.
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http://dx.doi.org/10.1021/acsomega.0c02678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482233PMC
September 2020

Ayurvedic processing of α-HgS gives novel physicochemistry and distinct toxicokinetics in zebrafish.

Chemosphere 2020 Jul 22;251:126295. Epub 2020 Feb 22.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, India; Wadhwani Research Centre for Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, India. Electronic address:

Rasasindura (RS) is an Ayurvedic medicine, which contains ∼99% α-HgS. It is used as a rejuvenating agent and commonly used to treat diseases such as syphilis, insomnia, high fever, and nervous disorders. Cinnabar ore (α-HgS) is a well-known mineral, which is readily available. Despite it, Ayurvedic practitioners adopted an involved and tedious procedure for the preparation of RS. In this study, three samples, one was Ayurvedic (RS), the second one was the commercial (HGS), and the third one was cinnabar ore (CN), were physiochemically examined. Zebrafish model was employed for toxicity study with an oral dose of 100 mg/kg/day for the three samples for 10 days. We found that RS conferred novel physicochemical properties, which were not seen in HGS and CN. Significantly, the average crystallite size of RS was lowest (26 nm) as compared to HGS (31 nm) and CN (34 nm), and the rate of increase of crystallite size with temperature was lowest in RS. RS did not show any significant behavioral toxicity in zebrafish, which was seen with the HGS-and CN-treated zebrafish. HGS-and CN-treated zebrafish showed a significantly high (∗∗∗p < 0.001) decrease (77 ± 7.6% and 51 ± 6.5%, respectively) of glutathione (GSH) levels in the brain, however, for RS-treated zebrafish, the change of GSH was insignificant (26 ± 2.5%, p > 0.05). Interestingly, HGS significantly altered the γ-aminobutyric acid (GABA) in brain tissue. Therefore, among all three samples, RS exhibited the lowest toxicity, which can be credited to the distinct toxicokinetics by these samples.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126295DOI Listing
July 2020

Effect of silver doping on antidiabetic and antioxidant potential of ZnO nanorods.

J Trace Elem Med Biol 2020 Mar 24;58:126448. Epub 2019 Dec 24.

Department of Physics, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand. Electronic address:

Background: Increasing resistance to available drugs and their associated side-effects have drawn wide attention towards designing alternative therapeutic strategies for control of hyperglycemia and oxidative stress. The roles of the sizes and shapes of the nanomaterials used in the treatment and management of Type 2 Diabetes Mellitus (T2DM) in preventing chronic hyperglycaemia and oxidative stress are investigated. We report specifically on the effects of doping silver (Ag) into the ZnO nanorods (ZnO:Ag NR's) as a rational drug designing strategy.

Methods: Inhibition of porcine pancreatic α-amylase, murine pancreatic amylase, α-glucosidase, murine intestinal glucosidase and amyloglucosidase are checked for evaluation of antidiabetic potential. In addition, the radical scavenging activities of ZnO:Ag NR's against nitric oxide, DDPH and superoxide radicals are evaluated.

Results: Quantitative radical scavenging and metabolic enzyme inhibition activities of ZnO:Ag NR's at a concentration of 100 μg/mL were found to depend on the amount of Ag doped in up to a threshold level (3-4 %). Circular dichroism analysis revealed that the interaction of the NR's with the enzymes altered their secondary conformation. This alteration is the underlying mechanism for the potent enzyme inhibition.

Conclusions: Enhanced inhibition of enzymes and scavenging of free radicals primarily responsible for reactive oxygen species (ROS) mediated damage, provide a strong scientific rationale for considering ZnO:Ag NR's as a candidate nanomedicine for controlling postprandial hyperglycaemia and the associated oxidative stress.
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http://dx.doi.org/10.1016/j.jtemb.2019.126448DOI Listing
March 2020

Accentuated osseointegration in osteogenic nanofibrous coated titanium implants.

Sci Rep 2019 12 9;9(1):17638. Epub 2019 Dec 9.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai, 400076, Maharashtra, India.

Anchoring of endosseous implant through osseointegration continues to be an important clinical need. Here, we describe the development of superior endosseous implant demonstrating enhance osseointegration, achieved through surface modification via coating of osteogenic nanofibres. The randomized bio-composite osteogenic nanofibres incorporating polycaprolactone, gelatin, hydroxyapatite, dexamethasone, beta-glycerophosphate and ascorbic acid were electrospun on titanium implants mimicking bone extracellular matrix and subsequently induced osteogenesis by targeting undifferentiated mesenchymal stem cells present in the peri-implant niche to regenerate osseous tissue. In proof-of-concept experiment on rabbit study models (n = 6), micro-computed tomography (Micro-CT), histomorphometric analysis and biomechanical testing in relation to our novel osteogenic nanofibrous coated implants showed improved results when compared to uncoated controls. Further, no pathological changes were detected during gross examination and necropsy on peri-implant osseous tissues regenerated in response to such coated implants. The findings of the present study confirm that osteogenic nanofibrous coating significantly increases the magnitude of osteogenesis in the peri-implant zone and favours the dynamics of osseointegration.
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http://dx.doi.org/10.1038/s41598-019-53884-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901521PMC
December 2019

Physicochemical characterization of Suvarna Bhasma, its toxicity profiling in rat and behavioural assessment in zebrafish model.

J Ethnopharmacol 2020 Mar 12;249:112388. Epub 2019 Nov 12.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, India; Wadhwani Research Centre for Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, India. Electronic address:

Ethnopharmacological Relevance: Suvarna Bhasma is a gold-based Ayurved medicine that has a wide range of therapeutic indications like tuberculosis, diabetes mellitus, rheumatoid arthritis and nervous diseases. Suvarna Bhasma is also used in Suvarnaprashana, an Ayurved advocated therapy being practised to improve immunity in children.

Aim Of The Study: To augment traditional understanding, here we present an evidence-based study on Suvarna Bhasma regarding its physicochemical properties, toxicity and efficacy.

Materials And Methods: Suvarna Bhasma was characterised by physicochemical characterization techniques such as scanning electron microscope (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and atomic emission spectroscopy (ICP-AES). Toxicity of Suvarna Bhasma was studied in Holtzman rats with daily oral dose from 3 mg/kg (therapeutic dose, TD) up to 30 mg/kg (10 TD) body weight for 90 days. Behavioural study, such as motor and geotactic behaviour were examined in zebrafish model to find out any sign of neurotoxicity or behavioural changes due to Suvarna Bhasma administration.

Results: Suvarna Bhasma has two types of gold particles, large ones (~60 μm) having irregular shapes, and nano-sized spherical particles (starting from ~10 nm), the latter coated with Fe, Si, O, P and Na. XRD study revealed that all the peaks of Suvarna Bhasma match well with pure gold (face centred cube) with crystallites size 45 ± 2.8 nm. In rat studies, some change in biochemical parameters such as urea, creatinine and alanine aminotransferase (ALT) was observed mainly at the higher therapeutic dose; however, those parameters were within the normal range. There were no significant macroscopic as well as microscopic treatment-related alteration observed, in any of the organs and tissues evaluated. In zebrafish behavioural study, the motor parameters of Suvarna Bhasma treated fish showed normal behaviour analogous to the vehicle control group. Interestingly, the geotactic behaviour showed anxiolytic effects of Suvarna Bhasma as evidenced by the time spent in the upper zone, and average swimming height. The anxiolytic effects persisted for more than 30 days after withdrawing the Suvarna Bhasma treatment.

Conclusions: Suvarna Bhasma contained spherical gold nanoparticles. It was nontoxic in rat model at the does tested. Suvarna Bhasma has anxiolytic effects in zebrafish behavioural model.
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http://dx.doi.org/10.1016/j.jep.2019.112388DOI Listing
March 2020

Dilution-Induced Physico-Chemical Changes of Metal Oxide Nanoparticles Due to Homeopathic Preparation Steps of Trituration and Succussion.

Homeopathy 2020 05 25;109(2):65-78. Epub 2019 Oct 25.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, India.

Background: Although the presence of starting materials in extreme dilutions of homeopathic medicines has been established, the physico-chemical changes of these materials induced by the manufacturing steps-that is, solid-solid mixing involving grinding (trituration) and slurry mixing involving impact (succussion), followed by dilution-are still unknown.

Methods: We subjected cupric oxide and zinc oxide nanoparticles (NPs) to the homeopathic processes of trituration and succussion, followed by dilution up to 6 cH. Particle image velocimetry was employed to analyze the fluid motion during succussion and its effect on the NPs. The resulting microstructural and chemical changes at different dilution steps were determined by X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy and transmission electron microscopy.

Results: The succussion triggered multi-sized bubble generation and turbulent fluid motion up to a duration of 400 ms, with maximum average velocity of 0.23 m/s. Due to 1% transfer of kinetic energy from a moving eddy with this velocity, upon collision, the rate of temperature change in a particle of size 1 µm and 1 nm was predicted to rise by approximately 10 K/s and 10 K/s respectively. During trituration, the oxide NPs reduced to metals and did not aggregate by remaining within lactose, but they converted to oxidized finer NPs after impact. Silicate chains leached from the vial cross-linked after third dilution, forming large macro-particles and encapsulating the NPs that were retained and carried at higher dilution steps.

Conclusion: The results showed that the NPs sustained significant rate of temperature change due to energy transfer from moving eddies during succussion. Different physico-chemical changes, such as size reduction, successive reduction and oxidation of NPs, and morphological changes, were achieved through trituration and succussion. The retention of NPs within cross-linked poly-siloxane chains reveals the importance of both the borosilicate glass vial and the ethanol solution during preparation of homeopathic medicines.
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http://dx.doi.org/10.1055/s-0039-1694720DOI Listing
May 2020

Polyethersulfone-carbon nanotubes composite hollow fiber membranes with improved biocompatibility for bioartificial liver.

Colloids Surf B Biointerfaces 2019 Sep 24;181:890-895. Epub 2019 Jun 24.

Department of Chemical Engineering, Indian Institute of Technology, Bombay Mumbai, 400076, India; Centre for Research in Nanotechnology & Sciences, Indian Institute of Technology Bombay Mumbai, 400076, India; Wadhwani Research Center for Bioengineering, Indian Institute of Technology, Bombay Mumbai, 400076, India. Electronic address:

Carbon nanotubes (CNTs) blended hollow fiber membranes (HFMs) are a promising new material in the area of biomedical engineering because they simultaneously provide tunable hydrophilicity along with selective permeability. In the present study, composite polyethersulfone (P) HFMs were fabricated using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS or T) as compatibilizer, and carboxylated multiwalled CNTs (MWCNTs or C) as filler. The amount of MWCNTs was optimized for the improved hemocompatibility, cell viability, and cellular functionality. An optimum was found with the composte HFMs (PTC-2), where MWCNTs were used at concentration of 0.030 wt.%, as it exhibited improved compatibility with human blood. Further, these PTC-2 HFMs showed enhanced liver (HepG2) cells growth with the enhanced cell functional activities, mainly albumin secretion and glucose consumption. These developed composite membrane can act as a membrane material for liver cell bioreactor and bioartificial liver development because of their 3D scaffold like characteristic which enables cell growth, and selective permeability which helps in immunoisolation.
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http://dx.doi.org/10.1016/j.colsurfb.2019.06.051DOI Listing
September 2019

Efficient separation of biological macromolecular proteins by polyethersulfone hollow fiber ultrafiltration membranes modified with FeO nanoparticles-decorated carboxylated graphene oxide nanosheets.

Int J Biol Macromol 2019 Aug 28;135:798-807. Epub 2019 May 28.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai 400076, India; Centre for Research in Nanotechnology & Science, Indian Institute of Technology Bombay, Mumbai 400076, India; Wadhwani Research Centre for Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India. Electronic address:

The separation of biological macromolecules, e.g., proteins, using ultrafiltration membranes in the biotechnology, food and pharmaceutical industries has gained the significant attention of the research community. In this work, iron oxide nanoparticles-decorated carboxylated graphene oxide nanosheets (FeO/cGO nanohybrid) were synthesized and incorporated in polyethersulfone (PES) hollow fiber ultrafiltration membranes (HFMs) and the resulting modified membranes were evaluated for the separation of proteins, namely lysozyme, trypsin, pepsin, human serum albumin, γ-globulin and fibrinogen. The physicochemical properties, mainly mechanical strength, hydrophilicity, porosity, pore size, and surface roughness were found to be favorable for the modified HFMs. These properties helped the composite membranes (HFMs modified with 0.1 wt% FeO/cGO nanohybrid) in achieving remarkably high pure water flux (110.0 ± 3.8 L/m h) and as high as 97.8% flux recovery. PES-FeO/cGO composite HFMs showed significantly high rejection of lysozyme (92.9 ± 1.3%), trypsin (94.5 ± 1.1%), pepsin (96.9 ± 1.2%), human serum albumin (99.5 ± 0.5%), human γ-globulin (100%), and human fibrinogen (100%). These composite HFMs also maintained their efficacious rejection performance during the long-term studies. Therefore, the HFMs modified with FeO/cGO nanohybrid are the potential membranes for the efficient separation of biomolecules, particularly proteins in the biotechnology, food and pharmaceutical industries.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.05.200DOI Listing
August 2019

Multiscale Porosity in Compressible Cryogenically 3D Printed Gels for Bone Tissue Engineering.

ACS Appl Mater Interfaces 2019 Jun 24;11(22):20437-20452. Epub 2019 May 24.

Chemical and Biomolecular Engineering , Johns Hopkins University , 323 E 33rd Street , Baltimore , Maryland 21218 , United States.

Three-dimensional (3D) printing technology has seen several refinements when introduced in the field of medical devices and regenerative medicines. However, it is still a challenge to 3D print gels for building complex constructs as per the desired shape and size. Here, we present a novel method to 3D print gelatin/carboxymethylchitin/hydroxyapatite composite gel constructs of a complex shape. The objective of this study is to fabricate a bioactive gel scaffold with a controlled hierarchical structure. The hierarchy ranges from 3D outer shape to macroporosity to microporosity and rough surface. The fabrication process developed here uses 3D printing in a local cryogenic atmosphere, followed by lyophilization and cross-linking. The gel instantly freezes after extrusion on the cold plate. The cooling action is not limited to the build plate, but the entire gel scaffold is cooled during the 3D printing process. This enables the construction of a stable self-sustaining large-sized 3D complex geometry. Further, lyophilization introduces bulk microporosity into the scaffolds. The outer shape and macroporosity were controlled with the 3D printer, whereas the microporous structure and desirable rough surface morphology were obtained through lyophilization. With cryogenic 3D printing, up to 90% microporosity could be incorporated into the scaffolds. The microporosity and pore size distribution were controlled by changing the cross-linker and total polymer concentration, which resulted in six times increase in surface open pores of size <20 μm on increasing the cross-linker concentration from 25 to 100 mg/mL. The introduction of bulk microporosity was shown to increase swelling by 1.8 times along with a significant increase in human umbilical cord mesenchymal stem cells and Saos-2 cell attachment (2×), proliferation (2.4×), Saos-2 cell alkaline phosphatase level (2×), and mineralization (3×). The scaffolds are spongy in nature in a wet state, thus making them potential implants for bone cavities with a small opening. The application of these cryogenically 3D printed compressible gel scaffolds with multiscale porosity extends to a small- as well as a large-sized open/partially open patient-specific bone defect.
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http://dx.doi.org/10.1021/acsami.9b05460DOI Listing
June 2019

Soft substrate maintains proliferative and adipogenic differentiation potential of human mesenchymal stem cells on long-term expansion by delaying senescence.

Biol Open 2019 Apr 25;8(4). Epub 2019 Apr 25.

Department of Chemical Engineering, Indian Institute of Technology Bombay (IITB), Mumbai 400076, India

Human mesenchymal stem cells (hMSCs), during expansion, gradually lose their distinct spindle morphology, self-renewal ability, multi-lineage differentiation potential and enter replicative senescence. This loss of cellular function is a major roadblock for clinical applications which demand cells in large numbers. Here, we demonstrate a novel role of substrate stiffness in the maintenance of hMSCs over long-term expansion. When serially passaged for 45 days from passage 3 to passage 18 on polyacrylamide gel of Young's modulus =5 kPa, hMSCs maintained their proliferation rate and showed nine times higher population doubling in comparison to their counterparts cultured on plastic Petri-plates. They did not express markers of senescence, maintained their morphology and other mechanical properties such as cell stiffness and cellular traction, and were significantly superior in adipogenic differentiation potential. These results were demonstrated in hMSCs from two different sources, umbilical cord and bone marrow. In summary, our result shows that a soft gel is a suitable substrate to maintain the stemness of mesenchymal stem cells. As preparation of polyacrylamide gel is a well-established, and well-standardized protocol, we propose that this novel system of cell expansion will be useful in therapeutic and research applications of hMSCs.
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http://dx.doi.org/10.1242/bio.039453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503999PMC
April 2019

Development of bone screw using novel biodegradable composite orthopedic biomaterial: from material design to in vitro biomechanical and in vivo biocompatibility evaluation.

Biomed Mater 2019 07 1;14(4):045020. Epub 2019 Jul 1.

NanoBios Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai-400076, India.

A novel composite biomaterial for bone-soft tissue fixation applications was developed. MgO-Silk-PCL, Silk-PCL and MgO-PCL composites were prepared with variable filler concentrations (0, 10, 20 and 30% w/w of MgO nanoparticles and 0%, 5%, 10%, 20% and 30% of degummed silk fiber) in PCL polymer. The highest mechanical properties were obtained with 10% MgO and 20% Silk composite (MSP) wih 1.7× better tensile strength and 7.5× tensile modulus over PCL. It exhibited good cell viability, adhesion and hemocompatibility, increased cell proliferation and differentiation. MgO filler contributed more in increasing tensile strength, whereas silk fiber towards modulus, imparting a synergistic effect on mechanical performance. Prototype bone screws were molded using the MSP composite in a custom-designed mold. It showed significantly increased degradation (2.7 fold after 60 days) in PBS attributable to binary filler phase as compared to PCL. In vivo biosafety studies of MgO-silk-PCL composite screw in SD rats by subcutaneous implantation showed moderate inflammation at 2 weeks which subsided after 4th week. No toxic effect was seen in histopathology of vital organs and in blood parameters. Composite screw showed 2× pull-out strength of PCL in synthetic bone, therefore a potential candidate for bone-soft fixation applications like resorbable orthopedic screws for ACL reconstruction.
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http://dx.doi.org/10.1088/1748-605X/ab16beDOI Listing
July 2019

- and -Mediated Synthesis of Novel Copper Nanoparticles as Promising Antidiabetic Agents.

Adv Pharmacol Sci 2019 11;2019:9080279. Epub 2019 Feb 11.

Department of Microbiology, School of Science, RK University, Kasturbadham, Rajkot 360020, India.

Rapid, eco-friendly, and cost-effective one-pot synthesis of copper nanoparticles is reported here using medicinal plants like and . Aqueous extracts of flower, leaf, and stem of and leaves of were prepared which could effectively reduce Cu ions to CuNPs within 5 h at 100°C which were further characterized using UV-visible spectroscopy, field emission scanning electron microscopy, high-resolution transmission electron microscopy, energy dispersive spectroscopy, dynamic light scattering, X-ray diffraction, and Fourier-transform infrared spectroscopy. Further, the CuNPs were checked for antidiabetic activity using porcine pancreatic -amylase and -glucosidase inhibition followed by evaluation of mechanism using circular dichroism spectroscopy. CuNPs were found to be predominantly spherical in nature with a diameter ranging from 1 to 5 nm. The phenolics and flavonoids in the extracts might play a critical role in the synthesis and stabilization process. Significant change in the peak at ∼1095 cm corresponding to C-O-C bond in ether was observed. CuNPs could inhibit porcine pancreatic -amylase up to 30% to 50%, while they exhibited a more significant inhibition of -glucosidase from 70% to 88%. The mechanism of enzyme inhibition was attributed due to the conformational change owing to drastic alteration of secondary structure by CuNPs. This is the first study of its kind that provides a strong scientific rationale that phytogenic CuNPs synthesized using and can be considered to develop candidate antidiabetic nanomedicine.
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http://dx.doi.org/10.1155/2019/9080279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388358PMC
February 2019

Oral dosing of pentoxifylline, a pan-phosphodiesterase inhibitor restores bone mass and quality in osteopenic rabbits by an osteogenic mechanism: A comparative study with human parathyroid hormone.

Bone 2019 06 9;123:28-38. Epub 2019 Mar 9.

Division of Endocrinology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, India. Electronic address:

The non-selective phosphodiesterase inhibitor pentoxifylline (PTX) is used for the treatment of intermittent claudication due to artery occlusion. Previous studies in rodents have reported salutary effects of the intraperitoneal administration of PTX in segmental bone defect and fracture healing, as well as stimulation of bone formation. We determined the effect of orally dosed PTX in skeletally mature ovariectomized (OVX) rabbits with osteopenia. The half-maximal effective concentration (EC) of PTX in rabbit bone marrow stromal cells was 3.07 ± 1.37 nM. The plasma PTX level was 2.05 ± 0.522 nM after a single oral dose of 12.5mg/kg, which was one-sixth of the adult human dose of PTX. Four months of daily oral dosing of PTX at 12.5 mg/kg to osteopenic rabbits completely restored bone mineral density, bone mineral content (BMC), microarchitecture and bone strength to the level of the sham-operated (ovary intact) group. The bone strength to BMC relationship between PTX and sham was similar. The bone restorative effect of PTX was observed in both axial and appendicular bones. In osteopenic rabbits, PTX increased serum amino-terminal propeptide, mineralized nodule formation by stromal cells and osteogenic gene expression in bone. PTX reversed decreased calcium weight percentage and poor crystal packing found in osteopenic rabbits. Furthermore, similar to parathyroid hormone (PTH), PTX had no effect on bone resorption. Taken together, our data show that PTX completely restored bone mass, bone strength and bone mineral properties by an anabolic mechanism. PTX has the potential to become an oral osteogenic drug for the treatment of post-menopausal osteoporosis.
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http://dx.doi.org/10.1016/j.bone.2019.03.010DOI Listing
June 2019

Modelling and optimization of NaOH-etched 3-D printed PCL for enhanced cellular attachment and growth with minimal loss of mechanical strength.

Mater Sci Eng C Mater Biol Appl 2019 May 4;98:602-611. Epub 2019 Jan 4.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India; Centre for Research in Nanotechnology & Science, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India; Tata Centre for Technology and Design, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India; Wadhwani Research Centre for Bioengineering (WRCB), Indian Institute of Technology Bombay, Powai, Mumbai 400076, India. Electronic address:

Despite having gained success in achieving intricate geometries for bone-graft fabrication, 3D printing technology still lacks good implant-tissue bonding. This can be addressed with alkaline surface post-treatment of 3D printed grafts, which improves the surface morphology and cellular response (attachment and proliferation), as shown in this study of polycaprolactone (PCL). The parameters for process optimization were NaOH-concentration, reaction temperature, and treatment time. Along with the hydrolysis reaction, its morphological implications at micro-level was also studied here for the first time. The modified surface was characterized by measuring surface porosity, surface roughness, and cellular response. A kinetic model was developed to correlate surface porosity with concentration, temperature and time. The concept of treatment intensity is introduced, which is a lumped parameter consisting of the product of the three governing parameters, which shows a concentration-temperature-time equivalency. With the increase in treatment intensity, surface porosity increased to ~60%, the surface roughness (RMS value) increased to ~700 nm, and cellular response improved till surface porosity reaches ~35%. This study establishes the importance of NaOH-PCL interaction and proposes that the surface reaction mechanism studied here can be exploited to enhance the in-vivo performance of bone grafts.
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http://dx.doi.org/10.1016/j.msec.2018.12.084DOI Listing
May 2019

Osteogenic Nanofibrous Coated Titanium Implant Results in Enhanced Osseointegration: Preliminary Study in a Rabbit Model.

Tissue Eng Regen Med 2018 Apr 19;15(2):231-247. Epub 2018 Jan 19.

2Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai, 400076 India.

A titanium implant surface when coated with biodegradable, highly porous, osteogenic nanofibrous coating has shown enhanced intrinsic osteoinductive and osteoconductive properties. This coating mimics extracellular matrix resulting in differentiation of stem cells present in the peri-implant niche to osteoblast and hence results in enhanced osseointegration of the implant. The osteogenic nanofibrous coating (ONFC) consists of poly-caprolactone, gelatin, nano-sized hydroxyapatite, dexamethasone, ascorbic acid and beta-glycerophosphate. ONFC exhibits optimum mechanical properties to support mesenchymal stem cells and steer their osteogenic differentiation. ONFC was subjected to various characterization tests like scanning electron microscopy, Fourier-transform infrared spectroscopy, x-ray diffractometry, thermal degradation, biomineralization, mechanical properties, wettability and proliferation assay. In pre-clinical animal trials, the coated implant showed enhanced new bone formation when placed in the tibia of rabbit. This novel approach toward implant bone integration holds significant promise for its easy and economical coating thus marking the beginning of new era of electrospun osteogenic nanofibrous coated bone implants.
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http://dx.doi.org/10.1007/s13770-017-0106-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171690PMC
April 2018

Dental Pulp Stem Cells in Customized 3D Nanofibrous Scaffolds for Regeneration of Peripheral Nervous System.

Methods Mol Biol 2020 ;2125:157-166

Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai, India.

Dental pulp stem cells (DPSCs) are adult multipotent stem cells of neuroectodermal origin; they provide an encouraging perspective in the domain of nerve tissue engineering. DPSCs could be transplanted in biodegradable electrospun neuro-supportive scaffold (optimized in various 3D geometries like coating on the surface of titanium implant, hollow/solid tubes, etc.) for enhanced in vivo recovery of peripheral nerves. Herein, we describe the fabrication of uniform bead-free nanofibrous scaffold which supports DPSCs, proliferation, and their subsequent neural differentiation and thus could be utilized for enhanced regeneration of peripheral nervous system.
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http://dx.doi.org/10.1007/7651_2018_194DOI Listing
February 2021

A biodegradable fluorescent nanohybrid for photo-driven tumor diagnosis and tumor growth inhibition.

Nanoscale 2018 Oct;10(40):19082-19091

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, India.

Specific targeting and phototriggered therapy in mouse model have recently emerged as the starting point of cancer theragnosis. Herein, we report a bioresponsive and degradable nanohybrid, a liposomal nanohybrid decorated with red emissive carbon dots, for localized tumor imaging and light-mediated tumor growth inhibition. Unsaturated carbon dots (C-dots) anchored to liposomes convert near-infrared (NIR) light into heat and also produce reactive oxygen species (ROS), demonstrating the capability of phototriggered cancer cell death and tumor regression. The photothermal and oxidative damage of breast tumor by the nonmetallic nanohybrid has also been demonstrated. Designed nanoparticles show excellent aqueous dispersibility, biocompatibility, light irradiated enhanced cellular uptake, release of reactive oxygen species, prolonged and specific tumor binding ability and good photothermal response (62 °C in 5 minutes). Safe and localized irradiation of 808 nm light demonstrates significant tumor growth inhibition and bioresponsive degradation of the fluorescent nanohybrid without affecting the surrounding healthy tissues.
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http://dx.doi.org/10.1039/c8nr05164jDOI Listing
October 2018

Matrix-entrapped cellular secretome rescues diabetes-induced EPC dysfunction and accelerates wound healing in diabetic mice.

PLoS One 2018 28;13(8):e0202510. Epub 2018 Aug 28.

National Centre for Cell Science, NCCS Complex, University of Pune Campus, Ganeshkhind, Pune, Maharashtra, India.

Cellular secretory products have infinite potential, which is only recently explored for research and therapeutic applications. The present study elaborated on the formation of a unique matrix-entrapped cellular secretome (MCS), a hydrogel-like secretome produced by bone marrow-derived mononuclear cells when cultured on a three-dimensional electrospun nanofiber matrix under specific conditions. These culture conditions support the growth of a mixed population predominantly comprising of endothelial precursor cells (EPCs), along with mesenchymal stromal cells and pericytes. Interestingly, such secretome is not formed in a pure culture of EPCs on the similarly formulated matrix, suggesting that a heterotypic cell-cell interaction is essential for the formation of MCS. In addition, the specific composition of the matrix was found to be a critical necessity for the formation of MCS. Furthermore, the application of the MCS as a substrate promotes the growth of EPCs in culture. It also rescues the diabetes-induced EPC dysfunction as assessed based on the parameters, such as viability, proliferation, colony formation, cellular adhesion, chemotactic migration, and tubule formation. MCS augments the levels of eNOS-specific mRNA (Nos3) and also promotes the restoration of the SDF1/CXCR4 axis in diabetic EPCs. Notably, a topical application of MCS on diabetic wounds leads to an accelerated wound closure. Thus, the current data showed that MCS forms an excellent cell-free biomaterial in the treatment of diabetic wounds and non-healing ulcers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0202510PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112628PMC
February 2019

Mediated Synthesis of Platinum and Palladium Nanoparticles for Induction of Apoptosis in Breast Cancer.

Bioinorg Chem Appl 2018 2;2018:4924186. Epub 2018 Jul 2.

Department of Microbiology, School of Science, RK University, Kasturbadham, Rajkot 360020, India.

Green chemistry approaches for designing therapeutically significant nanomedicine have gained considerable attention in the past decade. Herein, we report for the first time on anticancer potential of phytogenic platinum nanoparticles (PtNPs) and palladium nanoparticles (PdNPs) using a medicinal plant tuber extract (GSTE). The synthesis of the nanoparticles was completed within 5 hours at 100°C which was confirmed by development of dark brown and black colour for PtNPs and PdNPs, respectively, along with enhancement of the peak intensity in the UV-visible spectra. High-resolution transmission electron microscopy (HRTEM) showed that the monodispersed spherical nanoparticles were within a size range below 10 nm. Energy dispersive spectra (EDS) confirmed the elemental composition, while dynamic light scattering (DLS) helped to evaluate the hydrodynamic size of the particles. Anticancer activity against MCF-7 (human breast adenocarcinoma) cell lines was evaluated using MTT assay, flow cytometry, and confocal microscopy. PtNPs and PdNPs showed 49.65 ± 1.99% and 36.26 ± 0.91% of anticancer activity. Induction of apoptosis was most predominant in the underlying mechanism which was rationalized by externalization of phosphatidyl serine and membrane blebbing. These findings support the efficiency of phytogenic fabrication of nanoscale platinum and palladium drugs for management and therapy against breast cancer.
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http://dx.doi.org/10.1155/2018/4924186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051271PMC
July 2018

Hydrophilic ZIF-8 decorated GO nanosheets improve biocompatibility and separation performance of polyethersulfone hollow fiber membranes: A potential membrane material for bioartificial liver application.

Mater Sci Eng C Mater Biol Appl 2018 Oct 24;91:524-540. Epub 2018 May 24.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai 400076, India; Wadhwani Research Centre for Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India; Centre for Research in Nanotechnology & Science, Indian Institute of Technology Bombay, Mumbai 400076, India. Electronic address:

The hydrophobic nature of zeolitic imidazole framework-8 (ZIF-8) nanoparticles restricts their use as additives in hollow fiber membranes (HFMs) for biomedical applications. In this study, hydrophilic ZIF-8 decorated graphene oxide nanosheets (ZGs) were synthesized and used as additives (0-1 wt%) in polyethersulfone (P) HFMs with the aim of improving the biocompatibility and separation performance so as to make the ZGP HFMs suitable for bioartificial liver (BAL) application. Elemental mapping and Fourier transform infrared studies confirmed the efficacious incorporation of ZG nanohybrids in the ZGP HFMs, which resulted in their improved hydrophilicity. The remarkably improved biocompatibility was experimentally demonstrated for the ZGP HFMs, which also were antioxidative and hemocompatible. There was a significantly high attachment and proliferation of HepG2 cells on these HFMs, and they showed remarkably high urea synthesis and albumin secretion. Further, the ZGP HFMs showed high ultrafiltration coefficient (392.2 ± 26.5 mL/h/m/mm Hg), high flux recovery ratio (84.3%), low flux reduction (15.7%), and desirable molecular weight cutoff (125-135 kDa). Thus, these results experimentally demonstrated that the hydrophilic ZG nanohybrids improve the desirable properties of ZGP HFMs making them a potential biocompatible material for biomedical applications including BAL application.
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http://dx.doi.org/10.1016/j.msec.2018.05.051DOI Listing
October 2018

Extracellular matrix-coated polyethersulfone-TPGS hollow fiber membranes showing improved biocompatibility and uremic toxins removal for bioartificial kidney application.

Colloids Surf B Biointerfaces 2018 Jul 24;167:457-467. Epub 2018 Apr 24.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai 400076, India; Wadhwani Research Centre for Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India; Centre for Research in Nanotechnology & Science, Indian Institute of Technology Bombay, Mumbai 400076, India. Electronic address:

In this study, L-3, 4-dihydroxyphenylalanine and human collagen type IV were coated over the outer surface of the custom-made hollow fiber membranes (HFMs) with the objective of simultaneously improving biocompatibility leading to proliferation of human embryonic kidney cells-293 (HEK-293) and improving separation of uremic toxins, thereby making them suitable for bioartificial kidney application. Physicochemical characterization showed the development of coated HFMs, resulting in low hemolysis (0.25 ± 0.10%), low SC5b-9 marker level (7.95 ± 1.50 ng/mL), prolonged blood coagulation time, and minimal platelet adhesion, which indicated their improved human blood compatibility. Scanning electron microscopy and confocal laser scanning microscopy showed significantly improved attachment and proliferation of HEK-293 cells on the outer surface of the coated HFMs, which was supported by the results of glucose consumption and MTT cell proliferation assay. The solute rejection profile of these coated HFMs was compared favorably with that of the commercial dialyzer membranes. These coated HFMs showed a remarkable 1.6-3.2 fold improvement in reduction ratio of uremic toxins as compared to standard dialyzer membranes. These results clearly demonstrated that these extracellular matrix-coated HFMs can be a potential biocompatible substrate for the attachment and proliferation of HEK-293 cells and removal of uremic toxins from the simulated blood, which may find future application for bioartificial renal assist device.
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http://dx.doi.org/10.1016/j.colsurfb.2018.04.043DOI Listing
July 2018

Development of hybrid scaffold with biomimetic 3D architecture for bone regeneration.

Nanomedicine 2018 06 9;14(4):1325-1336. Epub 2018 Apr 9.

Wadhwani Research Center for Bioengineering, Indian Institute of Technology Mumbai, Mumbai, Maharashtra, India; Department of Chemical Engineering, Indian Institute of Technology Mumbai, Maharashtra, India. Electronic address:

In the present study, a biomimetic three-dimensional hybrid scaffold has been designed considering the bone natural architecture with favorable interconnected porous structure, nano-microscale features and mechanical strength. The chief components of the hybrid scaffold are core-sheath nanofibers and hydrogel, suitably arranged to create a bone like microenvironment. Specifically, the core-sheath nanofibers were coiled tightly into a ring to mimic the osteon, and reinforced in a hydrogel matrix. Morphological analysis using SEM and 4D-X-ray microscopy revealed that the hybrid scaffold consists of coiled rings of nanofibers in highly porous hydrogel matrix showing structural similarity to osteons. The reinforcement of electrospun nanofibers in hydrogel influenced the mechanical properties of scaffold. The potential application of the biomimetic hybrid scaffold, and the role of its specific architecture, was subsequently investigated in vitro using a human osteosarcoma fibroblast cell line. Furthermore, DNA quantification, alkaline-phosphatase and alizarin assay validated the potential of fabricated scaffold for bone tissue-regeneration.
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http://dx.doi.org/10.1016/j.nano.2018.03.011DOI Listing
June 2018
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