Vipul Agarwal

Hierarchical patterning of multifunctional conducting polymer nanoparticles as a bionic platform for topographic contact guidance

The use of programmed electrical signals to influence biological events has been a widely accepted clinical methodology for neurostimulation. An optimal biocompatible platform for neural activation efficiently transfers electrical signals across the electrode-cell interface and also incorporates large-area neural guidance conduits. Inherently conducting polymers (ICPs) have emerged as frontrunners as soft biocompatible alternatives to traditionally used metal electrodes, which are highly invasive and elicit tissue damage over long-term implantation. However, fabrication techniques for the ICPs suffer a major bottleneck, which limits their usability and medical translation. Herein, we report that these limitations can be overcome using colloidal chemistry to fabricate multimodal conducting polymer nanoparticles. Furthermore, we demonstrate that these polymer nanoparticles can be precisely assembled into large-area linear conduits using surface chemistry. Finally, we validate that this platform can act as guidance conduits for neurostimulation, whereby the presence of electrical current induces remarkable dendritic axonal sprouting of cells.

Biogenic production of palladium nanocrystals using microalgae and their immobilization on chitosan nanofibers for catalytic applications

Spherical palladium nanocrystals were generated from aqueous Na2[PdCl4] via photosynthetic reactions within green microalgae (Chlorella vulgaris). Electrospun chitosan mats were effective for immobilizing these biogenic nanocrystals, as a material for recycling as a catalyst for the Mizoroki–Heck cross-coupling reaction. This photosynthetically-driven metal transformation system can serve as a good candidate for an environmentally-friendly method for the synthesis of metal nanocatalysts.

Discovering Rules from Disk Events for Predicting Hard Drive Failures

Detecting impending failure of hard disks is an important prediction task which might help computer systems to prevent loss of data and performance degradation. Currently most of the hard drive vendors support self-monitoring, analysis and reporting technology (SMART) which are often considered unreliable for such tasks. The problem of finding alternatives to SMART for predicting disk failure is an area of active research. In this paper, we consider events recorded from live disks and show that it is possible to construct decision support systems which can detect such failures. It is desired that any such prediction methodology should have high accuracy and ease of interpretability. Black box models can deliver highly accurate solutions but do not provide an understanding of events which explains the decision given by it. To this end we explore rule based classifiers for predicting hard disk failures from various disk events. We show that it is possible to learn easy to understand rules, from disk events, which have extremely low false alarm rates on real world data.

Functional Reactive Polymer Electrospun Matrix

Synthetic multifunctional electrospun composites are a new class of hybrid materials with many potential applications. However, the lack of an efficient, reactive large-area substrate has been one of the major limitations in the development of these materials as advanced functional platforms. Herein, we demonstrate the utility of electrospun poly(glycidyl methacrylate) films as a highly versatile platform for the development of functional nanostructured materials anchored to a surface. The utility of this platform as a reactive substrate is demonstrated by grafting poly(N-isopropylacrylamide) to incorporate stimuli-responsive properties. Additionally, we demonstrate that functional nanocomposites can be fabricated using this platform with properties for sensing, fluorescence imaging, and magneto-responsiveness.

Evaluating the effects of nacre on human skin and scar cells in culture

Pearl nacre, a biomineralisation product of molluscs, has growing applications in cosmetics, as well as dental and bone restoration, yet a systematic evaluation of its biosafety is lacking. Here, we assessed the biocompatibility of nacre with two human primary dermal fibroblast cell cultures and an immortalised epidermal cell line and found no adverse effects.

Direct correlation of PNIPAM thermal transition and magnetic resonance relaxation of iron oxide nanoparticles

Poly(N-isopropylacrylamide) (PNIPAM), which undergoes a temperature dependent transition from hydrophilic to hydrophobic, has played a crucial role in the development of stimuli-responsive multifunctional nanoparticles. In particular, iron oxide nanoparticles coated with PNIPAM have been effectively developed to enable stimuli responsive drug delivery and imaging agents. However, the PNIPAM transition from hydrophilic to hydrophobic at physiologically relevant temperatures renders colloidal nanoparticles unstable resulting in aggregation and precipitation from solution. Consequently, a direct correlative analysis of the effect of the thermally induced phase transition of PNIPAM on the magnetic resonance properties of nanoparticles has not been possible as the changes in proton relaxivity have been dominated by the colloidal agglomeration of the nanoparticles. Herein, we report colloidally stable thermoresponsive PNIPAM-grafted-PGMA coated magnetite core/shell nanoparticles (PNIPAM–PGMA–NPs) that enable the direct analysis of the effect of PNIPAM phase changes in solution on the overall magnetic resonance relaxivity of nanoparticles in suspension.

Polymeric Nanofibre Scaffold for the Delivery of a Transforming Growth Factor β1 Inhibitor

Skin scarring is a highly prevalent and inevitable outcome of adult mammalian wound healing. Scar tissue is both pathologically and aesthetically inferior to the normal skin owing to elevated concentration of highly orientated collagen I architecture in the innate repaired tissue. With highly invasive surgery being the main treatment modality, there is a great need for alternative strategies to mitigate the problem of scar formation. Tissue engineering approaches using polymeric scaffolds have shown tremendous promise in various disease models including skin wound healing; however, the problem of skin scarring has been greatly overlooked. Herein, we developed an electrospun poly(glycidyl methacrylate) (ES-PGMA) scaffold incorporating a small-molecule antiscarring agent, PXS64. PXS64, a lipophilic neutral analogue of mannose-6-phosphate, has been shown to inhibit the activation of transforming growth factor β1 (TGFβ1). TGFβ1 is a primary protein cytokine regulating the expression of collagen I during wound healing and therefore governs the formation of scar tissue. The nanofibres were tested for biocompatibility as a tissue engineering scaffold and for their efficacy to inhibit TGFβ1 activation in human dermal skin fibroblasts.

Regulation of collagen expression using nanoparticle mediated inhibition of TGF-β activation

PXS64 is a stable mannose-6-phosphate (M6P) analogue which has been shown to be an effective anti-fibrotic agent by inhibiting the activation of latent TGF-β1. However PXS64 is insoluble in physiological conditions. Herein, we report a multifunctional poly(glycidyl methacrylate) (PGMA) polymeric nanoparticle system for intracellular delivery of PXS64 in human primary dermal scar fibroblasts. We demonstrate the efficacy of this anti-fibrotic platform by monitoring the expression of collagen production using an in vitro scar model.

In situ preparation of multicomponent polymer composite nanofibrous scaffolds with enhanced osteogenic and angiogenic activities

Bioactive ceramics are extensively used for bone repair and regeneration, which release ions to initiate apatite formation and promote osteogenic differentiation eventually resulting in strong bonding to bone. Toward enhancing the bioactivity of polymeric nanofibrous scaffolds, this work presents a one-step in situ sol-gel method to fabricate electrospun composite nanofibrous scaffolds encapsulating well dispersed ceramic nanoparticles overcoming the limitations of current preparation techniques. Transmission electron micrographs revealed uniform distribution of ceramic nanoparticles within the polymer nanofibers. The multicomponent scaffolds were found to release calcium, silicon and phosphate ions that mimic the dissolution and bioactivity of conventional bioactive glasses. The scaffolds enhanced the bioactivity of PCL fibers as observed through enhanced apatite formation in simulated body fluid. The released ions markedly enhanced the proliferation and osteogenic differentiation of human mesenchymal stem cells and the angiogenic activity of human endothelial cells in vitro. This work has important implications for engineering the next-generation nanostructured scaffolds that exhibit multi-biofunctional activities for bone tissue regeneration.

Systematic assessment of surface functionality on nanoscale patterns for topographic contact guidance of cells

The ability of surface topography to influence cellular response has been widely accepted, leading the way towards the development of potential neural prosthetics. Capillary force lithography (CFL) has emerged as a simple method to fabricate large-area sub-nanometer patterned conduits to guide neuronal cell adhesion, migration and aggregation. In addition to physical adhesion cues, an optimal guiding conduit will regulate neuronal differentiation behavior by introducing relevant chemical and biochemical cues. However, isolating the influence of surface chemical cues from the bulk properties of nano-conduits on cellular behavior remains a challenge. Herein, we demonstrate that polyglycidyl methacrylate (PGMA) can be used as a polymer substrate to manipulate the surface chemistry of nano-conduits. Furthermore, NGF immobilized onto the surfaces of the conduits has the ability to regulate neuronal differentiation as measured through neurite outgrowth. The approach developed highlights the importance of surface characteristics in addition to physical cues in controlling neuronal cell behavior.