Sumit Mehrotra
mehrotr4(at)msu.edu
sumitmehrotra(at)yahoo.com
2527 Engineering Building
Michigan State University
East Lansing, MI 48824
517.402.3991
Hometown: Lucknow, UP, India
Undergraduate Institution:
IIT Bombay, India
Interests: Drug delivery, tissue engineering,layer-by-layer assembled multilayer thin films, soft lithographic techniques such as microcontact printing, siRNA transfection, polymeric nanoparticle fabrication and property evaluation of different sizes and shapes, Analytical Characterization Techniques: SEM, TEM, AFM, standard and confocal microscopy, ellipsometry, fluorescence/UV/vis spectroscopy, contact angle, Zeta-potential, DLS
Project Description: Layer-by-layer (LbL) multilayer thin films are the sequential assembly of different polymers held together by various interactive forces such as, hydrogen bonds, electrostatic, hydrophobic or Vander Waals forces. Various strong and weak polyelectrolytes, including bio-molecules like nucleic acids and proteins, can be employed to fabricate LbL thin films, and their fabrication conditions can be easily tuned to give high control over the functionality of these films. Further, soft lithographic techniques such as microcontact printing can be employed to create polymer patterns to obtain varying surface functionality in 2-D or 3-D.
Space-controlled and time-controlled drug delivery are the two important aspects in the interrelated fields of gene therapy and tissue engineering that can help in the formation of organized tissue formation, either by generating gene expression patterns or by providing a controlled dosage of drug at the site of injury. Further, an aspect of tissue engineering is to develop new materials in vitro in a controlled 2-D or 3-D environment such that they mimic extracellular matrices with regard to multiple cell functionalities. LbL thin films along with soft lithographic techniques are the promising approaches to develop novel bio-functional materials for these applications.
Space-controlled and time-controlled drug delivery
Strategies to promote organized tissue formation patterns are highly dependent on the properties of the drug (therapeutic molecule) and the substrate (matrices) involved, and also on their mutual interactions. Undesired interactions or the lack of desired interactions between substrates and drugs can inhibit achieving the targets of controlled delivery. My work illustrates the real time applications of LbL thin films by providing novel strategies to release specific important therapeutic molecules, such as small interfering RNA (siRNA) and growth factors (brain derived neurotrophic factor, BDNF) from their matrices, and achieving controlled delivery. Specifically, hydrogen bonded LbL multilayers composed of biocompatible polymers such as polyethylene glycol and poly(acrylic acid) were studied and employed to control the release of these therapeutic molecules from their matrices.
Nanoparticle mediated siRNA delivery
Gene delivery is contingent on the optimal formulation of polymeric nanoparticles, whose function is to carry or transfer the therapeutics to inside the cell. The size and shape of these polymeric nanoparticles are the two critical parameters for their successful gene delivery to mammalian cells. My work describes the fabrication and characterization of siRNA incorporated polymeric nanoparticles, and optimization of cellular uptake of these nanoparticles as a function of their physiochemical properties, such as charge and size, to provide high siRNA transfection rates with minimal cytotoxicities. An interesting relationship between the size and UV/vis peak position of these nanoparticles was found for the first time (Mehrotra et al, Acta Biomater. 2009, 1474). In an on-going effort, the shapes of the nanoparticles are being studied to enhance the siRNA transfection efficiencies.
Three dimensional cellular co-cultures
Tissues and organs in vivo exhibit multiple layered cellular architectures to maintain differentiated cellular functions, and LbL multilayers along with soft lithographic techniques carries a potential to develop such multilayer cellular architectures in vitro. To this end, my work focused on creating a 3-D cellular scaffold by multilayer transfer printing onto the top of a monolayer of cultured cells and subsequently seeding a second layer of cells. The multilayer transfer printing was carried out in a non-contact stamping mode, where the non-contact transfer itself is a novel soft-lithographic method for transferring the multilayers from one substrate to other. In another approach, mechanically stable self-standing composite polyelectrolyte multilayer films were fabricate and characterized, which were then used to create free floating cell culture sheets. These composite films can release the growth factors/protein embedded within the degradable component of the film, and thus can help in achieving the desired phenotype of cells attached on the topmost non-degradable component of film. Also, these in-vitro developed cell sheets hold importance to create 3-D scaffolds and replace the damaged tissues sections in-vivo.
Reviewed Journal Publications:
Mehrotra S, Lynam D, Maloney R, Pawelec K M, Tuszynski M, Lee I, Sakamoto J, Chan C. Time controlled protein release from layer-by-layer assembled multilayer functionalized agarose hydrogels. Advanced Functional Materials 2009; revised manuscript under review.
Mehrotra S, Lee I, Chan C. Multilayer mediated forward and patterned siRNA transfection using linear-PEI at extended N/P ratios. Acta Biomaterialia 2009, 5, 1474-1488.
Patents:
“Patterned Delivery of siRNA Complexes”, Provisional patent filed on 10/24/08; Provisional patent application number: 61/108,065 (MSU Invention Disclosure Number: 08-0009F).
“Multifunctional Polyelectrolyte Layers for Integration into Nerve Repair Implants”, MSU Invention Disclosure Filed on 07/09/08 (MSU Invention Disclosure Number: TEC2009-0018).
PI: Christina Chan, Ilsoon Lee