Prof. Metlushko's "3D Nano-Fabrication for Drug Discovery and Bio-Medical Applications Lab"


MOTIVATION, by Rohit Nathani, MS Thesis “Three-Dimensional Fabrication of Scaffolds for Drug Discovery and Regenerative Medicine”


  • Limitations of traditional 2D Culture / Why do Drugs Fail?
  • Potential of 3D Culture / Why to use 3D Matrices for Drug Development & Discovery?
  • Types of 3D Culture Systems / 3D Matrices.
  • Techniques of 3D scaffold fabrication: Electrospinning, Gas-Foaming, 3D Printing, hanging-drop scaffolds. NO "exact 1:1 replication"!!! None of those fabricated scaffolds are similar to the actual 3D structures in nature.
  • Tissue Engineering
  • Advantages & Applications of 3D Culture
  • Fig.1. Drug discovery and development is an expensive process.
  • It costs the pharmaceutical industry on an average $2.6 billion (including the cost of failures) and more than 10 years to develop a new drug. Each year, on average of 25 novel drugs are approved by the FDA's CDER and approximately $51.2 billion was spent in the year of 2014 by the pharmaceutical industry on research and development.
  • Fig.2 Currently most of the standard screening procedures are dependent on animal testing or in vivo testing. The problem with this is that animals react differently to drugs as opposed to human reaction and we cannot accurately predict its effects on humans. Animal testing is extremely expensive and a time-consuming pre-clinical process which provides inaccurate results. Even though animal testing might be successful and promising, it may eventually result in the compound failing in late-stage clinical trials.
  • Researchers and regulatory organizations across the globe are pushing for alternative methods for in vivo testing. Thus, in vitro cell-based assays are beginning to replace the in vivo animal testing thereby providing more accurate data. .
  • Fig.3. Hard plastic or glass petri dish does not represent cellular environment
  • Many current assays are performed using two-dimensional (2D) cell culture, which, due to the "unnatural" configuration that cells take on a flat surface (Fig. 3), do not sufficiently predict how the human body will react to a drug. 3D cell cultures can improve cell-based screening and identify toxic and ineffective substances at an early stage of the drug discovery pipeline. The 3D scaffolds serve to mimic the actual in vivo microenvironment where cells interact and behave according to the mechanical cues obtained from the surrounding 3D environment.
    The fabrication of scaffolds for drug discovery using 3D electron-beam lithography (Fig. 4 and 5) is an innovative concept and a potential break-through idea which could possibly be a paradigm shift in the drug-testing process.
  • Fig.4. The state-of-the-art 3-D Nano-fabrication could be achieved by modulating the Electron-Beam Lithography exposure dose .
  • As the traditional 2D cell culture (Fig.2) does not accurately mimic the 3D environment in which cells reside, it may provide inaccurate data regarding the predicted response of cells to therapeutics. In vitro cell-based assays, our 3D fabricated scaffolds have the potential to replace in vivo animal testing and provide more reliable data.

  • Fig.5 The state-of-the-art 3-D nanofabrication.
  • (Left, B&W images) Scanning Electron Microscopy (SEM) images of the ECM underlying colon tissue.
  • (Right, orange) Atomic Force Microscopy (AFM) images of the 3D scaffolds fabricated with our Raith E-Line electron beam lithography system.
  • Fig.6 The state-of-the-art 3-D nanofabrication.
  • Our Raith E-Line system has been modified to create complex 3-D structures in polymers (PMMA and PDMS).
  • This feature enables fabrication and replication of any 3D surfaces.
  • Our Team (M.S. and Ph.D students):

  • Rohit Sunil Nathani (M.S. Thesis "Three-Dimensional Fabrication of Scaffolds for Drug Discovery and Regenerative Medicine"),
  • Alessandro Costanzo (M.S. Thesis "Anti-In flammatory Drug Delivery System for Implantable Human Intra Ocular Lens after Cataract Surgery"),
  • Khodr Maamari (Ph.D. Thesis, "3D Nanofabrication For Bio-medical Applications", now with Samsung),
  • Evan Zaker (M.S. Thesis "Nano-fabrication of Accommodative Intraocular Lenses Using Gray-scale Electron Beam and Soft Lithography", now with Intel),
  • Kasun Punchihewa (Ph.D. Thesis "Nano Fabricated Extracellular Matrix Topography could Alter the Cancer Cell Behavior", now with GlobalFoundries),
  • Federico Mazza (now Ph.D. Student at Inperial College, London),
  • Mattias Mengoni (now with Nikon and Essilor International Joint Research Center).


  • Our undergrad students:

    George Kokkinias, Nathan Piland, Florian Richter, Zeina Maamari, Daniel Poarch, Noah Hasenfang, Oliver Aispuro, Brenden Murray, Jason Moore, Christian Chkaiban, Robert Yildiz, Marcel Patel, Rapheal Ihonor



    Our collaborators: Prof. Michael Cho (Department of Bioengineering at The University of Texas at Arlington), Prof. Sarah Glover (University of Florida College of Medicine, Gainesville, FL), Bruce Gaynes (Department of Ophthalmology, Loyola University Medical Center)

    References:

  • Kasun A. Gardiye Punchihewa, Se Yong An, Michael Cho, Sarah Glover and Vitali Metlushko
  • The extracellular matrix microtopography drives critical changes in cellular motility and Rho A activity in colon cancer cells, Rebecca Rapier, Jameela Huq, Ramana Vishnubhotla, Marinka Bulic, Cecile M Perrault, Vitali Metlushko, Michael Cho, Roger Tran Son Tay, Sarah C Glover1, Rapier et al. Cancer Cell International 2010, 10:24 http://www.cancerci.com/content/10/1/24
  • 3D Fabrication of Scaffolds for Cancer Research and Drug Discovery, Rohit Sunil Nathani, Khodr Maamari, Federico Mazza, Mattias Mengoni, and Vitali Metlushko The Phase 1 Working Group meeting, UIC COM, May 15, 2014.
  • Rohit Sunil Nathani, “Three-Dimensional Fabrication of Scaffolds for Drug Discovery and Regenerative Medicine”, M.S. Thesis, University of Illinois at Chicago, 2015 :



    To complement our fabrication expertise and expand our technology application, we actively looking for collaborations with universities and industry.

  • E-mail vmetlush@uic.edu


  • According to ISI Web of Knowledge, Metlushko published 190 articles in refereed journals - Applied Physics Letters (29), Journal of Applied Physics (26), Phys. Rev. Letters (7) and Phys Rev. (34), 111 articles since joining UIC in 2000
  • Metlushko’s current h-index is ranging from 35 (Web of Science) to 38 (Google Scholar)
  • The h-index is an index that attempts to measure both the scientific productivity and the apparent scientific impact of a scientist. The index is based on the set of the scientist's most cited papers and the number of citations that they have received in other people's publications.