The Schmidt Lab THE UNIVERSITY OF TEXAS AT AUSTIN Neural Materials & Cellular Engineering Office: BME 4.202l, Lab: BME Phone: ELECTROACTIVE MATERIALS NATURAL MATERIALS Decellularized ECM for Tissue Engineering Native extracellular matrix (ECM) provides tissues with an optimized scaffold for proliferation, morphogenesis and regeneration. Acellular ECM has a 3-D architecture and molecular composition comparable to native ECM and can be obtained from readily available allogenic and xenogenic sources. Understanding the mechanism of interaction between acellular ECM scaffolds and native cells can guide tissue engineering strategies for peripheral nerve regeneration and vasculogenesis. Ryan Nagao (BME)  Electrically conducting nanofibers for neural scaffolds  Passivated electrodes using pyrrole-HA conjugate Using the electrically conducting polymer polypyrrole, I have created multi- functional conductive biomaterials that can modulate neural interaction for stimulating and/or recording neural activities. For instance, conducting polymers have been modified to display neurotrophic activity, nanofibrous features, and a biocompatible and non-cell adhesive polysaccharide (hyaluronic acid) layer. Jae Young Lee (CHE) Nerve Regeneration in the CNS My research focuses on plasticity and regeneration within the central nervous system. Currently, I am using spinal cord injury in rodents as a model system to study how engineered materials aid in axonal regeneration. I am particularly interested in extracellular matrix molecules and their role in scar formation and nerve regeneration. Current projects include studying the effects of 1) acellular nerve grafts, 2) hyaluronic acid-based scaffolds for axonal regeneration within the adult mammalian spinal cord, and 3) 3D in vitro culture systems using hyaluronic acid-based hydrogel for neural stem/progenitor cells differentiation. Dr. Zin Khaing Post Doc Current models for peripheral nervous system injury show that Schwann cell migration from both the distal and proximal ends of the injury site precedes and enhances neurite outgrowth and recovery. I am investigating the mechanism by which peripheral nervous system repair occurs on the conducting organic semiconductor, polypyrrole (PPy), in order to determine both the direct and indirect effect that electrical stimulation through a PPy surface has on SC migration. By approaching this problem from both a cellular and molecular perspective, we hope to determine the validity of PPy as a neural conduit and whether the effects observed are field or surface driven phenomena. Leandro Forciniti (CHE) Hyaluronic acid (HA) is a biodegradable, non-immunogenic biopolymer found in human connective tissue. We are designing HA hydrogels with unique super-swelling properties and micro-architectures that resemble native extra-cellular matrix while utilizing patterning techniques to control cellular adhesion. Dr. Scott Zawko Post Doc ‘Direct-Write’ of 3D Submicron Structures in Hyaluronic Acid (HA) Hydrogels Stephanie Seidlits( BME) Co-advisor: Dr. J. Shear HA-based hydrogels are modified with internal, 3D-patterned protein structures through a photochemical ‘direct-write’ process based on multiphoton excitation, where photocrosslinking is confined to the focal volume of a laser. Additionally, we are investigating the interaction of cells with HA hydrogels by a parallel approach, which aims to elicit any effects of hydrogel mechanical properties on neuronal and glial phenotypes in 3D culture. Erin Moffitt (BME) HA-based Hydrogels for Therapeutic Delivery of MSCs to the CNS Mesenchymal stem cell (MSC) therapy promotes functional improvement following traumatic injury to the central nervous system. We are investigating specific mechanisms that may be responsible for these improvements through the development of tunable hyaluronic acid-based hydrogels. By controlling the mechanical and biochemical properties of these 3D microenvironments, we hope to promote desirable growth factor release profiles in encapsulated stem cell populations, enhancing the regenerative potential of MSCs in a spinal cord injury model. The objective of our research is to develop a method using multiphoton excitation to fabricate micron-scale biopolymer matrices with tunable chemical and mechanical properties for use as a scaffold for neuronal networks. Central to this research is the use of multiphoton excitation, generated by focusing a pulsed laser through a high numerical aperture objective, to fabricate micron-scale solid matrices made of crosslinked biological and biocompatible polymers. Multiphoton Fabricated Biopolymer Matrices as Scaffolds for Neuronal Networks Eric Spivey (BME) Co-advisor: J. Shear Attenuating Inflammatory Wound-Healing Response through Bilayer, bifunctional HA materials Sarah Mayes (BME) Cells interact with their environment using an array of integrins. We are attempting to create 3D biomimetic scaffolds using a photocrosslinking method in order to reproducibly create submicron surface properties within a HA-based hydrogel. The hope is to optimize cell-surface communication through the utilization of gradients to better understand and control cell attachment, axon growth, and cell migration. Derek Hernandez (CHE) ‘Direct-Write’ of 3D Submicron Structures in Hyaluronic Acid (HA) Hydrogels Richelle Thomas (CHE) Crystal Templating of Hyaluronic Acid (HA) and Collagen Type I Hydrogels Hyaluronic acid and collagen type I are naturally occurring substrates that provide structure and reinforcing characteristics to bodily tissues. We attempt to mimic native micro-structures via crystal templating of these hydrogels in an effort to better control cell adhesion and nerve regeneration. By controlling hydrogel pore size and morphology we aim to develop a suitable scaffold for tissue engineering. John Fonner (BME) Collaborator: Dr. P. Ren Virtual Screening Methods for Biomaterial Surface Functionalization Affinity binding peptides support surface modification without altering bulk properties such as conductivity and degradation. We are adapting computational modeling techniques to discover new binding peptides for polypyrrole and to quantify the strength and underlying mechanisms of binding. Endogenous electric fields (EF) are developmental cues that direct cell growth in vivo. We mimic EF by applying a current across the cell substrate and study its effect on cell development. Control of EF will allow us to direct neuron growth for nerve repair. Effects of Electric Field (EF) on Neuronal Development Hieu Nguyen (BME) such as hyaluronan and decellularized nerve grafts have many physical, chemical, and biological properties suited to wound healing environments. Hyaluronan can be chemically crosslinked to produce tissue engineered scaffolds that facilitate cell migration, wound healing and angiogenesis. We also develop new techniques for nerve and spinal cord injury repair using engineered nerve fragments as graft materials for regeneration. Synthetic polymers are a versatile tissue engineering platform that can deliver localized physical, chemical, and electrical cues tailored to specific applications. In particular, electrical stimuli have been shown to promote wound healing. By customizing and characterizing degradation rates, surface properties, and structural conformations, electrically conductive polymers such as polypyrrole and polythiophene can provide a readily available, “off the shelf” scaffold for nerve regeneration and guided tissue growth. Vanessa Aguilar (BME) The objective of my research is to develop an anti cell-adhesive, biocompatible barrier material to isolate injury and prevent fibrilar network formation. Base material can be layered with other anti-inflammatory or Zawko, S., C. E. Schmidt (in press). Simple Benchtop Patterning of Hydrogel Grids for Living Cell Microarrays. Lab on a Chip.  advanced biomaterials for neural tissue interfacing Lee, J.Y., C. Bashur, A. Goldstein, C.E. Schmidt (2009). Polypyrrole-Coated Electrospun PLGA Nanofibers for Neural Tissue Applications. Biomaterials. 30(26): Seidlits, S.K., C.E. Schmidt, J.B. Shear (in press). High-Resolution Patterning of Hydrogels in Three Dimensions using Direct-Write Photofabrication for Cell Guidance. Advanced Functional Materials. Guimard, Gomez, Schmidt (2007). Conducting Polymers in Biomedical Applications. Prog Polymer Sci. 32: 876–92. (invited rev) Gomez, N., J.Y. Lee, J.D. Nickels, C.E. Schmidt (2007). Micropatterned Polypyrrole: Combination of Electrical and Topographical Characteristics for Stimulation of Cells. Adv. Functional Materials. 17: Sanghvi, A.B., K.P-H. Miller, A.M. Belcher, C.E. Schmidt (2005). Biomaterials functionalization using a novel peptide that selectively binds to an electrically conducting polymer. Nature Materials. 4: Winter, J.O., T.Y. Liu, B.A. Korgel, C.E. Schmidt (2001). Biomolecule-directed interfacing between semiconductor quantum dots and nerve cells. Advanced Materials.13: Rivers, T.J., T.W. Hudson, C.E. Schmidt (2002). Synthesis of a novel, biodegradable electrically conducting polymer for biomedical applications. Advanced Functional Materials.12: cell-adhesive materials. The non-immunogenic base barrier layer incorporates alginate and hyaluronic acid to provide biocompatibility. Directing alginate patterning through super-saturated salt crystallization and crosslinking the patterned alginate with calcium allows robust control of the mechanical properties of the material. Craig Milroy (CHE) O ptimization of conducting polymer materials for neural and tissue engineering applications, electrochemical properties of neuro-implantable electrodes, and biomaterial surface modification for enhanced cellular adhesion and growth. Enhance biocompatibility. Optimization of conducting polymer properties.