Molecular Tissue Engineering “Our ultimate goal is to develop therapeutic devices that either aid or augment the function and/or regeneration of damaged nerves.” Synthetic Electroactive Materials Natural Materials and Cell Mechanisms Natural Materials and Cell Mechanisms Current projects in this area focus on the design and characterization of electrically conducting polymers, polypyrrole (PPy) and polythiophene (PT). The body has inherent electrical properties and responds to electrical fields, and evidence suggests that electrical stimulation from conducting materials will potentially enhance nerve regeneration. Natural materials offer advantages for the repair of damaged tissue, as they inherently have many physical, chemical, and biological properties suited to wound healing environments. Projects in our lab focus on taking advantage of the properties of natural molecules and tissues and their interactions with cells to encourage peripheral nerve regeneration and vascularization of regenerating tissues. membrane HA molecule Kate Bivens CHE Size-dependent Effects of Hyaluronic Acid Scott Zawko CHE Hyaluronic Acid Biomaterials for Drug Release Applications We are designing a novel hydrogel for drug release applications. The hydrogel consists of HA and cyclodextrin (CD) derivatized with photoreactive groups. CD is a starch derivative consisting of seven glucose rings that form a hollow cone. The hollow interior of CD is more hydrophobic than the exterior which causes CD to form complexes with many poorly water soluble, low molecular weight molecules. The majority of the hydrogel consists of HA for biodegradability and biocompatibility. Cyclodextrin is included to confer on the hydrogel the property of molecule complexation. Jae Young Lee CHE Natalia Gomez CHE In this project, we are investigating neuron polarization (i.e., axon formation) on biomaterials with different surface properties. In particular, silicone polymers have been designed to simultaneously present physical cues (i.e., microchannels) and chemical cues (i.e., immobilized nerve growth factor, NGF) to nerve cells. Two different schemes are being investigated - Combination of both types of cues (see Figure A), and competition of both cues (see Figure B). Neuronal Responses to Physical and Chemical Stimuli Vs. B Competition Physical stimulus: grooves Chemical stimulus: NGF A Combination Physical + Chemical stimuli Conductive Polymer-Biological Molecule Composites as Bioactive Platforms for Cell Adhesion/Proliferation We present the potential use of electrically conductive poly(1-(2-carboxyethyl)pyrrole) (PPyCOOH) for surface modification and cell attachment. The ability to tailor the surface of biomaterials is critical to tissue engineering applications. HUVEC cells cultured on a PPyCOOH surface modified with cell-adhesive RGDs motif demonstrate an improved ability to attach to the surface and spread. The strategy to promote cell attachment brings this acid-functionalized PPy one step closer to the development of PPy composites with a variety of biological molecules, e.g., bioactive conducting platforms for specific biomedical purposes. Nathalie Guimard Chemistry Our goal is to synthesize a biocompatible, biodegradable polymer that is electrically conductive. To render the biomaterial electroconductive quaterthiophene units will be incorporated into the backbone of the polymer. These quaterthiophene oligomers will be linked by esters, which will permit the biodegradation of our polymer in vivo. Long-term work consists of functionalization of the polymer. Synthesis of Novel Electroactive PT-based Biomaterials Use of a versatile phage display technique for selecting high affinity peptides against polypyrrole. By selecting and identifying specific peptide sequences for PPy that bind tightly, one can quickly and easily modify the polymer surfaces using peptides containing the polymer binding sequence on one end, and a sequence that binds to cells, growth factors, enzymes, etc. on the other Optimization of Nerve Regeneration Factors Curt Deister CHE We are using an in vitro model (dorsal root ganglia explanted into hydrogels) to determine conditions that maximize neurite extension. We vary the concentration of neurotrophic factors (NGF, GDNF, CNTF) and proteins (collagen 1, fibronectin, laminin) in the hydrogel. The optimum determined with these experiments will serve as the design criteria for future nerve conduits. Stephanie Seidlits BME ‘Direct-Write’ of 3D Submicron Structures in Hyaluronic Acid Biomaterial A)Optical transmission images B)Confocal microscope image A) B) Our research explores the ability to ‘direct-write’ novel 3D biomaterials with submicron size scales that more closely mimic natural materials. Direct fabrication of crosslinked, 3D structures of biomolecules can be achieved using multiphoton excitation, where crosslinking is confined to the focal area of a femtosecond laser. Hyaluronic acid is an attractive material for tissue engineering applications because it is a biocompatible, bioactive, naturally occurring polysaccharide in the extracellular matrix that promotes wound healing. Clustering of CD44 receptors may be responsible for cell activation by small HA molecules. Changes in conformation, such as intra- molecular vs. intermolecular (up and down arrows, B) hydrogen bonding may take place dependent upon HA chain length, and may alter recognition of HA by CD44. PI: Christine Schmidt Polypyrrole (PPy) Functionalization Kiko Serna BME Joo-Woon Lee Post Doc Jon Nickels BME Shalu SurI BME We are developing natural-based hydrogels from hyaluronan (hyaluronic acid, HA) for use in peripheral nerve applications, and studying the mechanism of size-dependent effects on cells of large and small HA molecules via the CD44 receptor. Two possible but not exclusive explanations include clustering of CD44 by HA binding and differential recognition of different sizes of HA by CD44 based on tertiary structure in solution. Chemical Structure of PolypyrroleSEM images of PPy film surface and cross section Christine E. Schmidt, Ph.D. The Laurence E. McMakin, Jr. Associate Professor of Biomedical Engineering & Chemical Engineering Tel