The goal of these studies is to develop and characterize unique synthetic polymer-biological molecule composites for biomedical applications. As part of preliminary studies, combinatorial peptide phage display libraries and biopanning techniques have been used to select a unique peptide sequence (""""""""T59"""""""") that specifically and tightly binds directly to chlorine-doped polypyrrole (PPyCl), an electrically conductive polymer that has shown promise in biomedical applications, such as nerve regeneration. ? ? In the proposed studies, the binding affinity and stability of the T59 peptide interaction with PPyCl (both in vitro and in vivo) and the nature of this interaction will be investigated. This information will contribute to the understanding of surface interactions and biomaterials modification strategies, and is critical for effectively applying these sequences for either in vitro (e.g., biosensor) or in vivo (e.g., tissue engineering) applications. PPyCl will also be functionalized with large biomolecules (e.g., NGF) to illustrate the versatility and utility of this approach. These goals will be accomplished in the following Specific Aims: (1) Study the in vivo response to PPyCl modified with T59; (2) quantitatively analyze, using fluorescamine protein assays, atomic force microscopy, and isothermal titration calorimetry, the binding of T59 to PPyCl; (3) use chemical and polymer analogs in conjunction with peptide variants (designed using modeling and simulations of binding energetics) to study the mechanism of interaction between T59 and PPyCl; and (4) study the ability to attach large biomolecules (i.e., nerve growth factor or NGF) to PPyCl via the T59 peptide. ? ? Overall, these studies will explore an alternate approach for modifying synthetic polymers for tissue engineering applications. By selecting and identifying unique peptide sequences that interact with high affinity to synthetic polymers, one can easily modify the polymer surfaces using those peptides (i.e., peptides can be synthesized with the polymer binding sequence on one end, and a sequence that binds to cells, drugs, growth factors, etc. on the other end). This strategy for surface modification could serve as a versatile method to develop bioactive materials using existing polymers (including those that are already FDA approved and/or those polymers that lack functional chemical groups for coupling reactions, like PPyCl), without changing the bulk properties of the materials. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB004529-02
Application #
7093464
Study Section
Special Emphasis Panel (ZRG1-BMBI (01))
Program Officer
Henderson, Lori
Project Start
2005-07-07
Project End
2009-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
2
Fiscal Year
2006
Total Cost
$256,809
Indirect Cost
Name
University of Texas Austin
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
Lee, Jae Y; Schmidt, Christine E (2015) Amine-functionalized polypyrrole: Inherently cell adhesive conducting polymer. J Biomed Mater Res A 103:2126-32
Nickels, Jonathan D; Schmidt, Christine E (2013) Surface modification of the conducting polymer, polypyrrole, via affinity peptide. J Biomed Mater Res A 101:1464-71
Lee, Jae Y; Bashur, Chris A; Milroy, Craig A et al. (2012) Nerve growth factor-immobilized electrically conducting fibrous scaffolds for potential use in neural engineering applications. IEEE Trans Nanobioscience 11:15-21
Fozdar, David Y; Lee, Jae Young; Schmidt, Christine E et al. (2010) Hippocampal neurons respond uniquely to topographies of various sizes and shapes. Biofabrication 2:035005
Lee, Jae Young; Schmidt, Christine E (2010) Pyrrole-hyaluronic acid conjugates for decreasing cell binding to metals and conducting polymers. Acta Biomater 6:4396-404
Lee, Jae Young; Bashur, Chris A; Gomez, Natalia et al. (2010) Enhanced polarization of embryonic hippocampal neurons on micron scale electrospun fibers. J Biomed Mater Res A 92:1398-406
Guimard, Nathalie K E; Sessler, Jonathan L; Schmidt, Christine E (2009) Towards a Biocompatible, Biodegradable Copolymer Incorporating Electroactive Oligothiophene Units. Macromolecules 42:502-511
Lee, Jae Young; Lee, Joo-Woon; Schmidt, Christine E (2009) Neuroactive conducting scaffolds: nerve growth factor conjugation on active ester-functionalized polypyrrole. J R Soc Interface 6:801-10
Lee, Jae Y; Bashur, Chris A; Goldstein, Aaron S et al. (2009) Polypyrrole-coated electrospun PLGA nanofibers for neural tissue applications. Biomaterials 30:4325-35
Fonner, John M; Forciniti, Leandro; Nguyen, Hieu et al. (2008) Biocompatibility implications of polypyrrole synthesis techniques. Biomed Mater 3:034124

Showing the most recent 10 out of 14 publications