A fundamental challenge in tissue engineering is the nature and design of an appropriate 3D scaffold. We propose to use self-assembling peptides to engineer the 3D environment of cells with biologic functionality that can be modified and controlled, based on the basic biophysics of the material, which can be tailored for specific cell types. We employ a Partnership that brings together investigators in biophysics, bioengineering, cell biology, molecular biology, physiology, chemistry, and imaging. Team members are specialists in Electrical Engineering (Grodzinsky, PI), Mechanical Engineering (Kamm), Chemical Engineering (Griffith), Biological Sciences (Zhang, Semino, Lee-BWH), Chemistry (Klibanov) and Clinical Science (Lee, Frisbie-CSU). The use of self-assembling peptides in tissue engineering potentially enables the control of cellular adhesion, biomechanical properties, growth factor presentation and/or release, and vascularization. A fundamental theme of this Partnership is that no single tissue engineering approach is suitable for the diverse structure of all tissues. However, our central hypothesis is that by providing a physiologically appropriate, molecularly specific environment that can be modified by design, we can utilize the """"""""core technologies"""""""" of the Partnership to improve the approach for a given tissue. This Partnership brings together expertise in several specific tissues, allowing us to interact in ways that traditional individual grants and programs do not provide.
Our Specific Aims are (1) Design, &functionalization of peptide sequence of self-assembling peptides for 3D tissue engineering;(2) To explore the basic biophysics of the self-assembling peptide environment using state-of-the-art computational modeling and biophysical measurements;and (3) To explore the role of the self-assembling peptide environment in three major target tissues: myocardium, cartilage, and liver. The lead institution of the Partnership is MIT, with partners from BWH and CSU.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB003805-05
Application #
7664447
Study Section
Special Emphasis Panel (ZRG1-MOSS-G (52))
Program Officer
Hunziker, Rosemarie
Project Start
2005-08-01
Project End
2012-07-31
Budget Start
2009-08-01
Budget End
2012-07-31
Support Year
5
Fiscal Year
2009
Total Cost
$1,298,168
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Krishnan, Yamini; Grodzinsky, Alan J (2018) Cartilage diseases. Matrix Biol 71-72:51-69
Florine, Emily M; Miller, Rachel E; Liebesny, Paul H et al. (2015) Delivering heparin-binding insulin-like growth factor 1 with self-assembling peptide hydrogels. Tissue Eng Part A 21:637-46
Kopesky, Paul W; Byun, Sangwon; Vanderploeg, Eric J et al. (2014) Sustained delivery of bioactive TGF-?1 from self-assembling peptide hydrogels induces chondrogenesis of encapsulated bone marrow stromal cells. J Biomed Mater Res A 102:1275-85
Florine, Emily M; Miller, Rachel E; Porter, Ryan M et al. (2013) Effects of Dexamethasone on Mesenchymal Stromal Cell Chondrogenesis and Aggrecanase Activity: Comparison of Agarose and Self-Assembling Peptide Scaffolds. Cartilage 4:63-74
Jay, Steven M; Murthy, Ashwin C; Hawkins, Jessica F et al. (2013) An engineered bivalent neuregulin protects against doxorubicin-induced cardiotoxicity with reduced proneoplastic potential. Circulation 128:152-61
Hammond, Nathan A; Kamm, Roger D (2013) Mechanical characterization of self-assembling peptide hydrogels by microindentation. J Biomed Mater Res B Appl Biomater 101:981-90
Vickerman, Vernella; Kamm, Roger D (2012) Mechanism of a flow-gated angiogenesis switch: early signaling events at cell-matrix and cell-cell junctions. Integr Biol (Camb) 4:863-74
Williams, Courtney M; Mehta, Geeta; Peyton, Shelly R et al. (2011) Autocrine-controlled formation and function of tissue-like aggregates by primary hepatocytes in micropatterned hydrogel arrays. Tissue Eng Part A 17:1055-68
Han, Lin; Grodzinsky, Alan J; Ortiz, Christine (2011) Nanomechanics of the Cartilage Extracellular Matrix. Annu Rev Mater Res 41:133-168
Kopesky, Paul W; Vanderploeg, Eric J; Kisiday, John D et al. (2011) Controlled delivery of transforming growth factor ?1 by self-assembling peptide hydrogels induces chondrogenesis of bone marrow stromal cells and modulates Smad2/3 signaling. Tissue Eng Part A 17:83-92

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