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Sherri
Voytik-Harbin, Ph.D.
Assistant Professor, Basic Medical Sciences
Assistant Professor, Biomedical Engineering
BS ‘87, Indiana University; MS ’89, Purdue University;
PhD ‘92, Purdue University
E-mail:harbins@purdue.edu
Research Interests
Tissue Engineering/Biomaterials; Extracellular
Matrix; Cell-Extracellular Matrix Biomechanics; Mechanotransduction;
3D Culture Systems; Bioimaging and Image Analysis.
Cell-ECM Biomechanics and Mechanotransduction
In vivo, cells are continuously subjected to dynamic, mechanical
stimuli. Such biophysical cues are critical determinants of
fundamental cellular behavior not only during physiological
processes but also during the pathogenesis of disease states.
To date, it is not known which structural and mechanical features
of the extracellular matrix (ECM), in which cells reside,
control a cell's fate. Additionally, the mechanisms by which
cells sense and respond to such biophysical cues have not
been elucidated. We have developed a novel system that allows
simultaneous visualization in 3D of load-induced changes to
cells and their ECM within live tissue constructs. Computational
methods that allow quantification of the 3D strain state at
various functional levels including macroscopic (tissue-construct)
and microscopic (cellular and collagen fibril) levels have
also been developed. These tools are being applied to 1) determine
how ECM microstructural composition affects the distribution
and transfer of externally applied mechanical loads to resident
cells within 3D tissue constructs and 2) identify the role
of cell-matrix adhesion complex formation in the mechanotransduction
process. This research will contribute to the development
of engineered scaffolds that would deliver to cells specific
growth-inductive signals required for the development of functional
tissue constructs in vitro and in vivo.
Engineering Functional Biomaterials
and Tissues
A major challenge facing tissue engineers is the design of
scaffolds that mimic the ECM and its interface with cells.
With the hope of increased biocompatibility and elicitation
of a desirable cell response, we are seeking new ways to engineer
scaffolds from molecules isolated from the ECM portion of
tissues. Such molecules include collagens, glycosaminoglcans,
proteoglycans, and growth factors. Interestingly, many of
these molecules have the ability to form 3D, supramolecular
matrices in vitro by self-directed polymerization. Our laboratory
has shown that adjustment of polymerization conditions, including
composition and pH, provides a convenient means of producing
3D scaffolds with distinct microstructures, mechanical behavior,
and cell instructive properties. Utilization of confocal and
multi-photon microscopy in specific modalities allows us to
1) visualize and quantitate the kinetics of the matrix formation,
2) analyze matrix microstructural properties, and 3) determine
the ability of the matrix to predictively regulate cell behavior,
from a multi-dimensional perspective (e.g., x, y, z and time).
Our most recent initiative involves the integration of ECM
biochemistry and engineering with stem cell biology in the
design of new biomaterials that carry our very sophisticated
signaling needs, that is, directed differentiation of stem
cells into a specific cell type and function.
Publications
Voytik-Harbin SL, Roeder
BA, Sturgis JE, Kokini K, Robinson JP. Simultaneous mechanical
loading and confocal reflection microscopy for three-dimensional
microbiomechanical analysis of biomaterials and tissue constructs.
Microsc Microanal. 2003 Feb;9(1):74-85.
Roeder BA, Kokini K, Sturgis JE, Robinson
JP, Voytik-Harbin SL. Tensile mechanical
properties of three-dimensional type I collagen extracellular
matrices with varied microstructure. J Biomech Eng. 2002 Apr;124(2):214-22.
Lakey JR, Woods EJ, Zieger MA, Avila JG,
Geary WA, Voytik-Harbin SL, Critser JK. Improved
islet survival and in vitro function using solubilized small
intestinal submucosa. Cell Tissue Bank. 2001;2(4):217-24.
Voytik-Harbin SL, Rajwa
B, Robinson JP. Three-dimensional imaging of extracellular
matrix and extracellular matrix-cell interactions. Methods
Cell Biol. 2001;63:583-97.
Voytik-Harbin SL. Three-dimensional
extracellular matrix substrates for cell culture.
Methods Cell Biol. 2001;63:561-81
Brightman AO, Rajwa BP, Sturgis JE, McCallister
ME, Robinson JP, Voytik-Harbin SL Time-lapse
confocal reflection microscopy of collagen fibrillogenesis
and extracellular matrix assembly in vitro. Biopolymers. 2000
Sep;54(3):222-34.
Suckow MA, Voytik-Harbin SL,
Terril LA, Badylak SF. Enhanced bone regeneration using porcine
small intestinal submucosa. J Invest Surg. 1999 Sep-Oct;12(5):277-87
Voytik-Harbin SL, Brightman
AO, Waisner B, Lamar CH, Badylak SF. Application and evaluation
of the alamarBlue assay for cell growth and survival of fibroblasts.
In Vitro Cell Dev Biol Anim. 1998 Mar;34(3):239-46.
Narayanan PK, Carter WO, Ganey PE, Roth RA, Voytik-Harbin
SL, Robinson JP. Impairment of human neutrophil oxidative
burst by polychlorinated biphenyls: inhibition of superoxide
dismutase activity. J Leukoc Biol. 1998 Feb;63(2):216-24.
Voytik-Harbin SL, Brightman
AO, Kraine MR, Waisner B, Badylak SF. Identification of extractable
growth factors from small intestinal submucosa. J Cell Biochem.
1997 Dec 15;67(4):478-91.
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