(4ab) Benchtop Disease Models Using Tissue Engineering

Benchtop disease models
using tissue engineering

Jerald E. Dumas

Biomedical Engineering, Georgia
Institute of Technology, Atlanta, GA

Advances in biomaterial research have greatly impacted medicine
through new innovations in areas such as detection and treatment.  However, many grand challenges still
exist as the boundaries between biology, chemistry, and engineering continue to
merge.  I have used tools from each
area for both tissue repair and the study of diseases. 

As a doctorate student in the chemical and biomolecular engineering
department at Vanderbilt University, I developed a two-component allograft
mineralized bone particle (AMBP)/polyurethane (PUR) system for the treatment of
bone defects.  The biodegradable PUR
phase, which consisted of lysine triisocyanate and polyester polyol, had
tunable degradation rates and mechanical properties.  The AMBP phase, which is bound to the
PUR phase, was used as a filler to enhance the mechanical properties and
provide a resorbable pathway for cellular infiltration.  The adaptability of the AMBP/PUR
composite system made it suitable for multiple applications including an
implant or injectable platform.  Further,
the AMBP/PUR composites served as a delivery system for biologics such as
recombinant human morphogenic protein (rhBMP-2), accelerating new bone
formation in critical size defects in New Zealand White (NZW) rabbits.   

As an Institutional Research and Academic Career Development
Award (IRACDA) postdoctoral fellow in the biomedical engineering department at
Georgia Institute of Technology/Emory University, I am studying the role of
proteases in cancer.  I am
developing a detection device based from multiplex cathepsin zymography, which
uses a gelatin substrate in a SDS-PAGE gel to quantify enzyme activity.  Cathepsin activity has shown to be
upregulated in cancer tissue, and this difference is used to distinguish normal
from tumor tissue.  Concurrently, I
am utilizing hydrogel and polyurethane technology to create an in vitro bone
metastasis model that will study key parameters such as protease (i.e.,
cathepsin) activity and cell invasion rate.     

There have been great advances in understanding pathology
using in vivo models as in which host
animals provide a complex pathophysiological environment.  However, in vitro systems can provide more defined information as they
provide a more controlled environment that allows for the study of more
isolated factors in pathological states as compared to the unpredictable
variability of in vivo models.  In my lab, I will develop benchtop
tissue surrogates for co-culturing cells to: 1) model disease states, 2)
identify new biomarkers of disease, 3) model drug uptake and efficacy, and 4)
develop predictive computational models of disease progression and patient
treatment response. This work will be accomplished with the development of
responsive biomaterials that mimic the extracellular matrix (ECM), which is a
key component in pathological states. 
The engineered benchtop systems developed in my lab will accurately
predict in vivo results with a
fraction of the time and cost investments required of traditional animal
studies.