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.