In vitro Human Cartilage Tissue System for Putative Disease Model.
tissue engineering is a promising approach for the formation of in vitro tissue models.
Currently, progress in tissue engineering has been made in reproducing functional tissue
implants and disease models, and on predicting how the functional properties of
chondrocytes and the extracellular matrix change in response to physical perturbations
of the tissue models. In order ... read moreto gain insight into specific diseases, such as
osteoarthritis, improved in vitro cartilage tissue constructs are required. The goal of
the present program was to develop in vitro tissue systems that were closer
representatives of cartilage-related diseases, such as osteoarthritis, in order to be
able to exploit these systems for future study of disease formation and for drug
screening. Specifically, in the first part of the studies, the design of a tissue
engineered cartilage system mimicking inflammatory conditions in joints is described, as
a step toward understanding the response of primary human chondrocytes and extracellular
matrix components to inflammatory mediators. From these experiments, a broad spectrum of
inflammatory mediators from macrophages was applied and osteoarthritis-like symptoms
were observed at the cellular and tissue level. In the second part of the studies, a
strategy was established to improve the redifferentiation of human primary chondrocytes
and cartilage-specific matrix accumulation in engineered cartilage. In the third part of
the studies, the cartilage constructs, together with a specialized bioreactor, was
assessed for the study of cyclic compressive loading on the cartilage at the cellular
and tissue level as a physiologically-relevant approach to use the tissue model for the
study of osteoarthritis. In the last part of studies, physiochemical properties of silk
fibroin scaffolds prepared under different conditions were characterized in terms of
morphology, degradation rate, porosity and mechanical properties. The goal was to relate
the features of the biomaterial matrix to tissue remodeling, in the context of normal
vs. disease states. In conclusion, the strategies developed in this thesis offer a new
platform for cartilage tissue engineering and provide a basis for future work in the
study of cartilage related diseases using more refined cartilage tissue models in
Thesis (Ph.D.)--Tufts University, 2011.
Submitted to the Dept. of Chemical and Biological Engineering.
Advisor: David Kaplan.
Committee: Li Zeng, Yongzhong Wang, Catherine Kuo, and Kyongbum Lee.
Keyword: Biomedical Engineering.read less