Ying Zhang

Date of Graduation

2015

Document Type

Dissertation

Degree Type

PhD

College

Statler College of Engineering and Mineral Resources

Department

Chemical and Biomedical Engineering

Committee Chair

Ming Pei

Committee Co-Chair

Cerasela Zoica Dinu

Committee Member

Victor H Mucino

Committee Member

Ming Pei

Committee Member

Konstantinos A Sierros

Committee Member

Nithi T Sivaneri

Committee Member

Nian qiang Wu

Abstract

Osteoarthritis (OA) is predicted to be the fourth leading cause of disability worldwide by the year 2020. Stem cell-based therapy is a promising biological approach for the treatment of cartilage defects. However, adult stem cells tend to become replicatively senescent when they are expanded on conventional plastic flasks. Decellularized extracellular matrix (dECM) provides an expansion system to rejuvenate and maintain the chondrogenic phenotype of stem cells for cartilage repair. In addition, joints with cartilage defects normally have inflammation to some extent; several stimuli, such as Reactive Oxygen Species (ROS) and Interleukin-1 (IL-1), reportedly induce apoptosis of chondrocytes. The tolerance of transplanted cells to a harsh environment is a key determinant for successful cartilage repair. dECM expansion gives adult stem cells an ability to resist inflammation and oxidants. This anti-inflammatory effect was further optimized by the combined use of small molecules in inflammation-related signaling pathways. Furthermore, dECM is a three-dimensional nanofiber structure with unique micromechanical properties. The influence of dECM elasticity on expanded stem cells' chondrogenic differentiation has been studied. Our long-term goal is to develop an in vitro stem cell matrix with optimized micromechanical properties to enhance stem cell proliferation and boost chondrogenic differentiation in order to treat cartilage defects and OA.

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