Date of Award

2014

Document Type

Open Access Thesis

Department

Biomedical Engineering

First Advisor

James O Blanchette

Abstract

Musculoskeletal tissue engineering involves the creation of multiple tissue types that interact together to form a particular function related to motion and maintaining the body's frame. In order to create a fully functional musculoskeletal system, a concrete method for the creation of the different tissue types must first be completed. Of the different tissue components related to the function of a musculoskeletal system, these studies deal with preconditioning circumstances of stem cells that will differentiate into cartilage and bone. These studies also deal with methods for the creation of functional bone and cartilage to be combined for the creation of a musculoskeletal system. The idea of ischemic preconditioning, a solution for the improvement of implanted cerebral and cardiovascular tissues, was adapted in this study to show that it eases the transition of cells implanted into a injury site to have increased engraftment and survival compared to current methods. It was also determined that HIFs are vital to this increased survival of stem cells in a toxic injury environment. That information translated to the second study dealing with HIF-2's involvement in the onset of hypertrophy. This study contributes to the field that through HIF-2 inhibition stem cells undergoing chondrogenesis will maintain a healthy phenotype providing proper mechanical function as found in native cartilage. Overall, these two studies added information relating to how stem cells could be prepared for the creation of a musculoskeletal system for implantation into defect systems.

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