Date of Award

1-2010

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Bioengineering

Advisor

Burg, Karen J.L.

Committee Member

Martine , Martine

Committee Member

Bateman , Ted

Committee Member

Kellam , James

Abstract

The ability of human articular cartilage to respond to injury is poor. Once cartilage damage has occurred, an irreversible degenerative process can occur and will often lead to osteoarthritis (OA). An estimated 26.9 million of U.S. adults are affected by OA. Osteochondral grafting is currently used to treat OA and osteochondral defects; however, complications can develop at the donor site and defect area. Osteochondral tissue engineering provides a potential treatment option and alternative to osteochondral grafting. The long term goal of this work is to develop a tissue engineered mesenchymal stem cell (MSC) based osteochondral construct to repair cartilage damage.
The first set of studies evaluated the interactions between skeletal tissue cells and the effectiveness of conditioned media (CM) to modulate mesenchymal stem cell differentiation. The results showed that CM can enhance the differentiation of MSCs towards several different cell types depending on the type of CM.
The next set of studies involved the design and characterization of a novel biphasic osteochondral tissue engineered construct. The osteochondral constructs were designed to address some of the current limitations that osteochondral tissue engineering currently faces; i.e., providing an alternate method of anchoring the construct and providing the ability to generate large viable constructs. Based on the results of several studies, a composite of polylactide/polycaprolactone and hydroxyapatite was used for the bone phase, a barbed pin was used to create a stable implant, and agarose was chosen for use in the cartilage phase. In addition, capillary channel fibers were incorporated in the bone phase to provide nutrient and cell delivery. The bundles of capillary channel fibers embedded in large tissue engineering scaffolds were shown to facilitate a uniform cell distribution through large volume scaffolds.
In the next study, a modified bioreactor was designed and incorporated a pneumatically controlled syringe to generate hydrostatic pressure (HP) on both phases of the biphasic construct. The bioreactor was used to demonstrate synergistic effects of CM and HP on the chondrogenic and osteogenic differentiation of MSCs.
Ultimately, in a final study, the combination of CM, bioreactor cultivation, and the unique construct design generated a biphasic construct with a cartilage-like upper phase attached to a bone-like bottom phase.

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