Date of Award

12-2012

Document Type

Thesis

Degree Name

Master of Science (MS)

Legacy Department

Bioengineering

Advisor

Dean, Delphine

Committee Member

LaBerge , Martine

Committee Member

Yao , Hai

Abstract

Radiation therapy is necessary treatment for many cancer patients due to its non-surgical, yet aggressive and efficacious properties. In fact, over 50% of patients with cancer will undergo some form of radiotherapy during the course of their treatment. While the biological response to ionizing radiation has been examined over the years and many adverse effects have been identified, the effects of radiation on mature cartilage and musculoskeletal tissues are not well understood. Bone, once thought to be a tissue relatively resistant to radiation, has recently been shown to have osteoporosis-like bone atrophy after exposure to low doses (2 Gy) of radiation. The goal of this research was to determine if radiation has any adverse effects on articular cartilage. In our pilot study, we observed significant decreases in the stiffness of articular cartilage in mice one week after low doses of ionizing radiation. Young's modulus values were about 90% lower in irradiated tissue compared with controls using indentation-type atomic force microscopy (IT AFM). Histological analysis showed a qualitative decrease in proteoglycan staining in irradiated cartilage compared with the control samples. However, due to the limitations of IT AFM, we were unable to determine if radiation affects only mechanical properties at the articulating surface of the cartilage, or if it alters the bulk mechanical properties of the tissue. In our follow-up study, we exposed fresh porcine cartilage explants with a similar dose of radiation, and then cultured the cartilage samples for one week. At Day 7, mechanical testing was performed at multiple length scales, utilizing both IT AFM and microindentation. At both length scales, irradiated cartilage had significantly lower modulus values compared with control samples. Therefore, we believe that radiation affects the entire thickness of the tissue, not just the superficial zone. Irradiated explants also had an acute release of glycosaminoglycans (GAGs) 24 hours after exposure, and GAG content in irradiated tissue was about 50% lower than that of controls at Day 7. The results of these studies show that ionizing radiation has the potential to adversely affect the functional properties of articular cartilage. Therefore, more experiments are necessary to identify the severity of a radiation-induced injury using more realistic models. Further research must be performed to elucidate the exact mechanisms of this damage so that a viable therapy can be developed to protect against this damage.

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