Date of Award

May 2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Bioengineering

Committee Member

Delphine Dean

Committee Member

Jeremy Mercuri

Committee Member

Endre Takacs

Committee Member

Jeffrey Willey

Abstract

Articular cartilage is a specialized connective tissue, predominately composed of water, collagen, and proteoglycans, that provides a smooth, lubricated surface for articulation in joints. It has long been considered radioinsensitive and therefore unaffected by exposure to radiation in medical settings. Due to the increased amount of yearly radiation exposure through radiotherapy and ionizing radiation diagnostic procedures, there has been a renewed interest in how radioinsensitive articular cartilage actually is. Despite this renewed interest, the majority of studies do not focus on articular cartilage as their primary goal, but rather, have observed the effects of total body irradiation. These studies have drawn different conclusions on the effects of ionizing radiation on articular cartilage, but they have each drawn the same overall conclusion that this research needs to be continued and broadened in order to make a consistent conclusion on the radioinsensitivity of articular cartilage.

The purpose of this research was to investigate the mechanical and functional effects of low doses of Gamma radiation and X-ray radiation as well as the mechanical and functional effects of repeated exposures of low doses of Gamma radiation. This was accomplished by (1) analyzing the mechanical and functional effects of Gamma radiation at doses of 2Gy, 2.5Gy, and 3Gy, (2) analyzing the mechanical and functional effects of three repeated Gamma radiation exposures of 1Gy, 1.5Gy, and 2Gy as well as the mechanical and functional effects of three X-ray radiation doses of 1.5mGy, 25mGy, and 4000mGy, and (3) exploring two possible mechanisms for the mechanical changes seen in the irradiated articular cartilage.

Results showed that there were differences in the mechanics of the irradiated plugs over a seven-day period after exposure. The irradiated plugs demonstrated a significantly lower modulus seven days after exposure. When analyzing the release of proteoglycans from the single dose Gamma irradiated plugs there was an acute and persistent release, which may be a contributor in the modulus decrease. However, for the repeated doses of Gamma irradiation, the plugs showed a lower amount of proteoglycans released, indicating that fractionation of Gamma irradiation may allow the plugs to recover from the exposures. There was also little difference between the amount of proteoglycans remaining in the X-ray irradiated plugs when compared to the control plugs, potentially indicating that low doses of X-ray radiation does not lead to significant changes in the proteoglycan structure within articular cartilage. Finally, senescent staining indicated no senescence in the chondrocytes exposed to 1.5mGy and 25mGy of X-ray radiation, but there was an indication of the presence of ADAMTS5, an enzyme that degrades the proteoglycan aggrecan, in 25mGy and 4000mGy plugs on day 1 after X-ray exposure.

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