Defense Date
2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Biomedical Engineering
First Advisor
Dr. Jennifer Puetzer
Second Advisor
Dr. Michael McClure
Third Advisor
Dr. Rebecca Heise
Fourth Advisor
Dr. Matthew Halquist
Fifth Advisor
Dr. Gregory Golladay
Abstract
The collective focus of this work is to begin to unravel the mechanism of AGEs in aging menisci by developing an in vitro system to better probe the effect of AGEs on mechanics and cell-matrix interactions at multiple scales of collagen organization. We evaluated changes in human OA menisci with age, developed a system for inducing physiological levels of AGEs while maintaining cell viability, and explored the effect of AGEs on tissue mechanics and cell response at different degrees of hierarchical collagen fiber formation to better predict the impact of AGEs in menisci and connective tissues throughout the body. Collectively we found little to no changes in human meniscus matrix with age, other than the accumulation of AGEs, which supports AGEs play a major role in increased degeneration with age. We found AGEs had differential effects on mechanics and cells depending on the degree of collagen organization, possibly explaining contradicting reports on the effect of AGEs throughout the body. Lastly, we found that when meniscal cells are removed from their aged matrix, they are still capable of forming collagen fibers, while the addition of AGEs back into this matrix produces a senescent phenotype with increased inflammatory signaling. Collectively, this work provides insight into the mechanism of AGEs at multiple scales of collagen organization, and the compounding effect on cells, to better characterize aging and disease in connective tissues throughout the body.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-8-2024