Chapter 1 introduces emerging concepts in tissue engineering as well as the dynamic metabolism of immune cells, both of which underlie the motivation for my dissertation. Central to tissue engineering is the application of implanted biomaterials. By unraveling the underlying cause of immune cell activation by a widely used biomaterial (polylactide, PLA), Chapter 2 challenges a long-held theory behind host immune responses to PLA in the biomaterial microenvironment. Instead, a role for altered bioenergetics and metabolic reprogramming is postulated. Leveraging this discovery, Chapter 3 demonstrates that metabolic reprogramming can explain the reason why PLA stereochemistry is a determinant of immune cellular activation. Metabolic reprogramming could involve changes in glycolysis as well as oxidative phosphorylation. Consequently, Chapter 4 elucidates the role of glycolysis in chronic inflammation by polyethylene particles, polyethylene being another clinically used implant. Chapter 5 unravels the specific role mitochondrial respiration plays in chronic inflammation by PE particles. Lastly, Chapter 6 summarizes the overall findings in this dissertation, outlining ongoing and future experimental work. Chapters 2, 3, 4 and 5 are reprints of submitted articles.
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