The meniscus has a unique structure and composition that enables it to function under tension, compression, and shear. The interplay between proteoglycans and collagen throughout meniscal development allows the tissue to form a complex extracellular matrix, which is responsible for its impressive mechanical function. Recapitulating this intricate structure and the native levels of mechanical function in a tissue-engineered replacement model is challenging. Proteoglycans play major roles in facilitating the development and regulation of the collagen fiber network in fibrocartilage. By leveraging the relationship between proteoglycans and collagen and understanding how the timing and presence of proteoglycan deposition affect collagen architecture formation, we can potentially engineer more robust tissue-engineered menisci. Despite the known role of proteoglycans in the formation and homeostasis of the collagen fiber network, many questions remain about how this knowledge can be applied to recapitulate a meniscus-like collagen network in tissue-engineered models, or how proteoglycan accumulation due to injury might alter existing collagen structure in vivo. Therefore, the overarching goal of this dissertation is to investigate how the regulation or addition of large and small proteoglycans influences collagen fiber network formation and maintenance in both tissue-engineered and native menisci. In this dissertation, Chapter 1 reviews the role of both largeand small proteoglycans in collagen fibrillogenesis in fibrocartilage. Chapter 2 explores the effects of glycosaminoglycan degradation in tissue-engineered collagen gel-based meniscus constructs, focusing on fiber formation and the subsequent compressive and tensile properties. Chapter 3 investigates the use of siRNA in meniscal fibrochondrocytes, addressing the temporary suppression of aggrecan production by fibrochondrocytes in monolayer and 3D culture, examining how this suppression alters collagen fibrillogenesis and fiber architecture, and assessing its effects on mechanical properties. Chapter 4 examines the individual roles of decorin, biglycan, and fibromodulin in collagen gel-based con- structs by supplementing these gels with recombinant small leucine-rich proteoglycans, analyzing fiber structure after fibrillogenesis, and evaluating how this structure affects their tensile properties. Finally, while Chapters 2, 3, and 4 focus on proteoglycan roles in a collagen gel model, Chapter 5 investigates how the increase in proteoglycans in meniscus tissue following joint injury affects the existing and mature collagen structure, as well as tissue hypertrophy. Collectively, these findings can help inform the design of more structurally and functionally robust engineered menisci.