Impact of Perlecan Mimics on Cartilage Pericellular Matrix Biomechanics

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Osteoarthritis, which results from the degradation of the articular cartilage, is a condition that affects a significant portion of the population in the US, with increasing occurrence as individuals age. The pericellular matrix, a structure that surrounds cartilage cells (chondrocytes), has been shown to transmit information about mechanical loading in cartilage to the cells. If proteoglycans, a type of macromolecule, in the pericellular matrix degrade, this can lead to early onset osteoarthritis. However, the precise role of these macromolecules in the mechanical properties and response of articular cartilage is unknown. This project will use a molecule that mimics the behavior of an important proteoglycan molecule, perlecan, to determine its effect on the mechanical behavior and response of chondrocytes, the pericellular matrix, and the extracellular matrix. By increasing knowledge in this area, new directions of investigation will be opened up regarding cartilage degeneration and potential therapies to minimize the impact of osteoarthritis. The research team will involve undergraduates and underrepresented students in the research as well as participate in STEM summer camps that support the Philadelphia K12 community.This project is organized around three objectives. First, the diffusion kinetics and distribution of perlecan mimics will be confirmed in normal and osteoarthritic human articular cartilage. Second, the in situ nanomechanical behavior of the chondrocyte, pericellular matrix, and extracellular matrix will be determined using Atomic Force Microscopy for both normal and osteoarthritic articular cartilage, both in the presence and absence of the perlecan mimics. Finally, the molecular interactions of the perlecan mimics with naturally occurring pericellular and extracellular matrix biomolecules will be determined. An improved understanding of the role of perlecan in articular cartilage response could lead to the ability to engineer the pericellular matrix or extracellular matrix to support tissue regeneration and as an augmentation to cellular tissue engineering. The techniques developed in this study for articular cartilage will be appropriate for other musculoskeletal tissues as well as other soft tissues that are compromised through degeneration and aging, such as the skin or urethra.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.