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Access Type
WSU Access
Date of Award
January 2023
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Biomedical Engineering
First Advisor
Howard W. Matthew
Abstract
Articular cartilage (AC) tissue degeneration due to joint disease or traumatic injury results in a progressive and debilitating condition known as Osteoarthritis (OA). OA afflicts approximately 20% of the U.S. population, and approximately 3.8% of the global population. OA creates a significant socioeconomic burden, with more than $100 billion spent annually on treatment related expenses in the U.S. alone. Regardless of the initial cause, OA is a progressive, and often irreversible condition that results in a significant loss of quality of life, especially for patients in the later stages of disease. Current treatments range from analgesics in early-stage disease to biomaterial/cell-based repair strategies and finally to total joint replacement. Presently, there are no effective clinical approaches that prevent the progressive loss of AC tissue, and surgical approaches have been shown to be ineffective in preventing recurring pain for 20-30% of the patient population. Additionally, cell-based repair approaches often fail due to fibrocartilage formation or graft hypertrophy, resulting in the need for revision surgeries. Several challenges to the successful development of a functional AC graft include: the lack of tissue vascularity, the presence of catabolic enzymes that destroy matrix proteins, differences in material and architectural properties between healthy tissue and engineered grafts, and the effects of engineered scaffolds on the biological potential of seeded cells. Current research efforts have focused on scaffolds infused with bioactive factors and cell-free or cell-laden scaffolds. While some research efforts have shown promise, the major limitation has been the lack of AC grafts that exhibit consistent biophysical properties, and which have predictable physiological outcomes. Such consistency would allow clinicians to assess the qualitative and quantitative aspects of an AC graft, thus determining its safety and efficacy. Here, we propose the fabrication of a modular, polyelectrolyte complex microcapsule (PECM) platform for AC repair. The general question to be tested is whether the microcapsular platform sufficiently supports the biological potential of encapsulated Chondrocytes/bMSCs and promotes the development of a tissue-like structure that accurately mimics the biological and mechanical properties of native AC. Since diffusion is the major factor limiting the size of an engineered graft, we assessed the ability of methacrylic anhydride to promote the formation of a hydrated, crosslinked hyaluronic acid (HA)-based interior gel network in the PECM. Next, two cell types were entrapped in glycosaminoglycan (GAG) solution and encapsulated through the formation of chitosan-GAG/ polyelectrolyte complex membranes promotes to test the effect of our PECM on cellular activity. Then we further tuned our system with the addition of type I collagen and assessed the system over the long term. We determined that chondrocytes preferentially proliferate and deposit matrix materials over the long term. Our system promotes efficient handling and processing of cells, allowing for rapid transplantation of pre-conditioned AC grafts of patient matched dimensions.
Recommended Citation
Arhebamen, Ehinor P., "Design And Assembly Of A Modular Polyelectrolyte Complex Microcapsule Platform For Hyaline Cartilage Repair" (2023). Wayne State University Dissertations. 3815.
https://digitalcommons.wayne.edu/oa_dissertations/3815