Biomimetic Composite Scaffolds for the Functional Tissue Engineering of Articular Cartilage

Abstract

<p>Articular cartilage is the connective tissue that lines the ends of long bones in diarthrodial joints, providing a low-friction load-bearing surface that can withstand a lifetime of loading cycles under normal conditions. Despite these unique and advantageous properties, the tissue possesses a limited capacity for self-repair due to its lack of vasculature and innervation. Total joint replacement is a well-established treatment for degenerative joint disease; however, the materials used in these procedures have a limited lifespan in vivo and will likely fail over time, requiring additional - and increasingly complicated - revision surgeries. For younger or more active patients, this risk is unacceptable. Unfortunately, alternative surgical options are not currently available, leaving pain management as the only viable treatment. In seeking to discover a new therapeutic strategy, the goal of this dissertation was to develop a functional tissue-engineered cartilage construct that may be used to resurface an entire diseased or damaged joint.</p><p> A three-dimensional (3-D) woven textile structure, produced on a custom-built miniature weaving loom, was utilized as the basis for producing novel composite scaffolds and cartilage tissue constructs that exhibited initial properties similar to those of native articular cartilage. Using polyglycolic acid (PGA) fibers combined with chondrocyte-loaded agarose or fibrin hydrogels, scaffolds were engineered with anisotropic, inhomogeneous, viscoelastic, and nonlinear characteristics prior to cultivation. However, PGA-based constructs showed a rapid loss of mechanical functionality over a 28 day culture period suggesting that the inclusion of other, less degradable, biomaterial fibers could provide more stable properties. </p><p> Retaining the original 3-D architecture and fiber/hydrogel composite construction, poly (epsilon-caprolactone) (PCL)-based scaffolds demonstrated initial biomechanical properties similar to those of PGA-based scaffolds. Long-term culture of 3-D PCL/fibrin scaffolds seeded with human adipose-derived stem cells (ASCs) showed that scaffolds maintained their baseline properties as new, collagen-rich tissue accumulated within the constructs.</p><p> In an attempt to improve the bioactivity of the PCL scaffold and further induce chondrogenic differentiation of seeded ASCs, we produced a hybrid scaffold system by embedding the 3-D woven structure within a porous matrix derived from native cartilage. We then demonstrated how this multifunctional scaffold could be molded, seeded, and cultured in order to produce an anatomically accurate tissue construct with potential for resurfacing the femoral head of a hip. </p><p>In summary, these findings provide valuable insight into a new approach for the functional tissue engineering of articular cartilage. The results of this work will hopefully lead to the discovery of new strategies for the long-term treatment of cartilage pathology.</p>