Engineering zonally organized articular cartilage

dc.contributor.advisorRoy, Krishnenduen
dc.contributor.committeeMemberSchmidt, Christineen
dc.contributor.committeeMemberSuggs, Lauraen
dc.contributor.committeeMemberDa Silveira, Adrianaen
dc.contributor.committeeMemberChen, Shaochenen
dc.creatorNguyen, Lonnissa Hongen 2010en
dc.description.abstractCartilage regeneration is one of the most widely studied areas in tissue-engineering. Despite significant progress, most efforts to date have only focused on generating homogenous tissues whose bulk properties are similar to articular cartilage. However, anatomically and functionally, articular cartilage consists of four spatially distinct regions: the superficial, transitional, deep, and calcified zones. Each zone is characterized by unique extra-cellular matrix (ECM) compositions, mechanical properties, and cellular organization. The ECM is primarily composed of type II collagen and glycosaminoglycans (GAGs), whose relative concentrations vary between zones and therefore lead to distinctive mechanical properties. One of the major unsolved challenges in engineering cartilage has been the inability to regenerate tissue that mimics the zonal architecture of articular cartilage. Recent studies have attempted to imitate this spatial organization using zone-specific chondrocytes isolated from donor animal cartilage. Directed differentiation of a single stem population into zonally organized native-like articular cartilage has not yet been reported. This dissertation reports that hydrogels, incorporating both synthetic and natural polymers as well as cell-induced degradability, are suitable for generating zone-specific chondrogenic phenotypes from a single MSC population. Specifically, cues provided from the unique combinations of chondroitin sulfate (CS), hyaluronic acid (HA), and MMP-sensitive peptide (MMP-pep) within a PEG-based hydrogel, direct the chondrogenic differentiation of MSCs. The findings of this dissertation demonstrate the capability of creating native-like and mechanically relevant articular cartilage consisting of zone specific layers. This ability provides a new direction in cartilage tissue engineering and could be invaluable for cartilage repair if incorporated with current minimally invasive surgical techniques.en
dc.description.departmentBiomedical Engineeringen
dc.subjectBone marrow stromal cellsen
dc.subjectArticular cartilageen
dc.subjectDegradable hydrogelen
dc.subjectChondroitin sulfateen
dc.subjectHyaluronic aciden
dc.subjectMMP (matrix metalloproteinase)en
dc.subjectCartilage tissue engineeringen
dc.titleEngineering zonally organized articular cartilageen
dc.type.genrethesisen Engineeringen Engineeringen of Texas at Austinen of Philosophyen

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