Photocrosslinkable hydrogels as cell-scaffolds for tissue engineering cartilage: A study examining gel properties, degradation, mechanical loading and clinical relevance

Cartilage, unlike other tissues, has a limited ability for self-repair. Therefore, approaches to engineer cartilage through the development of cell-carriers are important. We are particularly interested in using photopolymerizable hydrogels as a chondrocyte-carrier. Photopolymerization is desirable because the scaffold can be formed in situ at physiological conditions with temporal and spatial control over the polymerization. In designing an in situ forming cell-scaffold, the scaffold should promote cell proliferation and tissue secretion, span the thickness of native cartilage, restore function initially, degrade at a similar rate to tissue formation, transfer mechanical signals to the cells, and integrate into the surrounding tissue. This thesis tests the hypothesis that photocrosslinked hydrogels will meet these design requirements for a suitable chondrocyte-carrier to engineer cartilage.; To test this hypothesis, photocrosslinked hydrogels based on poly(ethylene glycol) were employed as a model system. Using these gels, we have shown that chondrocytes survive the photoencapsulation process, remaining viable and functional, particularly in hydrogels that span the thickness of native cartilage and exhibit similar properties to the native tissue. The spatial distribution of secreted extracellular matrix (ECM) molecules was closely related to the crosslinking density (ρ_x) of the hydrogel and was controlled by incorporating degradable crosslinks into the hydrogel.; This knowledge was expanded into developing multivinyl macromers derived from natural components found in cartilage (negatively charged chondroitin sulfate) and from poly(vinyl alcohol) to design hydrogels that mimic the native tissue and to gain additional control over the gel macroscopic properties and degradation times. Interestingly, the ECM composition depended on the gel chemistry.; This research has also aimed to address issues associated with in situ formed cell-carriers, such as mechanical loading and clinical concerns. Mechanical loading influenced cell morphology and cell function in a ρ_x-dependent manner. From a clinical perspective, in situ polymerization was shown to improve initial adhesion of the gel to the adjacent cartilage, and the neocartilaginous tissue integrated into the surrounding native tissue.; In summary, photocrosslinked hydrogels are promising cell-carriers that can be in situ polymerized into any shaped defect, and the 3-D gel environment promotes the formation of a functional tissue rich in cartilage-like ECM components, facilitating integrative repair.