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Title: Self-assembling Peptide Networks for Treatment of Cartilage Degenerative Diseases
Author: Katta, Jayanth
ISNI:       0000 0001 3595 5358
Awarding Body: The University of Leeds
Current Institution: University of Leeds
Date of Award: 2007
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As the incidence of osteoarthritis incr~ases in the younger generation of patients, unconventional approaches are being researched ei~her to contain or treat· cartilage degeneration in its early· stages. The current study examined the utility of novel selfassembling peptides in developing therapeutic interventions for cartilage tissue degeneration, in the form of injectable joint lubricants and matrix repairing agents. In order to evaluate these peptide materials under different tribological conditions, suitable in vitro test models were developed that were specific to biphasic and boundary lubrication regimes of articular cartilage. Initially, the effect of load on the friction properties of cartilage under different tribological conditions was studied using a combination of friction, indentation tests and finite element modeling. Friction models based on these results were used to evaluate self-assembling peptides patterned after hyaluronic acid as joint lubricants for both native and degenerative cartilage tissue. These peptides were found to be as effective as native hyaluronic acid in reducing the friction levels under boundary lubrication conditions, but failed to influence the friction levels under biphasic lubrication conditions or with damaged cartilage tissue. It was proposed that lubricants/self-assembling peptides with glycosaminoglycan (GAG) . functionality and the ability to infiltrate the cartilage tissue and integrate themselves with the extracellular matrix of cartilage would be able to influence the fluid load support of cartilage under biphasic lubrication, and may have matrix-repairing capabilities. In order to verify this claim, short term and long term friction models, deformation models were developed involving both native and GAG deficient cartilage to evaluate lubricants/peptides that were .meant to address GAG loss in articular cartilage. Natural chondroitin sulphate was evaluated. using these· in vitro· models and was found to be an effective boundary lubricant,· but still lacked the abil1tY·'to integrate itself with the extracellular matrix of cartilage and hence influence the fluid load support of cartilag~. Self-assembling peptides with conjugated GAG side chains that have the ability to form in situ networks in the cartilage tissue are currently under development, and will be evaluated using the models developed here for their matrix repairing capability in the future.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available