Biomedical Engineering - Theses

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Start date: 2014 × Subject: tissue engineering × Author: Trengove, Anna Gei ×

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    Targeting seamless cartilage repair with a bioadhesive implant
    Trengove, Anna Gei ( 2022)
    Injury to articular cartilage in the knee can lead to post-traumatic osteoarthritis if untreated, causing debilitating problems later in life. Osteoarthritis impacts an individuals’ mobility, ability to work, and participation in daily activities. The broader impacts of this are significant, with osteoarthritis a leading cause of disability and an economic burden globally. Standard surgical treatments fail to ensure long lasting repair of damaged cartilage, often resulting in fibrotic tissue. The field of tissue engineering has seen a vast amount of research in cartilage regeneration, with few strategies reaching clinical trials. A common theme among failure of tissue engineered implants is their inability to integrate with the native tissue. Cartilage is a deceptively complex tissue despite its lack of innervation or blood supply. Its matrix is dense, heterogeneous and anti-adhesive, containing only a small number of cells and little ability for self-repair. This work seeks to understand if a cell-laden bioadhesive material can improve integration with cartilage, by bonding the regenerative implant to the native tissue. A novel bioadhesive comprised of photocrosslinkable gelatin methacryloyl and a biological enzyme, microbial transglutaminase, is reported. The material’s adhesion to cartilage ex vivo is assessed mechanically and chondrogenesis by human adipose derived stem cells (hADSCs) encapsulated within the material is evaluated. The enzyme significantly improved adhesion to cartilage ex vivo and did not impede the production of cartilage matrix by hADSCs cultured under chondrogenic stimulation conditions. In a preliminary study, the enzyme significantly improved integration with human cartilage explants over time under static culture conditions. The ability of the bioadhesive to support integration with cartilage ex vivo under cyclic compressive loading was then investigated, which is understood to be a first within the literature. No clear advantage of the bioadhesive was observed under loading, with good integration observed histologically in all conditions and a significant ten-fold increase in integration strength over the culture duration. This experimental model in combination with a biphasic finite element model allows future investigation of open questions in the field. Further work could see the bioadhesive material combined with other strategies to improve integration and long-term cartilage regeneration outcomes, providing an essential step towards clinical translation.