Echevarria, Iria (2022) Remote control healing for osteoarthritis repair. Doctoral thesis, Keele University.

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Articular cartilage is a key tissue for the normal functioning of the joints, with a trend for degradation with aging and physical activity. The lack of vascularisation hinders the self-repair, and often a scar tissue replaces the damaged cartilage, failing to fulfill the mechanical and functional needs for normal functioning of the joints. Current therapeutic approaches fail to stop the progression of this chronic disease, and represent a huge economic burden for the health system. The need for a less-invasive treatment for delaying the progression of the disease while improving the life quality of the patient has led to tissue engineering scientists to research for a potential therapy. Currently research has focused on MSCs for their expansion potential, multi-lineage differentiation and low immunogenicity. Despite the promising outcome of novel studied there is still need for techniques that manage to generate tissue matching those properties of the native cartilage.
This work aimed to develop a new technique for cartilage regeneration that could potentially deliver a remote therapy. UC-MSCs were studied as a potential cell source for chondrogenic differentiation using the MICA technology. Cells were labelled with MNPs targeted towards TRPV4, a mechanosensitive ion channel involved in cartilage homeostasis (1). The channel was activated following MNPs labelling of cells, by using a magnetic force bioreactor that generates an external alternating magnetic field. The force exerted by the activated MNPs trigger the activation of the ion channel, with the subsequent ion exchange and signaling activation pathway.
The effects of the MICA technology on the chondrogenic response were assessed by in-depth histological and immunohistochemical assessment of the cartilage constructs. In addition, gene expression analysis of chondrogenic markers and early transcription factors was performed on several cell sources.
The combination of the MICA technology together with the aid of biochemical cues resulted in constructs showing enhanced deposition of chondrogenic markers at early time points. Elevated collagen II, proteoglycans and SOX9 was observed for the 3D constructs without any presence of hypertrophy signs. This was observed for all tested cell sources with a promising potential for UCMSCs as candidates for cartilage repair. We believe that the work here has a great potential for developing a therapy for cartilage repair based on the combination of MSCs and MNPs with the aid of the MICA technology.

Item Type: Thesis (Doctoral)
Additional Information: Embargo on access until 7 September 2023 - The thesis is due for publication, or the author is actively seeking to publish this material.
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
Contributors: Forsyth, NR (Thesis advisor)
El Haj, AJ (Thesis advisor)
Depositing User: Lisa Bailey
Date Deposited: 14 Oct 2022 15:39
Last Modified: 14 Oct 2022 15:39

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