Fibrotic diseases account for an estimated 45% of the total number of deaths in the developed world (Wynn 2007). Tendons are an excellent model for studying the dysregulated response which leads to fibrosis, as tendons have an organized, parallel matrix, in which tissue defects could easily be distinguished. Wong et al. (2006b) demonstrated the presence of a bell-shaped region around sutures in tendons that was devoid of cells in histological sections. The mechanisms of the formation of this acellular zone, that was also noted in cornea and cartilage (Matsuda et al. 1999; Hunziker and Stähli 2008), were unknown. It was hypothesized that the acellular zone was formed by cell death and that suturing caused alterations to the extracellular matrix of sutured regions of tendon, which made the acellular zone refractory to cellular re-population. The acellular zone was tracked in sutured tendons for up to a year to determine the temporal properties of the acellular zone. Electron microscopic and time lapse studies were carried out to determine if the acellular zone formed by cell migration or cell death. Microarray analysis was conduced to confirm this and to reveal potential molecular targets for future studies. The extracellular matrix of sutured tendons was studied by electron, atomic, scanning and polarized light microscopy and mechanical measurements were obtained using nanoindentation. It was concluded that the acellular zone formed within 24 hours and persisted for up to a year. Tension and size of the suture's grasp were also shown to be important for acellular zone formation. Cell death was the main effector of acellular zone formation. Microarray analysis showed evidence of upregulation of inflammatory mediators and programmed necrosis pathways. The sutured extracellular matrix was denser, more disorganized and had a lower Young's modulus than unsutured regions of the same tendon. These differences in the properties of the extracellular matrix of sutured tendons may be the cause of the persistence of the acellular zone.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:538431 |
| Date | January 2011 |
| Creators | Al Youha, Sarah |
| Contributors | Mcgrouther, Duncan ; Kadler, Karl ; g, Jason |
| Publisher | University of Manchester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://www.research.manchester.ac.uk/portal/en/theses/towards-an-understanding-of-the-mechanisms-of-acellular-zone-formation-in-sutured-tendons(a942e6b2-44e4-44dc-a949-34ce3b39e6f4).html |
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