Gupta, A. (2021) Identification of damage-associated molecular patterns and extracellular matrix proteins as major constituents of the surface-proteome of lung implantable silicone/nitinol devices. thesis, Medicine.
Full text available on request.Abstract
Implanted airway devices are now widely incorporated as mechanical interventions for an increasing number of pulmonary pathologies. Despite successful initial treatment, long-term efficacy can often be impacted by fibrotic or granulation tissue formation at the implant sites. The pathological transformation of the implant site compromises device function and can also trigger biofilm formation, colonization and hemoptysis. This study aimed to investigate this biological response to silicone and nitinol airway devices by characterizing the surface of uni-directional endobronchial valves explanted from severe COPD patients. Using scanning electron microscopy, combined with energy-dispersive x-ray spectroscopy, we imaged the surface of an explanted valve and observed the adhesion of cells and proteins. Following this, we applied a discovery proteomic approach, using high-resolution mass�spectrometry, to characterize the surface proteome of eight explanted valves. We identified 263 unique protein speciesto be mutually adsorbed on the valves. Enrichment analysis of these proteins revealed dominant clusters of functionally-related ontology terms associated with coagulation, pattern recognition receptor (PRR) signaling, the immune response, cytoskeleton organization, cell adhesion and migration, results consistent with the clinical observation of granulation tissue formation. We further identified a heavy enrichment of extracellular terms, and following matching with known databases, we determined that especially ECM proteins and DAMPs are cardinal in the formation of the adhered proteome. These findings set the groundwork for hypothesis generation and further exploration of the cellular and molecular mechanisms contributing to pathological wound healing around lung implants.
| Item Type: | Thesis (UNSPECIFIED) |
|---|---|
| Supervisor name: | Slebos, prof. dr. D.J. and Pouwels, dr. S.D. |
| Faculty: | Medical Sciences |
| Date Deposited: | 06 Jan 2022 08:42 |
| Last Modified: | 06 Jan 2022 08:42 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2958 |
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