4.8 Article

Identification of damage associated molecular patterns and extracellular matrix proteins as major constituents of the surface proteome of lung implantable silicone/nitinol devices

Journal

ACTA BIOMATERIALIA
Volume 141, Issue -, Pages 209-218

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2022.01.016

Keywords

Medical device; Lung; Nitinol; Silicone; Protein adsorption

Funding

  1. ZonMW [91111.006]

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This study investigates the composition of the adhered proteome on explanted lung devices, which are widely used as mechanical interventions for pulmonary pathologies. The research reveals that long-term efficacy can be impacted by fibrotic or granulation tissue formation around the implant sites. The study identifies 263 unique protein species that are mutually adsorbed on the explanted lung devices, and pathway analyses suggest their association with coagulation, pattern recognition receptor signaling, immune responses, cytoskeleton organization, cell adhesion, and migration. The findings also highlight the importance of extracellular matrix proteins and damage-associated molecular patterns in the formation of the surface proteome.
Lung implantable devices have been widely adopted as mechanical interventions for a wide variety of pulmonary pathologies. Despite successful initial treatment, long-term efficacy can often be impacted by fibrotic or granulation tissue formation at the implant sites. This study aimed to explore the lung-device interface by identifying the adhered proteome on lung devices explanted from patients with severe emphysema. In this study, scanning electron microscopy is used to visualize the adhesion of cells and proteins to silicone and nitinol surfaces of explanted endobronchial valves. By applying high-resolution mass spectrometry, the surface proteome of eight explanted valves is characterized, identifying 263 unique protein species to be mutually adsorbed on the valves. This subset is subjected to gene enrichment analysis, matched with known databases and further validated using immunohistochemistry. Enrichment analyses reveal dominant clusters of functionally-related ontology terms associated with coagulation, pattern recognition receptor signaling, immune responses, cytoskeleton organization, cell adhesion and migration. Matching results show that extracellular matrix proteins and damage-associated molecular patterns are cardinal in the formation of the surface proteome. This is the first study investigating the composition of the adhered proteome on explanted lung devices, setting the groundwork for hypothesis generation and further exploration.Statement of significance This is the first study investigating the composition of the adhered proteome on explanted lung devices. Lung implantable devices have been widely adopted as mechanical interventions for pulmonary pathologies. Despite successful initial treatment, long-term efficacy can often be impacted by fibrotic or granulation tissue formation around the implant sites. We identified the adhered proteome on explanted lung devices using several techniques. We identified 263 unique protein species to be mutually adsorbed on explanted lung devices. Pathway analyses revealed that these proteins are associated with coagulation, pattern recognition receptor signaling, immune responses, cytoskeleton organization, cell adhesion and migration. Furthermore, we identified that especially extracellular matrix proteins and damage-associated molecular patterns were cardinal in the formation of the surface proteome.(c) 2022 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

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