Interactions of U937 macrophage-like cells with decellularized pericardial matrix materials: Influence of crosslinking treatment

While macrophages have been implicated in the failure of bioprosthetic heart valves, the macrophage response to crosslinked native pericardial collagen has not been previously investigated. Using decellularized bovine pericardium (DBP) as a model for native collagen, this study investigated the resp...

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Published inActa biomaterialia Vol. 9; no. 7; pp. 7191 - 7199
Main Authors McDade, Jonathan K., Brennan-Pierce, Ellen P., Ariganello, Marianne B., Labow, Rosalind S., Michael Lee, J.
Format Journal Article
LanguageEnglish
Published England Elsevier Ltd 01.07.2013
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Abstract While macrophages have been implicated in the failure of bioprosthetic heart valves, the macrophage response to crosslinked native pericardial collagen has not been previously investigated. Using decellularized bovine pericardium (DBP) as a model for native collagen, this study investigated the response of macrophage-like cells (U937s) to DBP, either: (i) untreated, or (ii) exogenously crosslinked with glutaraldehyde or 1-ethyl-3-(3-dimethyl-aminopropyl)-carbodiimide (EDC). We have previously validated the use of U937 cells as models for the response of human monocyte-derived macrophages to decellularized pericardial materials and, per our previous work, differentiated the U937 cells directly on the three material surfaces. After 72h in culture, the cells and medium were analyzed for DNA content, acid phosphatase activity, and cytokine and matrix metalloproteinase release. As well, cell/substrate samples were fixed for SEM. Fewer cells attached to or survived on the glutaraldehyde-treated substrate, and some showed an abnormal morphology compared to cells cultured on the other surfaces. Further, cells on glutaraldehyde-treated surfaces released more pro-inflammatory cytokines, more MMP-1 and less MMP-2 and MMP-9. The poor performance of the U937 macrophage-like cells on the glutaraldehyde-treated surfaces appears to be due to surface characteristics rather than to soluble aldehyde or other components leaching from the crosslinked material. These results provide evidence that crosslinking with glutaraldehyde is cytotoxic to macrophage-like cells, and that crosslinking with a zero-length crosslinker like EDC can be an acceptable alternative crosslinking treatment for biomaterials.
AbstractList While macrophages have been implicated in the failure of bioprosthetic heart valves, the macrophage response to crosslinked native pericardial collagen has not been previously investigated. Using decellularized bovine pericardium (DBP) as a model for native collagen, this study investigated the response of macrophage-like cells (U937s) to DBP, either: (i) untreated, or (ii) exogenously crosslinked with glutaraldehyde or 1-ethyl-3-(3-dimethyl-aminopropyl)-carbodiimide (EDC). We have previously validated the use of U937 cells as models for the response of human monocyte-derived macrophages to decellularized pericardial materials and, per our previous work, differentiated the U937 cells directly on the three material surfaces. After 72h in culture, the cells and medium were analyzed for DNA content, acid phosphatase activity, and cytokine and matrix metalloproteinase release. As well, cell/substrate samples were fixed for SEM. Fewer cells attached to or survived on the glutaraldehyde-treated substrate, and some showed an abnormal morphology compared to cells cultured on the other surfaces. Further, cells on glutaraldehyde-treated surfaces released more pro-inflammatory cytokines, more MMP-1 and less MMP-2 and MMP-9. The poor performance of the U937 macrophage-like cells on the glutaraldehyde-treated surfaces appears to be due to surface characteristics rather than to soluble aldehyde or other components leaching from the crosslinked material. These results provide evidence that crosslinking with glutaraldehyde is cytotoxic to macrophage-like cells, and that crosslinking with a zero-length crosslinker like EDC can be an acceptable alternative crosslinking treatment for biomaterials.
Author Michael Lee, J.
Brennan-Pierce, Ellen P.
Ariganello, Marianne B.
McDade, Jonathan K.
Labow, Rosalind S.
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/23454057$$D View this record in MEDLINE/PubMed
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Keywords Crosslinking
Macrophages
Collagen
Decellularized bovine
Pericardium
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Snippet While macrophages have been implicated in the failure of bioprosthetic heart valves, the macrophage response to crosslinked native pericardial collagen has not...
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SubjectTerms acid phosphatase
Animals
biocompatible materials
Cattle
Cell Line
Cell Proliferation
Cell Survival - physiology
Cell-Free System
Collagen
Cross-Linking Reagents - chemistry
Crosslinking
cultured cells
cytokines
cytotoxicity
Decellularized bovine
DNA
Extracellular Matrix - chemistry
glutaraldehyde
heart valves
humans
leaching
Macrophages
Macrophages - cytology
Macrophages - physiology
Materials Testing
metalloproteinases
Pericardium
Pericardium - chemistry
Pericardium - cytology
prostheses
scanning electron microscopy
Tissue Engineering - methods
U937
Title Interactions of U937 macrophage-like cells with decellularized pericardial matrix materials: Influence of crosslinking treatment
URI https://dx.doi.org/10.1016/j.actbio.2013.02.021
https://www.ncbi.nlm.nih.gov/pubmed/23454057
https://search.proquest.com/docview/1357497094
Volume 9
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