Characterization of Photo-Crosslinked Methacrylated Type I Collagen as a Platform to Investigate the Lymphatic Endothelial Cell Response

dc.contributor.authorRuliffson, Brian N. K.
dc.contributor.authorLarson, Stephen M.
dc.contributor.authorXhupi, Eleni K.
dc.contributor.authorHerrera-Diaz, Diana L.
dc.contributor.authorWhittington, Catherine F.
dc.date.accessioned2024-09-27T13:18:40Z
dc.date.available2024-09-27T13:18:40Z
dc.date.issued2024-09-19
dc.date.updated2024-09-27T13:18:40Z
dc.description.abstractDespite chronic fibrosis occurring in many pathological conditions, few in vitro studies examine how fibrosis impacts lymphatic endothelial cell (LEC) behavior. This study examined stiffening profiles of PhotoCol<sup>&reg;</sup>&mdash;commercially available methacrylated type I collagen&mdash;photo-crosslinked with the photoinitiators: Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), Irgacure 2959 (IRG), and Ruthenium/Sodium Persulfate (Ru/SPS) prior to evaluating PhotoCol<sup>&reg;</sup> permeability and LEC response to PhotoCol<sup>&reg;</sup> at stiffnesses representing normal and fibrotic tissues. Ru/SPS produced the highest stiffness (~6 kilopascal (kPa)) for photo-crosslinked PhotoCol<sup>&reg;</sup>, but stiffness did not change with burst light exposures (30 and 90 s). The collagen fibril area fraction increased, and dextran permeability (40 kilodalton (kDa)) decreased with photo-crosslinking, showing the impact of photo-crosslinking on microstructure and molecular transport. Human dermal LECs on softer, uncrosslinked PhotoCol<sup>&reg;</sup> (~0.5 kPa) appeared smaller with less prominent vascular endothelial (VE)-cadherin (cell&ndash;cell junction) expression compared to LECs on stiffer PhotoCol<sup>&reg;</sup> (~6 kPa), which had increased cell size, border irregularity, and VE-cadherin thickness (junction zippering) that is consistent with LEC morphology in fibrotic tissues. Our quantitative morphological analysis demonstrates our ability to produce LECs with a fibrotic phenotype, and the overall study shows that PhotoCol<sup>&reg;</sup> with Ru/SPS provides the necessary physical properties to systematically study LEC responses related to capillary growth and function under fibrotic conditions.
dc.description.departmentBiomedical Engineering and Chemical Engineering
dc.identifierdoi: 10.3390/lymphatics2030015
dc.identifier.citationLymphatics 2 (3): 177-194 (2024)
dc.identifier.urihttps://hdl.handle.net/20.500.12588/6630
dc.titleCharacterization of Photo-Crosslinked Methacrylated Type I Collagen as a Platform to Investigate the Lymphatic Endothelial Cell Response

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