title: *Collagen Cross-Linking: Biophysical, Biochemical, and Biological Response Analysis.
abstract: Extracted forms of collagen are subjected to chemical cross-linking to enhance their stability. However, traditional cross-linking approaches are associated with toxicity and inflammation. This work investigates the stabilization capacity, cytotoxicity and inflammatory response of collagen scaffolds cross-linked with glutaraldehyde (GTA), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, 4-arm polyethylene glycol (PEG) succinimidyl glutarate (4SP), genipin (GEN), and oleuropein. Although all cross-linking methods reduced free amine groups, variable data were obtained with respect to denaturation temperature, resistance to collagenase digestion, and mechanical properties. With respect to biological analysis, fibroblast cultures showed no significant difference between the treatments. Although direct cultures with human-derived leukemic monocyte cells (THP-1) clearly demonstrated the cytotoxic effect of GTA, THP-1 cultures supplemented with conditioned medium from the various groups showed no significant difference between the treatments. With respect to cytokine profile, no significant difference in secretion of proinflammatory (e.g., interleukin [IL]-1β, IL-8, tumor necrosis factor-α) and anti-inflammatory (e.g., vascular endothelial growth factor) cytokines was observed between the noncross-linked and the 4SP and GEN cross-linked groups, suggesting the suitability of these agents as collagen cross-linkers.
authors.affiliation: 1 Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway) , Galway, Ireland .|2 Science Foundation Ireland (SFI), Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway) , Galway, Ireland .
authors.forename: Luis M
authors.initials: LM
authors.lastname: Delgado
authors.affiliation: 1 Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway) , Galway, Ireland .|2 Science Foundation Ireland (SFI), Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway) , Galway, Ireland .
authors.forename: Kieran
authors.initials: K
authors.lastname: Fuller
authors.affiliation: 1 Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway) , Galway, Ireland .|2 Science Foundation Ireland (SFI), Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway) , Galway, Ireland .
authors.forename: Dimitrios I
authors.initials: DI
authors.lastname: Zeugolis
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D055592:Biophysical Phenomena; D002417:Cattle; D002460:Cell Line; D003094:Collagen / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D011489:Protein Denaturation; D012867:Skin / Q000166:cytology
chemical_list: D000588:Amines; D003432:Cross-Linking Reagents; D016207:Cytokines; D003094:Collagen
keywords: collagen cross-linking; collagen films; cytokine release; enzymatic stability; macrophage response; mechanical resilience