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Effect of Cross-Linking and Hydration on Microscale Flat Punch Indentation of Collagen-Hyaluronic Acid Films in the Viscoelastic Limit

25 Pages Posted: 20 Feb 2019 First Look: Under Review

See all articles by Colm McManamon

Colm McManamon

Trinity College (Dublin) - Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN); Royal College of Surgeons (UK) - Tissue Engineering Research Group

Andrew Cameron

Royal College of Surgeons (UK) - Tissue Engineering Research Group; Trinity College (Dublin) - Advanced Materials and Bioengineering Research (AMBER) Centre; Trinity College (Dublin) - Trinity Centre for Bioengineering

Johann P. de Silva

Trinity College (Dublin) - Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN); Trinity College (Dublin) - School of Physics

Ronan Daly

University of Cambridge - Department of Engineering

Fergal J. O’Brien

Royal College of Surgeons (UK) - Tissue Engineering Research Group; Trinity College (Dublin) - Advanced Materials and Bioengineering Research (AMBER) Centre; Trinity College (Dublin) - Trinity Centre for Bioengineering

Graham L. W. Cross

Trinity College (Dublin) - Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN); Trinity College (Dublin) - School of Physics

Abstract

The properties of the extracellular matrix (ECM) have profound impact upon cell behaviour. As an abundant protein in mammals, collagen is a desirable base material to engineer an ECM tissue scaffold, but its structural weakness generally requires molecular crosslinking or incorporation of additional ECM-based macromolecules such as glycosaminoglycans. We have performed microscopic indentation to test collagen films under dry and aqueous conditions prepared with different levels of physical and chemical crosslinking. Our technique isolates intrinsic properties of the poro-viscoelastic matrix in a regime minimizing the influence of drainage hydrodynamics and allows direct measurement of the effect of hydrating a specific sample. A doubling of the effective stress-strain stiffness under crosslinking could be directly correlated to structural changes in X-ray diffraction spectra, while electron microscopy revealed possible fibril bridging mechanisms explaining observed toughness. Overall, an intrinsic viscoelastic stress-strain response of collagen under various conditions of cross-linking was observed for both dry and wet conditions, with the latter most affected by indentation rate. Under creep testing, a three order of magnitude increase in dynamic compliance and factor three reduction in relaxation time was found going from the dry to hydrated state. When fitted to a viscoelastic model, crosslinking showed a tendency to decrease relaxation time but gave no recognizable trend to dynamic compliance. This is the first reported approach that allows for repeatable mechanical data on dry and hydrated ECM-derived biomaterials, accessing the intrinsic material mechanics under in vivo-like conditions.

Keywords: Nanoindentation, Collagen, Tissue scaffold

Suggested Citation

McManamon, Colm and Cameron, Andrew and Silva, Johann P. de and Daly, Ronan and O’Brien, Fergal J. and Cross, Graham L. W., Effect of Cross-Linking and Hydration on Microscale Flat Punch Indentation of Collagen-Hyaluronic Acid Films in the Viscoelastic Limit (February 15, 2019). Available at SSRN: https://ssrn.com/abstract=3335367

Colm McManamon

Trinity College (Dublin) - Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN)

2-3 College Green
Dublin, Leinster
Ireland

Royal College of Surgeons (UK) - Tissue Engineering Research Group

123 St Stephens Green
Dublin 2
Ireland

Andrew Cameron

Royal College of Surgeons (UK) - Tissue Engineering Research Group

123 St Stephens Green
Dublin 2
Ireland

Trinity College (Dublin) - Advanced Materials and Bioengineering Research (AMBER) Centre

2-3 College Green
Dublin
Ireland

Trinity College (Dublin) - Trinity Centre for Bioengineering

2-3 College Green
Dublin
Ireland

Johann P. de Silva

Trinity College (Dublin) - Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN)

2-3 College Green
Dublin, Leinster
Ireland

Trinity College (Dublin) - School of Physics

College Green
Dublin
Ireland

Ronan Daly

University of Cambridge - Department of Engineering

Cambridge
United Kingdom

Fergal J. O’Brien

Royal College of Surgeons (UK) - Tissue Engineering Research Group

123 St Stephens Green
Dublin 2
Ireland

Trinity College (Dublin) - Advanced Materials and Bioengineering Research (AMBER) Centre

2-3 College Green
Dublin
Ireland

Trinity College (Dublin) - Trinity Centre for Bioengineering

2-3 College Green
Dublin
Ireland

Graham L. W. Cross (Contact Author)

Trinity College (Dublin) - Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN) ( email )

2-3 College Green
Dublin, Leinster
Ireland

Trinity College (Dublin) - School of Physics ( email )

College Green
Dublin
Ireland

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