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On the Development of Mucin-based Biomaterial Coatings

Sandberg, Tomas, 1973- (författare)
Uppsala universitet,Institutionen för fysikalisk och analytisk kemi
Caldwell, Karin, Professor (preses)
Uppsala universitet,Institutionen för fysikalisk och analytisk kemi
Carlsson, Jan, Professor (preses)
Uppsala universitet,Institutionen för fysikalisk och analytisk kemi
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Arnebrant, Thomas, Professor (opponent)
Institutionen för biomedicinsk laboratorievetenskap, Malmö Högskola, Malmö
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 (creator_code:org_t)
ISBN 9789155473686
Uppsala : Universitetsbiblioteket, 2008
Engelska 83 s.
Serie: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, 1651-6214 ; 583
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
Abstract Ämnesord
Stäng  
  • Owing to their key role in mucosal functioning as surface barriers with biospecific interaction potentials, the mucins are interesting candidates for use as surface modifiers in biomaterials applications. In this work, “mild” fractionation procedures were used to prepare mucins of bovine (BSM), porcine (PGM), and human (MG1) origin. Biophysicochemical analysis showed the prepared mucins to differ in size, charge, conformation, and composition. In turn, these factors were shown to govern mucin adsorption on hydrophilic and hydrophobic model surfaces. To enable for detailed coating analysis, methods for the qualitative and quantitative analysis of mucin-based coatings were developed. Of particular interest, a method for the determination of the fraction of surface-exposed, presumed bioactive proteins in a complex mucin coating was described. It was shown, using microscopy and activation assays, that mucin precoating effectively suppresses the neutrophil response towards a polymeric model biomaterial. Under optimal coating conditions, all mucins performed equally well, thus indicating them to be functionally similar. Coating analysis suggested that efficient mucin surface-shielding is critical for good mucin coating performance. Following a study on the complexation of albumin with preadsorbed mucin, we investigated the effect of mucin precoating on the conformation and neutrophil-activating properties of adsorbed host proteins. We found that mucin precoating greatly reduces the strong immune-response normally caused by adsorbed proinflammatory proteins (IgG and sIgA). Detailed coating analysis revealed that the fraction of surface-exposed protein in the mucin-protein composite influences the neutrophil response. Unexpectedly low neutrophil activation for composites containing near-monolayer concentrations of exposed IgG, suggested IgG to act synergistically with mucin on the surface. Conformational analysis supported this by showing that a preadsorbed mucin layer could stabilize adsorbed IgG through complexation. Our findings link well to the complex in vivo situation and suggest that functional mucosal mimics can be created in situ for improved biomaterials performance.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Odontologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dentistry (hsv//eng)

Nyckelord

Mucin
Biomaterial
Surface-exposed protein
XPS
Neutrophil
Cell morphology
SEM
QCM-D
Viscoelasticity
Protein-stabilization
HNL
Coating
MG1
BSM
PGM
SEC-MALS-RI
Mucin quantification
Protein adsorption
Ellipsometry
Biomaterials
Biomaterial

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