title: Reducing the inflammatory responses of biomaterials by surface modification with glycosaminoglycan multilayers.
abstract: Chronic inflammatory responses after implantation of biomaterials can lead to fibrotic encapsulation and failure of implants. The present study was designed to reduce the inflammatory responses to biomaterials by assembling polyelectrolyte multilayers (PEMs) composed of glycosaminoglycans (GAGs) and chitosan (Chi) on glass as model surfaces through layer-by-layer (LBL) technique. Surface plasmon resonance (SPR) and water contact angle (WCA) investigations confirmed the multilayer build-up with alternating deposition of GAGs and Chi layers, while zeta potential measurements showed significant negative charges after multilayer deposition, which further proved the PEM formation. Macrophage adhesion, macrophage spreading morphology, foreign body giant cell (FBGC) formation, as well as β1 integrin expression and interleukin-1β (IL-1β) production were all significantly decreased by GAG-Chi multilayer deposition in comparison to the primary poly (ethylene imine) (PEI) layer. Thereby, the type of GAGs played a pivotal role in inhibiting the inflammatory responses to various extents. Especially heparin (Hep)-Chi multilayers hindered all inflammatory responses to a significantly higher extent in comparison to hyaluronic acid (HA)-Chi and chondroitin sulfate (CS)-Chi multilayer systems. Overall, the present study suggests a great potential of GAG-Chi multilayer coating on implants, particularly the Hep-Chi based systems, to reduce the inflammatory responses.
authors.affiliation: Biomedical Materials Group, Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Strasse 4, Halle (Saale), 06120, Germany.
authors.forename: Guoying
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Biomedical Materials Group, Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Strasse 4, Halle (Saale), 06120, Germany.
authors.forename: Marcus S
authors.initials: MS
authors.lastname: Niepel
authors.affiliation: Biomedical Materials Group, Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Strasse 4, Halle (Saale), 06120, Germany.
authors.forename: Shivam
authors.initials: S
authors.lastname: Saretia
authors.affiliation: Biomedical Materials Group, Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Strasse 4, Halle (Saale), 06120, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Groth
mesh_terms: D045744:Cell Line, Tumor; D048271:Chitosan / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D020099:Coated Materials, Biocompatible / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D005549:Foreign-Body Reaction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015743:Giant Cells, Foreign-Body / Q000378:metabolism* / Q000473:pathology; D006025:Glycosaminoglycans / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control
chemical_list: D020099:Coated Materials, Biocompatible; D006025:Glycosaminoglycans; D048271:Chitosan
keywords: cytokines; glycosaminoglycans; inflammation; layer-by-layer technique; macrophages