Institute of Biomaterials and Cell Therapy

Sweden

Institute of Biomaterials and Cell Therapy

Sweden
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Almqvist S.,Gothenburg University | Almqvist S.,Institute of Biomaterials and Cell Therapy | Almqvist S.,Molnlycke Health Care AB | Werthen M.,Institute of Biomaterials and Cell Therapy | And 6 more authors.
Cytokine | Year: 2012

Amelogenins are enamel matrix proteins with a proven ability to restore tissues in patients with advanced periodontitis and chronic skin wounds. To explore the mechanisms of action of amelogenins in wound inflammation, the in vitro effect on the expression of selected cell mediators involved in inflammation and tissue repair from human monocyte-derived macrophages was studied. Macrophages were treated with amelogenins in serum-enriched medium with simultaneous lipopolysaccharide (LPS) stimulation, for 6, 24 and 72. h, and the conditioned culture medium was analysed for 28 different cytokines. Amelogenin treatment directed the LPS-induced release of both pro- and anti-inflammatory cytokines towards an alternatively activated macrophage phenotype. This change in activation was also demonstrated by the amelogenin-induced secretion of alternative macrophage activation-associated CC chemokine-1 (AMAC-1, also known as CCL18; p<0.001), a well-documented marker of alternative activation. Amelogenins were also shown significantly to increase the macrophage expression of vascular endothelial growth factor and, to a lesser but significant extent, insulin-like growth factor-1 after 24. h of culture. The results of the present in vitro study show that monocyte-derived macrophages stimulated by inflammatory agonist LPS respond to the treatment with amelogenins by reducing the pro-inflammatory activity and increasing the expression of tissue repair mediators. © 2012 Elsevier Ltd.


Almqvist S.,Gothenburg University | Almqvist S.,Institute of Biomaterials and Cell Therapy | Almqvist S.,Molnlycke Health Care AB | Werthen M.,Gothenburg University | And 8 more authors.
Journal of Materials Science: Materials in Medicine | Year: 2010

Fibroblasts are central in wound healing by expressing important mediators and producing and remodelling extracellular matrix (ECM) components. This study aimed at elucidating possible mechanisms of action of the ECM protein amelogenin on normal human dermal fibroblasts (NHDF). Amelogenin at 100 and 1000 μg/ml increased binding of NHDF via several integrins, including αvβ3, αvβ5 and α5β1. Further, both surface interaction and cellular uptake of amelogenin by NHDF was observed using scanning and transmission electron microscopy. Gene microarray studies showed >8-fold up or down-regulation of genes, of which most are involved in cellular growth, migration and differentiation. The effect of amelogenin was exemplified by increased proliferation over 7 days. In conclusion, the beneficial effects of amelogenin on wound healing are possibly conducted by stimulating fibroblast signalling, proliferation and migration via integrin interactions. It is hypothesized that amelogenin stimulates wound healing by providing connective tissue cells with a temporary extracellular matrix. © 2009 Springer Science+Business Media, LLC.


Almqvist S.,Gothenburg University | Almqvist S.,Institute of Biomaterials and Cell Therapy | Almqvist S.,Molnlycke Health Care AB | Werthen M.,Institute of Biomaterials and Cell Therapy | And 5 more authors.
International Journal of Nano and Biomaterials | Year: 2011

Amelogenins are extracellular matrix proteins used for the topical treatment of chronically inflamed tissues. The influence of amelogenins on human monocyte-derived macrophages was studied by measuring the concentrations of cytokines in culture supernatants. The interactions of cells and protein aggregates were visualised by transmission electron microscopy. The amelogenin treatment of macrophages increased several pro- and anti-inflammatory cytokines, including alternative macrophage activation marker AMAC-1 (p < 0.001) and vascular endothelial growth factor (VEGF; p < 0.001). The levels were independent of cytochalasin B, although amelogenin aggregates were ingested by macrophages. Amelogenin effect was compared with that of tyrosine-rich amelogenin peptide, which apart from augmented VEGF levels (p < 0.05), had no significant influence on the other cytokines analysed. In conclusion, amelogenins increased the macrophage release of key cell mediators involved in tissue repair. The effect was independent of phagocytosis, implying a receptor-mediated signal. The markedly increased levels of AMAC-1 suggest that amelogenins promote a reparative macrophage phenotype. Copyright © 2011 Inderscience Enterprises Ltd.


Ramstedt S.,Uppsala University | Palmquist A.,Gothenburg University | Johansson A.,Gothenburg University | Breding K.,Doxa AB | And 3 more authors.
Trends in Biomaterials and Artificial Organs | Year: 2010

Biomaterials used for stabilisation of compressed vertebraes due to osteoporosis are currently mainly based on conventional bone cement, polymethyl methacrylate (PMMA). New material alternatives based on fully ceramic materials, e.g. calcium aluminates cements (CAC), are under development. In this in vivo study the early inflammatory response elicited by both cured and uncured CAC and PMMA cement was investigated in a rat model. Titanium (Ti) and sham sites were used as controls. Cell viability, cell proliferation, inflammatory cell recruitment and pro inflammatory cytokine secretion of tumour necrosis factor alpha (TNF-á) and monocyte chemoattractant protein-1 (MCP-1) was evaluated. The experimental observation period was 1 day and the results showed that both of the cured cements were more biocompatible and revealed a smaller inflammatory response than Ti, contrary to the uncured cements which provoked a larger inflammatory response and higher cell death than Ti. The inflammatory responses revealed by cured CAC and PMMA had no significant difference. © Society for Biomaterials and Artificial Organs (India), 20090622-45.


Omar O.,Gothenburg University | Svensson S.,Gothenburg University | Zoric N.,TATAA Biocenter AB | Lenneras M.,TATAA Biocenter AB | And 6 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2010

A quantitative polymerase chain reaction technique (qPCR) in combination with scanning electron microscopy was applied for the evaluation of early gene expression response and cellular reactions close to titanium implants. Anodically oxidized and machined titanium miniscrews were inserted in rat tibiae. After 1, 3, and 6 days the implants were unscrewed and the surrounding bone was retrieved using trephines. Both the implants and bone were analyzed with qPCR. A greater amount of cells, as indicated with higher expression of 18S, was detected on the oxidized surface after 1 and 6 days. Significantly higher osteocalcin (at day 6), alkaline phosphatase (at days 3 and 6), and cathepsin K (at day 3) expression was demonstrated for the oxidized surface. Higher expression of tumor necrosis factor-α (at day 1) and interleukin-1β (at days 1 and 6) was detected on the machined surfaces. SEM revealed a higher amount of mesenchymal-like cells on the oxidized surface. The results show that the rapid recruitment of mesenchymal cells, the rapid triggering of gene expression crucial for bone remodeling and the transient nature of inflammation, constitute biological mechanisms for osseointegration, and high implant stability associated with anodically oxidized implants. © 2009 Wiley Periodicals, Inc.

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