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Extracellular matrix-polymer hybrid materials produced in a pulsed-flow bioreactor system
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
2009 (English)In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, Vol. 3, no 3, 188-195 p.Article in journal (Refereed) Published
Abstract [en]

Cell adhesion, interaction with material, cell proliferation and the production of an extracellular matrix (ECM) are all important factors determining the successful performance of an engineered scaffold. Scaffold design should aim at creating structures which can guide cells into forming new, functional tissue. In this study, the concept of in situ deposition of ECM by human dermal fibroblasts onto a compliant, knitted poly (ethyleneterephtalate) support is demonstrated, creating in vitro produced ECM polymer hybrid materials for tissue engineering. Comparison of cells cultured under static and dynamic conditions were examined, and the structure and morphology of the materials so formed were evaluated, along with the amount collagen deposited by the seeded cells. In vitro produced ECM polymer hybrid scaffolds could be created in this way, with the dynamic culture conditions increasing ECM deposition. Histological analysis indicated a homogenous distribution of cells in the 1 mm thick scaffold, surrounded by a matrix-like structure. ECM deposition was observed throughout the materials wigh 81.6 µg/cm2 of collagen deposited after 6 weeks. Cell produced bundles of ECM fibres bridged the polymer filaments and anchored cells to the support. These findings open hereto unknown possibilities of producing materials with structure designed by engineering together with biochemical composition given by cells.

Place, publisher, year, edition, pages
John Wiley & Sons, Ltd , 2009. Vol. 3, no 3, 188-195 p.
Keyword [en]
extracellular matrix, scaffold, polymer support, fibroblasts, bioreactor, dynamic culture conditions
National Category
Chemical Sciences
Research subject
Inorganic Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-106096DOI: 10.1002/term.152ISI: 000265268400003OAI: oai:DiVA.org:uu-106096DiVA: diva2:223885
Available from: 2009-06-15 Created: 2009-06-15 Last updated: 2010-08-02Bibliographically approved
In thesis
1. Extracellular Matrix Based Materials for Tissue Engineering
Open this publication in new window or tab >>Extracellular Matrix Based Materials for Tissue Engineering
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The extracellular matrix is (ECM) is a network of large, structural proteins and polysaccharides, important for cellular behavior, tissue development and maintenance. Present thesis describes work exploring ECM as scaffolds for tissue engineering by manipulating cells cultured in vitro or by influencing ECM expression in vivo. By culturing cells on polymer meshes under dynamic culture conditions, deposition of a complex ECM could be achieved, but with low yields. Since the major part of synthesized ECM diffused into the medium the rate limiting step of deposition was investigated. This quantitative analysis showed that the real rate limiting factor is the low proportion of new proteins which are deposited as functional ECM. It is suggested that cells are pre-embedded in for example collagen gels to increase the steric retention and hence functional deposition.

The possibility to induce endogenous ECM formation and tissue regeneration by implantation of growth factors in a carrier material was investigated. Bone morphogenetic protein-2 (BMP-2) is a growth factor known to be involved in growth and differentiation of bone and cartilage tissue. The BMP-2 processing and secretion was examined in two cell systems representing endochondral (chondrocytes) and intramembranous (mesenchymal stem cells) bone formation. It was discovered that chondrocytes are more efficient in producing BMP-2 compared to MSC. The role of the antagonist noggin was also investigated and was found to affect the stability of BMP-2 and modulate its effect. Finally, an injectable gel of the ECM component hyaluronan has been evaluated as delivery vehicle in cartilage regeneration. The hyaluronan hydrogel system showed promising results as a versatile biomaterial for cartilage regeneration, could easily be placed intraarticulary and can be used for both cell based and cell free therapies.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 58 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 694
Keyword
Extracellular matrix, collagen synthesis, bioreactor, cell culture, bone morphogenetic protein-2, noggin, hyaluronan, cartilage
National Category
Biomedical Laboratory Science/Technology Cell and Molecular Biology Surgery Surgery Biomaterials Science Cell and Molecular Biology Biochemistry and Molecular Biology Polymer Chemistry Materials Chemistry
Research subject
Cell Research; Materials Science; Medical Cell Biology; Orthopaedics
Identifiers
urn:nbn:se:uu:diva-110631 (URN)978-91-554-7669-4 (ISBN)
Public defence
2010-01-15, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2009-12-18 Created: 2009-11-19 Last updated: 2009-12-18Bibliographically approved

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