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Comparative studies on BMP-2 processing and secretion in chondrocytes and mesenchymal cells and the effect of noggin
Uppsala University. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry.
Uppsala University. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry.
Department of orthopeadic surgery, UCLA School of medicine, Los Angeles, USA.
Stockholm Craniofacial Centre, Department of Reconstructive plastic surgery, Karolinska University hospital, Stockholm, Sweden.
(English)Manuscript (preprint) (Other academic)
Keyword [en]
bone formation, BMP-2, noggin, chondrocytes, mesenchymal stem cells
URN: urn:nbn:se:uu:diva-110746OAI: oai:DiVA.org:uu-110746DiVA: diva2:278190
Available from: 2009-11-24 Created: 2009-11-24
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.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 694
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
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)
Available from: 2009-12-18 Created: 2009-11-19 Last updated: 2009-12-18Bibliographically approved

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Aulin, Cecilia
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