uu.seUppsala universitets publikasjoner
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Hyaluronan Derivatives and Injectable Gels for Tissue Engineering
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi.
2008 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

The present work describes the preparation of hyaluronan derivatives and hydrogels with potential use in tissue engineering applications. A potentially injectable hydrogel consisting of hyaluronan and collagen was successfully used to grow neurons in vitro by encapsulation of neural stem and progenitor cells. Attempts were further made to establish a suitable modification strategy which could be used for the preparation of in vivo cross-linkable hyaluronan derivatives. The synthesis of a model substance consisting of a D-glucuronate derivative which could simplify the development of such a modification technique is described, although a new method to prepare hyaluronan derivatives was found without its use. The modification strategy involves the use of a triazine-reagent which enables the covalent attachment of hydrophilic and hydrophobic amines to hyaluronan carboxyl groups in a controlled fashion under mild conditions. Using triazine-activated amidation we synthesized an aldehyde-derivative of hyaluronan which was used to prepare gels by cross-linking with hydrazide-modified polyvinyl-alcohol. Gels were formed in less than 1 minute by mixing equal volumes of the polymer derivatives and they were subsequently used as a carrier for bone morphogenetic protein-2. An in vitro release study showed that approximately 88% of the growth factor is retained in the gel over a 4 week period. The ability to form new bone in vivo was further evaluated in an ectopic rat model by the injection of gels containing 30 µg BMP-2. Radiographic and histological examination 4 and 10 weeks after injection showed the formation of new bone without any signs of inflammation or foreign body response. Hydroxyapatite particles were further added to improve the mechanical properties of the gel, and a comparative study was conducted. This time the induced tissue consisted not only of bone, but also of interconnected cartilage and tendon, as confirmed by histology and immunohistochemistry.

sted, utgiver, år, opplag, sider
Uppsala: Universitetsbiblioteket , 2008. , s. 51
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 573
Emneord [en]
Hyaluronan, Hydrogel, Tissue Engineering, Scaffold, Minimally invasive strategy, Bone morphogenetic protein, Hydroxyapatite, Bone, Cartilage, Tendon
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-9357ISBN: 978-91-554-7335-8 (tryckt)OAI: oai:DiVA.org:uu-9357DiVA, id: diva2:172782
Disputas
2008-12-05, Polhemsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 09:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2008-11-14 Laget: 2008-11-14 Sist oppdatert: 2010-03-04bibliografisk kontrollert
Delarbeid
1. Enhanced neuronal differentiation in a three-dimensional collagen-hyaluronan matrix
Åpne denne publikasjonen i ny fane eller vindu >>Enhanced neuronal differentiation in a three-dimensional collagen-hyaluronan matrix
Vise andre…
2007 (engelsk)Inngår i: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 85, nr 10, s. 2138-2146Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Efficient 3D cell systems for neuronal induction are needed for future use in tissue regeneration. In this study, we have characterized the ability of neural stem/progenitor cells (NS/PC) to survive, proliferate, and differentiate in a collagen type I-hyaluronan scaffold. Embryonic, postnatal, and adult NS/PC were seeded in the present 3D scaffold and cultured in medium containing epidermal growth factor and fibroblast growth factor-2, a condition that stimulates NS/PC proliferation. Progenitor cells from the embryonic brain had the highest proliferation rate, and adult cells the lowest, indicating a difference in mitogenic responsiveness. NS/PC from postnatal stages down-regulated nestin expression more rapidly than both embryonic and adult NS/PC, indicating a faster differentiation process. After 6 days of differentiation in the 3D scaffold, NS/PC from the postnatal brain had generated up to 70% neurons, compared with 14% in 2D. NS/PC from other ages gave rise to approximately the same proportion of neurons in 3D as in 2D (9-26% depending on the source for NS/PC). In the postnatal NS/PC cultures, the majority of III-tubulin-positive cells expressed glutamate, -aminobutyric acid, and synapsin I after 11 days of differentiation, indicating differentiation to mature neurons. Here we report that postnatal NS/PC survive, proliferate, and efficiently form synapsin I-positive neurons in a biocompatible hydrogel.

Emneord
3D cultures, neural stem/progenitor cells, hydrogel, scaffold, neurogenesis
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-11683 (URN)10.1002/jnr.21358 (DOI)000248516700008 ()17520747 (PubMedID)
Tilgjengelig fra: 2007-10-17 Laget: 2007-10-17 Sist oppdatert: 2017-12-11bibliografisk kontrollert
2. Selective Michael-type addition of a D-glucuronic acid derivative in the synthesis of model substances for uronic acid containing polysaccharides
Åpne denne publikasjonen i ny fane eller vindu >>Selective Michael-type addition of a D-glucuronic acid derivative in the synthesis of model substances for uronic acid containing polysaccharides
2008 (engelsk)Inngår i: Express Polymer Letters, ISSN 1788-618X, Vol. 2, nr 8, s. 553-559Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

A flexible protocol for the preparation of model substances for uronic acid containing polysaccharides is presented.We have synthesized a D-glucuronic acid derivative which is designed so that it easily can be conjugated with differentstructures and architectures by selective Michael-type addition. By successful coupling of the glucuronic acidderivative to polyethylene glycol with high degree of conversion, products were obtained that were easily characterized andwhich resembled polysaccharides in terms of solubility and purification methods that could be employed. The model substancecan potentially be used to facilitate optimization of low-degree modification reactions of high molecular weightD-glucuronic acid containing polysaccharides.

Emneord
polymer gels, polysaccharides, Michael-type addition, model substance, NMR
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-97728 (URN)10.3144/expresspolymlett.2008.67 (DOI)000263687000004 ()
Tilgjengelig fra: 2008-11-14 Laget: 2008-11-14 Sist oppdatert: 2010-08-25bibliografisk kontrollert
3. Hyaluronic acid derivatives prepared in aqueous media by triazine-activated amidation
Åpne denne publikasjonen i ny fane eller vindu >>Hyaluronic acid derivatives prepared in aqueous media by triazine-activated amidation
Vise andre…
2007 (engelsk)Inngår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 8, nr 7, s. 2190-2195Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

A method is presented for the preparation of hyaluronic acid derivatives obtained through triazine-activated amidation. A number of amines were successfully reacted with hyaluronic acid carboxyl groups using 2-chloro-4,6-dimethoxy-1,3,5-triazine as an activating species in a mixture of water and acetonitrile under neutral conditions. By varying the amount of triazine reagent, it was possible to control the degree of modification. Depending on the amine chosen, degrees of modification ranging from 3 to 20% were obtained when using 0.5 equiv of the triazine to hyaluronic acid carboxyl groups. The possibility to perform the reaction in a mixture of water and acetonitrile facilitates the introduction of a wide range of both hydrophilic and hydrophobic amines. Triazine-activated amidation appears to be a highly versatile, controllable, and relatively mild technique for modification of hyaluronic acid, and we predict that it will be useful in the design of novel hyaluronic acid based biomaterials.

Emneord
Oside polymer, Experimental study, Mild operating conditions, Aqueous medium, Triazine derivatives, Activation, Primary amine, Amidation, Chemical modification, Preparation, Modified material, Hyaluronic acid
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-97729 (URN)10.1021/bm0701604 (DOI)000247820000022 ()17579475 (PubMedID)
Tilgjengelig fra: 2008-11-14 Laget: 2008-11-14 Sist oppdatert: 2017-12-14bibliografisk kontrollert
4. Injectable cell-free template for bone-tissue formation
Åpne denne publikasjonen i ny fane eller vindu >>Injectable cell-free template for bone-tissue formation
Vise andre…
2009 (engelsk)Inngår i: Journal of Biomedical Materials Research-Part A, ISSN 1549-3296, Vol. 91A, nr 4, s. 1111-1118Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Here we present a novel injectable hydrogel which forms a template for de novo formation of bone tissue. Hydrogel formation takes place in situ in less than 1 min by the cross-linking of multifunctional hyaluronic acid and polyvinyl alcohol derivatives. Endogenous cells are recruited in vivo by incorporating bone morphogenetic protein-2 (BMP-2), a powerful promoter for osteogenic differentiation. The hydrogel was evaluated in vitro by performing a cell viability test and a release study and in vivo by a rat ectopic model. Examination by X-ray, microcomputed tomography, and histology revealed a significant bone formation at the target site for gels containing BMP-2, and a complete degradation was observed for gels without BMP-2 four weeks after injection. There were no signs of inflammation or foreign body response in either group and we believe that this system has the potential as an off-the-shelf injectable to be used where bone tissue is needed.

sted, utgiver, år, opplag, sider
Wiley Periodicals, Inc, 2009
Emneord
hydrogel, hyaluronan, injectable, bone tissue engineering, bone morphogenetic protein, polyvinyl alcohol
HSV kategori
Forskningsprogram
Oorganisk kemi
Identifikatorer
urn:nbn:se:uu:diva-97730 (URN)10.1002/jbm.a.32289 (DOI)000272196900017 ()
Tilgjengelig fra: 2008-11-14 Laget: 2008-11-14 Sist oppdatert: 2010-06-23bibliografisk kontrollert
5. Ectopic induction of the tendon-bone interface
Åpne denne publikasjonen i ny fane eller vindu >>Ectopic induction of the tendon-bone interface
Vise andre…
Artikkel i tidsskrift (Fagfellevurdert) Submitted
Identifikatorer
urn:nbn:se:uu:diva-97731 (URN)
Tilgjengelig fra: 2008-11-14 Laget: 2008-11-14bibliografisk kontrollert

Open Access i DiVA

fulltekst(5366 kB)2735 nedlastinger
Filinformasjon
Fil FULLTEXT01.pdfFilstørrelse 5366 kBChecksum SHA-1
5d83f503aa6cb37ba30964392a37a96a919523c06c0485ec5be6cc063d3db56892a40e42
Type fulltextMimetype application/pdf
omslag(133 kB)56 nedlastinger
Filinformasjon
Fil COVER01.pdfFilstørrelse 133 kBChecksum SHA-1
7e64965fd2d7fe0c92112d59d9ca325e343bebc842e9caed977131b9ec75206f5d896aaa
Type coverMimetype application/pdf
Kjøp publikasjonen >>

Av organisasjonen

Søk utenfor DiVA

GoogleGoogle Scholar
Totalt: 2735 nedlastinger
Antall nedlastinger er summen av alle nedlastinger av alle fulltekster. Det kan for eksempel være tidligere versjoner som er ikke lenger tilgjengelige

isbn
urn-nbn

Altmetric

isbn
urn-nbn
Totalt: 1239 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf