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Exploiting chemical control in biomaterials
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Polymer Technology.ORCID iD: 0000-0002-9000-0156
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Chemistry and biology at the interphase will most likely give many of the answers to tomorrows medical challenges. Creating solutions to the problems at this interphase is benefiting from a collaborative research approach, driven by the need for development of chemistries or devices solving medical problems. However, several important challenges remain to fulfil a successful symphony. The most crucial aspect is to understand the communication between these processes while having fundamental control over the underlying processes.

The central theme of this thesis has been to develop functional degradable polymers and materials aimed to integrate with the cell microenvironment, and through control over the chemistry modulate the synthesis, material or biological processes. This was realized on several hierarchical levels. The primary initial focus on control over polymer microstructure was achieved by fundamental exploration on the kinetics and thermodynamics governing the reaction. The polymerization work was then transitioned into the controllable fabrication of a material bearing short-term tissue relevant properties with long-term degradability exploited by biorthogonal chemical control. Lastly, control over protein presentation was realized through two complimentary light-guided chemical reactions with an ultimate ability to control cellular fate.

This thesis reflects an academic research journey culminating in an appreciation of the importance of exploiting chemical control to enable well-defined polymers and materials enabling modulation of the overarching systems that they are aimed to exist within. To truly solve important biological problems; chemists, material scientists and biologists alike must remain truly engaged and fundamental to their own expertise but also continuously bridge their communication by maintaining curiosity and understanding for one another. Only then, will innovative solutions to tomorrow’s societal problems be created.

Abstract [sv]

Biomaterial, material ämnade att komma i kontakt med en cellbiologisk miljö, har under de senaste 30 åren utvecklats i en extraordinär takt. Livet för miljontals människor har förbättrats tack vare att vi nu kan diagnostisera och behandla patienter på ett mycket bättre sätt. Utvecklingen av biomaterial kräver att vi har kontroll över kemin och materialets egenskaper. I ett idealiserat scenario kan vi, genom den kontrollen, skapa material som efterliknar en cellbiologisk miljö och även addera in nya egenskaper så att vi kan dirigera celler på ett förutbestämt sätt. Ju mer kontroll vi har, desto mer avancerad, säkrare och effektivare biomaterial får vi.

I denna avhandling har det överhängande målet varit att utveckla funktionella och nedbrytbara polymerer och material ämnade att användas inom det biomedicinska området med ett specifikt mål att använda och kontrollera kemin bakom dessa processer. Resultaten visar på vikten av förståelse för kinetiken och termodynamiken i ett system för att kunna syntetisera polymerer med kontroll över dess mikrostruktur. De visar på hur material med olika egenskaper kan samverka utan att negativt påverka varandra för att komma fram till nya biomaterial. Därutöver visar resultaten i denna avhandling hur definierade material kan produceras genom att bestämma var och när signal-molekyler ska finnas på materialet och hur detta kan leda till att celler dirigeras på ett förutbestämt sätt.

Det är uppenbart att biomaterial har kunnat utvecklas i en märkvärdig takt, mycket tack vare samspelet mellan kemister, materialforskare och biologer. Men i den snabba takt som dessa discipliner närmar sig varandra till en symbios, är det lätt att glömma de viktiga grundstenarna och underliggande principer som faktiskt gjort denna förgrening möjlig. Vi måste ha en djup förståelse för de material vi utvecklar, samtidigt som vi måste fortsätta avancera samspelet mellan dessa discipliner. Endast då, kan vi lösa framtidens medicinska och samhällsmässiga problem.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2022. , p. 73
Series
TRITA-CBH-FOU ; 2022:44
Keywords [en]
biomaterial, controllable chemistry, polyester, ring-opening polymerization, hyaluronan, degradation, photoactivation, protein release, cell differentiation
Keywords [sv]
biomaterial, kontrollerbar kemi, polyester, ring-öppnings polymerisering, hyaluronsyra, nedbrytning, fotoaktivering, frigöring av protein, celldifferentiering
National Category
Polymer Chemistry
Research subject
Fibre and Polymer Science
Identifiers
URN: urn:nbn:se:kth:diva-320124ISBN: 978-91-8040-332-0 (print)OAI: oai:DiVA.org:kth-320124DiVA, id: diva2:1704824
Public defence
2022-11-18, F3, Lindstedtsvägen 26, via Zoom: https://kth-se.zoom.us/j/64931921012, Stockholm, 09:00 (English)
Opponent
Supervisors
Funder
Swedish Foundation for Strategic Research, RMA15-0010
Note

QC 2022-10-20

Available from: 2022-10-20 Created: 2022-10-19 Last updated: 2022-10-31Bibliographically approved
List of papers
1.
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2. Hybrid material based on hyaluronan hydrogels and poly(L-lactide-co-1,3-trimethylene carbonate) scaffolds toward a cell-instructive microenvironment with long-term in vivo degradability
Open this publication in new window or tab >>Hybrid material based on hyaluronan hydrogels and poly(L-lactide-co-1,3-trimethylene carbonate) scaffolds toward a cell-instructive microenvironment with long-term in vivo degradability
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(English)Manuscript (preprint) (Other academic)
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-320123 (URN)
Note

QC 20221019

Available from: 2022-10-14 Created: 2022-10-14 Last updated: 2022-10-19Bibliographically approved
3. Encoding tunable degradability through photopatterning and complimentary labile bond chemistry
Open this publication in new window or tab >>Encoding tunable degradability through photopatterning and complimentary labile bond chemistry
(English)Manuscript (preprint) (Other academic)
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-320121 (URN)
Note

QC 20221019

Available from: 2022-10-14 Created: 2022-10-14 Last updated: 2022-10-19Bibliographically approved
4. Photochemically Activated Notch Signaling Hydrogel Preferentially Differentiates Human Derived Hepatoblasts to Cholangiocytes
Open this publication in new window or tab >>Photochemically Activated Notch Signaling Hydrogel Preferentially Differentiates Human Derived Hepatoblasts to Cholangiocytes
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2021 (English)In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 31, no 5, p. 2006116-, article id 2006116Article in journal (Refereed) Published
Abstract [en]

Cholangiocytes form an intricate network of bile ducts to enable proper liver function; yet, recapitulating human stem cell differentiation to cholangiocytes in vitro requires Notch signaling and soluble ligands do not activate the Notch pathway. To overcome these limitations, jagged1 is immobilized on a chemically defined hyaluronan to specifically differentiate human embryonic stem cell-derived hepatoblasts to cholangiocytes. Hepatoblasts cultured on the jagged1-hydrogels upregulate Notch target genes and express key cholangiocyte markers including cystic fibrosis transmembrane conductance regulator. Moreover, cholangiocytes adopt morphological changes that resemble liver biliary structures. To emulate natural biliary system development, a new strategy is developed to achieve spatiotemporal control over the Jagged1–Notch2 interaction: jagged1 is first caged with a photocleavable streptavidin and then it is uncaged photochemically to restore the biological function of Jagged1, which is confirmed with Notch2 activation in a fluorescent reporter cell line. Moreover, the differentiation of human embryonic stem cell-derived hepatoblasts to cholangiocytes is temporally controlled with photochemical uncaging of this streptavidin-Jagged1-immobilized hyaluronan hydrogel. This strategy defines a framework to control protein signaling in time and space and specifically for Notch signaling for ultimate use in regenerative medicine strategies of the liver.

Place, publisher, year, edition, pages
Wiley, 2021
Keywords
hepatoblast differentiation, hyaluronan, hydrogel, liver, notch signaling, photocaging
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-291162 (URN)10.1002/adfm.202006116 (DOI)000581151400001 ()2-s2.0-85093536560 (Scopus ID)
Note

QC 20221109

Available from: 2021-03-04 Created: 2021-03-04 Last updated: 2022-11-09Bibliographically approved

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Kivijärvi, Tove

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