Engineering the extracellular matrix to model diseases and orchestrate regeneration
Söderlund, Zackarias LU
(2023)
In Lund University, Faculty of Medicine Doctoral Dissertation Series
- Abstract
- The extracellular matrix is not only a scaffold to which cells attach, but it is also a matrix that communicates cell signals. Because of the interplay between cells and the extracellular matrix, changes in the extracellular matrix can steer cell fate. This opens up the opportunity to design and engineer the extracellular matrix to communicate changes to the cells. Thus, this thesis has focused on understanding which parameters and signals influence cells, but also on how to utilise this knowledge to engineer a completely defined extracellular matrix. The extracellular matrix can be modulated in several ways, such as cell attachment, degradation properties, porosity, stiffness as well as being easily functionalised with molecules of... (More)
- The extracellular matrix is not only a scaffold to which cells attach, but it is also a matrix that communicates cell signals. Because of the interplay between cells and the extracellular matrix, changes in the extracellular matrix can steer cell fate. This opens up the opportunity to design and engineer the extracellular matrix to communicate changes to the cells. Thus, this thesis has focused on understanding which parameters and signals influence cells, but also on how to utilise this knowledge to engineer a completely defined extracellular matrix. The extracellular matrix can be modulated in several ways, such as cell attachment, degradation properties, porosity, stiffness as well as being easily functionalised with molecules of interest using click chemistry.
Two of the papers in this thesis focus on the development of new tools for glycosaminoglycan research to get a better understanding of how this can be modulated to steer cell signalling. Glycosaminoglycans bind growth factors, which can then either act as a co-receptor to increase the potency of the growth factor or to protect the growth factors from being broken down or inactivated. The tools that we have developed open the possibility to better study the production of glycosaminoglycans from different types of cells and better understand what changes occur in glycosaminoglycan synthesis during disease.
The second two papers in this thesis focus on understanding the extracellular matrix. Article number one focuses on the effect of different extracellular matrices and stretch on cells and their secretome. Article number two, which has been the focus of this thesis, utilises the new findings in the other articles about glycosaminoglycans and the extracellular matrix to create a synthetic and defined extracellular matrix. This extracellular matrix is modified with glycosaminoglycans to have a slow release of growth factors to instruct cells to differentiate both in vitro and in vivo. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3c860d57-af92-4acf-98e0-69d3c0e7e616
- author
- Söderlund, Zackarias
LU
- supervisor
- opponent
-
- Dr Barrias, Cristina C., Porto
- organization
- publishing date
- 2023
- type
- Thesis
- publication status
- published
- subject
- in
- Lund University, Faculty of Medicine Doctoral Dissertation Series
- issue
- 2023:49
- pages
- 66 pages
- publisher
- Lund University, Faculty of Medicine
- defense location
- Belfragesalen, BMC D15, Klinikgatan 32 i Lund
- defense date
- 2023-05-05 09:00:00
- ISSN
- 1652-8220
- ISBN
- 978-91-8021-389-9
- language
- English
- LU publication?
- yes
- id
- 3c860d57-af92-4acf-98e0-69d3c0e7e616
- date added to LUP
- 2023-03-22 16:18:00
- date last changed
- 2023-04-06 12:36:17
@phdthesis{3c860d57-af92-4acf-98e0-69d3c0e7e616,
abstract = {{The extracellular matrix is not only a scaffold to which cells attach, but it is also a matrix that communicates cell signals. Because of the interplay between cells and the extracellular matrix, changes in the extracellular matrix can steer cell fate. This opens up the opportunity to design and engineer the extracellular matrix to communicate changes to the cells. Thus, this thesis has focused on understanding which parameters and signals influence cells, but also on how to utilise this knowledge to engineer a completely defined extracellular matrix. The extracellular matrix can be modulated in several ways, such as cell attachment, degradation properties, porosity, stiffness as well as being easily functionalised with molecules of interest using click chemistry.<br/>Two of the papers in this thesis focus on the development of new tools for glycosaminoglycan research to get a better understanding of how this can be modulated to steer cell signalling. Glycosaminoglycans bind growth factors, which can then either act as a co-receptor to increase the potency of the growth factor or to protect the growth factors from being broken down or inactivated. The tools that we have developed open the possibility to better study the production of glycosaminoglycans from different types of cells and better understand what changes occur in glycosaminoglycan synthesis during disease.<br/>The second two papers in this thesis focus on understanding the extracellular matrix. Article number one focuses on the effect of different extracellular matrices and stretch on cells and their secretome. Article number two, which has been the focus of this thesis, utilises the new findings in the other articles about glycosaminoglycans and the extracellular matrix to create a synthetic and defined extracellular matrix. This extracellular matrix is modified with glycosaminoglycans to have a slow release of growth factors to instruct cells to differentiate both in vitro and in vivo.}},
author = {{Söderlund, Zackarias}},
isbn = {{978-91-8021-389-9}},
issn = {{1652-8220}},
language = {{eng}},
number = {{2023:49}},
publisher = {{Lund University, Faculty of Medicine}},
school = {{Lund University}},
series = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
title = {{Engineering the extracellular matrix to model diseases and orchestrate regeneration}},
url = {{https://lup.lub.lu.se/search/files/141151837/Engineering_the_extracellular_matrix_to_model_diseases_and_orchestrate_regeneration.pdf}},
year = {{2023}},
}