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Controlled release of growth factors using synthetic glycosaminoglycans in a modular macroporous scaffold for tissue regeneration

Söderlund, Z LU orcid ; Ibáñez-Fonseca, A LU orcid ; Hajizadeh, S LU orcid ; Rodríguez-Cabello, J C ; Liu, J LU ; Ye, L LU orcid ; Tykesson, E LU ; Elowsson, L LU and Westergren-Thorsson, G LU orcid (2022) In Communications Biology 5(1).
Abstract

Healthy regeneration of tissue relies on a well-orchestrated release of growth factors. Herein, we show the use of synthetic glycosaminoglycans for controlled binding and release of growth factors to induce a desired cellular response. First, we screened glycosaminoglycans with growth factors of interest to determine kon (association rate constant), koff (dissociation rate constant), and Kd (equilibrium rate constant). As proof-of-concept, we functionalized an elastin-like recombinamer (ELR) hydrogel with a synthetic glycosaminoglycan and immobilized fibroblast growth factor 2 (FGF2), demonstrating that human umbilical vein endothelial cells cultured on top of ELR hydrogel differentiated into tube-like structures. Taking this concept... (More)

Healthy regeneration of tissue relies on a well-orchestrated release of growth factors. Herein, we show the use of synthetic glycosaminoglycans for controlled binding and release of growth factors to induce a desired cellular response. First, we screened glycosaminoglycans with growth factors of interest to determine kon (association rate constant), koff (dissociation rate constant), and Kd (equilibrium rate constant). As proof-of-concept, we functionalized an elastin-like recombinamer (ELR) hydrogel with a synthetic glycosaminoglycan and immobilized fibroblast growth factor 2 (FGF2), demonstrating that human umbilical vein endothelial cells cultured on top of ELR hydrogel differentiated into tube-like structures. Taking this concept further, we developed a tunable macroporous ELR cryogel material, containing a synthetic glycosaminoglycan and FGF2 that showed increased blood vessel formation and reduced immune response compared to control when implanted in a subcutaneous mouse model. These results demonstrated the possibility for specific release of desired growth factors in/from a modular 3D scaffold in vitro and in vivo.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Animals, Mice, Glycosaminoglycans, Delayed-Action Preparations, Endothelial Cells, Health Status
in
Communications Biology
volume
5
issue
1
article number
1349
publisher
Nature Publishing Group
external identifiers
  • scopus:85143570194
  • pmid:36482075
ISSN
2399-3642
DOI
10.1038/s42003-022-04305-9
language
English
LU publication?
yes
id
204e54e7-7e24-48bd-a38c-4d53e4ea04bd
date added to LUP
2022-12-14 12:13:49
date last changed
2024-12-24 02:52:57
@article{204e54e7-7e24-48bd-a38c-4d53e4ea04bd,
  abstract     = {{<p>Healthy regeneration of tissue relies on a well-orchestrated release of growth factors. Herein, we show the use of synthetic glycosaminoglycans for controlled binding and release of growth factors to induce a desired cellular response. First, we screened glycosaminoglycans with growth factors of interest to determine kon (association rate constant), koff (dissociation rate constant), and Kd (equilibrium rate constant). As proof-of-concept, we functionalized an elastin-like recombinamer (ELR) hydrogel with a synthetic glycosaminoglycan and immobilized fibroblast growth factor 2 (FGF2), demonstrating that human umbilical vein endothelial cells cultured on top of ELR hydrogel differentiated into tube-like structures. Taking this concept further, we developed a tunable macroporous ELR cryogel material, containing a synthetic glycosaminoglycan and FGF2 that showed increased blood vessel formation and reduced immune response compared to control when implanted in a subcutaneous mouse model. These results demonstrated the possibility for specific release of desired growth factors in/from a modular 3D scaffold in vitro and in vivo.</p>}},
  author       = {{Söderlund, Z and Ibáñez-Fonseca, A and Hajizadeh, S and Rodríguez-Cabello, J C and Liu, J and Ye, L and Tykesson, E and Elowsson, L and Westergren-Thorsson, G}},
  issn         = {{2399-3642}},
  keywords     = {{Humans; Animals; Mice; Glycosaminoglycans; Delayed-Action Preparations; Endothelial Cells; Health Status}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Communications Biology}},
  title        = {{Controlled release of growth factors using synthetic glycosaminoglycans in a modular macroporous scaffold for tissue regeneration}},
  url          = {{http://dx.doi.org/10.1038/s42003-022-04305-9}},
  doi          = {{10.1038/s42003-022-04305-9}},
  volume       = {{5}},
  year         = {{2022}},
}