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Clickable decellula...
Clickable decellularized extracellular matrix as a new tool for building hybrid-hydrogels to model chronic fibrotic diseases in vitro
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- Petrou, Cassandra L. (author)
- University of Colorado
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- D'Ovidio, Tyler J. (author)
- University of Colorado
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- Bölükbas, Deniz (author)
- Lund University,Lunds universitet,Lungbioengineering och regeneration,Forskargrupper vid Lunds universitet,Lung Bioengineering and Regeneration,Lund University Research Groups
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- Tas, Sinem (author)
- Lund University,Lunds universitet,Lungbioengineering och regeneration,Forskargrupper vid Lunds universitet,Lung Bioengineering and Regeneration,Lund University Research Groups
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- Brown, R. Dale (author)
- University of Colorado
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- Allawzi, Ayed (author)
- University of Colorado
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- Lindstedt Ingemansson, Sandra (author)
- Lund University,Lunds universitet,Klinisk och experimentell lungtransplantation,Forskargrupper vid Lunds universitet,Lungbioengineering och regeneration,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Clinical and experimental lung transplantation,Lund University Research Groups,Lung Bioengineering and Regeneration,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,Skåne University Hospital
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- Nozik-Grayck, Eva (author)
- University of Colorado
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- Stenmark, Kurt R. (author)
- University of Colorado
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- Wagner, Darcy (author)
- Lund University,Lunds universitet,Lungbioengineering och regeneration,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Lung Bioengineering and Regeneration,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine
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- Magin, Chelsea M. (author)
- University of Colorado
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(creator_code:org_t)
- 2020
- 2020
- English.
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In: Journal of Materials Chemistry B. - 2050-7518. ; 8:31, s. 6814-6826
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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Abstract
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- Fibrotic disorders account for over one third of mortalities worldwide. Despite great efforts to study the cellular and molecular processes underlying fibrosis, there are currently few effective therapies. Dual-stage polymerization reactions are an innovative tool for recreating heterogeneous increases in extracellular matrix (ECM) modulus, a hallmark of fibrotic diseases in vivo. Here, we present a clickable decellularized ECM (dECM) crosslinker incorporated into a dynamically responsive poly(ethylene glycol)-α-methacrylate (PEGαMA) hybrid-hydrogel to recreate ECM remodeling in vitro. An off-stoichiometry thiol-ene Michael addition between PEGαMA (8-arm, 10 kg mol-1) and the clickable dECM resulted in hydrogels with an elastic modulus of E = 3.6 ± 0.24 kPa, approximating healthy lung tissue (1-5 kPa). Next, residual αMA groups were reacted via a photo-initiated homopolymerization to increase modulus values to fibrotic levels (E = 13.4 ± 0.82 kPa) in situ. Hydrogels with increased elastic moduli, mimicking fibrotic ECM, induced a significant increase in the expression of myofibroblast transgenes. The proportion of primary fibroblasts from dual-reporter mouse lungs expressing collagen 1a1 and alpha-smooth muscle actin increased by approximately 60% when cultured on stiff and dynamically stiffened hybrid-hydrogels compared to soft. Likewise, fibroblasts expressed significantly increased levels of the collagen 1a1 transgene on stiff regions of spatially patterned hybrid-hydrogels compared to the soft areas. Collectively, these results indicate that hybrid-hydrogels are a new tool that can be implemented to spatiotemporally induce a phenotypic transition in primary murine fibroblasts in vitro.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- ref (subject category)
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Petrou, Cassandr ...
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D'Ovidio, Tyler ...
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Bölükbas, Deniz
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Tas, Sinem
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Brown, R. Dale
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Allawzi, Ayed
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Lindstedt Ingema ...
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Nozik-Grayck, Ev ...
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Stenmark, Kurt R ...
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Wagner, Darcy
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Magin, Chelsea M ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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Journal of Mater ...
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Lund University