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Sci Rep. 2015 Mar 4;5:8729. doi: 10.1038/srep08729.

Macromolecularly crowded in vitro microenvironments accelerate the production of extracellular matrix-rich supramolecular assemblies.

Author information

1
Network of Excellence for Functional Biomaterials (NFB), National University of Ireland Galway (NUI Galway), Bioscience Research Building, Galway, Ireland.
2
Conway Institute of Biomolecular &Biomedical Research, University College Dublin, Dublin, Ireland.
3
School of Chemistry &Chemical Biology, University College Dublin, Dublin, Ireland.
4
BIDMC Genomics, Proteomics, Bioinformatics and Systems Biology Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.
5
Alimentary Glycoscience Research Cluster, NUI Galway, Galway, Ireland.
6
Department of Bioengineering, Faculty of Engineering, National University of Singapore Tissue Engineering Programme, Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Abstract

Therapeutic strategies based on the principles of tissue engineering by self-assembly put forward the notion that functional regeneration can be achieved by utilising the inherent capacity of cells to create highly sophisticated supramolecular assemblies. However, in dilute ex vivo microenvironments, prolonged culture time is required to develop an extracellular matrix-rich implantable device. Herein, we assessed the influence of macromolecular crowding, a biophysical phenomenon that regulates intra- and extra-cellular activities in multicellular organisms, in human corneal fibroblast culture. In the presence of macromolecules, abundant extracellular matrix deposition was evidenced as fast as 48 h in culture, even at low serum concentration. Temperature responsive copolymers allowed the detachment of dense and cohesive supramolecularly assembled living substitutes within 6 days in culture. Morphological, histological, gene and protein analysis assays demonstrated maintenance of tissue-specific function. Macromolecular crowding opens new avenues for a more rational design in engineering of clinically relevant tissue modules in vitro.

PMID:
25736020
PMCID:
PMC4348624
DOI:
10.1038/srep08729
[Indexed for MEDLINE]
Free PMC Article

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