Macromolecularly crowded in vitro microenvironments accelerate the production of extracellular matrix-rich supramolecular assemblies
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...
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Published in | Scientific reports Vol. 5; no. 1; p. 8729 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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Nature Publishing Group UK
04.03.2015
Nature Publishing Group |
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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
. |
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AbstractList | 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. 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 . 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 . |
ArticleNumber | 8729 |
Author | Collin, Estelle Dillon, Simon Joshi, Lokesh Raghunath, Michael Rochev, Yury Pandit, Abhay Kumar, Pramod Rodriguez, Brian J. Satyam, Abhigyan Fan, Xingliang Gorelov, Alexander Zeugolis, Dimitrios I. |
Author_xml | – sequence: 1 givenname: Pramod surname: Kumar fullname: Kumar, Pramod organization: Network of Excellence for Functional Biomaterials (NFB), National University of Ireland Galway (NUI Galway) – sequence: 2 givenname: Abhigyan surname: Satyam fullname: Satyam, Abhigyan organization: Network of Excellence for Functional Biomaterials (NFB), National University of Ireland Galway (NUI Galway) – sequence: 3 givenname: Xingliang surname: Fan fullname: Fan, Xingliang organization: Network of Excellence for Functional Biomaterials (NFB), National University of Ireland Galway (NUI Galway) – sequence: 4 givenname: Estelle surname: Collin fullname: Collin, Estelle organization: Network of Excellence for Functional Biomaterials (NFB), National University of Ireland Galway (NUI Galway) – sequence: 5 givenname: Yury surname: Rochev fullname: Rochev, Yury organization: Network of Excellence for Functional Biomaterials (NFB), National University of Ireland Galway (NUI Galway) – sequence: 6 givenname: Brian J. surname: Rodriguez fullname: Rodriguez, Brian J. organization: Conway Institute of Biomolecular & Biomedical Research, University College Dublin – sequence: 7 givenname: Alexander surname: Gorelov fullname: Gorelov, Alexander organization: School of Chemistry & Chemical Biology, University College Dublin – sequence: 8 givenname: Simon surname: Dillon fullname: Dillon, Simon organization: BIDMC Genomics, Proteomics, Bioinformatics and Systems Biology Center, Beth Israel Deaconess Medical Center, Harvard Medical School – sequence: 9 givenname: Lokesh surname: Joshi fullname: Joshi, Lokesh organization: Alimentary Glycoscience Research Cluster, NUI Galway – sequence: 10 givenname: Michael surname: Raghunath fullname: Raghunath, Michael organization: Department of Bioengineering, Department of Biochemistry, Faculty of Engineering, National University of Singapore Tissue Engineering Programme, Yong Loo Lin School of Medicine, National University of Singapore – sequence: 11 givenname: Abhay surname: Pandit fullname: Pandit, Abhay organization: Network of Excellence for Functional Biomaterials (NFB), National University of Ireland Galway (NUI Galway) – sequence: 12 givenname: Dimitrios I. surname: Zeugolis fullname: Zeugolis, Dimitrios I. organization: Network of Excellence for Functional Biomaterials (NFB), National University of Ireland Galway (NUI Galway) |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25736020$$D View this record in MEDLINE/PubMed |
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Title | Macromolecularly crowded in vitro microenvironments accelerate the production of extracellular matrix-rich supramolecular assemblies |
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