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Artificial cell membrane binding thrombin constructs drive in situ fibrin hydrogel formation

Research output: Contribution to journalArticle

Original languageEnglish
Article number1887
Number of pages10
JournalNature Communications
Volume10
DOIs
DateAccepted/In press - 31 Jan 2019
DatePublished (current) - 23 Apr 2019

Abstract

Cell membrane re-engineering is emerging as a powerful tool for the development of next generation cell therapies, as it allows the user to augment therapeutic cells to provide additional functionalities, such as homing, adhesion or hypoxia resistance. To date, however, there are few examples where the plasma membrane is re-engineered to display active enzymes that promote extracellular matrix protein assembly. Here, we report on a self-contained matrix-forming system where the membrane of human mesenchymal stem cells is modified to display a novel thrombin construct, giving rise to spontaneous fibrin hydrogel nucleation and growth at near human plasma concentrations of fibrinogen. The cell membrane modification process is realised through the synthesis of a membrane-binding supercationic thrombin-polymer surfactant complex. Significantly, the resulting robust cellular fibrin hydrogel constructs can be differentiated down osteogenic and adipogenic lineages, giving rise to self-supporting monoliths that exhibit Young’s moduli that reflect their respective extracellular matrix compositions.

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Springer Nature at https://www.nature.com/articles/s41467-019-09763-0 . Please refer to any applicable terms of use of the publisher.

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