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

Robert C. Deller, Thomas Richardson, Rebecca Richardson, Laura Bevan, Ioannis Zampetakis, Fabrizio Scarpa and Adam W. Perriman ()
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Robert C. Deller: University of Bristol
Thomas Richardson: University of Bristol
Rebecca Richardson: University of Bristol
Laura Bevan: University of Bristol
Ioannis Zampetakis: University of Bristol
Fabrizio Scarpa: University of Bristol
Adam W. Perriman: University of Bristol

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-09763-0

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