In situ regeneration of bioactive coatings enabled by an evolved Staphylococcus aureus sortase A

Hyun Ok Ham, Zheng Qu, Carolyn A. Haller, Brent M. Dorr, Erbin Dai, Wookhyun Kim, David R. Liu and Elliot L. Chaikof ()
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Hyun Ok Ham: Beth Israel Deaconess Medical Center, Harvard Medical School
Zheng Qu: Beth Israel Deaconess Medical Center, Harvard Medical School
Carolyn A. Haller: Beth Israel Deaconess Medical Center, Harvard Medical School
Brent M. Dorr: Howard Hughes Medical Institute, Harvard University
Erbin Dai: Beth Israel Deaconess Medical Center, Harvard Medical School
Wookhyun Kim: Beth Israel Deaconess Medical Center, Harvard Medical School
David R. Liu: Howard Hughes Medical Institute, Harvard University
Elliot L. Chaikof: Beth Israel Deaconess Medical Center, Harvard Medical School

Nature Communications, 2016, vol. 7, issue 1, 1-8

Abstract: Abstract Surface immobilization of bioactive molecules is a central paradigm in the design of implantable devices and biosensors with improved clinical performance capabilities. However, in vivo degradation or denaturation of surface constituents often limits the long-term performance of bioactive films. Here we demonstrate the capacity to repeatedly regenerate a covalently immobilized monomolecular thin film of bioactive molecules through a two-step stripping and recharging cycle. Reversible transpeptidation by a laboratory evolved Staphylococcus aureus sortase A (eSrtA) enabled the rapid immobilization of an anti-thrombogenic film in the presence of whole blood and permitted multiple cycles of film regeneration in vitro that preserved its biological activity. Moreover, eSrtA transpeptidation facilitated surface re-engineering of medical devices in situ after in vivo implantation through removal and restoration film constituents. These studies establish a rapid, orthogonal and reversible biochemical scheme to regenerate selective molecular constituents with the potential to extend the lifetime of bioactive films.

Date: 2016
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DOI: 10.1038/ncomms11140

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