Affibody-mediated controlled release of fibroblast growth factor 2

Chiara Bostock; Carter J Teal; Mickael Dang; Alex W Golinski; Benjamin J Hackel; Molly S Shoichet

doi:10.1016/j.jconrel.2022.09.004

Affibody-mediated controlled release of fibroblast growth factor 2

J Control Release. 2022 Oct:350:815-828. doi: 10.1016/j.jconrel.2022.09.004. Epub 2022 Sep 13.

Authors

Chiara Bostock¹, Carter J Teal², Mickael Dang¹, Alex W Golinski³, Benjamin J Hackel³, Molly S Shoichet⁴

Affiliations

¹ Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario M5S 3E5, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
² Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada; Institute of Biomedical Engineering, 164 College Street, Toronto, Ontario M5S 3G9, Canada.
³ Department of Chemical Engineering and Materials Science, University of Minnesota-Twin Cities, 421 Washington Avenue Southeast, 356 Amundson Hall, Minneapolis, MN 55455, United States.
⁴ Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario M5S 3E5, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada; Institute of Biomedical Engineering, 164 College Street, Toronto, Ontario M5S 3G9, Canada. Electronic address: molly.shoichet@utoronto.ca.

PMID: 36087800
DOI: 10.1016/j.jconrel.2022.09.004

Abstract

Protein therapeutics possess high target affinity and specificity, yet short residence times, which limit their broad utility. To overcome this challenge, we used affinity interactions to modulate protein release from a hydrogel delivery vehicle thereby prolonging therapeutic availability. Specifically, we designed an affibody-modified hyaluronan (HA)-based hydrogel as a delivery platform for fibroblast growth factor 2 (FGF2), a neuroprotective and neuroregenerative factor in the central nervous system (CNS). We identified a highly specific affibody binding partner with moderate affinity for FGF2 using yeast surface display and flow cytometry-based screening. Importantly, we demonstrated controlled release of bioactive FGF2 from the hydrogel by varying the ratio of affibody to protein and showed increased thermal stability of FGF2 in the presence of affibody. This versatile delivery platform will allow the distinct, simultaneous release of multiple proteins based on specific affinity interactions.

Keywords: Affinity interactions; Controlled release; Fibroblast growth factor 2; Hyaluronan; Hydrogel; Protein delivery.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Delayed-Action Preparations
Fibroblast Growth Factor 2*
Hyaluronic Acid*
Hydrogels

Substances

Delayed-Action Preparations
Hydrogels
Fibroblast Growth Factor 2
Hyaluronic Acid

Grants and funding

CIHR/Canada