Tunable growth factor delivery from injectable hydrogels for tissue engineering.
Current sustained delivery strategies of protein therapeutics are limited by the fragility of the protein, resulting in minimal quantities of bioactive protein delivered. In order to achieve prolonged release of bioactive protein, an affinity-based approach was designed which exploits the specific binding of the Src homology 3 (SH3) domain with short proline-rich peptides. Specifically, methyl cellulose was modified with SH3-binding peptides (MC-peptide) with either a weak affinity or strong affinity for SH3. The release profile of SH3-rhFGF2 fusion protein from hyaluronan MC-SH3 peptide (HAMC-peptide) hydrogels was investigated and compared to unmodified controls. SH3-rhFGF2 release from HAMC-peptide was extended to 10 days using peptides with different binding affinities compared to the 48 h release from unmodified HAMC. This system is capable of delivering additional proteins with tunable rates of release, while maintaining bioactivity, and thus is broadly applicable.
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada M5S 3H6.
Katarina
K
Vulic
Molly S
MS
Shoichet
D016503:Drug Delivery Systems; D004926:Escherichia coli / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D006820:Hyaluronic Acid; D020100:Hydrogels / Q000737:chemistry*; D010455:Peptides; D011392:Proline / Q000737:chemistry; D011485:Protein Binding; D011994:Recombinant Proteins; D023822:Tissue Engineering / Q000379:methods*; D018909:src Homology Domains
D020100:Hydrogels; D010455:Peptides; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D006820:Hyaluronic Acid; D011392:Proline