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Temporally Tunable, Enzymatically Responsive Delivery of Proangiogenic Peptides from Poly(ethylene glycol) Hydrogels
Author(s) -
Van Hove Amy H.,
Antonienko Erin,
Burke Kathleen,
Brown Edward,
Benoit Danielle S. W.
Publication year - 2015
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201500304
Subject(s) - self healing hydrogels , in vivo , ethylene glycol , drug delivery , peptide , matrix metalloproteinase , in vitro , chemistry , tissue engineering , biophysics , biomedical engineering , biochemistry , pharmacology , materials science , nanotechnology , medicine , biology , polymer chemistry , organic chemistry , microbiology and biotechnology
Proangiogenic drugs hold great potential to promote reperfusion of ischemic tissues and in tissue engineering applications, but efficacy is limited by poor targeting and short half‐lives. Methods to control release duration or provide enzymatically responsive drug delivery have independently improved drug efficacy. However, no material has been developed to temporally control the rate of enzymatically responsive drug release. To address this void, hydrogels are developed to provide sustained, tunable release of Qk, a proangiogenic peptide mimic of vascular endothelial growth factor, via tissue‐specific enzymatic activity. After confirmation that sustained delivery of Qk is necessary for proangiogenic effects, a variety of previously identified matrix metalloproteinase (MMP)‐degradable linkers are used to tether Qk to hydrogels. Of these, three (IPES↓LRAG, GPQG↓IWGQ, and VPLS↓LYSG) show MMP‐responsive peptide release. These linkers provide tunable Qk release kinetics, with rates ranging from 1.64 to 19.9 × 10 −3 h −1 in vitro and 4.82 to 8.94 × 10 −3 h −1 in vivo. While Qk is confirmed to be bioactive as released, hydrogels releasing Qk fail to induce significant vascularization in vivo after one week, likely due to the use of nonenzymatically degradable hydrogels. While Qk is the focus of this study, the approach could easily be adapted to control the delivery of a variety of therapeutic molecules.