Journal article
Selective Proteolytic Degradation of Guest-Host Assembled, Injectable Hyaluronic Acid Hydrogels
ACS biomaterials science & engineering, v 1(4), pp 277-286
01 Apr 2015
PMID: 33435051
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
There have been significant advances in the past decades toward the engineering of materials with biomimetic properties. In particular, hydrogels covalently cross-linked with protease degradable peptides have demonstrated the importance of protease mediated degradation for targeted therapeutic cargo delivery and controlling cell-material interactions. However, the incorporation of such degradation mechanisms into synthetic shear-thinning hydrogels has yet to be accomplished. Herein, we utilize supramolecular self-assembly mediated by the guest host interaction of hyaluronic acid (HA) separately modified by adamantane (Ad) or cyclodextrin (CD) to form shear-thinning and self-healing hydrogels. In this design, Ad is bound to HA via a proteolytically degradable peptide tether (attached via Michael-addition of a cysteine residue in an Ad-terminated peptide with maleimide modified HA), enabling subsequent proteolytic degradation of the assembly. Upon mixing of the Ad-peptide modified HA and the CD modified HA, a supramolecular hydrogel was formed (G' approximate to 300 Pa at 1 Hz), which displayed shear-thinning (>80% viscosity reduction at 0.5 s(-1)) and near-instantaneous self-healing properties. Rational, selective modification of amino acid residues near the proteolytic site enabled control over peptide cleavage kinetics, specifically with either collagenases or MMP-2. Hydrogel degradation, mediated by a combination of stochastically governed erosion and proteolytic degradation, was influenced by peptide susceptibility to proteolysis both in vitro and in vivo (>2 fold difference at 3 weeks in vivo) when injected subcutaneously. This material system provides unique opportunities for therapeutic delivery (e.g., growth factors, cells) through facile material formation, ease of injection, and bioresponsive material degradation.
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Details
- Title
- Selective Proteolytic Degradation of Guest-Host Assembled, Injectable Hyaluronic Acid Hydrogels
- Creators
- Christopher B. Rodell - University of PennsylvaniaRyan J. Wade - University of PennsylvaniaBrendan P. Purcell - University of PennsylvaniaNeville N. Dusaj - University of PennsylvaniaJason A. Burdick - University of Pennsylvania
- Publication Details
- ACS biomaterials science & engineering, v 1(4), pp 277-286
- Publisher
- American Chemical Society; Washington, DC
- Number of pages
- 10
- Grant note
- National Science Foundation; National Science Foundation (NSF) American Heart Association R01 HL107938; R01 HL111090 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000369347300009
- Scopus ID
- 2-s2.0-84969262134
- Other Identifier
- 991019176642004721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Materials Science, Biomaterials