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Publication
Enhanced stem cell retention and antioxidative protection with injectable,
ROS-degradable PEG hydrogels.
Authors Martin JR, Patil P, Yu F, Gupta MK, Duvall CL
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Biomaterials
Year 2020
Date Published 12/1/2020
Volume : Pages 263 : 120377
PubMed Reference 32947094
Abstract Poly(ethylene glycol) (PEG) hydrogels crosslinked with enzyme-cleavable peptides
are promising biodegradable vehicles for therapeutic cell delivery. However,
peptide synthesis at the level required for bulk biomaterial manufacturing is
costly, and fabrication of hydrogels from scalable, low-cost synthetic
precursors while supporting cell-specific degradation remains a challenge.
Reactive oxygen species (ROS) are cell-generated signaling molecules that can
also be used as a trigger to mediate specific in vivo degradation of
biomaterials. Here, PEG-based hydrogels crosslinked with ROS-degradable
poly(thioketal) (PTK) polymers were successfully synthesized via thiol-maleimide
chemistry and employed as a cell-degradable, antioxidative stem cell delivery
platform. PTK hydrogels were mechanically robust and underwent ROS-mediated,
dose-dependent degradation in vitro, while promoting robust cellular
infiltration, tissue regeneration, and bioresorption in vivo. Moreover, these
ROS-sensitive materials successfully encapsulated mesenchymal stem cells (MSCs)
and maintained over 40% more viable cells than gold-standard hydrogels
crosslinked with enzymatically-degradable peptides. The higher cellular survival
in PTK-based gels was associated with the antioxidative function of the
ROS-sensitive crosslinker, which scavenged free radicals and protected
encapsulated MSCs from cytotoxic doses of ROS. Improved MSC viability was also
observed in vivo as MSCs delivered within injectable PTK hydrogels maintained
significantly more viability over 11 days compared against cells delivered
within gels crosslinked with either a PEG-only control polymer or a
gold-standard enzymatically-degradable peptide. Together, this study establishes
a new paradigm for scalable creation and application of cell-degradable
hydrogels, particularly for cell delivery applications.




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