Oxidation‐Responsive, Tunable Growth Factor Delivery from Polyelectrolyte‐Coated Implants
Name
10.1002-adhm.202001941.pdf
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1.3 MB
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Checksum (MD5)
f2ba4b67d9456bcd2a73e6e68ee096f4
Author(s)
Martin, John R.
Howard, MayLin T.
Wang, Sheryl
Berger, Adam G.
Hammond, Paula T.
Date Issued
March 18, 2021
Journal
Advanced Healthcare Materials
Publisher
Wiley
Citation
Martin, J. R., Howard, M. T., Wang, S., Berger, A. G., Hammond, P. T., Oxidation-Responsive, Tunable Growth Factor Delivery from Polyelectrolyte-Coated Implants. Adv. Healthcare Mater. 2021, 10, 2001941.
Version
Author's final manuscript
Abstract
Polyelectrolyte multilayer (PEM) coatings, constructed on the surfaces of tissue engineering scaffolds using layer-by-layer assembly (LbL), promote sustained release of therapeutic molecules and have enabled regeneration of large-scale, pre-clinical bone defects. However, these systems primarily rely on non-specific hydrolysis of PEM components to foster drug release, and their pre-determined drug delivery schedules potentially limit future translation into innately heterogeneous patient populations. To trigger therapeutic delivery directly in response to local environmental stimuli, an LbL-compatible polycation solely degraded by cell-generated reactive oxygen species (ROS) was synthesized. These thioketal-based polymers were selectively cleaved by physiologic doses of ROS, stably incorporated into PEM films alongside growth factors, and facilitated tunable release of therapeutic bone morphogenetic protein-2 (BMP-2) upon oxidation. These coatings' sensitivity to oxidation was also dependent on the polyanions used in film construction, providing a simple method for enhancing ROS-mediated protein delivery in vitro. Correspondingly, when implanted in critically-sized rat calvarial defects, the most sensitive ROS-responsive coatings generated a 50% increase in bone regeneration compared with less sensitive formulations and demonstrated a nearly threefold extension in BMP-2 delivery half-life over conventional hydrolytically-sensitive coatings. These combined results highlight the potential of environmentally-responsive PEM coatings as tunable drug delivery systems for regenerative medicine.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Biological Engineering
Harvard University--MIT Division of Health Sciences and Technology
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DOI of Published Version
https://doi.org/10.1002/adhm.202001941
