Oxidation-Responsive, Tunable Growth Factor Delivery from Polyelectrolyte-Coated Implants.

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.

SUBMITTER: Martin JR 

PROVIDER: S-EPMC9280659 | biostudies-literature |

REPOSITORIES: biostudies-literature