Oxidation‐Responsive, Tunable Growth Factor Delivery from Polyelectrolyte‐Coated Implants

• DOI: 10.1002/adhm.202001941
• Publication Date: 2021-03-19T06:03:17Z
• Authors: John R. Martin; MayLin T. Howard; Sheryl Wang; Adam G. Berger; Paula T. Hammond
• Keywords: 0301 basic medicine; Drug Liberation; 03 medical and health sciences; Bone Regeneration; Tissue Engineering; Tissue Scaffolds; Animals; Bone Morphogenetic Protein 2; Humans; Polyelectrolytes; Rats; 3. Good health

AbstractPolyelectrolyte 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.