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.

pH-Responsive Polyelectrolyte Coatings that Enable Catheter-Mediated Transfer of DNA to the Arterial Wall in Short and Clinically Relevant Inflation Times

“…Thin polymer-based films fabricated by the layer-by-layer assembly of oppositely charged polymers (known as “polyelectrolyte multilayers” or PEMs) have attracted significant interest in many fundamental and applied biomedical and biotechnological contexts owing, in part, to their compositional complexity and the ease with which they can be applied to the surfaces of complex objects. − The mild aqueous conditions that are often used for the assembly of these materials can preserve the bioactivities of nucleic acids and proteins, rendering this approach particularly attractive for the design of coatings composed of bioactive agents. ,− The iterative nature of layer-by-layer assembly can also provide opportunities to manipulate structure and composition at the nanoscale or incorporate design elements that are useful for the subsequent controlled release or local delivery of macromolecular drugs. ,− The work reported here was motivated broadly by potential applications of PEMs as platforms for the local delivery of DNA during vascular interventions and, in particular, by key challenges associated with the design of coatings that can promote the rapid and uniform “contact transfer” of DNA to vascular tissue from the surfaces of interventional devices used during minimally invasive surgeries.…”

Reactive oxygen species–degradable polythioketal urethane foam dressings to promote porcine skin wound repair

“…www.science.org/doi/10.1126/scitranslmed.abm6586 Materials and Methods Figs. S1 to S15 Tables S1 and S2 Data file S1 MDAR Reproducibility Checklist References (119)(120)(121)(122)(123) View/request a protocol for this paper from Bio-protocol.…”

Encapsulated vaterite-calcite CaCO3 particles loaded with Mg2+ and Cu2+ ions with sustained release promoting osteogenesis and angiogenesis

“…Brito Barrera et al fabricated an osteogenic microenvironment relying on PEMs in combination with multilayers of type I collagen and chondroitin sulfate ( Brito Barrera et al, 2020 ). The LbL technique is a method to fabricate coatings by alternate adsorption of polyanions and polycations, which can neatly combine collagen and PEM ( Martin et al, 2021 ). In this study, the CaCO 3 particles were loaded with Cu 2+ and Mg 2+ via a co-precipitation process.…”