Controlled release of low-molecular weight, polymer-free corticosteroid coatings suppresses fibrotic encapsulation of implanted medical devices.

Inflammation-driven foreign body reactions, and the frequently associated encapsulation by fibrogenic fibroblasts, reduce the functionality and longevity of implanted medical devices and materials. Anti-inflammatory drugs, such as dexamethasone, can suppress the foreign body reaction for a few days post-surgery, but lasting drug delivery strategies for long-term implanted materials remain an unmet need. We here establish a thin-coating strategy with novel low molecular weight corticosteroid dimers to suppress foreign body reactions and fibrotic encapsulation of subcutaneous silicone implants.

Polymer-free corticosteroid dimer implants for controlled and sustained drug delivery.

Polymeric drug carriers are widely used for providing temporal and/or spatial control of drug delivery, with corticosteroids being one class of drugs that have benefitted from their use for the treatment of inflammatory-mediated conditions. However, these polymer-based systems often have limited drug-loading capacity, suboptimal release kinetics, and/or promote adverse inflammatory responses. This manuscript investigates and describes a strategy for achieving controlled delivery of corticosteroids, based on a discovery that low molecular weight corticosteroid dimers can be processed into drug delivery implant materials using a broad range of established fabrication methods, without the use of polymers or excipients.

Sequence-Controlled Polyurethane Block Copolymer Displays Differentiated Immunoglobulin-G Adsorption That Influences Human Monocyte Adhesion and Activity.

The ability to specify an adsorbed protein layer through the polymer chemistry design of immunomodulatory biomaterials is important when considering a desired immune response, such as reducing pro-inflammatory activity. Limited work has been undertaken to elucidate the role of monomer sequence in this process, when copolymeric systems are involved. In this study, we demonstrate the advantage of an alternating radical copolymerization strategy as opposed to a random statistical copolymerization to order monomers in the synthesis of degradable polar-hydrophobic-ionic polyurethanes (D-PHI), biomaterials originally designed to reduce inflammatory monocyte activation.

Synthesis and characterization of electrospun nanofibrous tissue engineering scaffolds generated from in situ polymerization of ionomeric polyurethane composites.

Tissue scaffolds need to be engineered to be cell compatible, have timely biodegradable character, be functional with respect to providing niche cell support for tissue repair and regeneration, readily accommodate multiple cell types, and have mechanical properties that enable the simulation of the native tissue. In this study, electrospun degradable polar hydrophobic ionic polyurethane (D-PHI) scaffolds were generated in order to yield an extracellular matrix-like structure for tissue engineering applications. D-PHI oligomers were synthesized, blended with a degradable linear polycarbonate polyurethane (PCNU), and electrospun with simultaneous in situ UV cross-linking in order to generate aligned nanofibrous scaffolds in the form of elastomeric composite materials.

Differential Regulation of Extracellular Matrix Components Using Different Vitamin C Derivatives in Mono- and Coculture Systems.

Vascular tissue engineering strategies using cell-seeded scaffolds require uniformly distributed vascular cells and sufficient extracellular matrix (ECM) production. However, acquiring sufficient ECM deposition on synthetic biomaterial scaffolds during the in vitro culture period prior to tissue implantation still remains challenging for vascular constructs. Two forms of vitamin C derivatives, ascorbic acid (AA) and sodium ascorbate (SA), are commonly supplemented in cell culture to promote ECM accumulation.