Painting blood vessels and atherosclerotic plaques with an adhesive drug depot

Abstract

The treatment of diseased vasculature remains challenging, in part because of the difficulty in implanting drug-eluting devices without subjecting vessels to damaging mechanical forces. Implanting materials using adhesive forces could overcome this challenge, but materials have previously not been shown to durably adhere to intact endothelium under blood flow. Marine mussels secrete strong underwater adhesives that have been mimicked in synthetic systems. Here we develop a drug-eluting bioadhesive gel that can be locally and durably glued onto the inside surface of blood vessels. In a mouse model of atherosclerosis, inflamed plaques treated with steroid-eluting adhesive gels had reduced macrophage content and developed protective fibrous caps covering the plaque core. Treatment also lowered plasma cytokine levels and biomarkers of inflammation in the plaque. The drugeluting devices developed here provide a general strategy for implanting therapeutics in the vasculature using adhesive forces and could potentially be used to stabilize rupture-prone plaques.biomaterials | catechol | delivery | endoluminal paving

A thermo-responsive protein treatment for dry eyes

“…By modulating the precise location and residence time of the therapeutic agent, side effects (such as those produced by CCh) can be reduced and efficacy may be enhanced [71]. ELPs have shown promise as reservoir scaffolds [30, 34], and now provide an emerging alternative to PLGA [72] or catechol-based gels [73]. Prior to this study, it was unclear if polymer modification and phase separation would sterically hinder Lacrt and thus impair its activity.…”

Influence of sacrificial bonds on the mechanical behaviour of polymer chains

“…Influence of sacrificial bonds on the mechanical behaviour of polymer chains Nabavi, Harrington, Fratzl and Hartmann properties of the mussel byssus, for example, strong biocompatible surgical adhesives, 21 implantable drug-eluting devices in human blood vessels capable of withstanding blood flow 22 and super tough hydrogel materials that may serve as artificial cartilage. 23 Additionally, a new generation of biomimetic self-repairing metallopolymers has arisen, which directly draw inspiration from the byssal threads.…”

Adaptive synergy between catechol and lysine promotes wet adhesion by surface salt displacement

“…The mussel holdfast or byssus contains ~15 adhesive mussel foot proteins (mfps), two of which, mfp-3 and mfp-5, are deposited first as a primer to condition the target surface and enable other mussel foot proteins to adhere (1) and are peculiar in containing between 20-30 mol% Dopa. Demonstration by atomic force microscopy of wet adhesion to titania by a single Dopa (2) sparked functionalization of synthetic polymeric adhesives and self-healing hydrogels with catechol (3)(4)(5)(6)(7)(8), but wet adhesion of these polymers to oxides and minerals remains controversial (9,10). In actuality, mfp-3 and -5 are rich in Lys as well as Dopa -frequently in adjacent positions along the protein backbone (1).…”