Abstract

The objective of the proposed work is to develop a silk-elastinlike protein polymer (SELP) embolic suitable for the treatment of aneurysms and pseudoaneurysms. SELPs have exquisitely defined monomer sequences and molecular weights to meet functional requirements by combining the thermoresponsive properties of mammalian tropoelastin and the strength of silk. We propose to combine SELP with radiopacifying agents to generate a novel hydrogel embolic that solidifies after injection without the use of potentially toxic organic solvents or chemical crosslinkers. SELP 815K, which contains 8 silk-like, 15 elastin-like, and 1 lysine-substituted elastin-like motif per monomer repeat, was combined with an organically bound iodine or micronized tantalum in order to bestow radiopacity. Radiopacity of materials was evaluated on an Atris Q® Fluoroscope. Rheological testing was performed using an AR550-Stress Controlled Rheometer. A cone-and-plate configuration with a 20 mm 4° cone geometry was used. Viscosity was measured from 18 to 37°C using an oscillatory procedure at an angular frequency of 6.283 rad/s. This was immediately followed by a 3 hr oscillatory sweep at 37°C using 0.1% strain to monitor gelation kinetics. The SELP embolic was used to embolize a simulated internal carotid artery aneurysm (4.5 mm neck, 5.60 mm depth) in a cerebrovascular controlled flow loop. SELP was injected into the aneurysmal sac with a 2.4F 110 cm Maestro® microcatheter while a 3 mm Advocate™ balloon catheter blocked the aneurysm neck. Catheters were removed after 5 minutes and the embolic material was administered. The radiopaque SELP embolic demonstrated an injectable viscosity profile and formed a solid gel within 5 minutes of being after injection. SELP formed a dense, porous network after gelation that did not adhere to catheters. Iodine-containing radiopacification agents distributed uniformly throughout the embolic, while micronized tantalum formed micro-aggregates that were not visually apparent except under high magnification. A radiopaque SELP based embolic was developed and validated in an in vitro model of a cerebral aneurysm.

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