Development of a shear-thinning biomaterial as an endovascular embolic agent for the treatment of type B aortic dissection

Abstract

False lumen embolisation is a promising treatment strategy in type B aortic dissection (TBAD) but it is limited by the lack of a disease-specific embolic agent. Our aim was to develop a biomaterial that could be delivered minimally-invasively into the TBAD false lumen and embolise the region. We created 24 shear-thinning biomaterials from blends of gelatin, silicate nanoparticles and silk fibroin, and evaluated their suitability as a false lumen embolic agent in TBAD. We determined the stability of mechanical properties by measuring the compressive modulus of samples stored in physiological conditions over a 21 day period. We quantified injectability by measuring the force required to inject each biomaterial through catheters of varying diameter. We also assessed in vitro degradation rates by measuring weight change over 30 days. Finally, we developed an in vitro experimental pulsatile flow setup with two different anatomically-correct TBAD geometries and performed 78 false lumen occlusion experiments under different operating conditions. We found that the compressive moduli changed rapidly on exposure to 37 °C before stabilising by Day 7. A high silicate nanoparticle to gelatin ratio resulted in greater compressive moduli, with a maximum of 117.6 ± 15.2 kPa. By reducing the total solid concentration, we could improve injectability and biomaterials with 8% (w/v) solids required <80 N force to be injected through a 4.0 mm catheter. Our in vitro degradation rates showed that the biomaterial only degraded by 1.5-8.4% over a 30 day period. We found that the biomaterial could occlude flow to the false lumen in 99% of experiments. In conclusion, blends with high silicate nanoparticle and low silk fibroin content warrant further investigation for their potential as false lumen embolic agents and could be a promising alternative to current TBAD repair methods.

Keywords: Aortic dissection; Biomaterial; Embolisation; Gelatin; Mechanical testing; Silicate nanoparticles; Silk fibroin.