Vascular Engineering Laboratory, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands and Centre for Medical Research, The University of Western Australia, Perth, Australia; School of Biomedical Science, The University of Western Australia, Perth, Australia.
Vascular Engineering Laboratory, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands and Centre for Medical Research, The University of Western Australia, Perth, Australia; School of Engineering, The University of Western Australia, Perth, Australia.
J Mech Behav Biomed Mater. 2019 Nov;99:66-77. doi: 10.1016/j.jmbbm.2019.07.016. Epub 2019 Jul 19.
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.
假腔栓塞是治疗 B 型主动脉夹层(TBAD)的一种有前途的治疗策略,但由于缺乏针对该疾病的专用栓塞剂而受到限制。我们的目的是开发一种可以微创输送到 TBAD 假腔并栓塞该区域的生物材料。我们从明胶、硅酸盐纳米粒子和丝素蛋白的混合物中创建了 24 种剪切稀化生物材料,并评估了它们作为 TBAD 假腔栓塞剂的适用性。我们通过测量在生理条件下储存 21 天的样品的压缩模量来确定机械性能的稳定性。我们通过测量通过不同直径的导管注射每种生物材料所需的力来量化可注射性。我们还通过测量 30 天内的重量变化来评估体外降解率。最后,我们开发了一种具有两种不同解剖学上正确的 TBAD 几何形状的体外脉动流实验装置,并在不同的操作条件下进行了 78 次假腔闭塞实验。我们发现,暴露于 37°C 后,压缩模量迅速变化,在第 7 天之前稳定下来。高硅酸盐纳米粒子与明胶的比例导致更高的压缩模量,最大可达 117.6±15.2kPa。通过降低总固体浓度,我们可以提高可注射性,并且固体浓度为 8%(w/v)的生物材料只需<80N 的力即可通过 4.0mm 导管注射。我们的体外降解率表明,生物材料在 30 天内仅降解 1.5-8.4%。我们发现,生物材料可以在 99%的实验中闭塞假腔的血流。总之,高硅酸盐纳米粒子和低丝素蛋白含量的混合物具有进一步研究的潜力,作为假腔栓塞剂,可能是当前 TBAD 修复方法的一种有前途的替代方法。