Li Zefu, Kong Pengxu, Liu Xiang, Feng Shuyi, Ouyang Wenbin, Wang Shouzheng, Hu Xiaopeng, Xie Yongquan, Zhang Fengwen, Zhang Yuxin, Gao Rui, Wang Weiwei, Pan Xiangbin
Department of Structural Heart Disease, National Center for Cardiovascular Disease, China & State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Health Commission Key Laboratory of Cardiovascular Regeneration Medicine, National Clinical Research Center for Cardiovascular Diseases, Beijing, China.
Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.
Bioact Mater. 2022 Dec 26;24:252-262. doi: 10.1016/j.bioactmat.2022.12.018. eCollection 2023 Jun.
Ventricular septal defect (VSD) is one of the commonest congenital heart diseases (CHDs). Current occluders for VSD treatment are mainly made of nitinol, which has the risk of nickel allergy, persistent myocardial abrasion and fatal arrythmia. Herein, a fully biodegradable polydioxanone (PDO) occluder equipped with a shape line and poly-l-lactic acid PLLA membranes is developed for VSD closure without the addition of metal marker. PDO occluder showed great mechanical strength, fatigue resistance, geometry fitness, biocompatibility and degradability. In a rat subcutaneous implantation model, PDO filaments significantly alleviated inflammation response, mitigated fibrosis and promoted endothelialization compared with nitinol. The safety and efficacy of PDO occluder were confirmed in a canine VSD model with 3-year follow-up, demonstrating the biodegradable PDO occluder could not only effectively repair VSD, induce cardiac remodeling but also address the complications associated with metal occluders. Furthermore, a pilot clinical trial with five VSD patients indicated that all the occluders were successfully implanted under the guidance of echocardiography and no adverse events occurred during the 3-month follow-up. Collectively, the fully bioresorbable PDO occluder is safe and effective for clinical VSD closure and holds great promise for the treatment of structural CHDs.
室间隔缺损(VSD)是最常见的先天性心脏病(CHD)之一。目前用于治疗VSD的封堵器主要由镍钛诺制成,存在镍过敏、持续性心肌磨损和致命性心律失常的风险。在此,开发了一种配备形状线和聚左旋乳酸(PLLA)膜的完全可生物降解的聚二氧六环酮(PDO)封堵器,用于关闭VSD,无需添加金属标记物。PDO封堵器具有良好的机械强度、抗疲劳性、几何适应性、生物相容性和可降解性。在大鼠皮下植入模型中,与镍钛诺相比,PDO细丝显著减轻了炎症反应,减轻了纤维化并促进了内皮化。在犬VSD模型中进行了3年随访,证实了PDO封堵器的安全性和有效性,表明可生物降解的PDO封堵器不仅可以有效修复VSD,诱导心脏重塑,还可以解决与金属封堵器相关的并发症。此外,一项针对5名VSD患者的临床试验初步结果表明,所有封堵器均在超声心动图引导下成功植入,且在3个月的随访期间未发生不良事件。总体而言,完全可生物吸收的PDO封堵器在临床VSD封堵中是安全有效的,对结构性CHD的治疗具有广阔前景。