Self-unfolding RV-PA 3D Printed Conduits

项目摘要/摘要 右室至肺动脉(RV-PA)导管经常被用作外科姑息性治疗。 适用于各种婴幼儿先天性心脏病。由于婴儿或儿童的成长，或 并发症，如设备扭结或血栓形成，这些管道需要更换，这可能涉及 成年前做过几次大的心脏直视手术。我们建议利用3D打印来设计和开发 一种新型的RV-PA管道，它通过流量和时间触发的定制自展开来增加其尺寸 维持和发展正常的肺部需要较少的并发症和手术 从婴儿期到成年期的血液流动。据设想，3D打印还将允许提高 患者定制和按需设计更改以实现更好的功能。我们期待着那个自我- 展开机构和相关的形状变化将导致管道在更长的时间内运行 婴儿和儿童成长到成年的过程。 在R21阶段，我们将设计、制造、表面修饰和体外测试自展开RV- PA导管。我们将首先对FDA批准的材料进行3D打印的打印参数研究 可变尺寸RV-PA导管的制作。同时，我们将利用数值模拟来 确定允许改变尺寸的设计参数，并使用体外功能测试和 生物兼容性。 在R33阶段，我们将升级我们的3D打印机并改进RV-PA管道，以实现更好的打印 解决方案和含氟聚合物油墨，消除了表面修饰的需要。最后，我们将在- 综合血流动力学评价和死后大体组织学评价的活体手术 在绵羊模型中。我们将分析细胞外基质的形成，表征内皮细胞的功能和白蛋白 血细胞活化，免疫组织化学定量进行炎症分析。 我们预计，这些研究将使一类新的RV-PA管道成为可能，并为 为婴儿设计针对患者特定形状的生物医学植入物，使其能够在 以相同的速度减少后续手术的次数。

Project Summary/Abstract Right ventricle–to–pulmonary artery (RV-PA) conduits are frequently used as a surgical palliative treatment for a variety of congenital heart diseases in infants and children. Due to the growth of the infant or child, or complications like kinking or thrombosis of the device, these conduits require replacement which may involve several major open heart surgery before adulthood. We propose to utilize 3D printing to design and develop a novel RV-PA conduit that increases its size via tailored self-unfolding triggered by flow and time so that fewer complications as well as surgeries are required to maintain and develop normal pulmonary blood flow from infancy to adulthood. It is envisioned that 3D printing will also allow for improved precision in patient customization and on-demand design changes to enable better functionality. We anticipate that self- unfolding mechanisms and associated shape changes will result in operation of the conduits over longer periods of infant and child growth into adulthood. In the R21 phase, we will design, fabrication, surface modification, and in-vitro testing of self-unfolding RV- PA conduits. We will first conduct printing parameter studies for 3D printing of FDA-approved materials for fabrication of RV-PA conduits with variable dimensions. Simultaneously, we will utilize numerical simulations to determine design parameters that allow size changes and validate these using in-vitro tests for functionality and biocompatibility. In the R33 phase, we will upgrade our 3D printer and refine the RV-PA conduits to enable printing with better resolution and with fluoropolymer inks to eliminate the need for surface modification. Finally, we will validate in- vivo operation using comprehensive hemodynamic evaluations and post-mortem gross-histological evaluation in a sheep model. We will analyze extracellular matrix formation, characterize endothelial cell function and white blood cell activation, and quantify immunohistochemistry for inflammation analysis. We anticipate that these studies will enable a new class of RV-PA conduits as well as serve as a model for designing patient-specific shape changing biomedical implants for infants that are capable of growing at the same rate to reduce the number of follow up operations.