Patient Specific Tissue Engineered Vascular Graft Creation Using 3D Printing Technology

先天性心脏病（CHD）是与先天性异常相关的死亡的主要原因。 尽管冠心病的外科治疗取得了显著进展，但一个重要的发病率来源， 死亡率是由于不同解剖结构的外科手术的复杂性引起的。先前的研究表明， 手术中狭窄或发育不良血管重建的理想设计对于减少 能量损失和移植物内的不希望的流动。然而，外科医生没有流动动力学的信息， 手术过程中重建路径的血液动力学数据，因为手术野需要 不流血因此，在手术前确保患者特定的移植物设计以获得理想的重建路径， 平衡的流量分布和最小的能量损失可以为患者健康带来长期的益处， 生活质量 本提案的目标是展示我们在3D方面最新进展的综合方法 成像，3D打印和组织工程技术可以创建手术前设计的患者， 特异性血管移植物，其可以随着时间的推移促进最佳新血管形成和生长。我们有 使用FDA证明了组织工程血管移植物（TEVG）的天然血管样新组织形成 在小型和大型动物研究中批准PGA/PCLA生物材料。根据这些经验，我们 开发了一种新型3D打印技术，将3D打印金属芯轴与静电纺丝相结合 技术.通过这种3D打印技术，我们展示了直导管形TEVG的天然发展， 比如绵羊模型中的新血管形成。对于下一步，我们的目标是开发具有复杂形状的TEVG 可以应用于具有复杂解剖结构的真实的患者。我们假设患者特异性TEVG 使用我们的3D打印技术由PGA/PCLA制成，可以使用CAD设计， 手术成像和血流动力学数据，并证明适当的新组织形成与生长 随着时间为此，在R21阶段，1）我们将优化3D打印血管移植物的患者特异性创建 2）我们将确定术前设计的估计流动动力学分析是否可以 与使用短期体内模型的实际3D打印移植物的性能相匹配。在R33阶段， 确定术前设计的估计血流动力学是否可以在术后生长的新组织中保留 使用长期动物模型观察移植物的降解。 该项目将是患者特异性血管移植物临床应用的重要一步， 再现了天然解剖结构和机械性能。这项工作的成果将产生更广泛的影响 设计和制造其他更复杂的心血管植入结构。这种范式 血管移植技术的转变将提高儿科患者护理的质量和安全性。

Congenital heart disease (CHD) is the leading cause of death associated with congenital anomalies. Despite significant advances in surgical management for CHD, one significant source of morbidity and mortality arises from the complexity of surgery for the diverse anatomies. Previous studies demonstrated that the ideal design of reconstruction for stenosis or hypoplastic vessels during surgery is important to reduce energy loss and undesirable flow inside of graft. However, surgeons have no information of flow dynamics and hemodynamics data of the reconstructed route during procedure because the surgical field needs to be bloodless. Therefore, ensuring a patient-specific graft design for ideal reconstructed route before surgery with a balanced flow distribution and minimum energy loss may yield long-term benefits for patient health and quality of life. The goal of this proposal is to demonstrate our integrated approach of recent progress in 3D imaging, 3D printing, and tissue engineering technology can create pre-surgically designed patient- specific vascular graft that can promote optimal neovessel formation with growth over time. We have demonstrated native vessel like neotissue formation of tissue engineered vascular graft (TEVG) using FDA approved biomaterials of PGA/PCLA in small and large animal studies. Based on these experiences, we have developed novel 3D printing technology combining 3D printed metal mandrels with nanofiber electrospun technology. With this 3D printing technology, we showed that straight conduit shaped TEVG developed native like neovessel formation in a sheep model. For this next step, we aim to develop TEVG with complex shapes that can be applied to real patients with complex anatomy. We hypothesized that patient-specific TEVG made of nanofiber PGA/PCLA using our 3D printing technology can be designed using CAD with pre- operative imaging and flow dynamics data, and demonstrate proper neotissue formation with growth over time. To this end, in R21 phase, 1) we will optimize patient-specific creation of 3D printed vascular grafts and test In-vitro and 2) We will determine if the estimated flow dynamics analysis of pre-operative design can match with the performance of actual 3D printed grafts using short-term in vivo model. In R33 phase, we will determine if the estimated flow dynamics of pre-operative design can be preserved in growing neotissue after degradation of graft using long-term animal model. This project will be an important step towards clinical application of patient-specific vascular grafts that recapitulate the native anatomy and mechanical properties. The results of this work will have a broader impact on the design and fabrication of other more complex cardiovascular structures for implantation. This paradigm shift in vascular graft technology will improve the quality and safety of pediatric patient care.