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

先天性心脏病(CHD)是与先天性畸形相关的主要死亡原因。 尽管在冠心病的外科治疗方面取得了重大进展，但发病率和 死亡率源于对不同解剖结构的手术的复杂性。此前的研究表明， 对于手术中狭窄或发育不良的血管，理想的重建设计对于减少 能量损失和移植物内部不受欢迎的流动。然而，外科医生对流动动力学和 术中重建入路的血流动力学数据，因为手术野需要 不流血。因此，在手术前确保针对患者的移植物设计是理想的重建路径 均衡的流量分配和最小的能量损失可能会对患者的健康和 生活质量。 该提案的目标是展示我们在3D方面的最新进展的综合方法 成像、3D打印和组织工程技术可以创造出手术前设计的患者- 随着时间的推移，特定的血管移植物可以促进最佳新生血管的形成。我们有 FDA展示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的PGA/PCLA生物材料。基于这些经验，我们有 开发3D打印金属芯棒与纳米纤维电纺相结合的新型3D打印技术 技术通过这种3D打印技术，我们展示了直管状TEVG开发的本地化 就像绵羊模型中的Neovessel队形。在下一步，我们的目标是开发复杂形状的TEVG 这可以应用于具有复杂解剖结构的真实患者。我们假设患者特有的TEVG 由纳米纤维制成的PGA/PCLA采用我们的3D打印技术，可以使用CAD进行设计，并预置 手术影像和血流动力学数据，并显示随着生长适当的肿瘤组织形成 随着时间的推移。为此，在R21阶段，1)我们将优化针对患者的3D打印血管移植物的创建 和体外测试以及2)我们将确定术前设计的估计流动动力学分析是否可以 采用短期活体模型，与实际3D打印移植物的性能相匹配。在R33阶段，我们将 确定术前设计的估计血流动力学是否可以在术后生长的肿瘤组织中保留 采用长期动物模型观察移植物的降解情况。 该项目将是向临床应用患者专用血管移植物迈出的重要一步 概括了土生土长的解剖和机械性能。这项工作的成果将产生更广泛的影响 用于植入的其他更复杂的心血管结构的设计和制造。这一范式 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.