AUTOMATED PROCESS FOR A TISSUE ENGINEERED BLOOD VESSEL

自1970年以来，冠心病的死亡率急剧下降，部分原因是积极的介入技术如冠状动脉旁路移植术（CABG）的成功。然而，由于CABG的通畅率在10年后急剧下降，许多患者需要二次手术。 由于之前的采集或外周血管疾病进展，可能无法获得合适的自体（自身）血管。由于合成移植物尚未成功用于冠状动脉重建，因此对于缺乏自体血管的CABG候选人没有临床替代方案。保守估计，每年有5万美国人死于缺乏合适的移植材料。最近，我们报道了一种从小的皮肤活检中产生功能性血管的技术。这些人体组织工程血管（TEBV）是完全自体的，完全生物的，能够承受20倍的生理血压。血管可缝合，并已成功植入动物体内。本研究计划的目的是加快临床相关TEBV（长度20 cm，直径4-6 mm）的商业可用性。 具体来说，我们将开发一种生物反应器，以自动化制造过程中的关键步骤。 将检查TEBV的组织学和机械性能，以优化和验证该过程。拟议的商业应用：最初的目标市场是没有合适的移植物供体部位和无法用PCTA或支架治疗的狭窄的危重CABG患者。 保守估计，美国市场目前每年有5万名候选患者，并呈指数级增长。TEBV还可以满足外周循环中对用于旁路的小直径血管的迫切临床需求。 用于该项目的基于片材的技术可以为其他组织工程应用提供平台，包括用于透析的A-V分流器、肌腱、韧带、心脏瓣膜和具有内置毛细血管网络的三维组织。

Since 1970, the death rate for coronary heart disease has declined dramatically, due in part to the success of aggressive interventional techniques such as coronary arterial bypass graft (CABG). However, since patency rates for CABG decrease dramatically after 10 years, many patients require a secondary procedure. Due to previous harvest or peripheral vascular disease progression, suitable autologous (self) vessels may not be available. Since synthetic grafts have not been used successfully for coronary- arterial reconstruction, there is no clinical alternative for CABG candidates lacking autologous vessels. Conservative estimates suggest 50,000 Americans die annually due to the lack of suitable graft material. Recently, we have reported a technique to produce functional blood vessels from a small skin biopsy. These human tissue engineered blood vessels (TEBVs) are fully autologous, fully biological, and capable of withstanding 20-fold physiological blood pressure. The vessels are suturable and have been implanted successfully in animals. The objective of this research plan is to expedite the commercial availability of clinically relevant TEBVs (20 cm in length and 4-6 mm in diameter). Specifically, we will develop a bioreactor to automate critical steps in the fabrication process. Histological and mechanical properties of the TEBVs will be examined to optimize and validate this process. PROPOSED COMMERCIAL APPLICATIONS: The initial target market is critical CABG patients with no suitable graft donor sites and stenoses untreatable with PCTA or stents. Conservative estimates suggest the U.S. market is currently 50,000 candidate patients per year and growing exponentially. TEBVs may also fulfill the imperative clinical need for small diameter vessels for bypass in the peripheral circulation. The sheet based technology used for this project may provide a platform for other tissue engineering applications, including A-V shunts for dialysis, tendons, ligaments, heart valves, and three dimensional tissues with a built in capillary network.