Galván Nhu Thao N, Paulsen Samantha J, Kinstlinger Ian S, Marini Juan C, Didelija Inka C, Yoeli Dor, Grigoryan Bagrat, Miller Jordan S
Department of Surgery, Baylor College of Medicine, Houston, TX, United States.
Department of Bioengineering, Rice University, Houston, TX, United States.
Front Cardiovasc Med. 2021 Jun 7;8:629313. doi: 10.3389/fcvm.2021.629313. eCollection 2021.
Recently developed biofabrication technologies are enabling the production of three-dimensional engineered tissues containing vascular networks which can deliver oxygen and nutrients across large tissue volumes. Tissues at this scale show promise for eventual regenerative medicine applications; however, the implantation and integration of these constructs remains poorly studied. Here, we introduce a surgical model for implantation and direct in-line vascular connection of 3D printed hydrogels in a porcine arteriovenous shunt configuration. Utilizing perfusable poly(ethylene glycol) diacrylate (PEGDA) hydrogels fabricated through projection stereolithography, we first optimized the implantation procedure in deceased piglets. Subsequently, we utilized the arteriovenous shunt model to evaluate blood flow through implanted PEGDA hydrogels in non-survivable studies. Connections between the host femoral artery and vein were robust and the patterned vascular channels withstood arterial pressure, permitting blood flow for 6 h. Our study demonstrates rapid prototyping of a biocompatible and perfusable hydrogel that can be implanted as a porcine arteriovenous shunt, suggesting a viable surgical approach for in-line implantation of bioprinted tissues, along with design considerations for future studies. We further envision that this surgical model may be broadly applicable for assessing whether biomaterials optimized for 3D printing and cell function can also withstand vascular cannulation and arterial blood pressure. This provides a crucial step toward generated transplantable engineered organs, demonstrating successful implantation of engineered tissues within host vasculature.
最近开发的生物制造技术能够生产包含血管网络的三维工程组织,这些血管网络可以在大体积组织中输送氧气和营养物质。这种规模的组织显示出在最终再生医学应用中的潜力;然而,这些构建体的植入和整合仍未得到充分研究。在这里,我们介绍一种手术模型,用于在猪动静脉分流配置中植入3D打印水凝胶并进行直接的在线血管连接。利用通过投影立体光刻制造的可灌注聚(乙二醇)二丙烯酸酯(PEGDA)水凝胶,我们首先在死亡仔猪中优化了植入程序。随后,我们利用动静脉分流模型在不可存活的研究中评估通过植入的PEGDA水凝胶的血流。宿主股动脉和静脉之间的连接牢固,有图案的血管通道能够承受动脉压力,允许血流持续6小时。我们的研究展示了一种生物相容性和可灌注水凝胶的快速原型制作,该水凝胶可以作为猪动静脉分流进行植入,这表明了一种可行的手术方法用于生物打印组织的在线植入,以及未来研究的设计考虑因素。我们进一步设想,这种手术模型可能广泛适用于评估为3D打印和细胞功能优化的生物材料是否也能承受血管插管和动脉血压。这为生成可移植的工程器官迈出了关键一步,证明了工程组织在宿主脉管系统内的成功植入。