Kimicata Megan, Allbritton-King Jules D, Navarro Javier, Santoro Marco, Inoue Takahiro, Hibino Narutoshi, Fisher John P
Department of Materials Science and Engineering, University of Maryland, 3121 A. James Clark Hall, College Park, MD 20742, United States; Center for Engineering Complex Tissues, University of Maryland, 3121 A. James Clark Hall, College Park, MD 20742, United States.
Center for Engineering Complex Tissues, University of Maryland, 3121 A. James Clark Hall, College Park, MD 20742, United States; Fischell Department of Bioengineering, University of Maryland, 3121 A. James Clark Hall, College Park, MD 20742, United States.
Acta Biomater. 2020 Jul 1;110:68-81. doi: 10.1016/j.actbio.2020.04.013. Epub 2020 Apr 16.
Autologous grafts are the current gold standard of care for coronary artery bypass graft surgeries, but are limited by availability and plagued by high failure rates. Similarly, tissue engineering approaches to small diameter vascular grafts using naturally derived and synthetic materials fall short, largely due to inappropriate mechanical properties. Alternatively, decellularized extracellular matrix from tissue is biocompatible and has comparable strength to vessels, while poly(propylene fumarate) (PPF) has shown promising results for vascular grafts. This study investigates the integration of decellularized pericardial extracellular matrix (dECM) and PPF to create a biohybrid scaffold (dECM+PPF) suitable for use as a small diameter vascular graft. Our method to decellularize the ECM was efficient at removing DNA content and donor variability, while preserving protein composition. PPF was characterized and added to dECM, where it acted to preserve dECM against degradative effects of collagenase without disturbing the material's overall mechanics. A transport study showed that diffusion occurs across dECM+PPF without any effect from collagenase. The modulus of dECM+PPF matched that of human coronary arteries and saphenous veins. dECM+PPF demonstrated ample circumferential stress, burst pressure, and suture retention strength to survive in vivo. An in vivo study showed re-endothelialization and tissue growth. Overall, the dECM+PPF biohybrid presents a robust solution to overcome the limitations of the current methods of treatment for small diameter vascular grafts. STATEMENT OF SIGNIFICANCE: In creating a dECM+PPF biohybrid graft, we have observed phenomena that will have a lasting impact within the scientific community. First, we found that we can reduce donor variability through decellularization, a unique use of the decellularization process. Additionally, we coupled a natural material with a synthetic polymer to capitalize on the benefits of each: the cues provided to cells and the ability to easily tune material properties, respectively. This principle can be applied to other materials in a variety of applications. Finally, we created an off-the-shelf alternative to autologous grafts with a newly developed material that has yet to be utilized in any scaffolds. Furthermore, bovine pericardium has not been investigated as a small diameter vascular graft.
自体移植物是目前冠状动脉搭桥手术护理的金标准，但受到可用性的限制且失败率高。同样，使用天然来源和合成材料制造小直径血管移植物的组织工程方法也存在不足，这主要是由于机械性能不合适。另外，来自组织的脱细胞细胞外基质具有生物相容性，并且与血管具有相当的强度，而聚富马酸丙二醇酯（PPF）已在血管移植物方面显示出有前景的结果。本研究调查了脱细胞心包细胞外基质（dECM）与PPF的整合，以创建一种适用于小直径血管移植物的生物杂交支架（dECM + PPF）。我们的脱细胞细胞外基质方法在去除DNA含量和供体变异性方面很有效，同时保留了蛋白质组成。对PPF进行了表征并添加到dECM中，它起到保护dECM免受胶原酶降解作用的影响，同时不干扰材料的整体力学性能。一项传输研究表明，扩散可通过dECM + PPF发生，且不受胶原酶的任何影响。dECM + PPF的模量与人冠状动脉和大隐静脉的模量相匹配。dECM + PPF表现出足够的周向应力、爆破压力和缝线保留强度，能够在体内存活。一项体内研究显示有再内皮化和组织生长。总体而言，dECM + PPF生物杂交物为克服当前小直径血管移植物治疗方法的局限性提供了一种强大的解决方案。重要性声明：在创建dECM + PPF生物杂交移植物时，我们观察到了一些将在科学界产生持久影响的现象。首先，我们发现可以通过脱细胞来减少供体变异性，这是脱细胞过程的一种独特应用。此外，我们将天然材料与合成聚合物结合，以利用各自的优势：分别为细胞提供的信号以及轻松调节材料性能的能力。这一原理可应用于各种应用中的其他材料。最后，我们用一种新开发的材料创建了一种现成的自体移植物替代品，该材料尚未在任何支架中使用。此外，牛心包尚未作为小直径血管移植物进行研究。
