Inconsistency in Graft Outcome of Bilayered Bioresorbable Supramolecular Arterial Scaffolds in Rats
Inconsistency in Graft Outcome of Bilayered Bioresorbable Supramolecular Arterial Scaffolds in Rats
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DOI：
10.1089/ten.tea.2020.0185
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发表时间：
2020-10-05
影响因子：
4.1
通讯作者：
Bouten, Carlijn V. C.
中科院分区：
文献类型：
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作者：
Duijvelshoff, Renee;di Luca, Andrea;Bouten, Carlijn V. C.
人们一直在寻找理想的生物可吸收材料来开发原位血管组织工程的支架。由于这些支架在从支架到新组织的整个转化过程中都处于恶劣的血流动力学环境中，因此始终保持其机械完整性和稳定性至关重要。采用双静电纺丝法制备了超分子聚碳酸酯-酯-双尿素双层支架。这些支架含有多孔的内层，允许细胞渗透，致密的外层提供强度。将21个支架置入雄性Lewis大鼠腹主动脉，分别于1、3、5个月体外移植，评估支架吸收后的机械功能和新组织形成情况。结果显示，尽管实验组和支架生产具有同质性，但移植物的结果却相互矛盾。大多数移植物表现出不良的重塑，导致动脉瘤扩张和钙化。然而，少数移植物没有表现出这些特征，而是在缺乏内皮的情况下表现出移植物延伸和平滑肌细胞增殖的特征，而在整个研究中都保持着专利。我们的结论是，在体内预测移植物的发育和性能仍然是非常困难的。除了合理的机械设计和良好的体外性能外，深入了解支架驱动动脉再生的机械生物学机制以及外科手术的潜在影响是进一步优化支架设计的必要条件。仔细分析临床前成功和失败之间的差异，正如本研究所做的那样，可能为支架优化和标准化手术程序提供初步处理，以提高移植物在体内的性能。在这种情况下，血管组织工程研究了使用无细胞生物可吸收支架作为在体内培养小口径动脉的现成选择。在这项研究中，我们开发了一种双层电纺丝超分子支架，外层致密，提供机械完整性，内层多孔，用于细胞招募和组织形成。尽管支架在体外具有相同的性能和机械性能，但作为大鼠主动脉间置移植物的体内试验显示出不同的移植物结果，从动脉瘤到功能动脉不等。对这种变异性的仔细分析，为支架设计和植入过程相关的材料驱动的原位动脉形成提供了有价值的见解。
There is a continuous search for the ideal bioresorbable material to develop scaffolds forin situvascular tissue engineering. As these scaffolds are exposed to the harsh hemodynamic environment during the entire transformation process from scaffold to neotissue, it is of crucial importance to maintain mechanical integrity and stability at all times. Bilayered scaffolds made of supramolecular polycarbonate-ester-bisurea were manufactured using dual electrospinning. These scaffolds contained a porous inner layer to allow for cellular infiltration and a dense outer layer to provide strength. Scaffolds (n = 21) were implanted as an interposition graft into the abdominal aorta of male Lewis rats and explanted after 1, 3, and 5 monthsin vivoto assess mechanical functionality and neotissue formation upon scaffold resorption. Results demonstrated conflicting graft outcomes despite homogeneity in the experimental group and scaffold production. Most grafts exhibited adverse remodeling, resulting in aneurysmal dilatation and calcification. However, a few grafts did not demonstrate such features, but instead were characterized by graft extension and smooth muscle cell proliferation in the absence of endothelium, while remaining patent throughout the study. We conclude that it remains extremely difficult to anticipate graft development and performancein vivo. Next to rational mechanical design and good performancein vitro, a thorough understanding of the mechanobiological mechanisms governing scaffold-driven arterial regeneration as well as potential influences of surgical procedures is warranted to further optimize scaffold designs. Careful analysis of the differences between preclinical successes and failures, as is done in this study, may provide initial handles for scaffold optimization and standardized surgical procedures to improve graft performancein vivo. Impact statement In situvascular tissue engineering using cell-free bioresorbable scaffolds is investigated as an off-the-shelf option to grow small caliber arteries inside the body. In this study, we developed a bilayered electrospun supramolecular scaffold with a dense outer layer to provide mechanical integrity and a porous inner layer for cell recruitment and tissue formation. Despite homogenous scaffold properties and mechanical performancein vitro,in vivotesting as rat aorta interposition grafts revealed distinct graft outcomes, ranging from aneurysms to functional arteries. Careful analysis of this variability provided valuable insights into materials-drivenin situartery formation relevant for scaffold design and implantation procedures.