Influence of different pressure regimes on the properties of an engineered small-diameter vascular scaffold tested in a custom-made bioreactor.

Pier Francesco Ferrari, Giulia De Negri Atanasio, Jan Oscar Pralits, Donatella Di Lisa, Laura Pastorino, Domenico Palombo, Patrizia Perego
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Abstract

Vascular tissue engineering endeavors to design, fabricate, and validate biodegradable and bioabsorbable small-diameter vascular scaffolds engineered with bioactive molecules, capable of meeting the challenges posed by commercial vascular prostheses. A comprehensive investigation of these engineered scaffolds in a bioreactor (BR) is deemed essential as a prerequisite before anyin vivoexperimentation in order to gather information regarding their behavior under physiological conditions and predict the biological activities they may exhibit. This study focuses on an innovative electrospun scaffold made of poly(caprolactone) and poly(glycerol sebacate), integrating quercetin (Q), which is able to modulate inflammation, and gelatin (G), which is necessary to reduce permeability. A custom-made BR was used to assess the performance of the scaffolds maintained under different pressure regimes, covering the human physiological pressure range. As a result, the 3D microfibrous architecture of the scaffolds was notably influenced by the release of bioactive molecules, while retaining the properties required forin vivoregeneration. Furthermore, the scaffolds exhibited mechanical properties comparable to those of native human arteries. The release of Q was effective in counteracting post-surgical inflammation, whereas the amount of released G was adequate to avoid blood leakage and useful to make the material porous during the testing period. This study showcases the successful validation of an engineered scaffold in a BR, supporting its potential as a promising candidate for vascular substitutes inin vivoapplications. Our approach represents a significant leap forward in the field of vascular tissue engineering, offering a multifaceted solution to the complex challenges associated with small-diameter vascular prostheses.

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在定制生物反应器中测试不同压力机制对工程小直径血管支架特性的影响。
血管组织工程学致力于设计、制造和验证生物可降解和生物可吸收的小直径血管支架,这些支架采用生物活性分子设计,能够应对商用血管假体带来的挑战。在进行任何体内实验之前,必须先在生物反应器中对这些工程支架进行全面研究,以便获得它们在生理条件下的行为信息,并预测它们将具有的生物活性。本研究的重点是一种由聚(己内酯)和聚(甘油癸二酸酯)制成的创新型电纺支架,其中集成了可调节炎症的槲皮素和降低渗透性所需的明胶。使用定制的生物反应器评估了支架在不同压力下的性能,压力范围涵盖人体生理压力。结果显示,三维微纤维结构受到生物活性物质释放的显著影响,保持了体内再生所需的适当特性,支架显示出与人体原生动脉相似的机械特性。明胶的释放足以避免血液渗漏,并有助于在测试期间使材料多孔化,而槲皮素的释放量则有助于对抗手术后的炎症。这项研究展示了工程支架在生物反应器中的成功验证,使我们能够考虑将其作为体内应用的血管替代物。我们的方法代表了血管组织工程领域的重大飞跃,为解决与小直径血管假体相关的复杂挑战提供了多方面的解决方案。
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