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Assessment of a long-term in vitro model to characterize the mechanical behavior and macrophage-mediated degradation of a novel, degradable, electrospun poly-urethane vascular graft.
Journal of the Mechanical Behavior of Biomedical Materials ( IF 3.9 ) Pub Date : 2020-09-03 , DOI: 10.1016/j.jmbbm.2020.104077
Marjan Enayati 1 , Sarah Puchhammer 2 , Jagoba Iturri 3 , Christian Grasl 4 , Christoph Kaun 5 , Stefan Baudis 6 , Ingrid Walter 7 , Heinrich Schima 4 , Robert Liska 6 , Johann Wojta 8 , José Luis Toca-Herrera 3 , Bruno K Podesser 1 , Helga Bergmeister 1
Affiliation  

An assessment tool to evaluate the degradation of biodegradable materials in a more physiological environment is still needed. Macrophages are critical players in host response, remodeling and degradation. In this study, a cell culture model using monocyte-derived primary macrophages was established to study the degradation, macro-/micro-mechanical behavior and inflammatory behavior of a new designed, biodegradable thermoplastic polyurethane (TPU) scaffold, over an extended period of time in vitro. For in vivo study, the scaffolds were implanted subcutaneously in a rat model for up to 36 weeks. TPU scaffolds were fabricated via the electrospinning method. This technique provided a fibrous scaffold with an average fiber diameter of 1.39 ± 0.76 μm and an average pore size of 7.5 ± 1.1 μm. The results showed that TPU scaffolds supported the attachment and migration of macrophages throughout the three-dimensional matrix. Scaffold degradation could be detected in localized areas, emphasizing the role of adherent macrophages in scaffold degradation. Weight loss, molecular weight and biomechanical strength reduction were evident in the presence of the primary macrophage cells. TPU favored the switch from initial pro-inflammatory response of macrophages to an anti-inflammatory response over time both in vitro and in vivo. Expression of MMP-2 and MMP-9 (the key enzymes in tissue remodeling based on ECM modifications) was also evident in vitro and in vivo. This study showed that the primary monocyte-derived cell culture model represents a promising tool to characterize the degradation, mechanical behavior as well as biocompatibility of the scaffolds during an extended period of observation.



中文翻译:

评估一个长期的体外模型,以表征新型,可降解的电纺聚氨基甲酸乙酯血管移植物的力学行为和巨噬细胞介导的降解。

仍然需要一种评估工具来评估可生物降解材料在更生理环境中的降解。巨噬细胞是宿主反应,重塑和降解的关键因素。在这项研究中,建立了使用单核细胞衍生的初级巨噬细胞的细胞培养模型,以研究新型,可生物降解的热塑性聚氨酯(TPU)支架在较长时间内的降解,宏观/微观力学行为和炎症行为。体外。对于体内在这项研究中,将支架皮下植入大鼠模型长达36周。TPU支架是通过静电纺丝法制造的。该技术提供了一种纤维支架,其平均纤维直径为1.39±0.76μm,平均孔径为7.5±1.1μm。结果表明,TPU支架在整个三维矩阵中支持巨噬细胞的附着和迁移。可以在局部区域检测到支架降解,强调粘附的巨噬细胞在支架降解中的作用。在存在初级巨噬细胞的情况下,体重减轻,分子量降低和生物力学强度降低是明显的。TPU青睐来自巨噬细胞的初始促炎性响应的开关在两个时间抗炎应答在体外体内。MMP-2和MMP-9(基于ECM修饰的组织重塑中的关键酶)的表达在体外体内也很明显。这项研究表明,原代单核细胞衍生的细胞培养模型代表了一种有前途的工具,可用于表征在延长的观察期内支架的降解,机械行为以及生物相容性。

更新日期:2020-09-14
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