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. (December 2020)

• Record Type: Journal Article
• Authors: Enayati, Marjan; Puchhammer, Sarah; Iturri, Jagoba; Grasl, Christian; Kaun, Christoph; Baudis, Stefan; Walter, Ingrid; Schima, Heinrich; Liska, Robert; Wojta, Johann; Toca-Herrera, José Luis; Podesser, Bruno K.; Bergmeister, Helga
• Is Part Of: Journal of the mechanical behavior of biomedical materials. Volume 112(2020)
• Publication Date: 2020-12
• Subjects: Biodegradation -- Mechanical stability -- Macrophages -- Thermoplastic polyurethane -- Cell culture -- Rat model; Biomedical materials -- Periodicals; Biomedical materials -- Mechanical properties -- Periodicals; Biomedical materials; Biomedical materials -- Mechanical properties; Periodicals; Electronic journals; 610.28
• DOI: 10.1016/j.jmbbm.2020.104077
• Languages: English
• ISSNs: 1751-6161

Abstract

Abstract: 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. Graphical abstract: Image 1 Highlights: Macrophages affect degradation & mechanical behavior of TPU in-vitro & in-vivo. Macrophages accelerate molecular weight reduction and creation of surface defects. AFM could not detect significant changes in modulus elasticity at micro level. Polarization of M1 pro-inflammatory to M2 anti-inflammatory macrophages occurred. Immunomodulatory behavior favors resolution of inflammation & initiates remodeling.