Biocompatibility Assessment of a New Biodegradable Vascular Graft via In Vitro Co-culture Approaches and In Vivo Model

Enayati, Marjan; Eilenberg, Magdalena; Grasl, Christian; Riedl, P.; Kaun, Christoph; Meßner, Barbara; Walter, Ingrid; Liska, Robert; Schima, Heinrich; Wojta, Johann; Podesser, Bruno K.; Bergmeister, Helga

doi:10.1007/s10439-016-1601-y

Cited by 21 publications

(15 citation statements)

References 22 publications

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“… 170 Enayati et al highlighted the potential of a fibroblast-macrophage coculture model to increase the predictive value of in vitro models. 174 Adding physiological complexity, bioengineered vascular tissues may serve as suitable in vitro models, as recently reviewed by Wolf et al 175…”

Section: Current Challengesmentioning

confidence: 99%

Biomaterial-driven in situ cardiovascular tissue engineering—a multi-disciplinary perspective

et al. 2017

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There is a persistent and growing clinical need for readily-available substitutes for heart valves and small-diameter blood vessels. In situ tissue engineering is emerging as a disruptive new technology, providing ready-to-use biodegradable, cell-free constructs which are designed to induce regeneration upon implantation, directly in the functional site. The induced regenerative process hinges around the host response to the implanted biomaterial and the interplay between immune cells, stem/progenitor cell and tissue cells in the microenvironment provided by the scaffold in the hemodynamic environment. Recapitulating the complex tissue microstructure and function of cardiovascular tissues is a highly challenging target. Therein the scaffold plays an instructive role, providing the microenvironment that attracts and harbors host cells, modulating the inflammatory response, and acting as a temporal roadmap for new tissue to be formed. Moreover, the biomechanical loads imposed by the hemodynamic environment play a pivotal role. Here, we provide a multidisciplinary view on in situ cardiovascular tissue engineering using synthetic scaffolds; starting from the state-of-the art, the principles of the biomaterial-driven host response and wound healing and the cellular players involved, toward the impact of the biomechanical, physical, and biochemical microenvironmental cues that are given by the scaffold design. To conclude, we pinpoint and further address the main current challenges for in situ cardiovascular regeneration, namely the achievement of tissue homeostasis, the development of predictive models for long-term performances of the implanted grafts, and the necessity for stratification for successful clinical translation.

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Section: Current Challengesmentioning

confidence: 99%

Biomaterial-driven in situ cardiovascular tissue engineering—a multi-disciplinary perspective

et al. 2017

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“…A pre-polymer method was used to synthesise the thermoplastic polyurethane polymer. 11,12 In contrast to the previously described polymers, the dPCU in this study was based on poly (hexamethylene carbonate), hexamethylene diisocyanate (HMDI), and bis(3-hydroxypropyl) carbonate. An average molecular weight of 860 Da for poly (hexamethylene carbonate) (which corresponds to a typical chain length in thermoplastic polyurethanes) and a molar ratio of the above mentioned components of 1:2:1 resulted in a good trade off between tensile strength and toughness of the material.…”

Section: Materials and Biomechanical Testingmentioning

confidence: 99%

“…Macrophages were isolated from adult male Spraguee Dawley rats (350e400 g, Centre for Biomedical Research, Vienna, Austria) by a peritoneal lavage technique as described elsewhere. 12 Isolated macrophages at a density of 2 Â 10 5 cells/well (24 well plate) were seeded on the luminal side of the grafts (10 mm* 1.8 mm) and incubated for one, three, seven, and 21 days. All experiments were repeated independently three times (n ¼ 3 per time point).…”

Section: In Vitro Evaluation By Macrophage Markers and Inflammatory Cytokinesmentioning

confidence: 99%

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Long Term Evaluation of Nanofibrous, Bioabsorbable Polycarbonate Urethane Grafts for Small Diameter Vessel Replacement in Rodents

Eilenberg

Enayati

Ehebruster

et al. 2020

European Journal of Vascular and Endovascular Surgery

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WHAT THIS PAPER ADDSThis study provides long term results of a novel, degradable, small diameter vascular graft in a rat model. The Degradable polycarbonate urethane (dPCU) exhibits appropriate biomechanical properties and improved biocompatibility with reduced secondary inflammation. dPCU conduits promoted rapid complete endothelialisation, increased and sustained transmural cellular ingrowth, proliferation of cells and microvessel formation with minimal inflammatory response.Objective: Biodegradable materials for in situ vascular tissue engineering could meet the increasing clinical demand for sufficient synthetic small diameter vascular substitutes in aortocoronary bypass and peripheral vascular surgery. The aim of this study was to design a new degradable thermoplastic polycarbonate urethane (dPCU) with improved biocompatibility and optimal biomechanical properties. Electrospun conduits made from dPCU were evaluated in short and long term follow up and compared with expanded polytetrafluoroethylene (ePTFE) controls. Methods: Both conduits were investigated prior to implantation to assess their biocompatibility and inflammatory potential via real time polymerase chain reaction using a macrophage culture. dPCU grafts (n ¼ 28) and ePTFE controls (n ¼ 28) were then implanted into the infrarenal abdominal aorta of Spraguee Dawley rats. After seven days, one, six, and 12 months, grafts were analysed by histology and immunohistochemistry (IHC) and assessed biomechanically. Results: Anti-inflammatory signalling was upregulated in dPCU conduits and increased significantly over time in vitro. dPCU and ePTFE grafts offered excellent long and short term patency rates (92.9% in both groups at 12 months) in the rat model without dilatation or aneurysm formation. In comparison to ePTFE, dPCU grafts showed transmural ingrowth of vascular specific cells resulting in a structured neovessel formation around the graft. The graft material was slowly reduced, while the compliance of the neovessel increased over time. Conclusion:The newly designed dPCU grafts have the potential to be safely applied for in situ vascular tissue engineering applications. The degradable substitutes showed good in vivo performance and revealed desirable characteristics such as biomechanical stability, non-thrombogenicity, and minimal inflammatory response after long term implantation.

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“…In addition, surface modification with bioactive molecules, such as SDF‐1 or heparin, is another alternative strategy to generate nonthrombogenic grafts. Several vascular scaffolds have demonstrated promise for clinical application by in vitro studies or short‐term in vivo studies (less than six months) . But some important challenges remain to be addressed before these materials can be used routinely for patient care, especially the potential adverse long‐term effects.…”

Section: Introductionmentioning

confidence: 99%

The regeneration of macro‐porous electrospun poly(ɛ‐caprolactone) vascular graft during long‐termin situimplantation

Qin

Wang

et al. 2017

J Biomed Mater Res

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Long-term evaluation of vascular grafts is an essential step to facilitate clinical translation. In this study, we investigate the long-term performance of a macro-porous poly(ɛ-caprolactone) (PCL) electrospun vascular graft using the rat abdominal artery replacement model. Long-term patency, endothelialization, and smooth muscle cell regeneration were evaluated, as well as calcification and degradation. The data showed that all the grafts remained open and unobstructed. There was no evidence of aneurysm, stenosis, or calcification one year after implantation. Importantly, neo-vessel was regenerated on the luminal surface of the graft, and was composed of a complete endothelial layer and several layers of smooth muscle cells. The neo-vessel showed vascular physiological function, although not as good as that in native blood vessels, likely due to the remaining scaffold fibers. These data indicated that the PCL macro-porous electrospun vascular graft has potential to be an artery substitute for long-term implantation. Also, this work indicates that continued efforts are needed to develop advanced vascular grafts that exhibit the appropriate balance between the regeneration of the neo-vessel and the complete degradation of the graft materials. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1618-1627, 2018.

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Biocompatibility Assessment of a New Biodegradable Vascular Graft via In Vitro Co-culture Approaches and In Vivo Model

Cited by 21 publications

References 22 publications

Biomaterial-driven in situ cardiovascular tissue engineering—a multi-disciplinary perspective

Biomaterial-driven in situ cardiovascular tissue engineering—a multi-disciplinary perspective

Long Term Evaluation of Nanofibrous, Bioabsorbable Polycarbonate Urethane Grafts for Small Diameter Vessel Replacement in Rodents

The regeneration of macro‐porous electrospun poly(ɛ‐caprolactone) vascular graft during long‐termin situimplantation

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