Biocompatibility Assessment of a New Biodegradable Vascular Graft via In Vitro Co-culture Approaches and In Vivo Model (original) (raw)
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Journal of the Mechanical Behavior of Biomedical Materials, 2020
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.
Biodegradable, thermoplastic polyurethane grafts for small diameter vascular replacements
Acta Biomaterialia, 2015
Biodegradable vascular grafts with sufficient in vivo performance would be more advantageous than permanent non-degradable prostheses. These constructs would be continuously replaced by host tissue, leading to an endogenous functional implant which would adapt to the need of the patient and exhibit only limited risk of microbiological graft contamination. Adequate biomechanical strength and a wall structure which promotes rapid host remodeling are prerequisites for biodegradable approaches. Current approaches often reveal limited tensile strength and therefore require thicker or reinforced graft walls. In this study we investigated the in vitro and in vivo biocompatibility of thin host-vessel-matched grafts (n = 34) formed from hard-block biodegradable thermoplastic polyurethane (TPU). Expanded polytetrafluoroethylene (ePTFE) conduits (n = 34) served as control grafts. Grafts were analyzed by various techniques after retrieval at different time points (1 week; 1, 6, 12 months). TPU grafts showed significantly increased endothelial cell proliferation in vitro (P < 0.001). Population by host cells increased significantly in the TPU conduits within 1 month of implantation (P = 0.01). After long-term implantation, TPU implants showed 100% patency (ePTFE: 93%) with no signs of aneurysmal dilatation. Substantial remodeling of the degradable grafts was observed but varied between subjects. Intimal hyperplasia was limited to ePTFE conduits (29%). Thin-walled TPU grafts offer a new and desirable form of biodegradable vascular implant. Degradable grafts showed equivalent long-term performance characteristics compared to the clinically used, non-degradable material with improvements in intimal hyperplasia and ingrowth of host cells.
European Journal of Vascular and Endovascular Surgery, 2019
WHAT THIS PAPER ADDS This 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. Objectives: 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.
Journal of Biomedical Materials Research Part A, 2013
Because of their suitable bio-mechanical properties, polymeric materials, such as Poly(L-lactic acid) (PLLA), and poly (lactic-co-glycolic acid) (PLGA), are often used in the biomedical field, in particular for cardiovascular applications. Implanted materials induce several events related to the inflammatory reaction, such as macrophage adhesion and activation with following cytokine release. This work considered the effect of macrophage adhesion and related cytokine release on endothelial cells (PAOEC) proliferation and migration. Slight differences have been shown by the macrophages reaction when in contact with PLLA, PLGA, or PLLA/PLGA blend. However, these differences showed to differently enhance endothelial cells behavior in terms of wound healing. These data suggest the inflammatory reaction as a useful way to consider concerning materials biocompatibility, in order to optimize the endothelial regeneration following vascular prosthetic implants. V C 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3131-3140, 2013.
2015
In the last decades cardiovascular diseases have become the number one single cause of death throughout the world. Naturally the demand for substitute materials to replace failing tissue related to these diseases increased as well. Vascular tissue engineering is a promising approach to meet these demands. Although there are synthetic materials available that can replace large diameter blood vessels, small diameter blood vessels of the same materials failed. Compliance and elastic mismatch as well as low hemocompatibility are considered to be the main reasons for failure. Thermoplastic polyurethane materials (TPUs) might offer a new approach for designing small diameter vascular grafts. This type of polymer usually shows good biocompatibility as well as elastomeric properties and usually can be processed from melt as well as from solution. The segmented configuration of these polyurethanes - consisting of a macrodiol, as flexible soft block, and a combination of diisocyanate and chai...
Vascularization and tissue infiltration of a biodegradable polyurethane matrix
Journal of Biomedical Materials Research, 2003
Urethanes are frequently used in biomedical applications because of their excellent biocompatibility. However, their use has been limited to bioresistant polyurethanes. The aim of this study was to develop a nontoxic biodegradable polyurethane and to test its potential for tissue compatibility. A matrix was synthesized with pentane diisocyanate (PDI) as a hard segment and sucrose as a hydroxyl group donor to obtain a microtextured spongy urethane matrix. The matrix was biodegradable in an aqueous solution at 37°C in vitro as well as in vivo. The polymer was mechanically stable at body temperatures and exhibited a glass transition temperature (Tg) of 67°C. The porosity of the polymer network was between 10 and 2000 m, with the majority of pores between 100 and 300 m in diameter. This porosity was found to be adequate to support the adherence and proliferation of bone-marrow stromal cells (BMSC) and chondrocytes in vitro. The degradation products of the poly-mer were nontoxic to cells in vitro. Subdermal implants of the PDI-sucrose matrix did not exhibit toxicity in vivo and did not induce an acute inflammatory response in the host. However, some foreign-body giant cells did accumulate around the polymer and in its pores, suggesting its degradation is facilitated by hydrolysis as well as by giant cells. More important, subdermal implants of the polymer allowed marked infiltration of vascular and connective tissue, suggesting the free flow of fluids and nutrients in the implants. Because of the flexibility of the mechanical strength that can be obtained in urethanes and because of the ease with which a porous microtexture can be achieved, this matrix may be useful in many tissue-engineering applications.