A degradable/polar/hydrophobic/ionic (D-PHI) polyurethane with properties intended to promote tissue regeneration in a small diameter peripheral artery vascular graft was evaluated for cell biocompatibility and growth. Films were cast in polypropylene 96 well plates for monocyte/endothelial cell (EC) co-culture in vitro studies and porous scaffold discs were implanted in an in vivo subcutaneous mouse model. After 7 days in culture the co-culture demonstrated cell adhesion and growth, low esterase activity (a measure of degradative potential and cell activation), no detectable release of pro-inflammatory cytokine (tumour necrosis factor -α) but measurable anti-inflammatory interleukin (IL)-10. The EC and the co-culture expressed the EC biomarker CD31, whereas the monocyte monoculture did not. Cytokine array analysis of the in vivo characterization of D-PH supported an anti-inflammatory phenotype of cells at the site of the implant. Levels of IL-6 significantly decreased over time while IL-10 was significantly higher at 6 weeks post implant. TNF-α levels did not change significantly from 24 hours onwards, however the trend was towards lesser amounts following the initial time point. Histological analysis of the explanted scaffolds showed excellent tissue ingrowth and vascularization. A live/dead stain showed that the cells infiltrating the scaffolds were viable. Both the in vitro and in vivo results of this thesis indicate that D-PHI is a good candidate material for tissue engineering a peripheral artery vascular graft.

A degradable/polar/hydrophobic/ionic (D-PHI) polyurethane with properties intended to promote tissue regeneration in a small diameter peripheral artery vascular graft was evaluated for cell biocompatibility and growth. Films were cast in polypropylene 96 well plates for monocyte/endothelial cell (EC) co-culture in vitro studies and porous scaffold discs were implanted in an in vivo subcutaneous mouse model. After 7 days in culture the co-culture demonstrated cell adhesion and growth, low esterase activity (a measure of degradative potential and cell activation), no detectable release of pro-inflammatory cytokine (tumour necrosis factor -α) but measurable anti-inflammatory interleukin (IL)-10. The EC and the co-culture expressed the EC biomarker CD31, whereas the monocyte monoculture did not. Cytokine array analysis of the in vivo characterization of D-PH supported an anti-inflammatory phenotype of cells at the site of the implant. Levels of IL-6 significantly decreased over time while IL-10 was significantly higher at 6 weeks post implant. TNF-α levels did not change significantly from 24 hours onwards, however the trend was towards lesser amounts following the initial time point. Histological analysis of the explanted scaffolds showed excellent tissue ingrowth and vascularization. A live/dead stain showed that the cells infiltrating the scaffolds were viable. Both the in vitro and in vivo results of this thesis indicate that D-PHI is a good candidate material for tissue engineering a peripheral artery vascular graft.

A degradable/polar/hydrophobic/ionic (D-PHI) polyurethane with properties intended to promote tissue regeneration in a small diameter peripheral artery vascular graft was evaluated for cell biocompatibility and growth. Films were cast in polypropylene 96 well plates for monocyte/endothelial cell (EC) co-culture in vitro studies and porous scaffold discs were implanted in an in vivo subcutaneous mouse model. After 7 days in culture the co-culture demonstrated cell adhesion and growth, low esterase activity (a measure of degradative potential and cell activation), no detectable release of pro-inflammatory cytokine (tumour necrosis factor -α) but measurable anti-inflammatory interleukin (IL)-10. The EC and the co-culture expressed the EC biomarker CD31, whereas the monocyte monoculture did not. Cytokine array analysis of the in vivo characterization of D-PH supported an anti-inflammatory phenotype of cells at the site of the implant. Levels of IL-6 significantly decreased over time while IL-10 was significantly higher at 6 weeks post implant. TNF-α levels did not change significantly from 24 hours onwards, however the trend was towards lesser amounts following the initial time point. Histological analysis of the explanted scaffolds showed excellent tissue ingrowth and vascularization. A live/dead stain showed that the cells infiltrating the scaffolds were viable. Both the in vitro and in vivo results of this thesis indicate that D-PHI is a good candidate material for tissue engineering a peripheral artery vascular graft.

A degradable/polar/hydrophobic/ionic (D-PHI) polyurethane with properties intended to promote tissue regeneration in a small diameter peripheral artery vascular graft was evaluated for cell biocompatibility and growth. Films were cast in polypropylene 96 well plates for monocyte/endothelial cell (EC) co-culture in vitro studies and porous scaffold discs were implanted in an in vivo subcutaneous mouse model. After 7 days in culture the co-culture demonstrated cell adhesion and growth, low esterase activity (a measure of degradative potential and cell activation), no detectable release of pro-inflammatory cytokine (tumour necrosis factor -α) but measurable anti-inflammatory interleukin (IL)-10. The EC and the co-culture expressed the EC biomarker CD31, whereas the monocyte monoculture did not. Cytokine array analysis of the in vivo characterization of D-PH supported an anti-inflammatory phenotype of cells at the site of the implant. Levels of IL-6 significantly decreased over time while IL-10 was significantly higher at 6 weeks post implant. TNF-α levels did not change significantly from 24 hours onwards, however the trend was towards lesser amounts following the initial time point. Histological analysis of the explanted scaffolds showed excellent tissue ingrowth and vascularization. A live/dead stain showed that the cells infiltrating the scaffolds were viable. Both the in vitro and in vivo results of this thesis indicate that D-PHI is a good candidate material for tissue engineering a peripheral artery vascular graft.

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Annually, about 80,000 people die in the United Kingdom due to myocardial infarction, congestive heart failure, stroke, or from other diseases related to blood vessels. The current gold standard treatment for replacing the damaged blood vessel is by autograft procedure, during which the internal mammary artery (IMA) graft or saphenous vein graft (SVG) are usually employed. However, some limitations are associated with this type of treatment, such as lack of donor site and post-surgery problems that could negatively affect the patient’s health. Therefore, this present work aims to fabricate a synthetic blood vessel that mimics the natural arteries and to be used as an alternative method for blood vessel replacement. Polymeric materials intended to be used for this purpose must possess several characteristics including: (1) Polymers must be biocompatible; (2) Biodegradable with adequate degradation rate; (3) Must maintain its structural integrity throughout intended use; (4) Must have ideal mechanical properties; and (5) Must encourage and enhance the proliferation of the cells. The feasibility of using synthetic biodegradable polymers such as poly (ε- caprolactone) (PCL) and poly (lactide-co-glycolic acid) (PLGA) for fabricating tubular vascular grafts was extensively investigated in this work. Many fundamental experiments were performed to develop porous tissue- engineered polymeric membranes for vascular graft purposes through electrospinning technique to achieve the main aim. Electrospinning was selected since the scaffolds produced by this method usually resemble structural morphology similar to the extracellular matrix (ECM). Hence, four 6mm in diameter tubular shape vascular grafts PCL only, PLGA only, coaxial (core-PCL and shell-PLGA), and bilayer (inner layer-PCL and outer layer-PLGA) was designed and fabricated successfully. The structure and properties of each scaffold membrane were observed by scanning electron microscopy (SEM), and these scaffolds were fully characterized by Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), water contact angle measurements, mechanical tensile test, as well as cell culture studies were carried out by seeding human umbilical vein cells (HUVEC) and human vascular Fibroblast cells (HVF). Moreover, all polymeric grafts underwent degradation process, and the change in their morphological structure properties was studied over 12 weeks at room temperature. All scaffolds were also exposed to a controlled temperature of 37°C for four weeks, in phosphate-buffered saline solution (pH, 7.3). It was found that all scaffolds displayed exceptional fibre structure and excellent degradability with adequate steady weight-loss confirming the suitability of the fabricated scaffolds for tissue engineering applications. The coaxial and bilayer scaffolds degraded at a much slower (and steadier) rate than the singular PCL and PLGA tubular scaffolds. Coaxial grafts fabricated via coaxial needle showed an increase in their fibre diameter and pore size volume than other membranes, but also showed to have significant tensile strength, elongation at fracture, and Young’s modulus. To conclude, all scaffolds have demonstrated to be reliable to adhere and proliferate HUVEC, and HVF cells, but these cells were attracted to the PLGA membrane more than other fabricated membranes.

1 Abstract Aim: To evaluate the diagnostic performance of FDG PET/CT in the detection of stent graft infection (SGI) with the use of visual and semiquantitative interpretation, to compare it with standalone CT analysis, to verify the transferability of the experience with FDG PET/CT in surgical prosthesis infection and to define the role of the method in the diagnostic algorithm of SGI. Subjects and Methods: In this retrospective study, two nuclear medicine physicians have independently analyzed 21 FDG PET/CT examinations performed in 20 subjects (16 men, 66 ± 8 years) between 2010 and 2019 for clinical suspicion of SGI. Six subjects examined from other reasons without signs of infection constituted a control group. The images were evaluated for the uptake pattern and intensity, and by the maximum standard uptake value (SUVmax), the target-to-background ratio with blood pool (TBRBP) and liver uptake (TBRhep) as a reference. The SGI was defined as the presence of focal hyperactivity with an intensity exceeding hepatic uptake. CT images were independently assessed for signs of SGI. Clinical review of all further patients' data served as the standard of reference. Results: Twelve cases were established as SGI by the clinical review. PET/CT correctly diagnosed SGI in eight and yielded a sensitivity of 92 % and...

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