The anisotropic mechanical behaviour of electro-spun biodegradable polymer scaffolds: Experimental characterisation and constitutive formulation

Electro-spun biodegradable polymer fibrous structures exhibit anisotropic mechanical properties dependent on the degree of fibre alignment. Degradation and mechanical anisotropy need to be captured in a constitutive formulation when computational modelling is used in the development and design optimisation of such scaffolds.Biodegradable polyester-urethane scaffolds were electro-spun and underwent uniaxial tensile testing in and transverse to the direction of predominant fibre alignment before and after in vitro degradation of up to 28 days. A microstructurally-based transversely isotropic hyperelastic continuum constitutive formulation was developed and its parameters were identified from the experimental stress–strain data of the scaffolds at various stages of degradation.During scaffold degradation, maximum stress and strain in circumferential direction decreased from 1.02±0.23 MPa to 0.38±0.004 MPa and from 46±11% to 12±2%, respectively. In longitudinal direction, maximum stress and strain decreased from 0.071±0.016 MPa to 0.010±0.007 MPa and from 69±24% to 8±2%, respectively. The constitutive parameters were identified for both directions of the non-degraded and degraded scaffold for strain range varying between 0% and 16% with coefficients of determination r2>0.871. The six-parameter constitutive formulation proved versatile enough to capture the varying non-linear transversely isotropic behaviour of the fibrous scaffold throughout various stages of degradation

The anisotropic mechanical behaviour of electro-spun biodegradable polymer scaffolds: Experimental characterisation and constitutive formulation

Electro-spun biodegradable polymer fibrous structures exhibit anisotropic mechanical properties dependent on the degree of fibre alignment. Degradation and mechanical anisotropy need to be captured in a constitutive formulation when computational modelling is used in the development and design optimisation of such scaffolds.Biodegradable polyester-urethane scaffolds were electro-spun and underwent uniaxial tensile testing in and transverse to the direction of predominant fibre alignment before and after in vitro degradation of up to 28 days. A microstructurally-based transversely isotropic hyperelastic continuum constitutive formulation was developed and its parameters were identified from the experimental stress–strain data of the scaffolds at various stages of degradation.During scaffold degradation, maximum stress and strain in circumferential direction decreased from 1.02±0.23 MPa to 0.38±0.004 MPa and from 46±11% to 12±2%, respectively. In longitudinal direction, maximum stress and strain decreased from 0.071±0.016 MPa to 0.010±0.007 MPa and from 69±24% to 8±2%, respectively. The constitutive parameters were identified for both directions of the non-degraded and degraded scaffold for strain range varying between 0% and 16% with coefficients of determination r2>0.871. The six-parameter constitutive formulation proved versatile enough to capture the varying non-linear transversely isotropic behaviour of the fibrous scaffold throughout various stages of degradation

Tailoring of the biomechanics of tissue-regenerative vascular scaffolds

The lack of long term patency of small diameter synthetic vascular grafts currently available on the market has directed research towards improving the performance of these grafts. Improved radial compliance matching and appropriate tissue ingrowth into the graft structure are main goals for an ideal vascular graft. In addition, the use of biodegradable materials offers the promising prospect of leaving behind a near native vessel with no synthetic material remaining. Tissue ingrowth into grafts alters their mechanics. This, combined with a loss of mechanical integrity over time, in the case of biodegradable scaffolds, brings the need to investigate how these changes play out and how to tailor them for optimal graft healing. This project set out to investigate the mechanics of electrospun Pellethane® 2363-80AE (Dow Chemicals) and DegraPol® (ab medica S.p.A) biostable DegraPol® DP0 and biodegradable DegraPol® DP30 scaffolds during in vivo animal studies. DegraPol® DP30 findings were used to investigate the scaffolds' potential use for vascular grafts by means of a finite element graft model. Porous, electrospun scaffolds were manufactured and implanted into two subcutaneous and one circulatory rat models. All studies consisted of four time points, namely 0, 7, 14 and 28 days. Scaffold morphology was characterised, and tissue ingrowth was quantified by histological analysis of explanted samples. Orthogonal, uni-axial tensile testing measured scaffold mechanical response of in-fibre and cross-fibre deformation. Tissue ingrowth brought about considerable changes in biostable DegraPol® DP0 scaffold mechanics. Tensile testing of degradable DegraPol® DP30 scaffolds in their load bearing circumferential direction showed a balance between a loss in mechanical strength and an increase in strength by tissue ingrowth. This resulted in constant radial compliance of 4.47 ± 0.14%/100 mmHg between 80 and 120 mmHg for the four week period predicted with the numerical models. The finite element model based on DegraPol® DP30 scaffold mechanics for 6 mm grafts showed better, i.e. higher, radial compliance than current grafts used clinically (polyethylene terephthalate and expanded polytetrafluoroethylene grafts). This stability in compliance, coupled with good tissue ingrowth is of scientific importance as it shows that highly aligned, porous electrospun DegraPol® DP30 scaffolds are a viable option for vascular grafting to achieve long term graft patenc

Design and implementation of an apparatus for hydrodynamic and fatigue testing of prosthetic aortic valves

Includes abstract.Includes bibliographical references.Aortic valve replacement in humans may be needed due to pathology leading to valve stenosis and regurgitation. Replacement is by either mechanical or soft tissue prosthetic valves. Before new valves are medically approved and introduced into the market they are required to undergo rigorous testing to verify performance and product life expectancy. Performance testing is done in a hydrodynamic test apparatus and life expectancy verified in an accelerated test apparatus. The Cardiology Department at Tygerberg Hospital has proposed a project for the design and implementation of a prosthetic aortic valve test apparatus. This device is to be used primarily for fatigue, but also limited hydrodynamic, testing of prosthetic heart valves. The design of the test apparatus was based on the four-element Windkessel model of the arterial system. This simple lumped parameter electrical analogy of the arterial system takes aortic and arterial resistance, arterial compliance, and blood inertance into account to simulate total arterial impedance. This model was developed with physiological reference and thus the element parameters only hold for physiological simulation as the equation governing impedance is speed sensitive. The model was adapted to provide theoretidal, physiological loads from physiological speeds of 60BPM through to accelerated speeds up to 1OOOBPM through mathematical optimisation of the Windkessel.The test apparatus was designed and built taking into account the varying Windkessel parameters where possible. Both compliance and resistance could be varied within an acceptable range, inertance however, could not be varied due to the limitations of the project. The apparatus was controlled and pressures on either side of the valve monitored with a LabView® graphical user interface. The apparatus was able to mimic in vivo closely and satisfied the ISO requirements for valve testing up to speeds of 230BPM. Various modifications are proposed to both the Windkessel model and the physical apparatus to compensate for hydrodynamic effects at high testing speeds in improve performance, as well as increase the maximum testing speed

Electrospun polyester-urethane scaffold preserves mechanical properties and exhibits strain stiffening during in situ tissue ingrowth and degradation

Consistent mechanical performance from implantation through healing and scaffold degradation is highly desired for tissue-regenerative scaffolds, e.g. when used for vascular grafts. The aim of this study was the paired in vivo mechanical assessment of biostable and fast degrading electrospun polyester-urethane scaffolds to isolate the effects of material degradation and tissue formation after implantation. Biostable and degradable polyester-urethane scaffolds with substantial fibre alignment were manufactured by electrospinning. Scaffold samples were implanted paired in subcutaneous position in rats for 7, 14 and 28 days. Morphology, mechanical properties and tissue ingrowth of the scaffolds were assessed before implantation and after retrieval. Tissue ingrowth after 28 days was 83 ± 10% in the biostable scaffold and 77 ± 4% in the degradable scaffold. For the biostable scaffold, the elastic modulus at 12% strain increased significantly between 7 and 14 days and decreased significantly thereafter in fibre but not in cross-fibre direction. The degradable scaffold exhibited a significant increase in the elastic modulus at 12% strain from 7 to 14 days after which it did not decrease but remained at the same magnitude, both in fibre and in cross-fibre direction. Considering that the degradable scaffold loses its material strength predominantly during the first 14 days of hydrolytic degradation (as observed in our previous in vitro study), the consistency of the elastic modulus of the degradable scaffold after 14 days is an indication that the regenerated tissue construct retains it mechanical properties

Remodeling leads to distinctly more intimal hyperplasia in coronary than in infrainguinal vein grafts

BACKGROUND: Flow patterns and shear forces in native coronary arteries are more protective against neointimal hyperplasia than those in femoral arteries. Yet, the caliber mismatch with their target arteries makes coronary artery bypass grafts more likely to encounter intimal hyperplasia than their infrainguinal counterparts due to the resultant slow flow velocity and decreased wall stress. To allow a site-specific, flow-related comparison of remodeling behavior, saphenous vein bypass grafts were simultaneously implanted in femoral and coronary positions. METHODS: Saphenous vein grafts were concomitantly implanted as coronary and femoral bypass grafts using a senescent nonhuman primate model. Duplex ultrasound-based blood flow velocity profiles and vein graft and target artery dimensions were correlated with dimensional and histomorphologic graft remodeling in large, senescent Chacma baboons (n = 8; 28.1 ± 4.9 kg) during a 24-week period. RESULTS: At implantation, the cross-sectional quotient (Q(c)) between target arteries and vein grafts was 0.62 ± 0.10 for femoral grafts vs 0.17 ± 0.06 for coronary grafts, resulting in a dimensional graft-to-artery mismatch 3.6 times higher (P < .0001) in coronary grafts. Together with different velocity profiles, these site-specific dimensional discrepancies resulted in a 57.9% ± 19.4% lower maximum flow velocity (P = .0048), 48.1% ± 23.6% lower maximal cycling wall shear stress (P = .012), and 62.2% ± 21.2% lower mean velocity (P = .007) in coronary grafts. After 24 weeks, the luminal diameter of all coronary grafts had contracted by 63%, from an inner diameter of 4.49 ± 0.60 to 1.68 ± 0.63 mm (P < .0001; subintimal diameter: -41.5%; P = .002), whereas 57% of the femoral interposition grafts had dilated by 31%, from 4.21 ± 0.25 to 5.53 ± 1.30 mm (P = .020). Neointimal tissue was 2.3 times thicker in coronary than in femoral grafts (561 ± 73 vs 240 ± 149 μm; P = .001). Overall, the luminal area of coronary grafts was an average of 4.1 times smaller than that of femoral grafts. CONCLUSIONS: Although coronary and infrainguinal bypass surgery uses saphenous veins as conduits, they undergo significantly different remodeling processes in these two anatomic positions

Tissue ingrowth markedly reduces mechanical anisotropy and stiffness in fibre direction of highly aligned electrospun polyurethane scaffolds

Purpose: The lack of long-term patency of synthetic vascular grafts currently available on the market has directed research towards improving the performance of small diameter grafts. Improved radial compliance matching and tissue ingrowth into the graft scaffold are amongst the main goals for an ideal vascular graft.Methods: Biostable polyurethane scaffolds were manufactured by electrospinning and implanted in subcutaneous and circulatory positions in the rat for 7, 14 and 28 days. Scaffold morphology, tissue ingrowth, and mechanical properties of the scaffolds were assessed before implantation and after retrieval.Results: Tissue ingrowth after 24 days was 96.5 ± 2.3% in the subcutaneous implants and 77.8 ± 5.4% in the circulatory implants. Over the 24 days implantation, the elastic modulus at 12% strain decreased by 59% in direction of the fibre alignment whereas it increased by 1379% transverse to the fibre alignment of the highly aligned scaffold of the subcutaneous implants. The lesser aligned scaffold of the circulatory graft implants exhibited an increase of the elastic modulus at 12% strain by 77% in circumferential direction.Conclusion: Based on the observations, it is proposed that the mechanism underlying the softening of the highly aligned scaffold in the predominant fibre direction is associated with scaffold compaction and local displacement of fibres by the newly formed tissue. The stiffening of the scaffold, observed transverse to highly aligned fibres and for more a random fibre distribution, represents the actual mechanical contribution of the tissue that developed in the scaffold.<br/