PET Vascular prostheses are susceptible to physical modification and chemical degradation leading sometimes to global deterioration and rupture of the product. To understand the mechanisms of degradation, we studied 6 vascular prostheses that were explanted due to medical complications. We characterized their level of degradation by comparing them with a virgin prosthesis and carried out physicochemical and mechanical analyses. Results showed an important reduction of the fabric’s mechanical properties in specific areas. Moreover, PET taken from these areas exhibited structural anomalies and was highly degraded even in virgin prostheses. These results suggest that vascular prostheses have weak areas prior to implantation and that these areas are much more prone to in vivo degradation by human metabolism. Manufacturing process could be responsible for these weaknesses as well as designing of the compound. Therefore, we suggest that a more controlled manufacturing process could lead to a vascular prosthesis with enhanced lifespan.
Arteries are blood vessels that carry oxygen and nutrients from the heart to the rest of the body. Healthy arteries are flexible, strong, and elastic. With age, vascular diseases can occur leading to a lumen with restricted section or to a loss of elastic properties of arteries (Figures
Dysfunctions of arteries and prostheses. Sources: (b)
Vascular diseases are often treated by replacing the dysfunctional blood vessel with a vascular prosthesis. Fabric materials were first used as vascular prostheses in the 1950s, when Voorhees et al. [
Dilatation and rupture (Figure
Macroscopic examination of Cooley Double Velour prosthesis: (a) ruptures on remeshing line. (b) rupture on guide line. (c) scanning electron microscopy examination of Cooley Double Velour prosthesis presenting a rupture on remeshing line.
The goal of the present study was to investigate the physical and chemical degradation of polyethylene terephthalate yarns and filaments taken from specimens of our previous series of 6 explanted grafts in order to confirm in vitro data and to understand this ageing mechanism.
The explanted prostheses were Cooley Double Velour (CDV) and the Microvel Double Velour (MDV) (virgin and explanted prostheses (Figure
Sample preparation.
For these prostheses, three different areas are distinguished (Figures
Main characteristics of the explanted grafts. Reference number is the reference number given in the first clinical description of the series. (MDV: Microvel Double Velour; CDV: Cooley Double Velour; RL: remeshing line; GL: guide line).
Explant reference | Prosthetic type | Year of implantation | Year of explantation | Lifetime (months) | Reason for explantation | Location of implantation | Prosthetic segment affected | Ruptured area |
---|---|---|---|---|---|---|---|---|
A | CDV | 1980 | 1993 | 156 | Bilateral false-aneurysm | Axillo bi-femoral | limb | RL |
B | CDV | 1981 | 1995 | 168 | Multiplefalse-aneurysms | Axillo bi-femoral | Entire prosthesis | RL, GL |
C | CDV | 1982 | 1999 | 204 | False-aneurysmand dilatation | Aorto bi-femoral | limb | GL |
D | CDV | 1979 | 1997 | 204 | False-aneurysm | Axillo bi-femoral | limb | RL, GL |
E | CDV | 1978 | 1998 | 240 | False-aneurysm | Aorto bi-femoral | body | RL |
F | MDV | 1978 | 1998 | 240 | False-aneurysm | Aorto bi-femoral | limb | GL |
Schematic characterization of the textile structure of the virgin Cooley Double Velour prosthesis and of the virgin Microvel Double Velours prosthesis; (RL: remeshing line; SK: standard Knit, GL:Guide Line).
Virgin prosthesis was used as a reference. So, in order to study only the effect of the chemical aging on the PET properties, this virgin prosthesis was sterilized and then it was cleaned with the same treatment as for the explants.
In this study, flat and texturized filaments of standard knit (FFP and FFT, resp. Figure
Scanning electron microscopy (Hitachi S-2360N; Elexience, Verrières le Buisson, France) was used to determine the deteriorations of the textile structure. The specimens were studied without metallization, in partial vacuum conditions (0.1–0.15 torr), and under an accelerating voltage ranging from 8 to 18 KeV. These conditions ensured that the specimens were not altered for further investigations, and that a maximum rate of magnification of 200 was achieved. We studied the aspect of the ruptures and the filaments inside the yarns.
Filaments taken from yarns of the standard knit were studied by filament dynamometry using a dynamometer (Lhomargy, Ivry-sur-Seine, France). Ten samples were tested for each type of filament. The distance between the dynamometer jaws was 10 mm (with a pretension) as proposed by the recommendations of the national and international textile standards NF EN ISO 5079. The curves obtained for each specimen were recorded. The results were expressed as the tenacity in cN/tex with the average value and the coefficient of variation.
The principle of this technique consists in immerging pieces of PET filaments (~1 mg) in a calibrated density gradient column obtained by mixing two miscible liquids at 23°C: carbon tetrachloride and petroleum ether (Figure
Experimental representation of the gradient density column. A: temperature controlled chamber; B: column of gradient density; C: capillary tubing; D: carbon tetrachloride solution; E: petroleum ether solution; F: magnetic agitator.
where
We used a Brucker Fourier transform infrared (FTIR) spectrophotometer (Brucker Optics, Marne la Vallée, France) equipped with Brucker Optic software. The IMS in a transmission spectrum of PET fibers was recorded directly in the range of 2000–4000 cm−1. Each spectrum was made from an average of 200 scans at a resolution of 2 cm−1. The diaphragm opening was 0.9, corresponding to an object diameter of 63
This technique was chosen to characterize the evolution of the macromolecular mass and to detect the presence of structural abnormalities of the polymer. NMR experiments were recorded at 400 MHz on a Brucker Acance Spectrometer (Brucker Optics, Marne la Vallée, France) equipped with a QNP Z-gradient probe. All the 1H NMR spectra were acquired with a 30° pulse corresponding to a pulse width of 3.1
Solutions were prepared by dissolving the PET samples in tetrachloroethane-d2 (Deuterated tetrachloroethane 99.9% atom D) at 140°C (typically 2–4 mg) directly in an NMR tube and waiting for about 90 seconds to ensure a complete dissolution of the polymer, then the mixture was cooled to ambient temperature. The experiments were run at room temperature. For these analyses, Topspin 1.3 software was used to treat the spectra and 1D NMR processor 11.0 (ACD Labs, Toronto, Canada) software was used to determine the peak integrals. Prior to signal integration, a linear baseline correction was applied between 2 and 12 ppm. We respected the same construction of the baseline for all spectra; so the choice of the baseline did not influence the obtained 1H NMR results.
The specimens were examined under scanning electron microscopy on the external and internal surfaces. We found major deteriorations in the texturized filaments from the standard knit and that constitute the velour (Figure
Scanning electron microscopy examination of Cooley Double Velours prosthesis: (a) virgin prosthesis, (b) explanted prosthesis, destruction of texturized yarn.
Scanning electron microscopy examination of Cooley Double Velours prosthesis. Transversal breaks of trilobar filament.
When compared to the virgin reference prosthesis, explanted prostheses demonstrated a higher heterogeneity in terms of tenacity and elongation at rupture characterized by an increase of the coefficient of variation (Table
Results of the filament dynamometry performed on short and long filaments of the specimens. Prosthesis number is the reference number given in the first clinical description of the series. (CDV: Cooley Double Velour; MDV: Microvel Double Velour; CV: coefficient of variation).
Prostheses | Tenacity (cN/tex) | Elongation at rupture (%) | |||
---|---|---|---|---|---|
Average | CV (%) | Average | CV (%) | ||
Virgin CDV | FFP (short) | 28.0 | 6.7 | 63.5 | 11.8 |
FFT (Long) | 26.4 | 11.8 | 74.4 | 14.8 | |
A | FFP (short) | 26.9 | 32.7 | 25.8 | 42.2 |
FFT (Long) | 24.7 | 33.9 | 27.8 | 48.1 | |
B | FFP (short) | 27.9 | 29.8 | 31.6 | 38.2 |
FFT (Long) | 23.8 | 40.1 | 35.5 | 37.3 | |
C | FFP (short) | 12.6 | 48.2 | 7.33 | 113.1 |
FFT (Long) | 12.2 | 46.8 | 20.8 | 84.7 | |
D | FFP (short) | 27.6 | 31.1 | 24.6 | 38.0 |
FFT (Long) | 25.9 | 40.1 | 28.9 | 45.8 | |
E | FFP (short) | 24.8 | 21.2 | 29.3 | 26.1 |
FFT (Long) | 23.6 | 29.4 | 35.6 | 41.3 | |
Virgin MDV | FFP (short) | 25.4 | 3.6 | 67.9 | 11.3 |
FFT (Long) | 22.8 | 14.4 | 62.7 | 19.1 | |
F | FFP (short) | 24.6 | 46.5 | 22.6 | 52.0 |
FFT (Long) | 21.7 | 48.3 | 23.8 | 55.9 |
The density gradient technique is an extremely accurate method for determining the density of polymers. Table
Density and the percent crystallinity value of prostheses.
Protheses | Density (g·cm−3) | Percent crystallinity (%) |
---|---|---|
vierge | 1.4017 | 57.75 |
A (156 mois) | 1.4086 | 63.41 |
B (168 mois) | 1.4099 | 64.47 |
C (204 mois) | 1.4098 | 64.39 |
D (204 mois) | 1.4106 | 65.04 |
E (240 mois) | 1.4178 | 70.88 |
F (240 mois) | 1.4167 | 69.99 |
Infrared (FTIR) spectroscopy provides a comprehensive view of chemical and conformational structures of molecules. First of all, this technique is used to analyse both virgin and explanted prosthesis in order to have an overview of the effect of chemical ageing. In this analysis, 30 fibers are extracted from various areas of each prosthesis (Figure
Figure
Secondly, the FTIR spectroscopy was used to follow changes in chain conformation of poly(ethylene terephthalate) (PET), which occur during physical ageing (Figure
The gauche (G) or trans (T) conformation of the ethylene glycol fragment through rotation around C–C bond accounts for major IR spectra differences in amorphous and crystalline phases [
These absorption bands exhibited a greater change in intensities after ageing (Figure
Classical dynamometry for various vascular prostheses.
percent of crystallinity value for texturized and flat yarn.
Qualitative analyses using infrared spectroscopy:
Change in absorbance of the 1340 (trans) and 1370 cm−1 (gauche) bands after implantation.
Many types of information can be obtained from an 1H-NMR spectrum, especially information regarding quantification of the number and type of chemical entities in a macromolecule. Typical NMR spectrum of PET at room temperature is shown in Figure
1H-NMR spectrum of PET (400 MHz, (CDCl2)2, reference (CDCl2)2, d (CHCl2)2 6 ppm). *13C satellite peak.
Ethylene-repeating unit comprising the PET macromolecular chain is generally the first and most important attribute of a PET polymer. To compare the ethylene groups, the signal at 4.87 ppm corresponding to 13C satellite of these groups (H2) was used.
Figure
Variation of the ethylene groups for different prostheses.
The study of polymers starts by understanding the methods used to synthesize the materials. Polymer synthesis is a complex procedure and can take place in a variety of ways. Certain secondary reactions can occur during the synthesis of the PET, leading to nonconforming groups such as the formation of DEG and PET cyclic oligomer.
The DEG groups are formed by secondary reaction during PET synthesis (Figure
Formation of diethylene glycol (DEG).
In the process of producing linear polymers by condensation, cyclic oligomers are inevitably formed and their formation considerably affects the macromolecular weight distribution even though the total amount formed is less than 5% [
Figures
Variation of the diethylene glycol groups.
Variation of the cyclic oligomers.
To clarify the effect of chemical aging, the macromolecular weights of PET fibers extracted from various vascular prostheses, using NMR technique, were quantified.
1H-NMR technique has been used to compare the macromolecular weight of a series of PET vascular prostheses, collected after different durations of in vivo stay.
Polymer properties are strongly dependent on the number of monomer units that comprise the macromolecular chain. Mathematically, the average number of macromolecular weight (Mn) is given by the following formula (
Direct 1H-NMR technique is not sensitive to the carboxyl end-groups because of line broadening of the signal caused by fast chemical exchange within impurities. COOH end-groups are very low in comparison to OH end-groups, even after aging (COOH < 20% and OH > 80%; these results are verified by chemical titration); therefore, the COOH groups have little influence on the evolution of (Mn) values. Thus, the macromolecular weight will be calculated by supposing that all chains are terminated by hydroxyl groups.
The average number macromolecular weight can be represented by the following formula (
The macromolecular weight of principal PET chain (
PET group intensities in macromolecular chain with hydroxyl termination.
To determine
Thus, this integral value (
Thus using the above equation,
The macromolecular weight of oligomer is equal to 576 g/mol (
where
Thus 1H-NMR technique has been used to compare the macromolecular weight of a series of PET vascular prostheses, collected after different durations of in vivo stay.
As a specific modification is induced by the increase of the end-groups, Figure
Macromolecular weight for various vascular prostheses using 1H-NMR method.
While the results showed that the macromolecular weight values (Mn) are significantly influenced by aging following implantation, the impact of the duration of in vivo stay on the chemical degradation was difficult to evaluate. We noticed that these (Mn) of the fibers extracted from vascular prostheses are not directly correlated to the duration of in vivo stay (e.g., the prosthesis (E: 156 months) is more degraded than the prosthesis (A: 204 months)). Therefore, the degradation level does not depend on the time of in vivo stay or the location of the implant (Table
Moreover, degraded chains (explants) with low molecular weight exhibit a remarkable reduction in DEG and PET oligomers.
Ruptures of polyester textile prostheses have been rarely reported in the literature. In a previous study [
The goal of the present study was to determine if these areas of weakness could have been predicted by in vitro investigations of virgin prostheses associating mechanical and chemical analyses. The prostheses that demonstrated ruptures in our series were Cooley Double Velour and Microvel Double Velour of the first generation incorporating texturized trilobate filaments. Unfortunately, the virgin prostheses corresponding to the first generation were no longer available so we used virgin prostheses from the second generation. The second-generation prostheses use cylindrical texturized filaments instead of the trilobate ones. Filament dynamometry highlighted modifications of the mechanical behavior of monofilaments after the manufacturing of the prosthesis. The resistance of a yarn is equal to the resistance of each filament multiplied by the number of filaments. The study of the mechanical behavior of the filaments taken from yarns extracted from the different areas of the prostheses highlighted two phenomena. First, we observed heterogeneity of the mechanical behavior of the filaments inside a same yarn, with this heterogeneity being characterized by major differences in terms of resistance and breaking extension. Secondly, we showed differences in mechanical behavior of the filaments according to the area from where the yarns were extracted. We believe that this heterogeneity of mechanical behavior may lead to the rupture observed in the textile structure. In these conditions of heterogeneous behavior of the filaments inside a yarn, the resistance of a yarn depends greatly on the resistance of the weakest filament. Consequently, such a yarn will be exposed to a gradual rupture of the filaments, which may generate longitudinal tears in the prosthesis as described on the explanted prostheses in human.
Both prostheses were constructed with a short yarn and a long texturized yarn. The texturization of a long yarn deeply modified the elongation properties of the filaments. Consequently, it is logical to find significant difference of mechanical behavior between short and long yarn inside the same column of stitches.
During the manufacturing process, the polyester filaments and yarns can be degraded by texturization. This is obtained by thermofixation after the application of longitudinal or transverse stresses and of torsion. It will generate irregularities of the structure and the geometry of the filaments. After knitting, the prostheses are compacted in order to decrease its porosity by a thermal and/or chemical swelling of the polyester filaments. This treatment can also modify the molecular arrangement, and the orientation or the crystallinity of the polymer, affecting its mechanical properties. Crimping can also modify the filaments since it is carried out by thermofixation. The application of mechanical and thermal constraints can also modify the structure of the polymer and create the deformations of the filaments as observed by scanning electron microscopy. Finally, the prosthesis is cleaned with chemical reactants that may modify the surface chemistry of the polyester filaments. The prosthesis can also be degraded at the time of its implantation. All these deteriorations of the textile structure occurring before or during the implantation of the prosthesis could promote an accelerated in vivo biodegradation of particular types of prostheses. After the implantation, the pulsatile arterial stress and the enzymatic environment of the tissular host response may accelerate the polymer degradation.
Table
Chain scission in macromolecules [
Infrared microscopic examination confirms filament dynamometry results. Similarly, the homogeneity properties of the filaments taken from the virgin prosthesis and the heterogeneity of the filaments taken from the explanted prosthesis were highlighted (Figure
Infrared (FTIR) spectroscopy can be a very powerful tool for studying chemical structure in bulk materials as well as providing molecular conformation details that are inaccessible to most analytical methods. Thus, we used the FTIR technique to measure the crystalline and amorphous content in PET, using absorption bands at 1340 cm−1 and 1370 cm−1, respectively, with the band at 1410 cm−1 as an internal standard. It has been shown that there is an increase in the population of transethylene glycol conformation (crystalline phase) at the expense of the gauche (amorphous phase) after physical ageing, that is, one structural alteration that occurs on physical ageing is the change from gauche to transconformations of the ethylene units in PET.
1H NMR method provides a convenient mean to quantify the effect of chemical ageing for various explants. Examination of a series of PET vascular prostheses showed significant chemical differences between the virgin prostheses and the explants collected after ageing, especially for diethylene glycol (DEG) groups. Ageing was investigated in terms of chemical scission of ester and ether linkages caused by hydrolytic and oxidative reaction during in vivo stay (Figure
All of these studies in the literature coupled with our results (formation of small crystallites in amorphous areas) allow establishing hypotheses about the structural evolution of the polymer after ageing. On the one hand, we showed that the explants had a higher degree of crystallinity than virgin prostheses, and on the other hand, there was a development of small crystallites in the amorphous areas for the explants. This crystallization would begin to occur by the rupture of macromolecular chains mainly at the amorphous areas. So, small more mobile chains appear, which would favor the crystallization in the amorphous areas after ageing. However, these small crystallites are not perfectly oriented along the fiber axis (Figure
appearance of crystallites in the amorphous areas: the break of diethylene glycol groups existing in the amorphous areas may promote the crystallization process and thus the transformation of CIS conformers (present in the amorphous zones) in TRANS (present in the crystalline regions).
Although, we distinguished a remarkable reduction of the average number of (Mn), it could be due to the fact that just small parts of some chains come off dramatically reducing number average molecular weight, but probably not weighted average molecular weight. Consequently, the ruptures of macromolecular chain do not cause a damage or a dramatically degradation of the vascular prostheses. But the classical dynamometry test (Figure
These failures are related to lesions during the implantation and the chemical degradation of materials in vivo. According to several authors [
Theoretical relationship between macromolecular weight and breaking stress [
In the future, we hope to find a correlation between Mn and the length of chain and therefore obtain a critical value of (Mn) to monitor the aging behavior. Also, it is relevant to determine polydispersity index to verify the found results and the macromolecular chain repartition.
The ruptures observed on explanted knitted vascular polyester prostheses in humans occurred on areas that can be qualified as areas of weakness. These areas of weakness seem to be related to the manufacturing process, the implantation, and the human metabolism, which may induce physical and chemical modifications of the polyester yarns. These alterations may be considered as a premature ageing of the polyester before its implantation.
So, this study confirmed the high level of polymer degradation in prostheses by the presence of structural anomalies. These anomalies are weaknesses that initiate the degradation and the ageing process.
New generations of vascular fabrics, who are also prone to rupture, should require a more controlled manufacturing process and the use of a PET specifically synthetized for medical applications. The synthetized PET should have less structural anomalies in order to be less prone to in vivo oxidation.
The authors’ work on the degradation of the prostheses was carried out at the Laboratory of Physics and Textile Mechanics of the Ecole Nationale Supérieure des Industries Textiles of Mulhouse in collaboration with the Laboratoire de Chimie Organique et Bio-organique, of the École Nationale Supérieure de Chimie de Mulhouse of Mulhouse. The authors’ would like to thank the the Lucien Dreyfuss Foundation, the Regional Council of Alsace, and the Entente Franco-allemande Foundation for their financial help. They would also like to thank the Institute of Biomechanics of Hamburg.