A new approach to improve the local compressive properties of PPDO self-expandable stent

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Abstract

The radial performance of bioabsorbable polymeric intravascular stents is extremely important in assessing the efficiency of these devices in expanding narrow lumen, reducing stent recoil, and recovering to their original states after suffering from pulsating pressure. However, these stents remain inferior to metallic stents. Several thermal treatment conditions (60 °C, 80 °C, and 100 °C for 1 h) were investigated to improve the characteristics of poly(p-dioxanone) (PPDO) self-expandable stents. The local compressive force, stiffness, and viscoelasticity of these stents were also evaluated. Wide-angle X-ray diffraction and different scanning calorimetry measurements were performed to evaluate the recrystalline and thermodynamic changes of molecular chains. The declining conformer entropy of PPDO monofilaments was examined via energy analysis. The untreated stents had compressive modules of 514.80±70.59 mN/mm, which was much higher than those of 80 °C and 100 °C treated stents (332.35±66.08 mN/mm and 394.31±64.71 mN/mm, respectively). Nevertheless, 100 °C annealing stents had less stress relaxation and prior elastic recovery rate of 82.32±3.43 mN and 92.55±1.61%, respectively, showing a much better shape stability than untreated stents (139.51±16.67 mN and 86.18±3.57%, respectively). These findings present important clinical implications in the stent manufacturing process and warrant further study to develop new bioabsorbable stents with outstanding clinical efficacy.

Introduction

Bioabsorbable polymeric intravascular stents are currently being used as promising devices for blood vessels that are narrowed or occluded by disease without long-term thrombosis and restenosis as often reported in permanent metal stents (Kraitzer et al., 2008, Mani et al., 2007, Nair and Laurencin, 2007, Ormiston and Serruys, 2009). These stents have witnessed significant improvements since their introduction, and several absorbable polymer stents are undergoing clinical trials, including Igaki-Tamai (Werner et al., 2016) (Kyoto Medical, MA), REVA stent (Onuma and Serruys, 2011) (Boston Scientific, Natick, MA), and Ideal stent (Onuma and Serruys, 2011) (Bioabsorbable Therapeutics Inc.). Abbott Absorb stent (Onuma et al., 2014) (Abbott Vascular, Santa Clara CA) was certified by FDA as the first commercial absorbable stent for coronary arteries. Given the semi-crystalline structure of the polymer, a monofilament is obtained after extrusion and drawn to achieve stents with excellent mechanical properties. Correspondingly, the braiding technique (Ahlhelm et al., 2009, King and Chung, 2013, Zou et al., 2014) for stent configuration offers a favorable alternative to the laser-cut technique, which is mostly used for metal stents. However, absorbable polymers remain mechanically weaker and have a relatively higher stent recoil degree than metals. The possibility of improving the mechanical properties of absorbable polymeric stents via thermal treatment has been proposed in this context (Welch et al., 2009, Li et al., 2015).

Stent implantation is expected to expand the diseased lumen, provide sufficient support, and maintain blood flow (Freeman et al., 2010, Vorwerk et al., 1994). In this case, significant radial performance and low intrinsic stent recoil must be emphasized to achieve a larger minimum lumen diameter and reduce the possibility of facing clinical complications (Barragan et al., 2000, Rieu et al., 1999). In engineering, compressive force in radial direction, instead of expansive force, is the foremost property for evaluating the ability of stents to hold vessels open immediately after they are released from the sheath (Duerig et al., 2000, Li et al., 2014b, Wang and Zhang, 2016). Furthermore, the intrinsic recoil of stents may be attributed to lack of stiffness, which is mainly determined by the crystallinity region of the material (Borghi et al., 2014). By contrast, the viscoelastic characterization of polymers can introduce undesirable creep and stress relaxation that can lead to the recoil of a stent.

Poly(p-dioxanone) (PPDO) monofilaments, which were certified by FDA as safe to humans (Ishikiriyama et al., 1998), were used in this research as raw materials for braiding bioabsorbable stents. Several studies have reported that the in-stent restenosis process peaks at the third month and rarely reaches its peak thereafter (Kimura et al., 1997, Kimura et al., 1996, Safian and Freed, 2001). Meanwhile, luminal enlargement occurs between six months and five years after balloon angioplasty for most patients (Erbel et al., 2007, Ormiston et al., 1996). And stents in body exist longer than 6 months may constrain lumen expansion process. Therefore, the ideal stent is expected to support lumen dilatation for more than three months but not beyond six months. To achieve this clinical requirement, PPDO presents a promising alternative for fabricating absorbable stents because its degradation time is approximately 180 days.

However, similar to other polymers, PPDO is inferior to metal in terms of its functional mechanical characteristics, thereby motivating researchers to improve the performance of this material through various design modifications and manufacturing techniques. Bai et al. reported that adding 10% poly(lactic-co-glycolic acid) (PLGA) to PPDO greatly increased the tensile strength of blends (Bai et al., 2015). Dang et al. incorporated hierarchical hemisphere-like CaCO3 (HSCC) into poly(p-dioxanone), which simultaneously enhanced the crystallinity, tensile strength, elongation at break, and Young's modulus of PPDO (Dang et al., 2015). Yang et al. polymerized p-dioxanone with montmorillonite to increase the crystallization rate and melt strength of PPDO materials (Yang et al., 2009). This process also blew PPDO into thin films with excellent mechanical properties. Blending and chemical modifications are frequently performed to improve the functional properties of PPDO materials. However, these advancements change the components of raw materials that are not certified by the FDA, thereby leading to safety issues and affecting the degradation time. Bernard et al. and Sabino et al. discussed the crystallinity and morphology of PPDO, and observed some variations in the morphology and diameter of spherulite when treated under different crystallization temperatures ranging from 60 °C to more than 90 °C (Sabino et al., 2001). Pezzin et al. reported the recrystallinity of PPDO treated between 70 °C and 85 °C (Pezzin et al., 2001). The structural change of polymers affected the mechanical characteristics of their products. Gang Li et al. studied the heat-setting treatment for biomedical PPDO weft-knitted stents (Li et al., 2015, Li et al., 2014a), and validated the potential of this technique in enhancing the properties of these stents. The mechanical properties of the knitted stents differed from those of the filaments treated under various conditions. Obviously, the structural variation of the devices may change the thermal treatment results obtained from treating raw materials. Base on the lack of research about annealing effect on radial performance of braided devices, the influence of thermal treatment on radial characteristics of PPDO stents must be analyzed to guide the design and manufacture.

In this work, PPDO braiding stents were thermally treated for 1 h under different temperatures (60 °C, 80 °C, and 100 °C). The related properties of these stents, including local compressive force, compressive module, elastic recovery rate, stress relaxation, and energy loss during the compression and recovery processes, were then measured and compared with those of untreated stents. Afterwards, wide-angle X-ray diffraction (WAXD) and different scanning calorimetry (DSC) were performed to evaluate the molecular structure of PPDO monofilaments from different thermally treated groups. Considering the initial strains and stresses as well as the polymer structure morphology introduced by the braiding process, the effects of thermal annealing temperature on these functional properties were discussed. Thermodynamics theory was also introduced to interpret the relationship between molecular structure and mechanical properties.

Section snippets

Materials

PPDO monofilaments were manufactured by melt spinning in our university. A blender instrument (DHY4/12, Shanghai Dehong Co., Ltd, China) and self-made drawing instrument were used. The temperature was 185 °C to 190 °C when melting. Drawing process was conducted in three zones, which were water bath for cooling, room temperature zone with drawing ratio of 7, and heating zone with temperature of 50–80 °C, drawing ratio of 1.2. These monofilaments had a diameter of 0.23±0.02 mm, measured by

Results

As shown in Fig. 4, the control group and the group treated at 60 °C obtained the highest local compressive force (1211.37±31.18 mN and 1200.29±104.22 mN, respectively), while that of the groups treated at 80 °C and 100 °C slightly decreased to 1143.33±103.24 mN and 1129.22±11.08 mN, respectively. Interestingly, no significant differences were observed among these groups despite their slight variation.

Fig. 5 presents the results of compressive module. The control group had a higher compressive module

Thermal treatment improves the radial performance of PPDO braiding stents

Thermal treatment has been used in various industries to improve the mechanical properties of polymers. Mohajir et al. studied polyvinylidene flouoride and found that the long-term mechanical behavior of this polymer could be improved by using an appropriate annealing treatment (El Mohajir and Heymans, 2001). Tsuji et al. reported that increasing the crystallinity of poly(L-lactide) films would also increase their Young's modules and tensile strength (Tsuji and Ikada, 1995). Chang et al. showed

Conclusions

The thermal treatment process improved the radial performance of PPDO self-expandable stents. The untreated and 60 °C annealing stents showed higher compressive stiffness, and prior viscoelasticity and shape stability were obtained at higher annealing temperatures (80 °C and 100 °C). Nevertheless, the local compressive force did not show any significant differences across various annealing conditions. These results demonstrated profitable changes in the crystalline content and morphology of the

Acknowledgements

The project is support by 111 project (grant No. B07024), the Fundamental Research Funds for the Central Universities (grant No. 2232015A3-02 and 16D110119), Science and Technology Support Program of Shanghai (grant No. 16441903803), and National Postdoctoral Foundation (grant No. 2016M590299).

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