Structural optimization of degradable polymer vascular stents based on surrogate models.

The clinical performance of biodegradable polymer stents implanted in blood vessels is affected by uneven degradation. Stress distribution plays an important role in polymer degradation, and local stress concentration leads to the premature fracture of stents. Numerical simulations combined with in vitro experimental validation can accurately describe the degradation process and perform structural optimization. Compared with traditional design techniques, optimization based on surrogate models is more scientifically effective. Three stent structures were designed and optimized, with the effective working time during degradation as the optimization goal. The finite element method was employed to simulate the degradation process of the stent. Surrogate models were employed to establish the functional relationship between the design parameters and the degradation performance. The proposed function models accurately predicted the degradation performance of various stents. The optimized stent structures demonstrated improved degradation performance, with the kriging model showing a better optimization effect. This study provided a novel approach for optimizing the structural design of biodegradable polymer stents to enhance degradation performance.

Symmetrical structure design of PLGA Biodegradable sinus stents and structure optimization based on surrogate models.

This study aims to enhance the degradation uniformity of PLGA sinus stents to minimize fracture risk caused by stress corrosion. Symmetric stent structures were introduced and compared to sinusoidal structure in terms of stress and degradation uniformity during implantation and degradation processes. Three surrogate models were employed to optimize the honeycomb-like structure. Results showed honeycomb-like structures exhibited the superior stress distribution and highest degradation uniformity. The kriging model achieved the smallest error and degradation uniformity of 83.24%. In conclusion, enhancing the symmetry of stent structures improves degradation uniformity, and the kriging model has potential for the optimization of stent structures.

Effect of ureteral stent length and implantation position on migration after implantation.

BACKGROUND: Ureteral obstruction is a urinary system disease that causes urinary retention, renal injury, renal colic, and infection. Ureteral stents are often used for conservative treatment in clinics, and their migration usually results in ureteral stent failure. The migrations include proximal migration to the kidney side and distal migration to the bladder side, but the biomechanism of stent migration is still unknown. METHOD: Finite element models of stents with lengths from 6-30 cm were developed. The stents were implanted into the middle of the ureter to analyze the effect of stent length on its migration, and the effect of stent implantation position on 6-cm-long stent migration was also observed. The stents' maximum axial displacement was used to assess the ease of stent migration. A time-varying pressure was applied to the ureter outer wall to simulate peristalsis. The stent and ureter adopted friction contact conditions. The two ends of the ureter were fixed. The radial displacement of the ureter was used to evaluate the effect of the stent on peristalsis. RESULTS AND DISCUSSION: The maximum migration occurs in the positive direction for a 6-cm-long stent implanted at the proximal ureter (CD and DE), but in the negative direction at the distal ureter (FG and GH). The 6-cm-long stent demonstrated almost no effect on ureteral peristalsis. The 12-cm-long stent diminished the radial displacement of the ureter from 3-5 s. The 18-cm stent diminished the radial displacement of the ureter from 0-8 s, and the radial displacement within 2-6 s was weaker than other time. The 24-cm stent diminished the radial displacement of the ureter from 0-8 s, and the radial displacement within 1-7 s was weaker than other time. CONCLUSION: The biomechanism of stent migration and ureteral peristalsis weakening after stent implantation was explored. Shorter stents were more likely to migrate. The implantation position had less influence on ureteral peristalsis compared with the stent length, which provided a reference for stent design aimed at reducing stent migration. Stent length was the main factor affecting ureteral peristalsis. This study provides a reference for the study of ureteral peristalsis.

The differences between surface degradation and bulk degradation of FEM on the prediction of the degradation time for poly (lactic-co-glycolic acid) stent.

The degradation time is a crucial factor in evaluating the performance of poly (lactic-co-glycolic acid) (PLGA) stents. Bulk degradation mode was commonly used to analyze the stent degradation behavior by finite element approach. However, the PLGA stents may present surface degradation more than bulk degradation under certain conditions, which will greatly affect the degradation time after implantation. In this study, the degradation processes of the poly (lactic-co-glycolic acid) stent were reproduced utilizing finite element analysis. Both bulk degradation and surface degradation modes were considered. The correlation between tensile stress and degradation rate was investigated. The degradation time was analyzed selectively. The stress distribution, fracture, and mass loss were also compared between bulk degradation mode and surface degradation mode. The simulation results showed that, in both evolution modes, the degradation began at the 'peak-valley' region and fracture occurred at the cross of links and rings. Additionally, high levels of Von-Mises stress were observed in these two regions. Compared with bulk degradation, the fracture time of the stent was delayed by 63% in the surface degradation mode. In conclusion, the mass loss rate and scaffolding period showed great differences between surface degradation and bulk degradation. Based on this study, it is suggested that bulk degradation mode is not applicable to the case of inadequate water uptake mode, such as the tracheal stent degradation process. More experimental research should be carried out to accurately predict the scaffolding period after implantation. The mechanical properties of the fracture zone should be strengthened.

Effect of strain on degradation behaviors of WE43, Fe and Zn wires.

The biodegradable metallic devices undergo stress/strain-induced corrosion when they are used for load-bearing applications. The stress/strain induced-corrosion behavior causes differences in corrosion rate, corrosion morphology, strain distribution and mechanical performance of the devices. One representative example is the biodegradable stent. Biodegradable stents undergo complex inhomogeneous deformation that can cause dramatic non-uniform stent degradation, resulting in stress concentration and stents failure. The degradation of biodegradable devices requires special attention to the mutual effect between the applied strain and degradation. The quantitative relationship between strain and corrosion of the sample alloys (WE43, Fe and Zn), selected from three typical biodegradable metals, is firstly investigated and compared in this study. The in vitro degradation and the strength retention of WE43, Fe and Zn wires were investigated under different elastic and plastic strain levels ranging from 0.1% to 30%. The results indicated that the applied strain could bring down the corrosion potential, increase corrosion current and accelerate the degradation of three biodegradable metals. Specifically, remarkable enhanced localized corrosion was observed for plastic strained WE43 compared with those with elastic strains. This localized corrosion morphology significantly accelerated the strength decline at first, while the differences diminished with longer immersion period. Fe and Zn exhibited increased degradation with plastic strain applications than those under elastic strains. However, the degradation was not further increased with the increasing magnitude of plastic strains. Moreover, the bended wires were subcutaneously implanted in the dorsal aspect of the rats and the effect of bending deformation on in vitro and in vivo degradation of three metallic wires were also compared. The U-bended WE43 wires suffered more severe in vitro degradation at the stress concentrated region. Surprisingly, the early fracture of the undeformed regions was observed in the in vivo test. In conclusion, the corrosion rate, corrosion morphology and mechanical properties of WE43, Fe and Zn was sensitive to magnitude of the applied strains. The quantification results provided new insights into understanding the strain-dependent corrosion of three biodegradable metals both in vitro and in vivo. STATEMENT OF SIGNIFICANCE: Biodegradable implants are subjected to various mechanical environment during the deployment and subsequent physiological activity. It is necessary to have a clear understanding of the effects of the applied stress on degradation. This study addresses the quantitative effects of applied strain/stress on the in vitro and in vivo degradation of three typical biodegradable metals (Mg, Fe and Zn). These quantification results provide new insights into understanding the strain-induced corrosion of three metals.

Effect of stress on corrosion of high-purity magnesium in vitro and in vivo.

Magnesium-based implants are subjected to complicated stresses during implantation in the human body. The stress effects on corrosion of magnesium (Mg) in vitro were investigated in previous studies, whereas in this study, the corrosion behaviors of high-purity (HP) Mg under stress were comparatively studied in vitro in Hank's solution and in vivo in the subcutaneous environment of rats. Loading devices were designed to apply compressive stress (15.1 ±â€¯0.5 MPa) and tensile stress (13.2 ±â€¯0.2 MPa) on HP Mg specimens both in vitro and in vivo. Corrosion rates of HP Mg were characterized by mass and volume losses. It was shown that the applied compressive stress had no effect on in vitro corrosion behaviors and the applied tensile stress accelerated the in vitro corrosion, thereby causing severe pitting corrosions and stress corrosion cracking (SCC). However, there was no significant change for corrosion behaviors in vivo under neither compressive stress nor tensile stress. Severe pitting corrosion and SCC did not occur in vivo. Histological evaluation revealed that a fibrotic capsule induced by foreign body reaction was formed on the corrosion surfaces of HP Mg in the subcutaneous environment. It was proposed that the fibrotic capsule suppressed the effects of stress in vivo by protecting the corrosion surfaces. These results provided new insights into understanding the stress effects on the corrosion of Mg both in vitro and in vivo. STATEMENT OF SIGNIFICANCE: Mg and its alloys have shown potential as biodegradable metallic materials. During implantation, Mg is subjected to various mechanical environments in the human body. It is necessary to have a clear understanding of different effects of stress on Mg corrosion. However, few studies were performed in vivo. It is important to analyze the effect of quantitative stress on Mg corrosion in vivo. Therefore, in this study, quantitative stresses were applied on Mg both in vitro and in vivo. The effects of stress on in vitro and in vivo corrosions of Mg were investigated and compared.

A quantitative study on magnesium alloy stent biodegradation.

Insufficient scaffolding time in the process of rapid corrosion is the main problem of magnesium alloy stent (MAS). Finite element method had been used to investigate corrosion of MAS. However, related researches mostly described all elements suffered corrosion in view of one-dimensional corrosion. Multi-dimensional corrosions significantly influence mechanical integrity of MAS structures such as edges and corners. In this study, the effects of multi-dimensional corrosion were studied using experiment quantitatively, then a phenomenological corrosion model was developed to consider these effects. We implemented immersion test with magnesium alloy (AZ31B) cubes, which had different numbers of exposed surfaces to analyze differences of dimension. It was indicated that corrosion rates of cubes are almost proportional to their exposed-surface numbers, especially when pitting corrosions are not marked. The cubes also represented the hexahedron elements in simulation. In conclusion, corrosion rate of every element accelerates by increasing corrosion-surface numbers in multi-dimensional corrosion. The damage ratios among elements with the same size are proportional to the ratios of corrosion-surface numbers under uniform corrosion. The finite element simulation using proposed model provided more details of changes of morphology and mechanics in scaffolding time by removing 25.7% of elements of MAS. The proposed corrosion model reflected the effects of multi-dimension on corrosions. It would be used to predict degradation process of MAS quantitatively.

Effects of different fluid shear stress patterns on the in vitro degradation of poly(lactide-co-glycolide) acid membranes.

The applications of poly (lactide-co-glycolide) acid (PLGA) for coating or fabricating polymeric biodegradable stents (BDSs) have drawn more attention. The fluid shear stress has been proved to affect the in vitro degradation process of PLGA membranes. During the maintenance, BDSs could be suffered different patterns of fluid shear stress, but the effect of these different patterns on the whole degradation process is unclear. In this study, in vitro degradation of PLGA membranes was examined with steady, sinusoid, and squarewave fluid shear stress patterns in 150 mL deionized water at 37°C for 20 days, emphasizing on the changes in the viscosity of the degradation solution, mechanical, and morphological properties of the samples. The unsteady fluid shear stress with the same average magnitude as the steady one accelerate the in vitro degradation process of PLGA membranes in terms of maximum fluid shear stress and "window" of effectiveness. Maximum fluid shear stress accelerates the in vitro degradation of molecular fragments that diffused out in the solution while the "window" of effectiveness affects too in the early stage. Besides, maximum fluid shear stress and "window" of effectiveness accelerates the in vitro loss of tensile modulus and ultimate strength of the PLGA membranes while the maximum fluid shear stress plays the leading role in the decrease of tensile modulus at the early degradation stage. This study could help advance the degradation design of PLGA membranes under different fluid shear stress patterns for biomedical applications like stents and drug release systems. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 23-30, 2017.

The complex fluctuations of probabilistic Boolean networks.

Probabilistic Boolean networks (PBNs) are extensions of Boolean networks (BNs), and both have been widely used to model biological systems. In this paper, we study the long-range correlations of PBNs based on their corresponding Markov chains. PBN states are quantified by the deviation of their steady-state distributions. The results demonstrate that, compared with BNs, PBNs can exhibit these dynamics over a wider and higher noise range. In addition, the constituent BNs significantly impact the generation of 1/f dynamics of PBNs, and PBNs with homogeneous steady-state distributions tend to sustain the 1/f dynamics over a wider noise range.

Pulmonary oligemia maneuver can alleviate pulmonary artery injury during pulmonary thromboendarterectomy procedure.

BACKGROUND: Pulmonary thromboendarterectomy (PTE) has evolved as a treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to characterize if pulmonary oligemia maneuver (POM) can alleviate pulmonary artery injury during PTE procedure. METHODS: A total of 112 cases of CTEPH admitted to Beijing Anzhen Hospital from March 2002 to August 2011 received PTE procedure. They were retrospectively classified as non-POM group (group A, n = 55) or POM group (group B, n = 57). Members from group B received POM during rewarming period, whereas members from group A did not. RESULTS: There were three (5.45%) early deaths in group A, no death in group B (0) (Fisher's exact test, P = 0.118). Six patients in group A needed extracorporeal membrane oxygenation (ECMO) as life support after the PTE procedure, no patients in group B needed ECMO (Fisher's exact test, P = 0.013). The patients in group B had a shorter intubation and ICU stay, lower mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR), higher partial pressure of oxygen in artery (PaO2) and arterial oxygen saturation (SaO2) and less medical expenditure than patients in group A. With a mean follow-up time of (58.3 ± 30.6) months, two patients in group A and one patient in group B died. The difference of the actuarial survival after the procedure between the two groups did not reach statistical significance. Three months post the PTE procedure, the difference of residual occluded pulmonary segment between the two groups did not reach statistical significance (P = 0.393). CONCLUSION: POM can alleviate pulmonary artery injury, shorten ICU stay and intubation time, and lower down the rate of ECMO after PTE procedure.

[Obstructive sleep apnea-hypopnea syndrome in patients with pulmonary thromboembolism: clinical features and management].

OBJECTIVE: To describe the clinical features of obstructive sleep apnea-hypopnea syndrome (OSAHS) in hospitalized pulmonary thromboembolism (PTE) patients, and to explore its impact on the severity of disease and management among patients with PTE. METHODS: Demographic and clinical characteristics of 28 PTE patients complicated with OSAHS admitted to this hospital from January 2002 to December 2010 were analyzed. A total of 30 PTE patients without OSAHS served as a control group. RESULTS: PTE patients with OSAHS had a significantly lower age of onset of disease [(55 ± 11) yr vs (66 ± 11) yr, t = 3.230, P < 0.01], an increased body mass index (BMI) [(30.1 ± 2.8) kg/m(2) vs (26.1 ± 3.1) kg/m(2), t = -4.161, P < 0.001] and a higher smoking index [(19 ± 6) packs/yr vs (8 ± 4) packs/yr, t = -1.713, P < 0.05] when compared with PTE patients without OSAHS. PaO2 [(70 ± 8) mm Hg vs (79 ± 6) mm Hg, 1 mm Hg = 0.133 kPa, t = 4.233, P < 0.05] and involved lung segments [(8 ± 4) vs (5 ± 3), t = -2.496, P < 0.05] in PTE patients with OSAHS were more severe than those in PTE patients without OSAHS. All patients received anticoagulation and/or thrombolysis treatment, and continuous positive airway pressure (CPAP) ventilation was used in some PTE patients with OSAHS. CONCLUSION: PTE patients with OSAHS had a significantly earlier age of onset of disease and more severe conditions than PTE patients without OSAHS. Treatments including anticoagulation and CPAP should be used in these patients.

Surgical treatment of pulmonary artery sarcoma.

OBJECTIVE: The study objectives were to characterize the prognostic perspectives of pulmonary artery sarcoma and to investigate the effect of distal embolectomy on the prognosis of surgical treatment of pulmonary artery sarcoma. METHODS: Nine patients with pulmonary artery sarcoma were surgically treated at Anzhen Hospital, and the data were retrospectively reviewed. Five patients underwent only pulmonary artery sarcoma resection, and 4 patients underwent both pulmonary artery sarcoma resection and distal embolectomy. RESULTS: There was no in-hospital mortality. Four patients had lung ischemia-reperfusion injury, 3 of whom recovered with the support of extended ventilation and positive end-expiratory pressure, and 1 of whom recovered with extracorporeal membrane oxygenation support. During the follow-up, 5 patients who did not undergo distal embolectomy died 6 to 29 months after the procedure, with a median survival time of 10 months. Of the 4 patients undergoing distal embolectomy, 3 died 30, 37, and 43 months after the procedure, and 1 is still alive 39 months after the procedure. All 8 deaths were due to local or systemic recurrence. The patients who underwent distal embolectomy lived longer than the patients who did not undergo distal embolectomy (log-rank test, x(2) = 7.914, P = .005). CONCLUSIONS: Radical surgical resection provides the only chance of survival for patients with pulmonary artery sarcoma, and distal embolectomy may further extend survival for these patients.

[Clinical analysis of 62 cases of chronic thromboembolic pulmonary hypertension treated with pulmonary thromboendarterectomy without early and late deaths].

OBJECTIVE: To retrospectively evaluate the effects of pulmonary thromboendarterectomy (PTE) on chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Sixty-two cases of CTEPH operated with PTE from October 2002 to September 2008 at Anzhen Hospital were retrospectively reviewed and were assigned into either proximal CTEPH group (n = 46) or distal CTEPH group (n = 16). RESULT: No early death was reported. 15 had residual pulmonary hypertension and 23 had pulmonary reperfusion injury postoperatively. And reperfusion injury was recovered with the support of ventilation or ECMO. Between pre and post-procedure, the pulmonary artery systolic pressure changed from 91 +/- 38 mm Hg to 53 +/- 21 mm Hg, the pulmonary vascular resistance from 916 +/- 548 dynxsxcm(-5) to 368 +/- 302 dynxsxcm(-5) (t = 6.896, P = 0.0001), and the arterial partial pressure of oxygen (PaO(2)) from 51 +/- 7 mm Hg to 90 +/- 7 mm Hg and the arterial oxygen saturation (SaO(2)) from 87.0% +/- 3.9% to 96.1% +/- 3.3%, P < 0.05. With the follow-up of (24.8 +/- 14.6) months (cumulative follow-up was 121.6 patient-years), there was no late death and 38 were in NYHA functional class I, 20 class II, 2 class III and 2 class IV. According to Kaplan-Meier actuarial curve, the freedom from reembolism at 3 years was 96.7% +/- 2.8%. The linear bleeding rate related to anticoagulation was 2.47% patient-years, and the linear thromboembolic rate related to anticoagulation is 1.64% patient-years. CONCLUSION: The early and mid-long term survival rate of PTE procedure on CTEPH is acceptable and the complication rate related to anticoagulation with warfarin is relatively low.

[Expression of various matrix metalloproteinases in mice with hyperoxia-induced acute lung injury].

OBJECTIVE: To investigate the role of matrix metalloproteinases (MMPs) and extracellular matrix metalloproteinase inducer (EMMPRIN) in the pathogenesis of acute lung injury induced by hyperoxia. METHODS: Fifty four mice were exposed in sealed cages to >98% oxygen (for 24-72 hours), and another 18 mice to room air. The severity of lung injury was assessed, and the expression of mRNA and protein of MMP-2, MMP-9 and EMMPRIN in lung tissue, after exposure for 24, 48 and 72 hours of hyperoxia were studied by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: Hyperoxia caused acute lung injury; this was accompanied by increased expression of an upregulation of MMP-2, MMP-9 and EMMPRIN mRNA and protein in lung tissues. CONCLUSION: Hyperoxia causes acute lung injury in mice; increases in MMP-2, MMP-9 and EMMPRIN may play an important role in the development of hyperoxia induced lung injury in mice.