Startseite Naturwissenschaften Study on the chronic toxicity and carcinogenicity of iron-based bioabsorbable stents
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Study on the chronic toxicity and carcinogenicity of iron-based bioabsorbable stents

  • Xiaoli Shi , Lu Zhang , Yanfen Liu , Jinyu Wang , Gui Zhang , Haiping Qi , Wanqian Zhang , Deyuan Zhang und Jin Wang EMAIL logo
Veröffentlicht/Copyright: 25. Februar 2023
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Nanotechnology Reviews
Aus der Zeitschrift Nanotechnology Reviews Band 12 Heft 1

Abstract

Fe-based stents have been made a figure in biodegradable stents by their good mechanical capacity and biocompatibility, appropriate strength–ductility combination. Although the iron corrosion rate was not ideal, which had been optimized by iron alloy and polymer coating introduction. As a long-term implanted biodegradable material, the real concern about iron-based stents mainly laid in long-term biosafety. In this work, rats were used as an animal model to study the chronic toxicity and carcinogenicity of iron-based stents. Two years later, the changes in body weight and the physiological status during the experiment were monitored, and the blood routine and blood analysis combined with the health of major organs and histopathological tests were performed. The results demonstrated that there was no significant difference compared with the control group (316L SS) in body weight, blood routine index, blood biochemical index, and carcinogenic rate that further confirmed the biosafety of iron-based material.

Keywords: Fe-based stents; chronic toxicity; carcinogenicity; bioabsorbable; coronary

Abbreviations

ALB

albumen

ALP

alkaline phosphatase

ALT

glutamate pyruvate transaminase

AST

glutamic oxalacetic transaminase

BASO

basophile granulocyte

BUN

urea nitrogen

Ca

calcium

CHOL

cholesterol

Cl

serum chloride

CRE

creatinine

EOS

eosinophile

GLU

glutamic acid

HCT

hematocrit

HGB

hemoglobin

K

serum potassium

LYM

lymphocyte

MCV

mean corpuscular volume

MONO

monocyte count

Na

serum natrium

NEU

neurilemmal

P

phosphorous

PLT

platelet

RBC

red blood cell

TB

serum total bilirubin

TG

triglyceride

WBC

whole blood cell

1 Introduction

Biodegradable stents (BDS), designed to support the arterial wall and disappear after its remodeling [1–3], address the problem of conventional stents that may form thrombus and impede revascularization [4–6]. As the fourth stent revolution following simple balloon expansion, bare metal stents, and drug-eluting stents [4,7], BDS has received widespread attention since it was first proposed 20 years ago [8]. However, some challenges in design need to be noticed and there is still room for performance optimization to reach a satisfactory goal. An ideal biodegradable scaffold should have good biocompatibility, appropriate strength–ductility combination, corrosion rate matching the tissue healing rate, and requisite fatigue strength [9–11]. Nowadays, there are two broad categories of materials generally used for BDS: biodegradable biopolymers and biodegradable metals and alloys [12]. However, no single material, whether it is a biodegradable polymer or metal, has been able to establish a perfect balance among biocompatibility, mechanical strength, and ductility.

Fe- and Mg-based alloys are the two kinds of biodegradable metallic materials for fabricating biodegradable stents [7,13,14]. Recently, Zn-based materials have also emerged as alternative biodegradable stent materials [15–19]. Comparable mechanical properties to 316L stainless steel (316L SS) give Fe-based alloys an advantage over Mg-based and Zn-based alloys as a material for stents [20]. Meanwhile, in the physical environment, the corrosion products of iron do not release gas or cause alkalization of body fluid [21]. In addition, iron is an essential element for the human body [22]. Nevertheless, currently, the magnesium-alloy resorbable stent devices are supported by the most robust data [23–25]. On the one hand, the lower-than-required degradation rate and the slow rate of clearance from the vessel up to 18 months after implantation limited its development in BDS [7,26].

To date, many efforts have been made to optimize the degradation rate of iron, and iron alloying is one of the commonly used methods [27,28]. Recently, it is reported that a new strategy, which takes advantage of the controllable degradation of polymers to accelerate iron degradation [29,30] can realize the controlled degradation of iron-based stents in the needed time. This strategy was inspired by the lower local pH generated by the polymer hydrolysis near the iron surface and the alleviation from the passivated layer produced by the polymer coating. Based on this strategy, directions are pointed to the balancing of rapid corrosion and good biocompatibility maintenance, which compensates for the deficiency of iron-based absorbable stent. In our previous work [31], we presented a novel drug-eluting absorbable iron stent (IBS stent), in which a nitriding technology [32] and a zinc buffer covering the whole strut before the sirolimus-eluted poly-L-lactic acid coating were proposed. IBS is a fully degradable scaffold, which begins to degrade after the completion of effective vascular support (i.e., 3–6 months after implantation) and completely degrades after about 2 years.

On the other hand, the concern about carcinogenicity also hinders the clinical transformation and application of iron-based stents. Epidemiological studies have demonstrated an association between excess iron and increased incidence and risk of cancer [33]. Iron is an essential co-factor for a multitude of enzymes involved in diverse physiological processes such as oxygen binding, DNA synthesis, and redox enzyme activity [34], and it could decrease the proliferation rate of vascular smooth muscle cells [35]. Iron is also a critical intermediate in the generation of reactive oxygen species (ROS) that can damage cellular structures and accelerate both aging and cancer [36,37]. Therefore, after the degradation of the iron-based stents is controlled, whether the excessive iron ions correlate with cancer in vivo still needs systematic research. To our knowledge, no study to date has systematically examined the carcinogenicity of iron-based stents in vivo through long-term animal implantation, while the internal environment with important research significance is different from and more complex than the cellular level.

So far, research on IBS stent [26,31,38–41] has mainly focused on the design, characterization, cytocompatibility, long-term in vivo biocorrosion, biotoxicity, and resorption of the stents. However, the link between iron from IBS and cancer still requires long-term in vivo scientific studies. In this study, rats were selected as model animals to investigate the iron concentrations before and after the degradation of the IBS stent, and the 316L SS stent was used as the control group. For the 2-year chronic toxicity and carcinogenicity research, rats were the model animals, and the IBS stent was implanted into the abdominal aorta of rats. The body weight and physiological status of the animals during the experiment were monitored. Two years later, blood routine, blood analysis, major organ health, and histopathological tests were obtained, providing systematic evidence for the association of IBS implantation with chronic toxicity and carcinogenicity.

2 Materials and methods

2.1 Materials

The iron bioabsorbable coronary scaffold (IBS) was designed and manufactured by Biotyx Medical (Shenzhen) Co., Ltd (Shenzhen, China). The technological parameters and characterizations have been described in our previous work [31]. IBS samples were used as the test group, and 316L SS stents were used as the control group. All stents were 2.5 mm in diameter and 12 mm in length, and the number of stents in each group was 120. To prepare the IBS stent, the iron strut was nitride and drawn to obtain a pure iron tube, which was further subjected to laser cutting, electrochemically polishing, development of point riveting, pure zinc layer (∼600 nm) coating, and sirolimus poly-dl-lactic acid (PDLLA, Amorphous; Evonik Industries, Germany) spraying. The IBS containing Fe–0.05%N, Zn, Au, PDLLA, and sirolimus is degradable and absorbed in coronary arteries. The control group used was 316L SS (316L stainless steel bare stent, Lifetech Scientific, Shenzhen, China), which was already in the market, with the same specification as the IBS scaffold (2.5 mm × 12 mm).

2.2 Animal models

The study protocol was compliant with the Regulations for the Administration of Affairs Concerning Experimental Animals (a Chinese Government publication). Around 240 Wistar rats with the weight of 250–350 g were randomly separated to the IBS scaffold group and 316L SS control group, with 120 animals in each group, half male and half female.

2.3 Implantation procedure

The weighed rats were marked with earmarks. After anesthetized with 0.3% pentobarbital sodium with a dose of 30 mg/kg via intraperitoneal injection, each animal received an intravenous injection of heparin (200 U/kg B.W.). The left common carotid artery was separated and punctured. From the puncture, a metal guidewire (0.014 in) was delivered into the abdominal aorta. The stent was delivered along the guidewire to the abdominal aorta, then inflated by the balloon with a pressure of 6–8 atm for 10 s. One scaffold was implanted in each animal. Prior to the removal of the balloon catheter and guidewire, decompression was applied for 2 s. The wound was closed with sutures before sterilization. Ampicillin sodium was administered subcutaneously at a dose of 50 mg/kg/day for the first 3 days and aspirin at a dose of 5 mg/kg/day for 14 days.

2.4 Postoperative care

The IBS scaffold group and the 316L SS control group animals were housed and care was provided, in accordance with the Guide for the Care and Use of Laboratory Animals. Animals were observed daily for recording significant changes in terms of the eating habits, alertness, obvious loss in body weight, and palpation, which were carried out at least once a week for detectable masses. This examination included, but was not limited to, the changes in the skin and fur, eyes and mucous membranes, as well as the respiratory, circulatory, autonomic and central nervous system, somatic motor activity, and behavioral patterns. Abnormalities in the examinations were recorded. The dead animals and the euthanatized animals were subjected to a full gross necropsy during the experiment. If euthanasia before the schedule was required for the welfare of an animal, a full necropsy was performed after euthanasia.

2.5 Terminal procedures

Recommended duration for the evaluation of tumorigenicity in rats is about 2 years. At the termination of study, a majority of the animals in each group should have been survived for euthanasia or been terminated early for study-related reasons such as increased tumor incidence, spontaneous tumors, or toxicity of the test article. It is expected that a minimum of 50% of the animals per sex and per group should survive until final study termination barring the above reasons. Moreover, the number of survivors or study-related terminations should be sufficient for the detection of effects at the P < 0.05 level of significance.

2.6 Hematology and blood chemistry assays

At the end of the experiment, the animals were weighed and food was withheld for up to 20 h before anesthesia. Blood samples were collected from the posterior vena cava for a complete blood cell count with differential and chemistry analyses. Hematology and biochemical determination on blood were performed by a biochemical blood analyzer (Hitachi 7080, Tokyo, Japan). Specific items are listed below:

  1. Hematology: WBC, RBC, HGB, MCV, HCT, PLT, NEU, LYM, MONO, EOS, BASO.

  2. Biochemistry: ALT, AST, ALP, ALB, GLU, Ca, CHOL, CRE, P, K, TB, TG, Na, Cl, BUN.

2.7 Gross pathology

All animals were subjected to full gross necropsy including examination of the external surface of the body, all orifices, cranial, thoracic, abdominal cavities, and their contents. The adrenals, brain, epididymis, heart, kidneys, liver, ovaries, spleen, testes, thymus, and uterus were wet-weighed as soon as possible after dissection. Paired organs were weighted together. The tissues were preserved in 10% neutral buffered formalin until further processing.

2.8 Histopathology

A full histopathological examination of organs and tissues of animals in the IBS and 316L SS control group was carried out. All gross lesions were examined, documented, and photographed. The implantation sites were analyzed and documented in detail. As for the carcinogenicity study, the types and numbers of tumors in both the test and the control group were recorded. The tissues were processed using standard histological techniques, sectioned, and stained with hematoxylin and eosin. Microscopic evaluation was conducted.

2.9 Evaluation and statistical analysis

The test and control groups were considered as the variables of comparison. Data were analyzed separately for male and female animals. Statistical analyses were performed for the body weight, organ weight, organ/body weight ratios, hematology, and chemical pathology values. Descriptive statistics and group comparisons of data were accomplished with a validated statistical software package. After screening the data for normality and equal variance, the appropriate parametric or nonparametric tests were performed. Normally distributed data with equal variance were considered parametric and evaluated using an “unpaired t-test.” If the data were nonparametric, two-sample t-test of unequal variance was used to compare the two groups. The statistical significance was determined with the aid of the commercially available software (SPSS version 15). The calculated probability (P) values less than 0.05 were considered statistically significant.

3 Results

3.1 Postoperative care

No toxicity response was found in animal experiment observations during the test period in the test group and in the control group. In the two groups, deaths were caused by common diseases and spontaneous tumorigenesis. The death rate of the test group was similar to the control group, as shown in Table 1.

Table 1

Death of test group and control group

Groups Male Female
IBS group 316L SS group IBS group 316L SS group
Death number during the test period 22 24 25 26
Death number euthanized at the end of the test 38 36 35 34
Total number 60 60 60 60
Survival rate at the end of the test (%) 63.3 60.0 58.3 56.7

Body weights of the animals of each sex in the sample and control group were measured every month after implantation. The measured weights of male and female animals are shown in Figure 1, there was no significant difference in body weight between the test group and the control group, P＞0.05. Individual weight gain and mean group body weight for both male and female animals were considered to be clinically acceptable after implantation.

Figure 1 The curves of body weight.
Figure 1

The curves of body weight.

3.2 Hematology and blood chemistry assays

As shown in Figure 2, the hematology values showed no evidence of treatment-induced effects and the results of the test and control groups were comparable. Compared with the control group, the platelet (PLT) was lower in the male rats of the test group (P＜0.05). The RBC, NEU, and BASO were higher in the female rats of the test group than in the control group (P＜0.05). The differences between the two groups had no relation to sex and the data were all within the normal laboratory ranges. The rest of the data in the test group had no significant difference from the data in the control group. The results are shown in Table 2.

Figure 2 Hematology results.
Figure 2

Hematology results.

Table 2

Summary of hematology data

Sex Parameter IBS 316L SS
Mean ± SD Mean ± SD
Male WBC (×109/L) 5.27 ± 1.60 5.85 ± 1.74
RBC (×1012/L) 8.70 ± 0.89 8.59 ± 0.26
HGB (g/L) 148.78 ± 14.25 149.50 ± 13.47
MCV (%) 42.93 ± 4.87 43.49 ± 1.19
HCT (fL) 56.30 ± 1.01 55.65 ± 1.39
PLT (×109/L) 920 ± 84.15* 989.40 ± 67.6
NEU (%) 15.10 ± 3.85 14.48 ± 5.45
LYM (%) 79.74 ± 5.57 77.66 ± 6.36
MONO (%) 6.24 ± 2.17 6.09 ± 1.66
EOS (%) 1.29 ± 0.97 1.76 ± 0.35
BASO (%) 0.00 ± 0.00 0.01 ± 0.03
Female WBC (×109/L) 4.50 ± 0.55 3.11 ± 0.86
RBC (×1012/L) 7.85 ± 0.45* 7.32 ± 0.22
HGB (g/L) 141.60 ± 16.95 140.90 ± 14.01
MCV (%) 44.49 ± 2.81 39.70 ± 4.42
HCT (fL) 60.53 ± 1.88 59.26 ± 1.43
PLT (×109/L) 828.00 ± 63.32 832.40 ± 54.47
NEU (%) 14.86 ± 4.74* 12.78 ± 5.54
LYM (%) 75.21 ± 4.62 74.54 ± 10.54
MONO (%) 6.22 ± 1.22 6.18 ± 2.10
EOS (%) 0.51 ± 0.03 0.50 ± 0.02
BASO (%) 2.20 ± 0.87* 1.9 ± 0.98

SD, standard deviation.

*Data showed a statistically significant difference between the control and test group (P＜0.05).

The biochemistry values showed no evidence of the treatment-induced effects and were comparable between the test and control groups. Compared with the control group of the same sex, male rats in the test group had lower ALT (P＜0.05) and higher CRE (P＜0.05), while female rats had lower ALP (P＜0.01), GLU, and P (P＜0.05). The data are all within the normal laboratory ranges. The rest of the data in the test group had no significant difference from the data in the control group. The specific values are shown in Table 3 (Figure 3).

Table 3

Summary of chemical pathology data

Parameter Males Females
IBS (Mean ± SD) 316L SS (Mean ± SD) IBS (Mean ± SD) 316L SS (Mean ± SD)
ALT (U/L) 62.00 ± 24.3* 74.39 ± 16.30 86.04 ± 24.47 76.04 ± 25.94
AST (U/L) 170.7 ± 37.8 154.11 ± 19.94 147.86 ± 29.47 164.32 ± 26.91
ALP (U/L) 102.11 ± 22.91 106.32 ± 22.00 87.00 ± 15.85* 108.55 ± 18.52
ALB (g/dL) 3.25 ± 0.31 3.15 ± 0.25 3.03 ± 0.25 2.90 ± 0.20
GLU (mg/dL) 148.72 ± 25.32 133.81 ± 32.28 113.71 ± 34.11* 152.99 ± 20.37
Ca (mg/dL) 9.47 ± 0.85 9.74 ± 0.61 9.38 ± 0.52 9.74 ± 0.74
CHOL (mg/dL) 93.58 ± 18.49 95.65 ± 14.68 95.84 ± 14.58 93.10 ± 20.86
CRE (mg/dL) 0.34 ± 0.10* 0.27 ± 0.04 0.32 ± 0.03 0.34 ± 0.07
P (mg/dL) 9.33 ± 2.27 8.52 ± 1.54 7.04 ± 1.63* 9.32 ± 2.25
K (mmol/L) 4.47 ± 0.18 4.38 ± 0.20 4.29 ± 0.14 4.42 ± 0.25
TB (mg/dL) 0.10 ± 0.03 0.10 ± 0.02 0.10 ± 0.01 0.09 ± 0.02
TG (mg/dL) 173.53 ± 43.03 164.52 ± 16.65 146.34 ± 29.88 163.23 ± 22.48
Na (mmol/L) 144.42 ± 2.43 143.97 ± 1.54 143.37 ± 1.64 144.37 ± 1.80
Cl (mmol/L) 105.69 ± 1.96 105.95 ± 1.24 105.36 ± 0.94 106.98 ± 2.11
BUN (mg/dL) 33.53 ± 6.19 35.20 ± 3.89 32.41 ± 6.61 34.52 ± 3.75

SD, standard deviation.

* Data showed a statistically significant difference between the control and test group (P＜0.05).

Figure 3 Chemical pathology results.
Figure 3

Chemical pathology results.

3.3 Gross pathology

Organ-to-body weight ratios were similar between the test and control groups. There was no difference between the two groups that were considered to be related to treatment. Compared with the control group of the same sex, male rats in the test group had a lower testis coefficient (P＜0.05) and higher liver coefficient (P＜0.05), while female rats had a higher kidney coefficient (P＜0.05). The data are all within the normal ranges of healthy rats. The rest of the data of the test group had no significant difference from those of the control group. The results are shown in Figure 4 and Table 4.

Figure 4 Organ/body weight ratios (%).
Figure 4

Organ/body weight ratios (%).

Table 4

Summary of organ/body weight ratios (%)

Sex Organ IBS (Mean ± SD) 316L SS (Mean ± SD)
Male Heart 0.38 ± 0.09 0.39 ± 0.08
Liver 2.52 ± 0.35* 2.44 ± 0.36
Spleen 0.18 ± 0.03 0.19 ± 0.05
Kidneys (2) 0.66 ± 0.08 0.66 ± 0.08
Adrenal glands (2) 0.02 ± 0.00 0.02 ± 0.00
Testis (2) 0.77 ± 0.09* 0.83 ± 0.03
Female Heart 0.43 ± 0.10 0.40 ± 0.05
Liver 2.48 ± 0.64* 2.68 ± 0.28
Spleen 0.21 ± 0.05 0.22 ± 0.03
Kidneys (2) 0.66 ± 0.08* 0.59 ± 0.11
Adrenal glands (2) 0.01 ± 0.00 0.02 ± 0.00
Uterus and ovaries (2) 0.40 ± 0.00 0.42 ± 0.03

SD, standard deviation.

*Data showed a statistically significant difference between the control and test group (P＜0.05).

The types and numbers of tumors were somewhat different between the test and the control animals, but there were no significant differences in the type and numbers of the main tumors between them. In both the groups, the probability of tumorigenesis in the animals increased with age. The types and numbers of tumor in the two groups are show in Tables 5 and 6.

Table 5

Summary of tumor types and numbers (male)

Sex Tumor types IBS 316L SS
Animal number Percentage Animal number Percentage
Male Subcutaneous fibroma 6 10.00 4 6.67
Pituitary adenoma 4 6.67 6 10.00
Thyroid adenoma 1 1.67 2 3.33
Islet cell adenoma 1 1.67 1 1.67
Salivary adenoma 0 0 1 1.67
Fibroadenoma 1 1.66 0 0
Lipomyoma 0 0 0 0
Fibroangioma 4 6.67 3 5.00
Lung cancer 2 3.33 3 5.00
Renal cell cancer 2 3.33 1 1.67
Hemangiosarcoma 2 3.33 2 3.33
Fibrosarcoma 2 3.33 2 3.33
Stromal cell tumor of testis 1 1.67 1 1.67
Squamous-cell carcinoma 1 1.67 1 1.67
Total 27 45 27 45
Table 6

Summary of tumor types and numbers (female)

Sex Tumor types IBS 316L SS
Animal number Percentage Animal number Percentage
Female Subcutaneous fibroma 5 8.33 4 6.67
Breast fibroadenoma 5 8.33 4 6.67
Pituitary adenoma 4 6.67 3 5.00
Adenocarcinoma 1 1.67 1 1.67
Breast cancer 4 6.67 4 6.67
Breast adenoma 4 6.67 3 5.0
Brain glioma 2 3.33 3 5.0
Salivary adenoma 2 3.33 0 0
Lipomyoma 2 3.33 2 3.33
Lung cancer 2 3.33 2 3.33
Uterine leiomyosarcoma 1 1.67 2 3.33
Squamous cell carcer 3 5.00 3 5.00
Total 35 58.33 31 51.67

3.4 Histopathology

The diseases of the animals were diagnosed by gross lesions and histopathology. The H&E staining of each tissue and organ is shown in Figure 5. The shape of each organ was clear, and no serious inflammatory cell aggregation was observed. No significant difference between the test group and the control group was observed. Conclusively, there was no microscopic tissue change indicating any systemic toxicity.

Figure 5 Histopathologic observations on organ tissues 2 years after implantation of the IBS and 316L SS (scar bar is 100 or 200 µm).
Figure 5

Histopathologic observations on organ tissues 2 years after implantation of the IBS and 316L SS (scar bar is 100 or 200 µm).

The corrosion of IBS should not cause cancer or mutations after implantation. Studies have shown that Fe2+ is involved in the Fenton/Haber–Weiss reaction along with peroxides during iron corrosion, resulting in hydroxyl radicals (HO˙) [42,43], whereas HO˙ damages DNA the most in ROS produced by aerobic cell metabolism and has been well reported in chemomutagenicity/genotoxicity [44–46]. In our study, iron-based scaffold implantation was not observed to be carcinogenic in rats for the duration of 2 years. This may be due to the fact that the iron balance and ROS balance in the body is not disturbed. Iron ions are released by corrosion of IBS in the body and enter the normal iron pathway of the body to participate in physiological activities [47]. Protein-bound iron does not produce wandering iron ions, so it cannot participate in ROS production [43]. Or iron corrosion products are swallowed by phagocytes and form ferritin deposited in tissues, leaving no free iron ions [48,49]. Besides, the body has oxidation and antioxidant homeostasis [50], which eliminates HO˙ that forms around the iron stent and prevents oxidative damage before the equilibrium is disturbed, so no carcinogenicity of IBS has been observed (Figure 6).

Figure 6 Pathological images of tumor in the IBS group and 316L SS group (scar bar is 100 µm).
Figure 6

Pathological images of tumor in the IBS group and 316L SS group (scar bar is 100 µm).

4 Conclusions

In this study, stent implantation experiments in rats proved that IBS breaks through the limits of slow degradation of iron-based stents. The iron ions produced after degradation do not cause significant fluctuations in the blood iron ion levels, and there was no significant difference between the widely used 316L SS stent in terms of blood ions. Furthermore, through a 2-year stent implantation test in the abdominal aorta of rats, the pertinence between the chronic toxicity in vivo and the carcinogenicity of IBS was studied. Combining the comprehensive analysis of the body weight, hematology data, death, and pathological results of animal experiments, there was no significant difference between the IBS group and the 316L SS group, and the samples did not cause chronic systemic toxicity in rats. In addition, the occurrence of tumors of the same sex in the sample group was not significantly different from that of the control group, except for animal deaths or natural tumors caused by accidental factors such as environment, food, and water. The incidence is within the range of the spontaneous tumor rate in rats, and IBS is not carcinogenic.

Although a lot of effort still needs to be done, the biodegradation stent platform has become another alternative option for patients with coronary artery disease, especially for pediatric patients, which potentially allows for late vessel growth [51]. As a new type of fully degradable iron-based stent, IBS with good biocompatibility fulfills the mission of a degradable stent and shows great potential in clinical transformation.

  1. Funding information: This work was financially supported by the National Natural Science Foundation of China (NSFC Project 32071328), Sichuan Science and Technology Program (2022NSFSC0809), the International Cooperation Project by Science and Technology Department of Sichuan Province (2021YFH0056), and the High-Level Talents Research and Development Program of Affiliated Dongguan Hospital (K202102).

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Conflict of interest: The authors state no conflict of interest.

  4. Ethical approval: The research related to animals’ use has been complied with all the relevant national regulations and institutional policies for the care and use of animals.

  5. Data availability statement: The datasets used and analyzed in this work can be available from the authors on reasonable request.

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Received: 2022-01-21
Revised: 2022-12-08
Accepted: 2023-01-02
Published Online: 2023-02-25

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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https://doi.org/10.1515/ntrev-2022-0507
Schlagwörter für diesen Artikel
Fe-based stents; chronic toxicity; carcinogenicity; bioabsorbable; coronary
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Research Articles
  2. Preparation of CdS–Ag2S nanocomposites by ultrasound-assisted UV photolysis treatment and its visible light photocatalysis activity
  3. Significance of nanoparticle radius and inter-particle spacing toward the radiative water-based alumina nanofluid flow over a rotating disk
  4. Aptamer-based detection of serotonin based on the rapid in situ synthesis of colorimetric gold nanoparticles
  5. Investigation of the nucleation and growth behavior of Ti2AlC and Ti3AlC nano-precipitates in TiAl alloys
  6. Dynamic recrystallization behavior and nucleation mechanism of dual-scale SiCp/A356 composites processed by P/M method
  7. High mechanical performance of 3-aminopropyl triethoxy silane/epoxy cured in a sandwich construction of 3D carbon felts foam and woven basalt fibers
  8. Applying solution of spray polyurea elastomer in asphalt binder: Feasibility analysis and DSR study based on the MSCR and LAS tests
  9. Study on the chronic toxicity and carcinogenicity of iron-based bioabsorbable stents
  10. Influence of microalloying with B on the microstructure and properties of brazed joints with Ag–Cu–Zn–Sn filler metal
  11. Thermohydraulic performance of thermal system integrated with twisted turbulator inserts using ternary hybrid nanofluids
  12. Study of mechanical properties of epoxy/graphene and epoxy/halloysite nanocomposites
  13. Effects of CaO addition on the CuW composite containing micro- and nano-sized tungsten particles synthesized via aluminothermic coupling with silicothermic reduction
  14. Cu and Al2O3-based hybrid nanofluid flow through a porous cavity
  15. Design of functional vancomycin-embedded bio-derived extracellular matrix hydrogels for repairing infectious bone defects
  16. Study on nanocrystalline coating prepared by electro-spraying 316L metal wire and its corrosion performance
  17. Axial compression performance of CFST columns reinforced by ultra-high-performance nano-concrete under long-term loading
  18. Tungsten trioxide nanocomposite for conventional soliton and noise-like pulse generation in anomalous dispersion laser cavity
  19. Microstructure and electrical contact behavior of the nano-yttria-modified Cu-Al2O3/30Mo/3SiC composite
  20. Melting rheology in thermally stratified graphene-mineral oil reservoir (third-grade nanofluid) with slip condition
  21. Re-examination of nonlinear vibration and nonlinear bending of porous sandwich cylindrical panels reinforced by graphene platelets
  22. Parametric simulation of hybrid nanofluid flow consisting of cobalt ferrite nanoparticles with second-order slip and variable viscosity over an extending surface
  23. Chitosan-capped silver nanoparticles with potent and selective intrinsic activity against the breast cancer cells
  24. Multi-core/shell SiO2@Al2O3 nanostructures deposited on Ti3AlC2 to enhance high-temperature stability and microwave absorption properties
  25. Solution-processed Bi2S3/BiVO4/TiO2 ternary heterojunction photoanode with enhanced photoelectrochemical performance
  26. Electroporation effect of ZnO nanoarrays under low voltage for water disinfection
  27. NIR-II window absorbing graphene oxide-coated gold nanorods and graphene quantum dot-coupled gold nanorods for photothermal cancer therapy
  28. Nonlinear three-dimensional stability characteristics of geometrically imperfect nanoshells under axial compression and surface residual stress
  29. Investigation of different nanoparticles properties on the thermal conductivity and viscosity of nanofluids by molecular dynamics simulation
  30. Optimized Cu2O-{100} facet for generation of different reactive oxidative species via peroxymonosulfate activation at specific pH values to efficient acetaminophen removal
  31. Brownian and thermal diffusivity impact due to the Maxwell nanofluid (graphene/engine oil) flow with motile microorganisms and Joule heating
  32. Appraising the dielectric properties and the effectiveness of electromagnetic shielding of graphene reinforced silicone rubber nanocomposite
  33. Synthesis of Ag and Cu nanoparticles by plasma discharge in inorganic salt solutions
  34. Low-cost and large-scale preparation of ultrafine TiO2@C hybrids for high-performance degradation of methyl orange and formaldehyde under visible light
  35. Utilization of waste glass with natural pozzolan in the production of self-glazed glass-ceramic materials
  36. Mechanical performance of date palm fiber-reinforced concrete modified with nano-activated carbon
  37. Melting point of dried gold nanoparticles prepared with ultrasonic spray pyrolysis and lyophilisation
  38. Graphene nanofibers: A modern approach towards tailored gypsum composites
  39. Role of localized magnetic field in vortex generation in tri-hybrid nanofluid flow: A numerical approach
  40. Intelligent computing for the double-diffusive peristaltic rheology of magneto couple stress nanomaterials
  41. Bioconvection transport of upper convected Maxwell nanoliquid with gyrotactic microorganism, nonlinear thermal radiation, and chemical reaction
  42. 3D printing of porous Ti6Al4V bone tissue engineering scaffold and surface anodization preparation of nanotubes to enhance its biological property
  43. Bioinspired ferromagnetic CoFe2O4 nanoparticles: Potential pharmaceutical and medical applications
  44. Significance of gyrotactic microorganisms on the MHD tangent hyperbolic nanofluid flow across an elastic slender surface: Numerical analysis
  45. Performance of polycarboxylate superplasticisers in seawater-blended cement: Effect from chemical structure and nano modification
  46. Entropy minimization of GO–Ag/KO cross-hybrid nanofluid over a convectively heated surface
  47. Oxygen plasma assisted room temperature bonding for manufacturing SU-8 polymer micro/nanoscale nozzle
  48. Performance and mechanism of CO2 reduction by DBD-coupled mesoporous SiO2
  49. Polyarylene ether nitrile dielectric films modified by HNTs@PDA hybrids for high-temperature resistant organic electronics field
  50. Exploration of generalized two-phase free convection magnetohydrodynamic flow of dusty tetra-hybrid Casson nanofluid between parallel microplates
  51. Hygrothermal bending analysis of sandwich nanoplates with FG porous core and piezomagnetic faces via nonlocal strain gradient theory
  52. Design and optimization of a TiO2/RGO-supported epoxy multilayer microwave absorber by the modified local best particle swarm optimization algorithm
  53. Mechanical properties and frost resistance of recycled brick aggregate concrete modified by nano-SiO2
  54. Self-template synthesis of hollow flower-like NiCo2O4 nanoparticles as an efficient bifunctional catalyst for oxygen reduction and oxygen evolution in alkaline media
  55. High-performance wearable flexible strain sensors based on an AgNWs/rGO/TPU electrospun nanofiber film for monitoring human activities
  56. High-performance lithium–selenium batteries enabled by nitrogen-doped porous carbon from peanut meal
  57. Investigating effects of Lorentz forces and convective heating on ternary hybrid nanofluid flow over a curved surface using homotopy analysis method
  58. Exploring the potential of biogenic magnesium oxide nanoparticles for cytotoxicity: In vitro and in silico studies on HCT116 and HT29 cells and DPPH radical scavenging
  59. Enhanced visible-light-driven photocatalytic degradation of azo dyes by heteroatom-doped nickel tungstate nanoparticles
  60. A facile method to synthesize nZVI-doped polypyrrole-based carbon nanotube for Ag(i) removal
  61. Improved osseointegration of dental titanium implants by TiO2 nanotube arrays with self-assembled recombinant IGF-1 in type 2 diabetes mellitus rat model
  62. Functionalized SWCNTs@Ag–TiO2 nanocomposites induce ROS-mediated apoptosis and autophagy in liver cancer cells
  63. Triboelectric nanogenerator based on a water droplet spring with a concave spherical surface for harvesting wave energy and detecting pressure
  64. A mathematical approach for modeling the blood flow containing nanoparticles by employing the Buongiorno’s model
  65. Molecular dynamics study on dynamic interlayer friction of graphene and its strain effect
  66. Induction of apoptosis and autophagy via regulation of AKT and JNK mitogen-activated protein kinase pathways in breast cancer cell lines exposed to gold nanoparticles loaded with TNF-α and combined with doxorubicin
  67. Effect of PVA fibers on durability of nano-SiO2-reinforced cement-based composites subjected to wet-thermal and chloride salt-coupled environment
  68. Effect of polyvinyl alcohol fibers on mechanical properties of nano-SiO2-reinforced geopolymer composites under a complex environment
  69. In vitro studies of titanium dioxide nanoparticles modified with glutathione as a potential drug delivery system
  70. Comparative investigations of Ag/H2O nanofluid and Ag-CuO/H2O hybrid nanofluid with Darcy-Forchheimer flow over a curved surface
  71. Study on deformation characteristics of multi-pass continuous drawing of micro copper wire based on crystal plasticity finite element method
  72. Properties of ultra-high-performance self-compacting fiber-reinforced concrete modified with nanomaterials
  73. Prediction of lap shear strength of GNP and TiO2/epoxy nanocomposite adhesives
  74. A novel exploration of how localized magnetic field affects vortex generation of trihybrid nanofluids
  75. Fabrication and physicochemical characterization of copper oxide–pyrrhotite nanocomposites for the cytotoxic effects on HepG2 cells and the mechanism
  76. Thermal radiative flow of cross nanofluid due to a stretched cylinder containing microorganisms
  77. In vitro study of the biphasic calcium phosphate/chitosan hybrid biomaterial scaffold fabricated via solvent casting and evaporation technique for bone regeneration
  78. Insights into the thermal characteristics and dynamics of stagnant blood conveying titanium oxide, alumina, and silver nanoparticles subject to Lorentz force and internal heating over a curved surface
  79. Effects of nano-SiO2 additives on carbon fiber-reinforced fly ash–slag geopolymer composites performance: Workability, mechanical properties, and microstructure
  80. Energy bandgap and thermal characteristics of non-Darcian MHD rotating hybridity nanofluid thin film flow: Nanotechnology application
  81. Green synthesis and characterization of ginger-extract-based oxali-palladium nanoparticles for colorectal cancer: Downregulation of REG4 and apoptosis induction
  82. Abnormal evolution of resistivity and microstructure of annealed Ag nanoparticles/Ag–Mo films
  83. Preparation of water-based dextran-coated Fe3O4 magnetic fluid for magnetic hyperthermia
  84. Statistical investigations and morphological aspects of cross-rheological material suspended in transportation of alumina, silica, titanium, and ethylene glycol via the Galerkin algorithm
  85. Effect of CNT film interleaves on the flexural properties and strength after impact of CFRP composites
  86. Self-assembled nanoscale entities: Preparative process optimization, payload release, and enhanced bioavailability of thymoquinone natural product
  87. Structure–mechanical property relationships of 3D-printed porous polydimethylsiloxane films
  88. Nonlinear thermal radiation and the slip effect on a 3D bioconvection flow of the Casson nanofluid in a rotating frame via a homotopy analysis mechanism
  89. Residual mechanical properties of concrete incorporated with nano supplementary cementitious materials exposed to elevated temperature
  90. Time-independent three-dimensional flow of a water-based hybrid nanofluid past a Riga plate with slips and convective conditions: A homotopic solution
  91. Lightweight and high-strength polyarylene ether nitrile-based composites for efficient electromagnetic interference shielding
  92. Review Articles
  93. Recycling waste sources into nanocomposites of graphene materials: Overview from an energy-focused perspective
  94. Hybrid nanofiller reinforcement in thermoset and biothermoset applications: A review
  95. Current state-of-the-art review of nanotechnology-based therapeutics for viral pandemics: Special attention to COVID-19
  96. Solid lipid nanoparticles for targeted natural and synthetic drugs delivery in high-incidence cancers, and other diseases: Roles of preparation methods, lipid composition, transitional stability, and release profiles in nanocarriers’ development
  97. Critical review on experimental and theoretical studies of elastic properties of wurtzite-structured ZnO nanowires
  98. Polyurea micro-/nano-capsule applications in construction industry: A review
  99. A comprehensive review and clinical guide to molecular and serological diagnostic tests and future development: In vitro diagnostic testing for COVID-19
  100. Recent advances in electrocatalytic oxidation of 5-hydroxymethylfurfural to 2,5-furandicarboxylic acid: Mechanism, catalyst, coupling system
  101. Research progress and prospect of silica-based polymer nanofluids in enhanced oil recovery
  102. Review of the pharmacokinetics of nanodrugs
  103. Engineered nanoflowers, nanotrees, nanostars, nanodendrites, and nanoleaves for biomedical applications
  104. Research progress of biopolymers combined with stem cells in the repair of intrauterine adhesions
  105. Progress in FEM modeling on mechanical and electromechanical properties of carbon nanotube cement-based composites
  106. Antifouling induced by surface wettability of poly(dimethyl siloxane) and its nanocomposites
  107. TiO2 aerogel composite high-efficiency photocatalysts for environmental treatment and hydrogen energy production
  108. Structural properties of alumina surfaces and their roles in the synthesis of environmentally persistent free radicals (EPFRs)
  109. Nanoparticles for the potential treatment of Alzheimer’s disease: A physiopathological approach
  110. Current status of synthesis and consolidation strategies for thermo-resistant nanoalloys and their general applications
  111. Recent research progress on the stimuli-responsive smart membrane: A review
  112. Dispersion of carbon nanotubes in aqueous cementitious materials: A review
  113. Applications of DNA tetrahedron nanostructure in cancer diagnosis and anticancer drugs delivery
  114. Magnetic nanoparticles in 3D-printed scaffolds for biomedical applications
  115. An overview of the synthesis of silicon carbide–boron carbide composite powders
  116. Organolead halide perovskites: Synthetic routes, structural features, and their potential in the development of photovoltaic
  117. Recent advancements in nanotechnology application on wood and bamboo materials: A review
  118. Application of aptamer-functionalized nanomaterials in molecular imaging of tumors
  119. Recent progress on corrosion mechanisms of graphene-reinforced metal matrix composites
  120. Research progress on preparation, modification, and application of phenolic aerogel
  121. Application of nanomaterials in early diagnosis of cancer
  122. Plant mediated-green synthesis of zinc oxide nanoparticles: An insight into biomedical applications
  123. Recent developments in terahertz quantum cascade lasers for practical applications
  124. Recent progress in dielectric/metal/dielectric electrodes for foldable light-emitting devices
  125. Nanocoatings for ballistic applications: A review
  126. A mini-review on MoS2 membrane for water desalination: Recent development and challenges
  127. Recent updates in nanotechnological advances for wound healing: A narrative review
  128. Recent advances in DNA nanomaterials for cancer diagnosis and treatment
  129. Electrochemical micro- and nanobiosensors for in vivo reactive oxygen/nitrogen species measurement in the brain
  130. Advances in organic–inorganic nanocomposites for cancer imaging and therapy
  131. Advancements in aluminum matrix composites reinforced with carbides and graphene: A comprehensive review
  132. Modification effects of nanosilica on asphalt binders: A review
  133. Decellularized extracellular matrix as a promising biomaterial for musculoskeletal tissue regeneration
  134. Review of the sol–gel method in preparing nano TiO2 for advanced oxidation process
  135. Micro/nano manufacturing aircraft surface with anti-icing and deicing performances: An overview
  136. Cell type-targeting nanoparticles in treating central nervous system diseases: Challenges and hopes
  137. An overview of hydrogen production from Al-based materials
  138. A review of application, modification, and prospect of melamine foam
  139. A review of the performance of fibre-reinforced composite laminates with carbon nanotubes
  140. Research on AFM tip-related nanofabrication of two-dimensional materials
  141. Advances in phase change building materials: An overview
  142. Development of graphene and graphene quantum dots toward biomedical engineering applications: A review
  143. Nanoremediation approaches for the mitigation of heavy metal contamination in vegetables: An overview
  144. Photodynamic therapy empowered by nanotechnology for oral and dental science: Progress and perspectives
  145. Biosynthesis of metal nanoparticles: Bioreduction and biomineralization
  146. Current diagnostic and therapeutic approaches for severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) and the role of nanomaterial-based theragnosis in combating the pandemic
  147. Application of two-dimensional black phosphorus material in wound healing
  148. Special Issue on Advanced Nanomaterials and Composites for Energy Conversion and Storage - Part I
  149. Helical fluorinated carbon nanotubes/iron(iii) fluoride hybrid with multilevel transportation channels and rich active sites for lithium/fluorinated carbon primary battery
  150. The progress of cathode materials in aqueous zinc-ion batteries
  151. Special Issue on Advanced Nanomaterials for Carbon Capture, Environment and Utilization for Energy Sustainability - Part I
  152. Effect of polypropylene fiber and nano-silica on the compressive strength and frost resistance of recycled brick aggregate concrete
  153. Mechanochemical design of nanomaterials for catalytic applications with a benign-by-design focus
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Heruntergeladen am 21.1.2026 von https://www.degruyterbrill.com/document/doi/10.1515/ntrev-2022-0507/html?lang=de
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