A pilot study of a novel biodegradable magnesium alloy airway stent in a rabbit model

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Abstract

Objective

To preliminarily investigate the feasibility of bioabsorption tracheal stenting for the therapeutic application of congenital tracheal stenosis (CTS).

Study design

Experimental research.

Setting

Shanghai Children Medical Center, National Children's Medical Center.

Subjects and methods

Five kinds of magnesium alloys with different compositions were studied in this paper, a patented Mg–Nd–Zn–Zr alloy series namely JDBM (JiaoDa BioMg) and four Mg-Ca-Zn alloys. The cytotoxicity of alloys was evaluated by the MTS ([3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay in rabbit tracheal epithelial cells. Specific magnesium alloys had been immersed in the cell culture medium for 24 h. The tracheal stents that were made of magnesium alloy were implanted into the trachea of New Zealand rabbits and the ablation of the stent was monitored by fiber bronchoscopy. The routine blood examination was conducted prior to and following the stent placement. The rabbits were euthanized following 2–3 months of stenting. H&E staining of the main organs was conducted and the induction of apoptosis of the tracheal tissues was monitored.

Results

The cytotoxicity of the JDBM magnesium alloy was mild and lower than the remaining 4 alloys. The stents were placed successfully in five animals. The tracheal stents were successfully placed and gradually biodegradated as monitored by fiber bronchoscopy; no significant systemic inflammatory response was noted. No significant differences in the liver and/or kidney function prior to and following stent placement were noted. H&E staining indicated the absence of pathological changes in the trachea, liver, heart and/or kidney tissues. The apoptotic assay indicated that the apoptosis ratio of the tracheal tissues was comparable between rabbits with and without tracheal stenting.

Conclusion

The results suggested the feasibility of bioabsorption stents made of biodegradable magnesium alloys using in patients with tracheal stenosis, especially in infants.

Introduction

Congenital tracheal stenosis (CTS) describes a wide range of tracheal anomalies. The symptoms are mainly characterized by the narrowing of the trachea [1]. The airway obstruction may be caused by inherited abnormalities of the trachea itself (such as complete tracheal rings or the membranous trachea lacking the normal structure) or by external forces (such as abnormal cardiovascular malformation) [2,3]. Although the disease is estimated to affect only 1 in 64,500 live births, it poses a significant health challenge to affected individuals and could become a life-threatening condition if adequate medical treatment is not provided [[4], [5], [6]].

The therapeutic objective for CTS patients is to maintain a stable and open airway in order to provide sufficient ventilation and oxygen to patients [7]. Currently, the most effective treatment for CTS is surgery [[8], [9], [10]]. However, the incidence of mortality during operation and the incidence of postoperative complications are relatively high. In the Shanghai Children's Medical Center, the percentage of postoperative mortality in children who suffer from tracheal stenosis and congenital heart disease is estimated at 15% [11,12].

Airway stent placement is considered as an alternative or supplementary treatment for tracheal stenosis. The main materials for stents include the following: nitinol alloy, stainless steel, selenium or fabric [[13], [14], [15]]. However, the application of the airway stent placement in infants suffering from CTS is not always used in clinical practice, due to the inability of the current tracheal stents being dilated to meet the rapid growth of the airways of the infants [[16], [17], [18]]. During the last decade, a new generation of biodegradable biomedical metallic materials has been developed [19,20]. One of these materials is the biodegradable magnesium alloy. It is hypothesized that the application of biodegradable materials in the airway stent placement for infants will significantly decrease the incidence of relevant complications, as it does not require the removal of the tracheal stent during the growth of the airway.

Therefore, the present study examined the concept of a biodegradable magnesium alloy tracheal stent and investigated the therapeutic application of the magnesium–alloy airway stent for the treatment of congenital tracheal stenosis.

Section snippets

Magnesium alloys

The magnesium alloys were provided by Materials Institute of Tianjin University and the School of Materials Science at the Shanghai Jiao Tong University. The material composition and machining process of each magnesium-alloy differed slightly (Fig. 1A). A patented Mg–Nd–Zn–Zr alloy series namely JDBM (JiaoDa BioMg) [21] and a 3–dimensional laser carving process were used to construct the airway stents (Fig. 1B).

Culture of rabbit tracheal epithelial cells

The tracheal tissues were immersed in 0.25% trypsin solution (Sigma, St. Louis, USA)

Characterization of rabbit tracheal epithelial cells during primary culture

Rabbit tracheal epithelial cells exhibited cluster growth and formed typical “islands” (Fig. 2A). The majority of the cells appeared spindle shaped, whereas some of the cells appeared as elongated antennae. The cells exhibited optimal growth capability and connective ability. Furthermore, the cells were identified following 72 h of the primary culture with epithelial cytokeratin staining (Fig. 2B).

Cytotoxicity measurement of magnesium–alloys

The cytotoxicity of magnesium–alloy on rabbit tracheal epithelial cells was evaluated following

Discussion

In the present study, evidence is presented regarding the potential application of the JDBM alloy in the therapy of airway obstruction. The in vivo data clearly demonstrated that JDBM had no significant effect on vital organs of the experimental rabbits. In addition, the apoptosis rates of trachea intimal cells in the control group and the experimental group were similar, whereas no significant changes in the tracheal wall structure and no apparent morphological abnormalities in either tracheal

Conclusion

Taken collectively, the data demonstrated that the JDBM series magnesium alloy stents did not cause a severe inflammatory response in the airway tissue and/or an induction in the growth of granulation tissue. No pathological changes were induced in the inner tracheal wall and/or other airway tissues and no local tracheal apoptosis was noted. Most importantly, the JDBM series magnesium–alloy stent was not harmful to vital organs. Thus, the present study demonstrates the feasibility of the

Conflicts of interest

The authors declare that they have no competing interests.

Funding

Not applicable.

Authors' contributions

BDX, BBL conceived and coordinated the study, designed, performed and analyzed the experiments, wrote the paper. GYY, LMZ, HW carried out the data collection, data analysis, and revised the paper. ZHL, ZWX designed the study and revised the paper. All authors reviewed the results and approved the final version of the manuscript.

Conflicts of interest

There are no conflicts to declare.

Acknowledgments

This article is supported by National Natural Science Foundation of China (GRANT No. 30972960) and Medical&Engineering Cross Project (GRANT No. YG2014MS62) from Shanghai Jiao Tong University.

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    These authors contributed equally to this study.

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