A pilot study of a novel biodegradable magnesium alloy airway stent in a rabbit model
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.
References (36)
- et al.
Usefulness of three-dimensional electron beam computed tomography for evaluating tracheobronchial anomalies in children with congenital heart disease
Am. J. Cardiol.
(2003) - et al.
Tracheoplasty with pericardial patch for extensive tracheal stenosis in infants and children
J. Thorac. Cardiovasc. Surg.
(1984) - et al.
Congenital tracheobronchial stenosis
Semin. Pediatr. Surg.
(2016) - et al.
Patterns of management of congenital tracheal stenosis
J. Pediatr. Surg.
(2003) - et al.
Outcomes of slide tracheoplasty in 101 children: a 17-year single-center experience
J. Thorac. Cardiovasc. Surg.
(2014) - et al.
Treatment of cuff-related tracheal stenosis with a fully covered retrievable expandable metallic stent
Clin. Radiol.
(2013) - et al.
In vivo corrosion of four magnesium alloys and the associated bone response
Biomaterials
(2005) - et al.
Degradable biomaterials based on magnesium corrosion
Curr. Opin. Solid State Mater. Sci.
(2008) - et al.
Hydrophilic polymers--biocompatibility testing in vitro
Toxicol. Vitro
(2005) - et al.
Microstructure, mechanical and corrosion properties and biocompatibility of Mg–Zn–Mn alloys for biomedical application
Mater. Sci. Eng. C
(2009)
In vitro corrosion and biocompatibility of binary magnesium alloys
Biomaterials
Design of magnesium alloys with controllable degradation for biomedical implants: from bulk to surface
Acta Biomater.
Biodegradable polydioxanone stent as a new treatment strategy for tracheal stenosis in a rabbit model
J. Pediatr. Surg.
Tracheal self-expandable metallic stents: a comparative study of three different stents in a rabbit model
Arch. Bronconeumol.
In vitro and in vivo degradation of rapamycin-eluting Mg-Nd-Zn-Zr alloy stents in porcine coronary arteries
Mater Sci Eng C Mater Biol Appl
Evaluation of short-term effects of rare earth and other elements used in magnesium alloys on primary cells and cell lines
Acta Biomater.
Congenital tracheal stenosis. The otolaryngologist's perspective
Arch. Otolaryngol. Head Neck Surg.
Congenital anomalies of the tracheobronchial tree, lung, and mediastinum: embryology, radiology, and pathology
Radiographics
Cited by (0)
- 1
These authors contributed equally to this study.