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Original Research: Pulmonary Procedures |

Biodegradable Cisplatin-Eluting Tracheal Stent for Malignant Airway ObstructionBiodegradable Cisplatin-Eluting Trachea Stent: In Vivo and In Vitro Studies FREE TO VIEW

Yin-Kai Chao, MD, PhD; Kuo-Sheng Liu, MD; Yi-Chuan Wang, MS; Yen-Lin Huang, MD, PhD; Shih-Jung Liu, PhD
Author and Funding Information

From the Department of Thoracic and Cardiovascular Surgery (Drs Chao and K.-S. Liu), and the Department of Pathology (Dr Huang), Chang Gung Memorial Hospital, Linkou, College of Medicine; the Department of Mechanical Engineering (Drs K.-S. Liu and S.-J. Liu); and the Graduate Institute of Medical Mechatronics (Ms Wang), Chang Gung University, Tao-Yuan, Taiwan.

Correspondence to: Shih-Jung Liu, PhD, Biomaterials Laboratory, Mechanical Engineering, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan; e-mail: shihjung@mail.cgu.edu.tw


Drs Chao and K.-S. Liu have contributed equally to this study and are co-first authors of this paper.

Funding/Support: This work was financially supported by Chang Gung Memorial Hospital (Linkou, Taiwan) under Contract No. CMRPD2A0082.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(1):193-199. doi:10.1378/chest.12-2282
Text Size: A A A
Published online

Background:  Self-expandable metallic stents (SEMSs) are effective in the palliation of malignant airway obstruction. Tumor ingrowth, however, frequently occurs because of a shortage of effective local therapy. Additionally, SEMSs are frequently associated with problems of fracture, migration, and difficult removals. Our goal was to develop a novel bioabsorbable stent with cisplatin elution to circumvent such problems.

Methods:  Biodegradable stents made of polycaprolactone were fabricated by a laboratory-made, microinjection molding machine. In vitro mechanical strength of the stents was compared with the strength of Ultraflex SEMSs. Polylactide-polyglycolide copolymer and cisplatin were coated onto the surfaces of the stents. Elution method and high-performance liquid chromatography (HPLC) analysis were used to examine the in vitro cisplatin release characteristics. In vivo, the stents were surgically implanted into the cervical trachea of 15 New Zealand white rabbits. Bronchoscopic examination was performed weekly (1 to approximately 5 weeks) before killing. Cisplatin concentrations in trachea, lung, and blood were analyzed by HPLC. Histologic examination was also performed.

Results:  The biodegradable stent exhibited mechanical strength comparable to the strength of Ultraflex SEMSs and provided a steady release of cisplatin for > 4 weeks in vitro. The in vivo study showed sustained cisplatin levels in rabbit trachea for > 5 weeks with a minimum drug level in blood. Histologic examination showed an intact ciliated epithelium and marked leukocyte infiltration in the submucosa of the stented area.

Conclusions:  Our study demonstrated that the biodegradable stents provided physical properties comparable to the properties of SEMSs and a sustained release of cisplatin for > 5 weeks, which showed great potential in the treatment of malignant airway obstruction.

Figures in this Article

Approximately 30% of patients with lung cancer have central airway obstruction.1 Self-expandable metallic stents (SEMSs) are commonly used in these patients for the palliation of the symptom.2 Stent tumor regrowth, however, commonly occurs because there is no effective in situ therapy.3,4 Despite external radiation after airway stenting providing borderline survival benefits, it was reported that 37% of the patients were not able to complete radiation therapy, and more than one-third of patients still died because of tumor growth-related asphyxia.3,5

On the other hand, SEMs are also notorious for various troublesome complications, including stent fracture, migration, impaired mucociliary clearance, and increased bacterial infection.4,6,7 Additionally, the embedded nature of the stent makes subsequent bronchoscopic removal difficult and risky. We believe that an ideal airway stent should (1) possess sufficient strength to perform its mechanical function, (2) be biodegradable (no need for removal after serving its purpose), (3) be biocompatible so that the material breakdown process will not cause any tissue irritation, and/or (4) provide effective pharmaceuticals for a sustained period of time.

Endobronchial intratumoral chemotherapy (EITC) (ie, the injection of conventional cytotoxic drugs directly into the tumor tissue through a flexible bronchoscope) has been described in several clinical studies with encouraging results.810 Local high doses of cytotoxic action can reduce large local tumor cell burdens, with rapid alleviation of endobronchial obstruction.810 Furthermore, unlike conventional IV chemotherapy, EITC exhibits no significant systemic toxicity. However, such drug delivery was transient and could be prolonged for only a few hours to days in the gel-form or oil-form injection.11 Hence, the clinical indication was only limited to cases of asymptomatic endobronchial tumors with < 50% obstruction.8

In our laboratory, we had successfully designed and fabricated a mesh-type, biodegradable stent with a backbone of polycaprolactone (PCL)12 that permitted airway remodeling in rabbits.13 In this report, following our previous work, we aimed to develop biodegradable drug-eluting stents that can provide a sustainable release of cisplatin, which is the most commonly used antitumor medication in lung cancer for the treatment of malignant tracheal obstruction. An elution method and a high-performance liquid chromatography (HPLC) analysis were used to determine the in vitro release of cisplatin from the biodegradable stents. In addition, the stents were surgically implanted into the cervical trachea of 15 rabbits. The level of cisplatin by in vivo release in the trachea, lung, and blood were analyzed weekly. Histologic examination was also performed.

Composition of Biodegradable Stents

The biodegradable polymers used were poly(ε-caprolactone), with a molecular weight of 80,000 Da (Sigma-Aldrich Co LLC). A DuPont model TA-2000 differential scanning calorimeter (TA Instruments) was used to characterize the thermal properties of the polymer. The measured results suggested that the melting temperature of the polymer was approximately 60.7°C.

Fabrication of Bare PCL Stents

To fabricate a biodegradable stent, a stent element design, as shown in Figure 1A, was first developed. The stent elements were fabricated by a laboratory-made, microinjection molding machine. The machine was used for transporting, melting, and pressurizing the polymeric materials, which were fed into the machine in granular form. It mainly consists of two parts: the injection unit and the clamping unit. The function of the injection unit is to melt the polymer and inject it into the mold, whereas the clamping unit holds the mold, opens and closes it, and ejects the finished product. The plasticization of the polymers inside the barrel was completed by the energy provided by the surrounding heater, which was controlled by a temperature moderator. The melt temperature used was 100°C. This is followed by injection, wherein the pneumatically actuated plunger pushes downward to force the polymer melt into the relatively cold, empty cavity of the already closed mold. The temperature of the mold was maintained at room temperature. When the stent element is cooled to a state of sufficient rigidity, which occurs when all regions of the part have cooled down to below the melting temperature of the polymer, the mold opens and the stent element is obtained.

Figure Jump LinkFigure 1. A, Stent element design. B, Each stent element was interconnected with another stent element. C, The final assembled biodegradable stents.Grahic Jump Location

After molding, each stent element was interconnected with another stent element (Fig 1B). By interconnecting six and 10 elements, respectively, the assembly was rolled into mesh tubes, and the final connecting points were welded by a hot spot welding. During the hot welding process, the thermoplastic PCL was melted and used as glue in its molten state to join the components. No other agents were used. Biodegradable stents of two different external diameters (6 mm and 10 mm) were obtained (Fig 1C).

Spray Coating of Cisplatin

After the assembly process, the PCL stents were coated with cisplatin by a spray coating device, which was designed and built in our laboratory. Poly (d,l)-lactide-co-glycolide (PLGA) (75:25, Resomer RG 756; Boehringer Ingelheim GmbH) and cisplatin (Sigma-Aldrich Co LLC) were first dissolved in acetonitrile at predetermined ratios (90/10, 80/20, 70/30, 50/50, weight/weight) and were then delivered by the spray coater with a volumetric flow rate of 4 mL/h. All spray coating experiments were carried out at room temperature.

Mechanical Properties of PCL Stents

To compare the PCL stents manufactured in this study with the commercial 10-mm-covered Ultraflex SEMSs (Boston Scientific), both PCL (10 mm in diameter) and Ultraflex stents were compressed by a 1-N force, and the deformation rates were recorded. Area load was applied over the full length of the stents with a 1,500-mm2 plate mounted on a LLOYD tensiometer (AMETEK, Inc). The cross-head speed was 1 mm/min.

In Vitro Elution of Cisplatin From the Stents

An in vitro elution method was used to determine the release characteristics of cisplatin from the stents. A phosphate buffer, 0.15 mol/L (pH 7.4), was used as the dissolution medium. The stents’ elements were placed in glass test tubes with 1 mL of phosphate buffer. All tubes were incubated at 37°C. The dissolution medium was collected daily for subsequent HPLC analyses. Fresh phosphate buffer (1 mL) was then added for the next 24-h period, and this procedure was repeated for 6 weeks.

HPLC Analysis

The drug concentrations in the buffer for the elution studies were determined by a HPLC assay standard curve for cisplatin. The HPLC analyses were conducted on a Hitachi D-2000 Elite Delivery System. The column used for separation of the cisplatin was a Zorbax ODS (Agilent Technologies), C18, 5 μm, 4.6 cm × 250 mm HPLC column. The mobile phase contained distilled water and acetonitrile (Covidien) (10/90, volume/volume). The absorbency was monitored at 280 nm, and the flow rate was 2.0 mL/min. All samples were assayed in triplicate, and sample dilutions were performed to bring the unknown concentrations into the range of the assay standard curve. A calibration curve was made for each set of the measurements (correlation coefficient > 0.99). The elution product can be specifically identified and quantified with high sensitivity using the HPLC system.

In Vivo Animal Model

Fifteen New Zealand white rabbits (Banqiao Animal Center), with an average weight of 3.0 kg, were divided into five groups in this study. During the surgical procedure, the animals were anesthetized with an intramuscular injection of 1 mL 2% xylazine hydrochloride (Rompun; Bayer HealthCare AG) and 1 mL 50% tiletamine/50% zolazapam (both as hydrochloride) (Zoletil 50; Virbac Laboratories). All rabbits maintained spontaneous breathing without intubation. The cervical trachea was exposed. A longitudinal incision was made at the midline of the trachea, crossing six cartilage rings, starting from the third. The 6-mm PCL stent was implanted under direct vision. The tracheotomy was then closed with a 7-0 polypropylene suture. All animal procedures received institutional approval, and all studied animals were cared for in accordance with regulations of the National Institutes of Health of the Republic of China (Taiwan), under the supervision of a licensed veterinarian at the Animal Center of Chang Gung University (CGU 12-070).

Blood concentrations of cisplatin were collected by syringes via puncture on the marginal ear vein on postoperative days 1, 4, and 7. Animals were killed by intravascular injection of lethal-dose lidocaine at postoperative 1, 2, 3, 4, and 5 weeks. The cervical trachea (at the stented and adjacent unstented areas), lung tissue from the right upper lobe, and the liver were excised and submitted for histologic examination and HPLC analysis.

Mechanical Properties of the PCL Stent vs SEMs

Figure 2 shows the deformation of both PCL stents and commercial SEMs subjected to a 1-N load. The experimental results suggest that the PCL stent exhibited a mechanical strength approximately 90% of the strength of SEMs. Furthermore, when subjected to repeated dynamic loads, the PCL stents exhibited good flexibility and fully regained their shapes as the loads were removed (see Video 1).

PCL_stents_video_1

Figure Jump LinkFigure 2. Mechanical property of the PCL stent vs SEMs. PCL stent exhibited a mechanical strength approximately 90% of that of SEMs. PCL = polycaprolactone; SEMs = self-expandable metallic stents.Grahic Jump Location
In Vitro Release of Cisplatin From the PCL Stents

The HPLC analysis results in Figure 3 suggested that the release curves of PCL stents showed a biphasic drug release (ie, a mild initial burst followed by a diffusion-controlled release). The released drug concentration increased somewhat with the loading of cisplatin in the coating layer. Furthermore, the in vitro elution test showed that the drug-eluting stents developed in this study could release high concentrations of cisplatin for > 30 days.

Figure Jump LinkFigure 3. A, Daily in vitro release of cisplatin from the PCL stents. B, Accumulated in vitro release of cisplatin from the PCL stents. PLGA = poly (d,l)-lactide-co-glycolide. See Figure 2 legend for expansion of the other abbreviation.Grahic Jump Location
In Vivo Animal Study and Cisplatin Level in Blood and Tissue

No animal died of airway complications during the period of study. Intermittent stridor was noted at times of agitation in two rabbits; bronchoscopy of these animals showed a moderate amount of airway secretion. The activity and appetite of all animals were normal. Obvious weight gain was noted during the period of study. Figure 4 shows the bronchoscopic findings 1, 3, and 4 weeks after stent insertion. Bronchoscopic pictures revealed excellent lumen patency, with only minimal airway secretions in most of the animals. We did not observe stent fragmentation in any of the animals. Furthermore, no evidence of facture at the surfaces or at the welded spots was noted for the biodegradable stents.

Figure Jump LinkFigure 4. A, Bronchoscopic findings at 1 week after surgery, B, Bronchoscopic findings at 3 weeks after surgery. C, Bronchoscopic findings at 4 weeks after surgery.Grahic Jump Location

Figure 5 shows the in vivo release characteristics of the biodegradable drug-eluting stents. The cisplatin levels in the stented trachea were measurable from the first week and stably maintained at high levels until the end of the observation period (5 weeks). Similar trends were observed in the trachea segment near the stent and over the right upper lung parenchyma. In contrast, the serum levels of cisplatin were low throughout the experiment.

Figure Jump LinkFigure 5. The cisplatin levels in tissue and blood.Grahic Jump Location
Histologic Examination

Figure 6 displays the trachea with stent in place. Grossly, the stented area showed mild edematous change with mucosa congestion. Microscopically, there were marked mononuclear cell infiltrates of various proportions of lymphocytes, plasma cells, and eosinophils in the submucosa of the stented area 1 week after implantation (Fig 7A). The cilia of the epithelium were preserved (Fig 7B). Similar findings were noted at weeks 3 and 5 (Figs 7C, 7D).

Figure Jump LinkFigure 6. Photograph of the trachea with stent in place.Grahic Jump Location
Figure Jump LinkFigure 7. Microscopic finding of trachea stented area at 1 week after surgery. A, Microscopic examination showed marked mononuclear cell infiltrates of lymphocytes, plasma cells, and eosinophils in the submucosa of stented area (hematoxylin and eosin [H&E], original magnification ×200). B, The cilia were preserved on the epithelium (H&E, original magnification ×1,000). C, Submucosal mononuclear cell infiltrates at 3 weeks postsurgery (H&E, original magnification ×200). D, Submucosal mononuclear cell infiltrates at 5 weeks postsurgery (H&E, original magnification ×200).Grahic Jump Location

SEMSs have been of great value in palliation of malignant airway obstruction but are also notorious for various troublesome complications.4,6,7 This is partly due to the embedded nature of the stent but is also related to the lack of effective locoregional therapy for endobronchial lesions.5 Given the promising results from several EITC studies, we believe that a biodegradable stent that exerts strong stenting force and sustainable drug-eluting characteristics would be an ideal combination.810 In the current study, we successfully demonstrated that the biodegradable PCL stents have mechanical strength comparable to the strength of SEMSs, with minimal tissue reaction. Furthermore, for the first time, to our knowledge, through the combined use of PLGA materials and the spray coating technique, a controlled amount of cisplatin could be released locally over a few weeks with minimal systemic concentration.

Currently, there are five biodegradable polymers that have been approved by US Food and Drug Administration for making medical devices, and there are several studies of biodegradable trachea stents in rat or rabbit models that involved mainly materials of polydioxanone, poly(l-lactide), and PLGA.14,15 In the current study, we chose PCL for several reasons. First, PCL degrades at a slower pace than other biodegradable polymers, such as poly(l-lactide) or PLGA and their copolymers, and can, therefore, be used in drug-delivery devices that remain active for > 1 year. The experimental result of our previous study suggested that stent degradation was minimal, and the mechanical strength was well preserved in vivo at the end of 33 weeks.13 Second, PCL is a semicrystalline polymer with a low melting point (59-64°C) and exhibits good flexibility at room temperature and at 37°C. It also exhibits the ability to undergo repeated dynamic shape changes without exerting too much force on the airway wall or succumbing to stress fracture. This would avoid the occurrence of stent fragmentation. Furthermore, stents with good flexibility are more easily manipulated and deployed with minimal invasion.

The concept of a drug-eluting stent is not new, and there are many successful examples in the cardiology field, yet the application of a trachea stent is limited.16 Heo et al17 reported in vitro results of nanofiber-coated, indomethacin-eluting metallic stents for trachea regeneration. Whether such a concept could be further applied in anticancer drugs remained controversial. One of the major concerns is the unpredictable local and systemic toxicity brought on by the anticancer drug if the release is not controllable. Generally, the drug release from biodegradable devices has three different stages of release kinetics: an initial burst, a diffusion-controlled release, and a degradation-controlled release. Luckily, we only noted a mild initial burst release in our in vitro observations (Fig 3). This will eliminate the possible risk of toxicity associated with the burst release of cisplatin. Theoretically, the initial burst can be further reduced by using multilayer coatings, which is because the hydrophobicity of PLGA limits the water uptake of thin films to about 2% and reduces the rate of backbone hydrolysis. The presence of multilayer coatings also provides barriers for each individual layer and slows down its release rate, which in turn will minimize the initial burst of the drug release. In addition, we could also adjust the release period by changing the ratio of PLGA/cisplatin and drug loading percentage. As shown in Figure 3, the total release period of the drug-eluting stents increases with the loading percentage of cisplatin. This can be explained by the fact that the degradation rate of polymers and the daily release of cisplatin from stents of various drug loading were comparable. A stent with a higher drug loading, based on the same releasing rate, can thus release the drug for a longer period of time.

This is the first study, to our knowledge, that investigates the in vitro and in vivo releases of cisplatin in an airway model over a few weeks via a novel biodegradable drug-elution stent, and we are aware that there are some inherent caveats. First, this drug-releasing model was constructed on nondiseased rabbit trachea. The actual response of the stent to endobronchial cancerous tissue remains unknown. Second, our stent was inserted surgically but not via endobronchial route, which is not similar to the current clinical practice. All these will be topics of future research in our laboratory.

In summary, we proved that the drug release from our biodegradable stent was not only sustained but also controllable. Together with the comparable mechanical strength to SEMSs, we believe the biodegradable drug-eluting stent could serve as a good tool in both therapeutic use and stenting of malignant airway obstruction.

In the present study, we have successfully developed biodegradable, drug-eluting stents for the palliation of malignant airway obstruction. An elution method and HPLC assay were used to characterize the in vitro release rates of cisplatin from the stents. The experimental results show that the biodegradable stents released high concentrations of cisplatin in vitro for 4 weeks. In addition, the cisplatin levels in the stented tracheas of rabbits were measurable from the first week and stably maintained at high levels until the end of the observation period (5 weeks), whereas the serum levels of cisplatin were low throughout the course. By adopting the biodegradable drug-eluting stents, we will be able to achieve local and sustainable delivery of cisplatin to the trachea for the treatment of malignant airway obstruction.

Author contributions: Drs Chao and S.-J. Liu had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Chao: contributed to the conception and design of the study, performing the animal experiment, analysis and interpretation of the data, and writing and revision of the manuscript.

Dr K.-S. Liu: contributed to the conception and design of the study, performing the animal experiment, and analysis and interpretation of the data.

Ms Wang: contributed to the design of the study, data acquisition and analysis, laboratory work, and the content of the manuscript.

Dr Huang: contributed to performing the pathological examination, and revision of the manuscript.

Dr S.-J. Liu: contributed to the conception and design of the study; analysis and interpretation of the data; and revision, review, and approval of the final manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or in the reparation of the manuscript.

Other contributions: We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property.

Additional information: The Video can be found in the “Supplemental Materials” area of the online article.

EITC

endobronchial intratumoral chemotherapy

HPLC

high-performance liquid chromatography

PCL

polycaprolactone

PLGA

poly (d,l)-lactide-co-glycolide

SEMS

self-expandable metallic stent

Ernst A, Feller-Kopman D, Becker HD, Mehta AC. Central airway obstruction. Am J Respir Crit Care Med. 2004;169(12):1278-1297. [CrossRef] [PubMed]
 
Husain SA, Finch D, Ahmed M, Morgan A, Hetzel MR. Long-term follow-up of Ultraflex metallic stents in benign and malignant central airway obstruction. Ann Thorac Surg. 2007;83(4):1251-1256. [CrossRef] [PubMed]
 
Kim JH, Shin JH, Song HY, et al. Palliative treatment of inoperable malignant tracheobronchial obstruction: temporary stenting combined with radiation therapy and/or chemotherapy. AJR Am J Roentgenol. 2009;193(1):W38-42. [CrossRef] [PubMed]
 
Lemaire A, Burfeind WR, Toloza E, et al. Outcomes of tracheobronchial stents in patients with malignant airway disease. Ann Thorac Surg. 2005;80(2):434-437. [CrossRef] [PubMed]
 
Rochet N, Hauswald H, Schmaus M, et al. Safety and efficacy of thoracic external beam radiotherapy after airway stenting in malignant airway obstruction. Int J Radiat Oncol Biol Phys. 2012;83(1):e129-e135. [CrossRef] [PubMed]
 
Chung FT, Lin SM, Chen HC, et al. Factors leading to tracheobronchial self-expandable metallic stent fracture. J Thorac Cardiovasc Surg. 2008;136(5):1328-1335. [CrossRef] [PubMed]
 
Madden BP, Park JE, Sheth A. Medium-term follow-up after deployment of Ultraflex expandable metallic stents to manage endobronchial pathology. Ann Thorac Surg. 2004;78(6):1898-1902. [CrossRef] [PubMed]
 
Celikoglu F, Celikoglu SI, Goldberg EP. Bronchoscopic intratumoral chemotherapy of lung cancer. Lung Cancer. 2008;61(1):1-12. [CrossRef] [PubMed]
 
Celikoglu F, Celikoglu SI, York AM, Goldberg EP. Intratumoral administration of cisplatin through a bronchoscope followed by irradiation for treatment of inoperable non-small cell obstructive lung cancer. Lung Cancer. 2006;51(2):225-236. [CrossRef] [PubMed]
 
Celikoglu SI, Celikoglu F, Goldberg EP. Endobronchial intratumoral chemotherapy (EITC) followed by surgery in early non-small cell lung cancer with polypoid growth causing erroneous impression of advanced disease. Lung Cancer. 2006;54(3):339-346. [CrossRef] [PubMed]
 
Smith JP, Kanekal S, Patawaran MB, et al. Drug retention and distribution after intratumoral chemotherapy with fluorouracil/epinephrine injectable gel in human pancreatic cancer xenografts. Cancer Chemother Pharmacol. 1999;44(4):267-274. [CrossRef] [PubMed]
 
Liu SJ, Chiang FJ, Hsiao CY, Kau YC, Liu KS. Fabrication of balloon-expandable self-lock drug-eluting polycaprolactone stents using micro-injection molding and spray coating techniques. Ann Biomed Eng. 2010;38(10):3185-3194. [CrossRef] [PubMed]
 
Liu KS, Liu YH, Peng YJ, Liu SJ. Experimental absorbable stent permits airway remodeling. J Thorac Cardiovasc Surg. 2011;141(2):463-468. [CrossRef] [PubMed]
 
Saito Y, Minami K, Kobayashi M, et al. New tubular bioabsorbable knitted airway stent: biocompatibility and mechanical strength. J Thorac Cardiovasc Surg. 2002;123(1):161-167. [CrossRef] [PubMed]
 
Robey TC, Välimaa T, Murphy HS, Tôrmâlâ P, Mooney DJ, Weatherly RA. Use of internal bioabsorbable PLGA “finger-type” stents in a rabbit tracheal reconstruction model. Arch Otolaryngol Head Neck Surg. 2000;126(8):985-991. [PubMed]
 
Fattori R, Piva T. Drug-eluting stents in vascular intervention. Lancet. 2003;361(9353):247-249. [CrossRef] [PubMed]
 
Heo DN, Lee JB, Bae MS, Hwang YS, Kwon KH, Kwon IK. Development of nanofiber coated indomethacin-eluting stent for tracheal regeneration. J Nanosci Nanotechnol. 2011;11(7):5711-5716. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. A, Stent element design. B, Each stent element was interconnected with another stent element. C, The final assembled biodegradable stents.Grahic Jump Location
Figure Jump LinkFigure 2. Mechanical property of the PCL stent vs SEMs. PCL stent exhibited a mechanical strength approximately 90% of that of SEMs. PCL = polycaprolactone; SEMs = self-expandable metallic stents.Grahic Jump Location
Figure Jump LinkFigure 3. A, Daily in vitro release of cisplatin from the PCL stents. B, Accumulated in vitro release of cisplatin from the PCL stents. PLGA = poly (d,l)-lactide-co-glycolide. See Figure 2 legend for expansion of the other abbreviation.Grahic Jump Location
Figure Jump LinkFigure 4. A, Bronchoscopic findings at 1 week after surgery, B, Bronchoscopic findings at 3 weeks after surgery. C, Bronchoscopic findings at 4 weeks after surgery.Grahic Jump Location
Figure Jump LinkFigure 5. The cisplatin levels in tissue and blood.Grahic Jump Location
Figure Jump LinkFigure 6. Photograph of the trachea with stent in place.Grahic Jump Location
Figure Jump LinkFigure 7. Microscopic finding of trachea stented area at 1 week after surgery. A, Microscopic examination showed marked mononuclear cell infiltrates of lymphocytes, plasma cells, and eosinophils in the submucosa of stented area (hematoxylin and eosin [H&E], original magnification ×200). B, The cilia were preserved on the epithelium (H&E, original magnification ×1,000). C, Submucosal mononuclear cell infiltrates at 3 weeks postsurgery (H&E, original magnification ×200). D, Submucosal mononuclear cell infiltrates at 5 weeks postsurgery (H&E, original magnification ×200).Grahic Jump Location

Tables

PCL_stents_video_1

References

Ernst A, Feller-Kopman D, Becker HD, Mehta AC. Central airway obstruction. Am J Respir Crit Care Med. 2004;169(12):1278-1297. [CrossRef] [PubMed]
 
Husain SA, Finch D, Ahmed M, Morgan A, Hetzel MR. Long-term follow-up of Ultraflex metallic stents in benign and malignant central airway obstruction. Ann Thorac Surg. 2007;83(4):1251-1256. [CrossRef] [PubMed]
 
Kim JH, Shin JH, Song HY, et al. Palliative treatment of inoperable malignant tracheobronchial obstruction: temporary stenting combined with radiation therapy and/or chemotherapy. AJR Am J Roentgenol. 2009;193(1):W38-42. [CrossRef] [PubMed]
 
Lemaire A, Burfeind WR, Toloza E, et al. Outcomes of tracheobronchial stents in patients with malignant airway disease. Ann Thorac Surg. 2005;80(2):434-437. [CrossRef] [PubMed]
 
Rochet N, Hauswald H, Schmaus M, et al. Safety and efficacy of thoracic external beam radiotherapy after airway stenting in malignant airway obstruction. Int J Radiat Oncol Biol Phys. 2012;83(1):e129-e135. [CrossRef] [PubMed]
 
Chung FT, Lin SM, Chen HC, et al. Factors leading to tracheobronchial self-expandable metallic stent fracture. J Thorac Cardiovasc Surg. 2008;136(5):1328-1335. [CrossRef] [PubMed]
 
Madden BP, Park JE, Sheth A. Medium-term follow-up after deployment of Ultraflex expandable metallic stents to manage endobronchial pathology. Ann Thorac Surg. 2004;78(6):1898-1902. [CrossRef] [PubMed]
 
Celikoglu F, Celikoglu SI, Goldberg EP. Bronchoscopic intratumoral chemotherapy of lung cancer. Lung Cancer. 2008;61(1):1-12. [CrossRef] [PubMed]
 
Celikoglu F, Celikoglu SI, York AM, Goldberg EP. Intratumoral administration of cisplatin through a bronchoscope followed by irradiation for treatment of inoperable non-small cell obstructive lung cancer. Lung Cancer. 2006;51(2):225-236. [CrossRef] [PubMed]
 
Celikoglu SI, Celikoglu F, Goldberg EP. Endobronchial intratumoral chemotherapy (EITC) followed by surgery in early non-small cell lung cancer with polypoid growth causing erroneous impression of advanced disease. Lung Cancer. 2006;54(3):339-346. [CrossRef] [PubMed]
 
Smith JP, Kanekal S, Patawaran MB, et al. Drug retention and distribution after intratumoral chemotherapy with fluorouracil/epinephrine injectable gel in human pancreatic cancer xenografts. Cancer Chemother Pharmacol. 1999;44(4):267-274. [CrossRef] [PubMed]
 
Liu SJ, Chiang FJ, Hsiao CY, Kau YC, Liu KS. Fabrication of balloon-expandable self-lock drug-eluting polycaprolactone stents using micro-injection molding and spray coating techniques. Ann Biomed Eng. 2010;38(10):3185-3194. [CrossRef] [PubMed]
 
Liu KS, Liu YH, Peng YJ, Liu SJ. Experimental absorbable stent permits airway remodeling. J Thorac Cardiovasc Surg. 2011;141(2):463-468. [CrossRef] [PubMed]
 
Saito Y, Minami K, Kobayashi M, et al. New tubular bioabsorbable knitted airway stent: biocompatibility and mechanical strength. J Thorac Cardiovasc Surg. 2002;123(1):161-167. [CrossRef] [PubMed]
 
Robey TC, Välimaa T, Murphy HS, Tôrmâlâ P, Mooney DJ, Weatherly RA. Use of internal bioabsorbable PLGA “finger-type” stents in a rabbit tracheal reconstruction model. Arch Otolaryngol Head Neck Surg. 2000;126(8):985-991. [PubMed]
 
Fattori R, Piva T. Drug-eluting stents in vascular intervention. Lancet. 2003;361(9353):247-249. [CrossRef] [PubMed]
 
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    Print ISSN: 0012-3692
    Online ISSN: 1931-3543