Tracheal Replacement Using an In-Body Tissue-Engineered Collagenous Tube “BIOTUBE” with a Biodegradable Stent in a Beagle Model: A Preliminary Report on a New Technique

Shohei Hiwatashi; Yasuhide Nakayama; Satoshi Umeda; Yuichi Takama; Takeshi Terazawa; Hiroomi Okuyama

doi:10.1055/s-0038-1673709

European Journal of Pediatric Surgery, Inhaltsverzeichnis

Eur J Pediatr Surg 2019; 29(01): 090-096
DOI: 10.1055/s-0038-1673709

Original Article

Georg Thieme Verlag KG Stuttgart · New York

Tracheal Replacement Using an In-Body Tissue-Engineered Collagenous Tube “BIOTUBE” with a Biodegradable Stent in a Beagle Model: A Preliminary Report on a New Technique

Authors

Shohei Hiwatashi

¹Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
Yasuhide Nakayama

²Department of Biomedical Engineering, NCVC Research Institute, Suita, Osaka, Japan
Satoshi Umeda

¹Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
Yuichi Takama

¹Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
Takeshi Terazawa

²Department of Biomedical Engineering, NCVC Research Institute, Suita, Osaka, Japan
Hiroomi Okuyama

¹Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan

Abstract

Introduction Tracheal reconstruction for long-segment stenosis remains challenging. We investigate the usefulness of BIOTUBE, an in-body tissue-engineered collagenous tube with a biodegradable stent, as a novel tracheal scaffold in a beagle model.

Materials and Methods We prepared BIOTUBEs by embedding specially designed molds, including biodegradable stents, into subcutaneous pouches in beagles. After 2 months, the molds were filled with ingrown connective tissues and were harvested to obtain the BIOTUBEs. The BIOTUBEs, cut to 10- or 20-mm lengths, were implanted to replace the same-length defects in the cervical trachea of five beagles. Endoscopic and fluoroscopic evaluations were performed every week until the lumen became stable. The trachea, including the BIOTUBE, was harvested and subjected to histological evaluation between 3 and 7 months after implantation.

Results One beagle died 28 days after 20-mm BIOTUBE implantation because of insufficient expansion and retention force of the stent. The remaining four beagles were implanted with a BIOTUBE reinforced by a strong stent, and all survived the observation period. Endoscopy revealed narrowing of the BIOTUBEs in all four beagles, due to an inflammatory reaction, but patency was maintained by steroid application at the implantation site and balloon dilatation against the stenosis. After 2 months, the lumen gradually became wider. Histological analyses showed that the internal surface of the BIOTUBEs was completely covered with tracheal epithelial cells.

Conclusion This study demonstrated the usefulness of the BIOTUBE with a biodegradable stent as a novel scaffold for tracheal regeneration.

Keywords

trachea replacement - congenital tracheal stenosis - tracheal scaffold - biodegradable stent - tissue engineered trachea

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References
1 Manning PB, Rutter MJ, Lisec A, Gupta R, Marino BS. One slide fits all: the versatility of slide tracheoplasty with cardiopulmonary bypass support for airway reconstruction in children. J Thorac Cardiovasc Surg 2011; 141 (01) 155-161
2 Butler CR, Speggiorin S, Rijnberg FM. , et al. Outcomes of slide tracheoplasty in 101 children: a 17-year single-center experience. J Thorac Cardiovasc Surg 2014; 147 (06) 1783-1789
3 Jacobs JP, Elliott MJ, Haw MP, Bailey CM, Herberhold C. Pediatric tracheal homograft reconstruction: a novel approach to complex tracheal stenoses in children. J Thorac Cardiovasc Surg 1996; 112 (06) 1549-1558
4 Grillo HC. Tracheal replacement: a critical review. Ann Thorac Surg 2002; 73 (06) 1995-2004
5 Maughan EF, Butler CR, Crowley C. , et al. A comparison of tracheal scaffold strategies for pediatric transplantation in a rabbit model. Laryngoscope 2017; 127 (12) E449-E457
6 Taniguchi D, Matsumoto K, Tsuchiya T. , et al. Scaffold-free trachea regeneration by tissue engineering with bio-3D printing. Interact Cardiovasc Thorac Surg 2018; 26 (05) 745-752
7 Nakanishi R, Shirakusa T, Mitsudomi T. Maximum length of tracheal autografts in dogs. J Thorac Cardiovasc Surg 1993; 106 (06) 1081-1087
8 Hung SH, Su CH, Lin SE, Tseng H. Preliminary experiences in trachea scaffold tissue engineering with segmental organ decellularization. Laryngoscope 2016; 126 (11) 2520-2527
9 Ishii D, Enmi JI, Iwai R, Kurisu K, Tatsumi E, Nakayama Y. One year rat study of iBTA-induced “microbiotube” microvascular grafts with an ultra-small diameter of 0.6 mm. Eur J Vasc Endovasc Surg 2018; 55 (06) 882-887
10 Nakayama Y, Furukoshi M. Feasibility of in-body tissue architecture in pediatric cardiovascular surgery: development of regenerative autologous tissues with growth potential. J Pediatr Cardiol Cardiovasc Surg 2016; 32 (03) 199-207
11 Satake R, Komura M, Komura H. , et al. Patch tracheoplasty in body tissue engineering using collagenous connective tissue membranes (biosheets). J Pediatr Surg 2016; 51 (02) 244-248
12 Rose KG, Sesterhenn K, Wustrow F. Tracheal allotransplantation in man. Lancet 1979; 1 (8113): 433
13 Martinod E, Seguin A, Radu DM. , et al; FREnch Group for Airway Transplantation (FREGAT). Airway transplantation: a challenge for regenerative medicine. Eur J Med Res 2013; 18: 25
14 Vogel G. Trachea transplants test the limits. Science 2013; 340 (6130): 266-268
15 Delaere PR, Van Raemdonck D. The trachea: the first tissue-engineered organ?. J Thorac Cardiovasc Surg 2014; 147 (04) 1128-1132
16 Crowley C, Birchall M, Seifalian AM. Trachea transplantation: from laboratory to patient. J Tissue Eng Regen Med 2015; 9 (04) 357-367
17 Badylak SF, Freytes DO, Gilbert TW. Extracellular matrix as a biological scaffold material: structure and function. Acta Biomater 2009; 5 (01) 1-13
18 Delaere P, Vranckx J, Verleden G, De Leyn P, Van Raemdonck D. ; Leuven Tracheal Transplant Group. Tracheal allotransplantation after withdrawal of immunosuppressive therapy. N Engl J Med 2010; 362 (02) 138-145
19 Wurtz A, Porte H, Conti M. , et al. Tracheal replacement with aortic allografts. N Engl J Med 2006; 355 (18) 1938-1940
20 Elliott MJ, Butler CR, Varanou-Jenkins A. , et al. Tracheal replacement therapy with a stem cell-seeded graft: lessons from compassionate use application of a GMP-compliant tissue-engineered medicine. Stem Cells Transl Med 2017; 6 (06) 1458-1464
21 Hortensius RA, Harley BA. Naturally derived biomaterials for addressing inflammation in tissue regeneration. Exp Biol Med (Maywood) 2016; 241 (10) 1015-1024