Experimental application of tissue engineered constructions for urethroplasty

Introduction. For diseases such as stricture and obliteration of the urethra, urethral hypospadias, reconstructive operations are required. The buccal mucosa is the material most commonly used for these operations. The search for alternative materials, carried out in order to reduce trauma and complications in the donor area, is an urgent area of modern urology. Tissue engineered constructions (TEC) can be used as such material.

Objective. Justification of the possibility of applying a TEC based on the biodegradable polymers and seeded with autologous buccal epithelium (BE) cells as an implantable material for urethroplasty in an experiment.

Methods and Materials. TEC based on poly-L-lactide-caprolactone (PLC) and poly-L-lactide-glycolide (PLG) seeded with BCs was created. Rabbits (n=12) underwent a biopsy of the oral mucosa, BCs were isolated, cultured and PLC-PLG scaffold was seeded with cells. TECs seeded with autological BCs were used on the model of acute trauma of rabbit urethra for replacement urethroplasty.

Results. The results were evaluated after 12 weeks, according to the histological examination, there was a repair of the urethral mucosa. According to the data of retrograde urethrography, no impaired urethra patency was detected.

Conclusion. TEC (PLK-PLG) seeded with autologous BCs ensured the maintenance of the rabbit urethral lumen which is necessary for adequate urination. This TEC could be recommended for the further clinical studies. 

1. Gallentine M. L., Morey A. F., Thompson I. M. Jr. Hypospadias: a contemporary epidemiologic assessment. Urology. 2001;57(4):788–790.

2. Fossum M., Nordenskjöld A. Tissue-engineered transplants for the treatment of severe hypospadias. Hormone research in paediatrics. 2010;73(2):148–152.

3. Santucci R. A., Joyce G. F., Wise M. Male urethral stricture disease. The Journal of Urology. 2007;177(5):1667–1674.

4. Lazzeri M., Sansalone S., Guazzoni G., Barbagli G. Incidence, causes, and complications of urethral stricture disease. European Urology Supplements. 2016;15(1):2–6.

5. Gallegos M. A., Santucci R. A. Advances in urethral stricture management. F1000Research. 2016;5:2913.

6. Chapple C. Tissue engineering of the urethra: where are we in 2019? World Journal of Urology. 2019;38:2107.

7. Ram-Liebig G., Barbagli G., Heidenreich A., Fahlenkamp D., Romano G., Rebmann U. et al. Results of use of tissue-engineered autologous oral mucosa graft for urethral reconstruction: a multicenter, prospective, observational trial. EBioMedicine. 2017;23:185–192.

8. Versteegden L. R. M., de Jonge P. K., IntHout J., van Kuppevelt T. H., Oosterwijk E., Feitz W. F. et al. Tissue engineering of the urethra: a systematic review and meta-analysis of preclinical and clinical studies. European urology. 2017;72(4):594–606.

9. Sanitary rules and norms 2.2.1.3218-14. Sanitary and epidemiological requirements for the design, equipment and maintenance of experimental biological clinics (vivariums). (In Russ.).

10. State standard 33215-2014. Guidelines for accommodation and care of animals. Environment, housing and management. (In Russ.).

11. Order of the Ministry of Health of the Russian Federation of April 1, 2016 № 200n. On approval of the rules of good clinical practice. (In Russ.).

12. Order of the Ministry of Health of the Russian Federation № 512n, August 8, 2018. On the approval of the rules of good practice for working with biomedical cellular products. (In Russ.).

13. State standard 33216-2014 Guidelines for accommodation and care of animals. Species-specific provisions for laboratory rodents and rabbits (In Russ.).

14. State standard Р 33044-2014. Principles of good laboratory practice. (In Russ.).

15. Borzenok S. A., Gerasimov M. Yu., Ostrovskiy D. S., Malyugin B. E. Culture of human labial mucosal epithelial cell for use in patients with bilateral limbal stem cell deficiency. Russian Journal of Transplantology and Artificial Organs. 2019;21(3):111–120. (In Russ.). Doi: 10.15825/1995- 1191-2019-3-111-120.

16. Bhargava S., Patterson J. M., Inman R. D., MacNeil S., Chapple C. R. Tissue-engineered buccal mucosa urethroplasty – clinical outcomes. European Urology. 2008;53(6):1263–1271.

17. Mikami H., Kuwahara G., Nakamura N., Yamato M., Tanaka M., Kodama S. Two-layer tissue engineered urethra using oral epithelial and muscle derived cells. The Journal of urology. 2012;187(5): 1882–1889.

18. Gorelova A. A., Muraviov A. N., Vinogradova T. I., Gorelov A. I., Yudinceva N. M., Orlova N. V., Nashchekina Yu. A., Hotin M. G., Lebedev A. A., Peshkov N. O., Yablonskij P. K. Tissue-engineered technologies in the urethra reconstruction. Medical alliance. 2018;3:75–82. (In Russ.).