Substitutional urethroplasty with tissue-engineered structures in an experiment

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Abstract

Introduction. In order to exclude the difficulties arising in the course of traditional surgical interventions in the scope of substitutional urethroplasty, in recent years, alternative materials have been developed using tissue engineering. This study is devoted to the development of new tissue-engineered constructions for urethroplasty using cells of different tissue origins and biopolymers, which is an urgent problem of modern medicine.

Aim. Experimental provision of a rationale for the possibility of using tissue-engineered constructions to replace urethral defects.

Methods and materials. Two-staged, experimental, controlled study. Dedicated to the development of tissue-engineered constructions (TEC) based on biopolymers seeded with mesenchymal stem cells or buccal epithelial cells. The prepared TECs were implanted into the rabbit’s urethra wall in a acute trauma model. Comparison of the results of the TECs usage with the “gold standard” – buccal urethraplasty was carried out.

Results. Urethrography showed similar results in all groups of animals, regardless the type of implanted material. No urethral patency was found, and confocal microscopy of urethral cryosections revealed the presence of nanoparticle-labeled mesenchymal stem cells / buccal epithelium cells with signs of their differentiation in the urothelial direction in the mucous layer.

Conclusion. The possibility of using tissue-engineered constructions based on biopolymers containing autologous mesenchymal stem cells or buccal epithelium cells for experimental substitutional urethroplasty was shown. The developed TECs can be used as an alternative to buccal urethroplasty in an experiment.

About the authors

Anna A. Gorelova

St. Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation; St. Petersburg State University

Author for correspondence.
Email: gorelovauro@gmail.com
ORCID iD: 0000-0002-7010-7562

Postgraduate Student; Assistant-Professor, Department of Hospital Surgery

Russian Federation, Saint Petersburg

Aleksandr N. Murav’ev

St. Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation; St. Petersburg Medico-Social Institute

Email: urolog5@gmail.com
ORCID iD: 0000-0002-6974-5305

Candidate of Medical Science, Head of Urology, Gynecology and Abdominal Surgery Direction; Associate Professor, Department of Surgical Diseases

Russian Federation, Saint Petersburg

Tatiana I. Vinogradova

St. Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation

Email: vinogradova@spbniif.ru
ORCID iD: 0000-0002-5234-349X

Doctor of Medical Science, Professor, Chief Researcher

Russian Federation, Saint Petersburg

Andrei I. Gorelov

St. Petersburg State University; Pokrovskaya Municipal Hospital

Email: gorelov_a_i@mail.ru
ORCID iD: 0000-0002-2858-5317

Doctor of Medical Science, Professor, Department of Hospital Surgery; Head, Urology Department

Russian Federation, Saint Petersburg

Natalia M. Yudintseva

Institute of Cytology of the Russian Academy of Sciences

Email: yudintceva@mail.ru
ORCID iD: 0000-0002-7357-1571

Candidate of Biological Sciences, Senior Researcher

Russian Federation, Saint Petersburg

Yulia A. Nashchekina

Institute of Cytology of the Russian Academy of Sciences

Email: ulychka@mail.ru
ORCID iD: 0000-0002-4371-7445

Candidate of Biological Sciences, Research Fellow

Russian Federation, Saint Petersburg

Igor A. Samusenko

Nikiforov Russian Center of Emergency and Radiation Medicine of the Ministry of Russian Federation for Civil Defense, Emergencies and Elimination of Consequences of Natural Disasters

Email: egors_2000@mail.ru
ORCID iD: 0000-0003-0622-3515

Candidate of Medical Science, Pathologist

Russian Federation, Saint Petersburg

Petr K. Yablonsky

St. Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation; St. Petersburg State University

Email: glhirurgb2@mail.ru
ORCID iD: 0000-0003-4385-9643

Doctor of Medical Science, Professor, Director; Head, Department of Hospital Surgery

Russian Federation, Saint Petersburg

References

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  6. Yudintceva NM, Nashchekina YA, Blinova MI, et al. Experimental bladder regeneration using a poly-l-lactide/silk fibroin scaffold seeded with nanoparticle-labeled allogenic bone marrow stromal cells. Int J Nanomedicine. 2016;11:4521-4533. https://doi.org/10.2147/IJN.S111656.
  7. Feng C, Xu YM, Fu Q, et al. Evaluation of the biocompatibility and mechanical properties of naturally derived and synthetic scaffolds for urethral reconstruction. J Biomed Mater Res A. 2010;94(1):317-325. https://doi.org/10.1002/jbm.a.32729.

Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Samples of prepared scaffolds: a – porous two-layer scaffold based on PL + PC; b – flat two-layer scaffold based on PLG + PLC

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3. Fig. 2. Subcutaneous implantation of scaffolds in the rat back

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4. Fig. 3. Urethroplasty with implantation of the TEC, based on PL + PC with MSCs: a – the urethra is exposed dorso-laterally; b – the lumen of the urethra is opened; c – TEC with MSC; d – comparison of the TEC and the edges of the urethral defect

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5. Fig. 4. Human bone marrow mesenchymal stem cells after 1 day of cultivation on polymer films (light microscopy ×4; confocal microscopy ×40)

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6. Fig. 5. The process of scaffold biodegradation — the studied scaffolds (1, 2 – PL + PC; 3, 4 – PLC + PLG) were implanted subcutaneously in rats: a – 1 week after implantation, the intervention zone is determined; b – after 4 weeks, the intervention zone is not visualized macroscopically

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7. Fig. 6. Retrograde urethrograms: a – the lumen of the urethra is preserved; b – the extravasation of the contrast agent outside the lumen of the urethra

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8. Fig. 7. Macro preparations of the rabbit urethra: a – visualization of the TEC implantation zone (group 1); b – the TEC implantation zone is not visualized (group 2); c – visualization of the buccal graft; d – urethrocutaneous fistula (arrow)

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9. Fig. 8. Confocal microscopy, visualization of nanoparticles in the mucous layer at different time after implantation of TECs with MSCs. The scale bars correspond to 100 μm

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10. Fig. 9. Confocal microscopy, visualization of nanoparticles in the mucous layer 12 weeks after implantation of TECs with buccal epithelial cells . The scale bars correspond to 100 μm

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Copyright (c) 2020 Gorelova A.A., Murav’ev A.N., Vinogradova T.I., Gorelov A.I., Yudintseva N.M., Nashchekina Y.A., Samusenko I.A., Yablonsky P.K.

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This work is licensed under a Creative Commons Attribution 4.0 International License.
 


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