Tissue-engineered Construct Based on Buccal Mucosa Cells and Matrix From Collagen and Polylactoglycolide Fibers

Study Overview
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Brief Summary
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This study investigates safety and efficacy of surgical treatment of patients with anterior urethral stricture using a tissue-engineered construct based on autologous buccal mucosa cells and matrix from reconstituted collagen and reinforcing polylactoglycolide fibers. This is a single arm study with no control. Success will be assessed via objective and subjective methods; complications will be tallied in a standardized fashion. Outcomes will be measured at five years.

Detailed Description
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Treatment of urethral strictures longer than 2 cm is an actual clinical challenge. In this case, the common method is replacement surgery using a buccal mucosa graft. However, the main disadvantage of this method is associated with limited donor resources and donor site morbidity. The aim of this study is to assess safety and efficacy of surgical treatment of patients with anterior urethral stricture using a tissue-engineered construct. The construct consists of autologous buccal mucosa cells and matrix from reconstituted collagen and reinforcing polylactoglycolide fibers. Patients will be followed up for 5 years within this study. The follow-up regimen includes retrograde and pericatheter urethrography, voiding cystourethrography, uroflowmetry, biopsy, and quality of life monitoring. Telephone follow-up will take place in between these assessments. The data obtained from this study will have practical implications for the urethral stricture treatment and will be based on the principles of evidence-based medicine.

Official Title
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An Open Prospective Clinical Study on Safety and Efficacy of Surgical Treatment of Patients With Anterior Urethral Stricture Using a Tissue-engineered Construct Based on Autologous Buccal Mucosa Cells and Matrix From Reconstituted Collagen and Reinforcing Polylactoglycolide Fibers

Conditions
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Urethral Stricture

Intervention / Treatment
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* Procedure: Urethroplasty with a tissue-engineered construct


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient signed informed consent form Diagnosed anterior urethral stricture longer than 2.0 cm and shorter than 4.0 cm At least one prior internal optical urethrotomy and/or urethral bougienage Non-inclusion Criteria: Acute infectious diseases Patient with decompensated heart and renal failure Patient with non-compensated diabetes mellitus Patient with malignant tumor Patient with polyvalent allergy Mental disorders Post traumatic urethral strictures Subtotal and total urethral strictures Sexually transmitted infections Hypersensitivity to any components of tissue-engineered constructs Any clinical state which does not ensure the safe implementation of study procedure (investigator's view) Other associated urethral strictures Laboratory markers of active urethritis Exclusion Criteria: Patient's refusal from the further participation in trial Confirmed syphilis, HIV, hepatitis B or C infections Patient who cannot be regularly examined due to any circumstances

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 78 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Urethroplasty with a tissue-engineered construct<br>The investigators will take a sample of the buccal mucosa to isolate epithelial cells. Autologous cells will be seeded on a hybrid matrix. Urethroplasty with this tissue-engineered construct will be performed. This is a single arm study with no control. All patients will undergo the surgical operation. | Procedure: Urethroplasty with a tissue-engineered construct<br>* The investigators will perform urethroplasty with the tissue-engineered construct - epithelial cells isolated from patient's buccal mucosa and seeded on a collagen-polylactoglycolide matrix.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious adverse events | Frequency, type and severity of serious adverse events (SAE) | 4 weeks after surgery | 
| Serious adverse reactions | Frequency, type and severity of serious adverse reactions (SAR) | 4 weeks after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retrograde urethrography | Influence of the surgery on the urethral lumen | 5 years | 
| Voiding cystourethrography | Full assessment of the urethral lumen after the surgery | 5 years | 
| Pericatheter urethrography | Assessment of absence or presence of contrast medium leakage outside the urethra | 4 weeks after surgery | 
| Biopsy | Control of anatomical urethral structure in the intervention place | 4 months after surgery | 
| Urodynamic changes via uroflowmetry - 1 | Influence of the surgery on urinary flow rate: maximum flow rate | 5 years | 
| Urodynamic changes via uroflowmetry - 2 | Influence of the surgery on urinary flow rate: average flow rate | 5 years | 
| Urodynamic changes via uroflowmetry - 3 | Influence of the surgery on urinary flow rate: total volume voided | 5 years | 
| Urodynamic changes via uroflowmetry - 4 | Influence of the surgery on urinary flow rate: maximum flow time | 5 years | 
| Quality of life monitoring - 1 | Quality of life estimated by validated questionnaires: Short Form (SF-36) | 5 years | 
| Quality of life monitoring - 2 | Quality of life estimated by validated questionnaires: International Prostatic Symptom Score (IPSS) | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Buccal Mucosa, Urethroplasty, Tissue-engineered Construct, Hybrid matrix, Collagen, Polylactoglycolide Fibers, Autologous Cells