Creation of Tissue-Engineered Urethras for Large Urethral Defect Repair in a Rabbit Experimental Model (original) (raw)

Urethral Reconstruction Using Cell-Based Tissue Engineering Approaches

Urethral reconstruction for complex conditions remains a challenge because of the unsatisfactory long-term results and problems associated with the harvesting of adequate replacement tissues. Tissue engineered substitutes, either scaffolds alone or in combination with cells, can overcome some of the aforementioned problems. Currently, such tissue engineered substitutes have been gaining popularity, as evidenced by >80 published preclinical and 20 clinical studies. This review summarises the currently available literature on the cell-based tissue engineered substitutes (11 studies) for urethral reconstruction. Clinical translational challenges and future directions are also discussed.

Tissue Engineering for Human Urethral Reconstruction: Systematic Review of Recent Literature

PLOS ONE, 2015

Background Techniques to treat urethral stricture and hypospadias are restricted, as substitution of the unhealthy urethra with tissue from other origins (skin, bladder or buccal mucosa) has some limitations. Therefore, alternative sources of tissue for use in urethral reconstructions are considered, such as ex vivo engineered constructs. Purpose To review recent literature on tissue engineering for human urethral reconstruction. Methods A search was made in the PubMed and Embase databases restricted to the last 25 years and the English language.

Future Prospects for Human Tissue Engineered Urethra Transplantation: Decellularization and Recellularization-Based Urethra Regeneration

Annals of Biomedical Engineering, 2017

To evaluate the histological characteristics of decellularized human urethra after transplantation into the rat omentum and compare in vivo cell seeding with perfusionbased and cell sheet urethral regeneration. Eight adult human male urethras accompanied with the surrounding corpus spongiosum were obtained. The tissues were decellularized with detergent-based method. The efficacy of decellularization and extracellular matrix preservation was evaluated by several techniques. Decellularized scaffolds were transplanted into the omentum of 12 male rats and located into the scrotum. Biopsies were taken 1, 3, and 6 months postoperatively to assess the natural recellularization. Mesenchymal stem cells obtained from preputial tissue were seeded with perfusion-based and cell sheet techniques as well. Immunohistochemical staining with a-actin, cytokeratin AE1/AE3, synaptophysin, and CD31 antibodies were performed. Removal of nuclear components and preservation of biomechanical properties was confirmed. In-vivo recellularization revealed promising results in progressive angiogenesis and cell seeding of epithelium-like cells in the lining of the urethra as well as smooth muscle cells in the wall structure. In-vitro urethral regeneration revealed that cell sheet engineering was the technique of choice compared to perfusionbased technique. This study may paw the road for clinical application of acellular urethral matrix with the surrounding corpus spongiosum in urological reconstructive surgery.

Tissue Engineering of Urinary Bladder and Urethra: Advances from Bench to Patients

The Scientific World Journal, 2013

Urinary tract is subjected to many varieties of pathologies since birth including congenital anomalies, trauma, inflammatory lesions, and malignancy. These diseases necessitate the replacement of involved organs and tissues. Shortage of organ donation, problems of immunosuppression, and complications associated with the use of nonnative tissues have urged clinicians and scientists to investigate new therapies, namely, tissue engineering. Tissue engineering follows principles of cell transplantation, materials science, and engineering. Epithelial and muscle cells can be harvested and used for reconstruction of the engineered grafts. These cells must be delivered in a well-organized and differentiated condition because water-seal epithelium and well-oriented muscle layer are needed for proper function of the substitute tissues. Synthetic or natural scaffolds have been used for engineering lower urinary tract. Harnessing autologous cells to produce their own matrix and form scaffolds is a new strategy for engineering bladder and urethra. This self-assembly technique avoids the biosafety and immunological reactions related to the use of biodegradable scaffolds. Autologous equivalents have already been produced for pigs (bladder) and human (urethra and bladder). The purpose of this paper is to present a review for the existing methods of engineering bladder and urethra and to point toward perspectives for their replacement.

Challenges and Perspectives in Male Anterior Urethra Reconstruction Using Tissue Engineering

2019

Repair or replacement of the male anterior urethra remains a challenge in 2019 especially in the case of patients presenting severe defects due to the paucity of tissues available for reconstructive surgeries. Nowadays, surgeons mainly use buccal mucosa, which can come with complications not only at the donor site but also at the graft site. This option is sometimes invasive in the case of long defects when large pieces of tissue are needed. Tissue engineering is an emerging field in regenerative medicine and offers promising avenue. It allows reconstruction of large amount of autologous tissues using small biopsies. Several strategies of tissue engineering use biomaterials, which can cause adverse effects. A new option appears with the use of the "self-assembly" protocol to reconstruct tissues using only the cells of the patients and avoiding the use of biomaterials. Human-derived tubular structures were produced by this technique and present mechanical and functional properties compatible with grafting. Moreover, these tissues can be endothelialized to prevent graft ischemia. New challenges in tissue engineering is to differentiate the cells needed for the reconstruction from induced pluripotent stem cells derived from patient blood cells, and to avoid the use of animal serum for cell culture.

Engineered human organ-specific urethra as a functional substitute

Scientific Reports

Urologic patients may be affected by pathologies requiring surgical reconstruction to re-establish a normal function. The lack of autologous tissues to reconstruct the urethra led clinicians toward new solutions, such as tissue engineering. Tridimensional tissues were produced and characterized from a clinical perspective. The balance was optimized between increasing the mechanical resistance of urethral-engineered tissue and preserving the urothelium’s barrier function, essential to avoid urine extravasation and subsequent inflammation and fibrosis. The substitutes produced using a mix of vesical (VF) and dermal fibroblasts (DF) in either 90%:10% or 80%:20% showed mechanical resistance values comparable to human native bladder tissue while maintaining functionality. The presence of mature urothelium markers such as uroplakins and tight junctions were documented. All substitutes showed similar histological features except for the noticeable decrease in polysaccharide globules for th...

Tissue Engineering in Urology- Progress and Prospects - A Review Article

Open Access Journal of Urology & Nephrology

Regenerative medicine is a new branch of medicine based on tissue engineering technology. This field of science has many things to offer in reconstructive urology where native organ is non-functional, and no substitute is available. Despite the initial promising results, it has not become a reality in the true sense. There are numerous obstacles that are slowing down the process of regenerative medicine. The progress shown in stem cell biotechnology and material science provides new vistas to translate experimental methods clinical reality. Tissue engineering encompasses a multidisciplinary approach with the main aim of development of biological substitutes designed to restore and maintain normal function in diseased or injured organs. This review is done to ascertain its current status and the progress that has been made in regenerative medicine in the reconstruction of various Genito-urinary organs.

Tissue Engineering in Lower Urinary Tract Reconstruction

2018

Urology diseases and disorders are often diagnosable by special clinical symptoms. Congenital disorders, iatrogenic injuries, inflammatory diseases, infections, tumors, cancers and other conditions of the genitourinary system are in this category. The treatment of these disorders usually involve classical surgeries including organ transplant from deceased or other methods, which are associated with transplant related side effects and complications. Tissue engineering is a rapidly expanding, promising field which addresses tissue and organ failure and organ reconstruction. A myriad of Clinical and preclinical studies have been conducted on different treatment methods and tissue engineering in the field of urology, which have been reviewed in our present study.

The promise of regenerative medicine in the treatment of urogenital disorders

Journal of Biomedical Materials Research Part A, 2020

Polymers and scaffolds are the most significant tools in regenerative medicine. Urogenital disorders are an important group of diseases that greatly affect the patient's life expectancy and quality. Reconstruction of urogenital defects is one of the current challenges in regenerative medicine. Regenerative medicine, as well as tissue engineering, may offer suitable approaches while the tools needed are appropriate materials and cells. Autologous urothelial cells obtained from biopsy, bone marrow-derived stem cells, adipose stem cells and urine-derived stem cells that expressed mesenchymal cell markers are the cells that mainly used. In addition, two main types of biomaterials mainly exist; synthetic polymers and composite scaffolds that are biodegradable polymers with controllable properties and naturally derived biomaterials such as extracellular matrix components and acellular tissue matrices. In this review, we present and evaluate the most This article is protected by copyright. All rights reserved. appropriate and suitable scaffolds (naturally derived and synthetic polymers) and cells applied in urogenital reconstruction.