Natalia Yudintceva
Abstract
In recent years the interest of urologists to use the methods of tissue engineering in the treatment of pathologies of the urinary tract has increased. This refers to diseases in which organ substitution is required, and the tissues of the gastrointestinal tract and various tissues of the body are used as substitutes. The disadvantages of this approach are postoperative complications, a shortage of tissues for plastics, and an increase in the time of surgery due to the need for a patient's flap. The aim of the study was to investigate the effectiveness of the tissue engineering graft (TEG) application for the repair of damaged urine bladder (UB) tissue and urethra. TEGs based on bilayer polymer scaffolds seeded with allogeneic mesenchymal stem cells (MSCs) of rabbit bone marrow were prepared for the reconstruction of UB and urethra. To specifically track the used cells in vivo, the later were labeled with superparamagnetic iron oxide nanoparticles (SPIONs). TEGs were implanted on the model of partial resection of the UB and defect of the dorsal surface of the urethra of rabbits. Evaluation of the results of the TEGs application and cell therapy was performed following 4, 8 and 12 weeks after the operation. After animal sacrifice, histological and immunohistochemical analyses were performed and tissue cryosections were prepared. The nanoparticle-labeled cells were detected in various layers of reconstructed tissues that convincingly demonstrate their active participation in the reconstruction process. The developed TEGs with allogenic MSCs facilitated to the effective reparation of damaged tissues of UB and urethra, which is especially important for treatment of pathologies without a possibility of using autologous tissue. A few urinary tract pathologic conditions, for example, injuries, malignancy, and decimations, require reconstructive plastic medical procedure. Remaking of the urinary tract is an obstinate undertaking for urologists because of lacking autologous tissue. Confinements of autologous tissue application incited urologists to explore perfect substitutes. Tissue designing is another course in these cases. Advances in tissue designing in the course of the most recent 2 decades may offer elective methodologies for the urinary tract reproduction. The fundamental parts of tissue designing incorporate biomaterials and cells. Biomaterials can be utilized with or without refined cells. The fundamental driver of ureter harm is injury brought about by, for instance, engine mishaps, firearm shots, or iatrogenic wounds acquired during medical procedure. While ureteral injury is moderately exceptional, the inability to remember it can prompt serious reactions, including sepsis or loss of renal capacity. Careful ureteral recreation prospects are restricted because of explicit anatomical attributes of the ureter (e.g., segmental vascular flexibly), site of ureteral injury, and the absence of local tissue for fix. A few careful strategies are prescribed to fix ureteral defects.2 For long-fragment reproduction, the formation of neotissue utilizing autologous reaped entrail tissue remains the best quality level. In any case, the utilization of this inconsequential tissue source is related with extreme symptoms and numerous negative results. By and large, numerous methods are required after some time, for the most part because of (re-)stenosis and (re-)injuries, and eventually nephrectomy might be required. For muscle-intrusive bladder malignant growth (MIBC) and non-MIBC with high danger of movement, the European rules suggest radical cystectomy followed by urinary diversion.5 The most utilized type of urinary preoccupation is the ileal conductor utilizing autologous digestive tract segments.6 However, fundamentally the same as ureteral remaking, this is related with numerous postoperative entanglements. Recreation Strategies in Preclinical Studies Using Tissue-Engineered Constructs Direct implantation of unions Ureter As ureteral harm is normally intense, it requires prompt recreation, stressing the requirement for a promptly accessible "off-the-rack" item. To be sure, this methodology was utilized in most preclinical examinations ("An" in Table 1). Direct implantation of decellularized tissue to fill a full ureteral deformity (Fig. 2A) indicated constrained tissue recovery: urothelial cells (UCs) secured the join lumen, however smooth muscle cell (SMC) ingrowth remained chiefly restricted to the anastomosis side of the graft,12–16,18,20,21 paying little mind to the creature model utilized. Subsequently, most creatures gave (serious) fibrosis of the ureteral unite and join shrinkage, injuries, hindrance, just as hydronephrosis happened in practically all examinations, an undesired result. In different examinations, platforms made from collagen-rich decellularized rodent ureter indicated upgraded epithelial coating and muscle arrangement all through the transplanted framework in little imperfections <0.8 cm in a rodent model.22 However, muscle ingrowth stayed constrained when bigger deformities were fixed in an enormous creature model (hound) utilizing consistent rounded platforms made out of decontaminated common collagen. Fibrosis and dilatation of the ureter over the anastomosis side happened, demonstrating dynamic obstacle. To upgrade unite acknowledgment and join redesigning, GFs have been added to improve tissue recovery. In pig examines, frameworks were stacked with vascular endothelial GF and fundamental fibroblast GF through heparin restricting that is intended to support vascularization and tissue redesigning. In all creatures, join shrinkage (∼24%) and tightening at the anastomosis site was seen just as hydronephrosis. Postimplantation, the lumen of the neoureter was secured with a solitary layer of urothelium, whether or not GFs were included. Muscle ingrowth was restricted and mostly happened at the anastomosis site, and all in all, expansion of GFs didn't improve the result. Stacking of SIS with the sort I collagen inhibitor halofuginone intended to forestall injury arrangement in the wake of joining, which was conceivably brought about by quick collagen corruption and tissue renovating and furthermore didn't improve result in porcine models. Direct implantation of completely engineered nondegradable unions, which would be anything but difficult to deliver and kept as off-the-rack unites, has met little achievement. Joining brought about generous entanglements, for example, fibrosis, intense and constant irritation around the embed, just as impediment/impediment and injury at the anastomosis site in a canine model. Implantation of biodegradable electrospun poly(L-lactide-co-caprolactone) (PLCL) frameworks in Wistar rodents with a full ureteral imperfection brought about a generous size decrease of the join (30%), and implantation of the PLCL format brought about patent uretero-platform anastomosis in 4/6 creatures contemplated, however ureter result and kidney capacity and its combination with local ureter were commonly more terrible contrasted with decellularized platform. Notwithstanding the join (bio)material and creature model utilized, direct implantation of uncovered frameworks to connect full circumferential ureteral surrenders has been reliably connected with extreme symptoms, for example, fibrosis, unite shrinkage, injuries, dilatation, as well as hydronephrosis. In spite of the fact that urothelium recovery was conceivable by and large, development of utilitarian muscle tissue has stayed restricted. Thusly, direct implantation of current sans cell unions may not fitting.