Reproduction of different tissues using scaffolds and materials is a major element in regenerative medicine. The regeneration of whole organs with decellularized extracellular matrix (dECM) has remained a goal despite the use of these materials for different purposes. Recently, decellularization techniques have been widely used in producing scaffolds that are appropriate for regenerating damaged organs and may be able to overcome the shortage of donor organs. Decellularized ECM offers several advantages over synthetic compounds, including the preserved natural microenvironment features. Different decellularization methods have been developed, each of which is appropriate for removing cells from specific tissues under certain conditions. A variety of methods have been advanced for evaluating the decellularization process in terms of cell removal efficiency, tissue ultrastructure preservation, toxicity, biocompatibility, biodegradability, and mechanical resistance in order to enhance the efficacy of decellularization methods. Modification techniques improve the characteristics of decellularized scaffolds, making them available for the regeneration of damaged tissues. Moreover, modification of scaffolds makes them appropriate options for drug delivery, disease modeling, and improving stem cells growth and proliferation. However, considering different challenges in the way of decellularization methods and application of decellularized scaffolds, this field is constantly developing and progressively moving forward. This review has outlined recent decellularization and sterilization strategies, evaluation tests for efficient decellularization, materials processing, application, and challenges and future outlooks of decellularization in regenerative medicine and tissue engineering.

Attaining a well-qualified whole decellularized organ applicable for an enduring and successful transplantation, decellularization protocols should be organ specific in terms of decellularizing agents and time of tissue exposure. Since a bioscaffold resulting from a large solid organ should have the potential to preserve its three-dimensional architecture and consistency for at least several months in the site of transplantation, evaluating the mechanical properties of the bioscaffold is mandatory before transplantation. In the current study, we compared five different decellularization protocols and also two main decellularization techniques (perfusion vs. diffusion) to decellularize the sheep liver, which is similar to the human liver in terms of size and anatomy. Moreover, we assessed the retaining of vascular network by dye injection and angiography. We also determined the most proper sterilization method by comparing six different sterilization methods. The mechanical properties of the scaffolds were assessed by applying tensile strength, suture retention, and compressive strength tests. The perfusion technique showed better results compared to the diffusion technique. The protocol containing ammonium hydroxide and triton X-100 was the most proper decellularization protocol leading to completely decellularized livers along with intact vascular network. Furthermore, we noted that application of streptokinase in washing step facilitates decellularization. Our results also showed that a combination of two sterilization methods is necessary for complete sterilization of a sheep liver and peracetic acid or ethylene oxide+gamma irradiation was associated with the best outcome. Determining the most appropriate decellularization and sterilization method for each organ along with assessing the mechanical properties of the resulting bioscaffold are principal steps before fabricating efficient artificial organs in the foreseeable future.

Animated biofeedback is an established treatment for pediatric dysfunctional voiding. Bowel dysfunction is closely associated with dysfunctional voiding. We evaluated the efficacy of animated biofeedback urotherapy in bowel and voiding dysfunction in children with dysfunctional elimination syndrome. A total of 80 children with dysfunctional elimination syndrome were randomly assigned to undergo animated biofeedback (group A, 40 patients) or conservative therapy (group B, 40 patients). Group A underwent animated biofeedback along with pelvic floor muscle exercises and behavioral modification (hydration, high fiber diet, scheduled voiding). Group B underwent behavioral modification only. Dysfunctional voiding symptom score, constipation and fecal soiling episodes per week (according to Paris Consensus on Childhood Constipation Terminology criteria), and uroflowmetry parameters were evaluated before and 6 and 12 months after treatment in both groups. Subjective and objective voiding problems were significantly improved. Vesicoureteral reflux resolved in 7 of 9 children (78%) and urinary tract infection did not recur in 10 of 14 children (71%) within 1 year. Bladder capacity and voided volume did not significantly improve. Post-void residual and voiding time decreased considerably, while maximum and average urine flow increased significantly. All children with fecal soiling and 17 of 25 with constipation (68%) in group A were symptom-free within 1 year after treatment. Animated biofeedback therapy was more efficient than nonbiofeedback management regarding objective and subjective voiding problems and bowel dysfunction (p <0.05). Animated biofeedback effectively treats bowel and voiding dysfunction in children with dysfunctional voiding. Pelvic floor muscle exercises coordinate breathing and pelvic floor muscle contractions, and are beneficial in improving bowel dysfunction.

We assessed the smooth muscle cell apoptosis along with changes in cellular and extracellular components of the ureteropelvic junction in 23 patients with unilateral obstruction and compared them with 25 autopsies from ureteropelvic junction regions of age matched cadavers. Tissue specimens obtained from pyeloplasty were divided into 3 sections-renal pelvis above the obstruction, obstructed ureteropelvic junction and ureter below the obstructed region. For the control group the normal ureteropelvic junctions of age matched infants were autopsied. In paraffin embedded sections we determined myocyte apoptosis index (using TUNEL assay), and the amount of muscular components and nerve terminals (using image analysis techniques after immunohistochemical staining). The collagen and elastin fibers were specifically stained for evaluation of changes in extracellular matrix. Smooth muscle cell apoptosis index was significantly increased at the site of ureteropelvic junction obstruction (5.68 +/- 0.18) compared to normal autopsied ureteropelvic junctions (3.60 +/- 0.11) and 2 other sections of obstructed ureteropelvic junction complex (renal pelvis 4.73 +/- 0.16, and ureter 3.97 +/- 0.16). The number of nerve terminals and the percentage of muscular component were significantly lower at the obstructed segments of affected patients compared to normal ureteropelvic junctions. Meanwhile, collagen fibers formed a significantly higher proportion of ureteral wall at the site of obstruction. Interestingly, there was negative correlation between myocyte apoptosis indices and number of nerve endings as well as amount of muscular components at the site of ureteropelvic junction obstruction. However, positive correlations were found between smooth muscle cell apoptosis and the percentage of collagen and elastin fibers. Our findings suggest an important role for myocyte apoptosis and defective neural development in the pathogenesis of congenital ureteropelvic junction obstruction that could pave the road for the emergence of new therapeutic modalities.