Search Results (24)

Tissue engineering enables autologous reconstruction of human tissues, addressing limitations in tissue availability and immune compatibility. Several tissue engineering techniques, such as self-assembly, rely on or benefit from extracellular matrix (ECM) secretion by fibroblasts to produce biomimetic scaffolds. Models have been developed for use in humans, such as skin and corneas. Ascorbic acid (vitamin C, AA) is essential for collagen biosynthesis. However, AA is chemically unstable in culture, with a half-life of 24 h, requiring freshly prepared AA with each change of medium. This study aims to demonstrate the functional equivalence of 2-phospho-L-ascorbate (2PAA), a stable form of AA, for tissue reconstruction. Dermal, vaginal, and bladder stroma were reconstructed by self-assembly using tissue-specific protocols. The tissues were cultured in a medium supplemented with either freshly prepared or frozen AA, or with 2PAA. Biochemical analyses were performed on the tissues to evaluate cell density and tissue composition, including collagen secretion and deposition. Histology and quantitative polarized light microscopy were used to evaluate tissue architecture, and mechanical evaluation was performed both by tensiometry and atomic force microscopy (AFM) to evaluate its macroscopic and cell-scale mechanical properties. The tissues produced by the three ascorbate conditions had similar collagen deposition, architecture, and mechanical properties in each organ-specific stroma. Mechanical characterization revealed tissue-specific differences, with tensile modulus values ranging from 1–5 MPa and AFM-derived apparent stiffness in the 1–2 kPa range, reflecting the nonlinear and scale-dependent behavior of the engineered stroma. The results demonstrate the possibility of substituting AA with 2PAA for tissue engineering. This protocol could significantly reduce the costs associated with tissue production by reducing preparation time and use of materials. This is a crucial factor for any scale-up activity. Full article

Background and Objectives: The male urethra is a complex structure that plays a critical role in genitourinary health and function. Despite its importance, histological descriptions of the penile urethra, particularly its epithelial components, remain incomplete. This study offers a comprehensive histological analysis of the penile urethra, focusing on the epithelium across distinct anatomical regions, including the glans, distal and proximal fossa navicularis and spongy urethra. Materials and Methods: Utilizing five human penile specimens, we employed various staining techniques to elucidate the structural characteristics of these epithelial tissues. Results: Our findings reveal notable variations in epithelial composition, such as the presence of glycogen-rich cells in the distal fossa navicularis and the presence of mucous glands in the spongy urethra and proximal fossa navicularis. Additionally, we identified a previously underreported valvule-like structure in the distal fossa navicularis in two of the specimens. In addition, the epithelium of the glans and the distal fossa navicularis are thicker than the ones of the proximal fossa navicularis and the spongy urethra. With a similar vascular density, the orientation of the blood vessels also diverges starting with the distal fossa navicularis. Conclusions: This study provides new insights into the histological organization of the penile urethra, offering critical reference data that can enhance our understanding of urethral pathologies and improve the outcomes of surgical interventions, particularly in the context of tissue engineering and reconstructive surgery. Full article

Urethral reconstruction remains a challenge. Indeed, the use of oral mucosa, the reference biomaterial for urethroplasty, is associated with two main drawbacks: the limited availability of autologous tissues and potential short- and long-term complications, especially for patients with recurrences or severe anomalies. Therefore, the development of alternative approaches, such as urethral tissue engineering, is necessary. A new type of human urethral substitute devoid of exogenous biomaterials has been reconstructed in vitro. It presented sufficient mechanical strength and had histological and functional properties comparable to native tissues. These reconstructed tissues were implanted in vivo to repair hypospadias induced in tacrolimus-immunosuppressed rabbits via a two-stage urethroplasty. In the first stage, the distal part of the native urethra was removed, and a flat graft was implanted, leaving the urethra open proximally. Twelve weeks later, the graft was tubularized to create a neourethra, reproducing the usual clinical scenario. The results obtained for the experimental group were less effective than for the control group, with a success rate of 50% after excluding the animal affected by unwanted events unrelated to urethroplasty, and it is possible that the animal model or surgical technique used was not suitable and should be modified. Nevertheless, half of the urethral substitutes grafted on rabbits showed successful integration. These self-assembled artificial tissues represent promising substitutes for urethroplasty. Full article

Over the last decades, the human species has seen an increase in the incidence of pathologies linked to the genitourinary tract. Observations in animals have allowed us to link these increases, at least in part, to changes in the environment and, in particular, to an increasing presence of endocrine disruptors. These can be physical agents, such as light or heat; natural products, such as phytoestrogens; or chemicals produced by humans. Endocrine disruptors may interfere with the signaling pathways mediated by the endocrine system, particularly those linked to sex hormones. These factors and their general effects are presented before focusing on the male and female genitourinary tracts by describing their anatomy, development, and pathologies, including bladder and prostate cancer. Full article

Uropathogenic Escherichia coli are the main causal agent of urinary tract infections. These diseases can affect more than half of women during their lifetime. Moreover, recurrent urinary tract infections can affect up to 30% of patients, leading to higher social and economic costs for the community. No efficient treatment against the recurrent form of the disease has been discovered. Due to the low average rate of successful translation from 2D cell culture and in vivo animal models into clinical trials, new models that mimic pathologies, such as those produced by tissue engineering, are needed. A model of human-derived 3D bladder mucosa was produced by tissue engineering techniques using collagen gels and organ-specific primary human stromal and epithelial cell populations. This model was used to mimic the different steps of a urinary tract infection: adhesion, invasion, intracellular bacterial community and quiescent intracellular reservoir formation and, finally, bacteria resurgence after umbrella cell exfoliation through chitosan exposure to mimic the recurrent infection. The uropathogenic strain UTI-89-GFP was used as infectious bacteria and BL-21-GFP strain as a control. Our model is unique and is the first step toward mimicking the different phases of a UTI in a human context. Full article

The penis is a complex organ with a development cycle from the fetal stage to puberty. In addition, it may suffer from either congenital or acquired anomalies. Penile surgical reconstruction has been the center of interest for many researchers but is still challenging due to the complexity of its anatomy and functionality. In this review, penile anatomy, pathologies, and current treatments are described, including surgical techniques and tissue engineering approaches. The self-assembly technique currently applied is emphasized since it is considered promising for an adequate tissue-engineered penile reconstructed substitute. Full article

The melanoma cell adhesion molecule, shed from endothelial and cancer cells, is a soluble growth factor that induces tumor angiogenesis and growth. However, the molecular mechanism accounting for its generation in a tumor context is still unclear. To investigate this mechanism, we performed in vitro experiments with endothelial/cancer cells, gene expression analyses on datasets from human colorectal tumor samples, and applied pharmacological methods in vitro/in vivo with mouse and human colorectal cancer cells. We found that soluble MCAM generation is governed by ADAM17 proteolytic activity and NOX1-regulating ADAM17 expression. The treatment of colorectal tumor-bearing mice with pharmacologic NOX1 inhibitors or tumor growth in NOX1-deficient mice reduced the blood concentration of soluble MCAM and abrogated the anti-tumor effects of anti-soluble MCAM antibodies while ADAM17 pharmacologic inhibitors reduced tumor growth and angiogenesis in vivo. Especially, the expression of MCAM, NOX1, and ADAM17 was more prominent in the angiogenic, colorectal cancer-consensus molecular subtype 4 where high MCAM expression correlated with angiogenic and lymphangiogenic markers. Finally, we demonstrated that soluble MCAM also acts as a lymphangiogenic factor in vitro. These results identify a role for NOX1/ADAM17 in soluble MCAM generation, with potential clinical therapeutic relevance to the aggressive, angiogenic CMS4 colorectal cancer subtype. Full article

Urethral reconstruction strategies are limited with many associated drawbacks. In this context, the main challenge is the unavailability of a suitable tissue that can endure urine exposure. However, most of the used tissues in clinical practices are non-specialized grafts that finally fail to prevent urine leakage. Tissue engineering has offered novel solutions to address this dilemma. In this technology, scaffolding biomaterials characteristics are of prime importance. Biological macromolecules are naturally derived polymers that have been extensively studied for various tissue engineering applications. This review discusses the recent advances, applications, and challenges of biological macromolecule-based scaffolds in urethral reconstruction. Full article

Congenital vaginal anomalies and pelvic organ prolapse affect different age groups of women and both have significant negative impacts on patients’ psychological well-being and quality of life. While surgical and non-surgical treatments are available for vaginal defects, their efficacy is limited, and they often result in long-term complications. Therefore, alternative treatment options are urgently needed. Fortunately, tissue-engineered scaffolds are promising new treatment modalities that provide an extracellular matrix (ECM)-like environment for vaginal cells to adhere, secrete ECM, and be remodeled by host cells. To this end, ECM-based scaffolds or the constructs that resemble ECM, generated by self-assembly, decellularization, or electrospinning techniques, have gained attention from both clinicians and researchers. These biomimetic scaffolds are highly similar to the native vaginal ECM and have great potential for clinical translation. This review article aims to discuss recent applications, challenges, and future perspectives of these scaffolds in vaginal reconstruction or repair strategies. Full article

The gastrointestinal and genitourinary tracts share several similarities. Primarily, these tissues are composed of hollow structures lined by an epithelium through which materials need to flow with the help of peristalsis brought by muscle contraction. In the case of the gastrointestinal tract, solid or liquid food must circulate to be digested and absorbed and the waste products eliminated. In the case of the urinary tract, the urine produced by the kidneys must flow to the bladder, where it is stored until its elimination from the body. Finally, in the case of the vagina, it must allow the evacuation of blood during menstruation, accommodate the male sexual organ during coitus, and is the natural way to birth a child. The present review describes the anatomy, pathologies, and treatments of such organs, emphasizing tissue engineering strategies. Full article

Bisphenol A (BPA) and bisphenol S (BPS) are synthetic chemicals used to produce plastics which can be released in food and water. Once ingested, BPA and BPS are metabolized by the liver, mainly as glucuronidated metabolites, and are excreted through urine. Since urine can be stored for many hours, the bladder is chronically exposed to BP metabolites, and studies have shown that these metabolites can remain active in the organism. Therefore, the effect of physiological concentrations of glucuronidated BPs was evaluated on the bioenergetics (glycolysis and mitochondrial respiration), migration and proliferation of normal urothelial cells, and non-invasive and invasive bladder cancer cells. The results demonstrated that an exposure of 72 h to glucuronidated BPA or BPS decreased the bioenergetics and activity of normal urothelial cells, while increasing these parameters for bladder cancer cells. These findings suggest that BP metabolites are not as inactive as initially believed, and their ubiquitous presence in the urine could promote bladder cancer progression. Full article

Female gynecological organ dysfunction can cause infertility and psychological distress, decreasing the quality of life of affected women. Incidence is constantly increasing due to growing rates of cancer and increase of childbearing age in the developed world. Current treatments are often unable to restore organ function, and occasionally are the cause of female infertility. Alternative treatment options are currently being developed in order to face the inadequacy of current practices. In this review, pathologies and current treatments of gynecological organs (ovaries, uterus, and vagina) are described. State-of-the-art of tissue engineering alternatives to common practices are evaluated with a focus on in vivo models. Tissue engineering is an ever-expanding field, integrating various domains of modern science to create sophisticated tissue substitutes in the hope of repairing or replacing dysfunctional organs using autologous cells. Its application to gynecology has the potential of restoring female fertility and sexual wellbeing. Full article

Current therapeutic modalities to treat urethral strictures are associated with several challenges and shortcomings. Therefore, significant strides have been made to develop strategies with minimal side effects and the highest therapeutic potential. In this framework, electrospun scaffolds incorporated with various cells or bioactive agents have provided promising vistas to repair urethral defects. Due to the biomimetic nature of these constructs, they can efficiently mimic the native cells’ niches and provide essential microenvironmental cues for the safe transplantation of multiple cell types. Furthermore, these scaffolds are versatile platforms for delivering various drug molecules, growth factors, and nucleic acids. This review discusses the recent progress, applications, and challenges of electrospun scaffolds to deliver cells or bioactive agents during the urethral defect repair process. First, the current status of electrospinning in urethral tissue engineering is presented. Then, the principles of electrospinning in drug and cell delivery applications are reviewed. Finally, the recent preclinical studies are summarized and the current challenges are discussed. Full article

Over the past decade, growing demand from many domains (research, cosmetics, pharmaceutical industries, etc.) has given rise to significant expansion of the number of in vitro cell cultures. Despite the widespread use of fetal bovine serum, many issues remain. Among them, the whole constitution of most serums remains unknown and is subject to significant variations. Furthermore, the presence of potential contamination and xenogeny elements is challenging for clinical applications, while limited production is an obstacle to the growing demand. To circumvent these issues, a Serum-Free Medium (SFM) has been developed to culture dermal and vesical fibroblasts and their corresponding epithelial cells, namely, keratinocytes and urothelial cells. To assess the impact of SFM on these cells, proliferation, clonogenic and metabolic assays have been compared over three passages to conditions associated with the use of a classic Fetal Bovine Serum-Containing Medium (FBSCM). The results showed that the SFM enabled fibroblast and epithelial cell proliferation while maintaining a morphology, cell size and metabolism similar to those of FBSCM. SFM has repeatedly been found to be better suited for epithelial cell proliferation and clonogenicity. Fibroblasts and epithelial cells also showed more significant mitochondrial metabolism in the SFM compared to the FBSCM condition. However, the SFM may need further optimization to improve fibroblast proliferation. Full article

Bisphenol A (BPA) and bisphenol S (BPS) are used in the production of plastics. These endocrine disruptors can be released into the environment and food, resulting in the continuous exposure of humans to bisphenols (BPs). The bladder urothelium is chronically exposed to BPA and BPS due to their presence in human urine samples. BPA and BPS exposure has been linked to cancer progression, especially for hormone-dependent cancers. However, the bladder is not recognized as a hormone-dependent tissue. Still, the presence of hormone receptors on the urothelium and their role in bladder cancer initiation and progression suggest that BPs could impact bladder cancer development. The effects of chronic exposure to BPA and BPS for 72 h on the bioenergetics (glycolysis and mitochondrial respiration), proliferation and migration of normal urothelial cells and non-invasive and invasive bladder cancer cells were evaluated. The results demonstrate that chronic exposure to BPs decreased urothelial cells’ energy metabolism and properties while increasing them for bladder cancer cells. These findings suggest that exposure to BPA and BPS could promote bladder cancer development with a potential clinical impact on bladder cancer progression. Further studies using 3D models would help to understand the clinical consequences of this exposure. Full article