Search Results (17)

Background: Microtia is a congenital outer ear deformity that causes the auricle to be absent or underdeveloped. It is frequently associated with external auditory canal atresia and causes hearing and psychosocial problems. Objectives: We thoroughly investigate the aspects of microtia and explore both current and innovative therapies. Methods: A systematic literature review was conducted following PRISMA guidelines, focusing on microtia and reconstruction methodologies. This review utilized three databases: PubMed, Scopus, and Web of Science. Results: The etiology involves both genetic and environmental factors and can occur as part of a syndrome or as an isolated condition. Clinically, it has esthetic and functional implications, potentially leading to conductive hearing loss. A multidisciplinary approach is essential for treatment, which includes surgical reconstruction using autologous cartilage or synthetic prostheses. Advances in bioengineering and 3D printing offer new, less invasive solutions. Conclusions: This review aims to synthesize current knowledge on microtia, focusing on tissue engineering for auricular reconstruction, identifying research gaps, evaluating techniques, and providing a resource for clinicians to improve decision-making and foster further research. Full article

With the increasing number of people suffering from heart valve diseases (e.g., stenosis and/or insufficiency), the attention paid to prosthetic heart valves has grown significantly. Developing a prosthetic device that fully replaces the functionality of the native valve remains a huge challenge. Polymeric heart valves (PHVs) represent an appealing option, offering the potential to combine the robustness of mechanical valves with the enhanced biocompatibility of bioprosthetic ones. Over the years, novel biomaterials (such as promising new polymers and nanocomposites) and innovative designs have been explored for possible applications in manufacturing PHVs. This work provides a comprehensive overview of PHVs’ evolution in terms of materials, design, and fabrication techniques, including in vitro and in vivo studies. Moreover, it addresses the drawbacks associated with PHV implementation, such as their limited biocompatibility and propensity for sudden failure in vivo. Future directions for further development are presented. Notably, PHVs can be particularly relevant for transcatheter application, the most recent minimally invasive approach for heart valve replacement. Despite current challenges, PHVs represent a promising area of research with the potential to revolutionize the treatment of heart valve diseases, offering more durable and less invasive solutions for patients. Full article

The production of biomedical devices able to appropriately interact with the biological environment is still a great challenge. Synthetic materials are often employed, but they fail to replicate the biological and functional properties of native tissues, leading to a variety of adverse effects. Several commercial products are based on chemically treated xenogeneic tissues: their principal drawback is due to weak mechanical stability and low durability. Recently, decellularization has been proposed to bypass the drawbacks of both synthetic and biological materials. Acellular materials can integrate with host tissues avoiding/mitigating any foreign body response, but they often lack sufficient patency and impermeability. The present paper investigates an innovative approach to the realization of hybrid materials that combine decellularized bovine pericardium with polycarbonate urethanes. These hybrid materials benefit from the superior biocompatibility of the biological tissue and the mechanical properties of the synthetic polymers. They were assessed from physicochemical, structural, mechanical, and biological points of view; their ability to promote cell growth was also investigated. The decellularized pericardium and the polymer appeared to well adhere to each other, and the two sides were distinguishable. The maximum elongation of hybrid materials was mainly affected by the pericardium, which allows for lower elongation than the polymer; this latter, in turn, influenced the maximum strength achieved. The results confirmed the promising features of hybrid materials for the production of vascular grafts able to be repopulated by circulating cells, thus, improving blood compatibility. Full article

Background: Nowadays, a challenging task concerns the biomechanical study of the human lower urinary tract (LUT) due to the variety of its tissues and the low availability of samples. Methods: This work attempted to further extend the knowledge through a comprehensive mechanical characterization of the male LUT by considering numerous tissues harvested from the same cadaver, including some never studied before. Samples of the bladder, urethra, prostate, Buck’s fascia and tunica albuginea related to corpora cavernosa were considered and distinguished according to testing direction, specimen conformation and anatomical region. Uniaxial tensile and indentation tests were performed and ad hoc protocols were developed. Results: The tissues showed a non-linear and viscoelastic response but different mechanical properties due to their specific functionality and microstructural configuration. Tunica albuginea longitudinally displayed the highest stiffness (12.77 MPa), while the prostate transversally had the lowest one (0.66 MPa). The minimum stress relaxation degree (65.74%) was reached by the tunica albuginea and the maximum (88.55%) by the bladder. The prostate elastic modulus was shown to vary according to the presence of pathological changes at the microstructure. Conclusions: This is the first experimental work that considers the mechanical evaluation of the LUT tissues in relation to the same subject, setting the basis for future developments by expanding the sample population and for the development of effective in silico models to improve the solutions for most LUT pathologies. Full article

Urinary incontinence is still an underestimated problem due to its anatomical complexity and social taboo. Most of the time, it is believed to affect predominantly the elderly female population, and the literature still lacks data on its presence in the younger and male populations. Its relationship with other pelvic floor dysfunctions (PFDs) and sport activity remains an open topic. Thus, the present study surveyed 342 subjects of both genders, ranging from 18 to 39 y/o and with different sport activity levels, to understand the prevalence of PFDs (such as haemorrhoids, anal fissures, involuntary urinary/faecal leakage, and urgency). The results also showed a significative prevalence in younger, sporty, and male people. Approximately one third of the population had urinary incontinence mostly during stress activities (sport activity: 17%, cough/sneeze: 13%). The statistical analysis confirmed a higher prevalence in the cases of a light (32%) and intense (41%) sport activity level and a protective role of sport if practiced between 5 and 10 h/week, with bodybuilding/CrossFit and running seeming to be the riskiest sports. The relationship with the other PFDs showed a statistically significant dependence with most of them, confirming that urinary incontinence cannot be considered a separate problem from the other PFDs. Full article

The main purpose of tissue engineering is to fabricate and exploit engineered constructs suitable for the effective replacement of damaged tissues and organs to perfectly integrate with the host’s organism without eliciting any adverse reaction. Ideally, autologous materials represent the best option, but they are often limited due to the low availability of compatible healthy tissues. So far, one therapeutic approach relies on the exploitation of synthetic materials as they exhibit good features in terms of impermeability, deformability, and flexibility, but present chronic risks of infections and inflammations. Alternatively, biological materials, including naturally derived ones and acellular tissue matrices of human or animal origin, can be used to induce cells growth and differentiation, which are needed for tissue regeneration; however, this kind of material lacks satisfactory mechanical resistance and reproducibility, affecting their clinical application. In order to overcome the above-mentioned limitations, hybrid materials, which can be obtained by coupling synthetic polymers and biological materials, have been investigated with the aim to improve biological compatibility and mechanical features. Currently, the interest in these materials is growing, but the ideal ones have not been found yet. The present review aims at exploring some applications of hybrid materials, with particular mention to urological and cardiovascular fields. In the first case, the efforts to find a construct that can guarantee impermeability, mechanical resistance, and patency is herein illustrated; in the second case, the search for impermeability, hemocompatibility and adequate compliance is disclosed. Full article

Conduit substitutes are increasingly in demand for cardiovascular and urological applications. In cases of bladder cancer, radical cystectomy is the preferred technique: after removing the bladder, a urinary diversion has to be created using autologous bowel, but several complications are associated with intestinal resection. Thus, alternative urinary substitutes are required to avoid autologous intestinal use, preventing complications and facilitating surgical procedures. In the present paper, we are proposing the exploitation of the decellularized porcine descending aorta as a novel and original conduit substitute. After being decellularized with the use of two alternative detergents (Tergitol and Ecosurf) and sterilized, the porcine descending aorta has been investigated to assess its permeability to detergents through methylene blue dye penetration analysis and to study its composition and structure by means of histomorphometric analyses, including DNA quantification, histology, two-photon microscopy, and hydroxyproline quantification. Biomechanical tests and cytocompatibility assays with human mesenchymal stem cells have been also performed. The results obtained demonstrated that the decellularized porcine descending aorta preserves its major features to be further evaluated as a candidate material for urological applications, even though further studies have to be carried out to demonstrate its suitability for the specific application, by performing in vivo tests in the animal model. Full article

Right ventricle outflow tract obstruction (RVOTO) is a congenital pathological condition that contributes to about 15% of congenital heart diseases. In most cases, the replacement of the right ventricle outflow in pediatric age requires subsequent pulmonary valve replacement in adulthood. The aim of this study was to investigate the extracellular matrix scaffold obtained by decellularization of the porcine pulmonary valve using a new detergent (Tergitol) instead of Triton X-100. The decellularized scaffold was evaluated for the integrity of its extracellular matrix (ECM) structure by testing for its biochemical and mechanical properties, and the cytotoxicity/cytocompatibility of decellularized tissue was assessed using bone marrow-derived mesenchymal stem cells. We concluded that Tergitol could remove the nuclear material efficiently while preserving the structural proteins of the matrix, but without an efficient removal of the alpha-gal antigenic epitope. Therefore, Tergitol can be used as an alternative detergent to replace the Triton X-100. Full article

The covalent functionalization of synthetic peptides allows the modification of different biomaterials (metallic, polymeric, and ceramic), which are enriched with biologically active sequences to guide cell behavior. Recently, this strategy has also been applied to decellularized biological matrices. In this study, the covalent anchorage of a synthetic peptide (REDV) to a pericardial matrix decellularized via Schiff base is realized starting from concentrated peptide solutions (10⁻⁴ M and 10⁻³ M). The use of a labeled peptide demonstrated that as the concentration of the working solution increased, the surface density of the anchored peptide increased as well. These data are essential to pinpointing the concentration window in which the peptide promotes the desired cellular activity. The matrices were extensively characterized by Water Contact Angle (WCA) analysis, Differential Scanning Calorimetry (DSC) analysis, geometric feature evaluation, biomechanical tests, and preliminary in vitro bioassays. Full article

Among the urinary tract’s malignancies, bladder cancer is the most frequent one: it is at the tenth position of most common cancers worldwide. Currently, the gold standard therapy consists of radical cystectomy, which results in the need to create a urinary diversion using a bowel segment from the patient. Nevertheless, due to several complications associated with bowel resection and anastomosis, which significantly affect patient quality of life, it is becoming extremely important to find an alternative solution. In our recent work, we proposed the decellularized porcine small intestinal submucosa (SIS) as a candidate material for urinary conduit substitution. In the present study, we create SIS-based hybrid membranes that are obtained by coupling decellularized SIS with two commercially available polycarbonate urethanes (Chronoflex AR and Chronoflex AR-LT) to improve SIS mechanical resistance and impermeability. We evaluated the hybrid membranes by means of immunofluorescence, two-photon microscopy, FTIR analysis, and mechanical and cytocompatibility tests. The realization of hybrid membranes did not deteriorate SIS composition, but the presence of polymers ameliorates the mechanical behavior of the hybrid constructs. Moreover, the cytocompatibility tests demonstrated a significant increase in cell growth compared to decellularized SIS alone. In light of the present results, the hybrid membrane-based urinary conduit can be a suitable candidate to realize a urinary diversion in place of an autologous intestinal segment. Further efforts will be performed in order to create a cylindrical-shaped hybrid membrane and to study its hydraulic behavior. Full article

Esophageal reconstruction through bio-engineered allografts that highly resemble the peculiar properties of the tissue extracellular matrix (ECM) is a prospective strategy to overcome the limitations of current surgical approaches. In this work, human esophagus was decellularized for the first time in the literature by comparing three detergent-enzymatic protocols. After decellularization, residual DNA quantification and histological analyses showed that all protocols efficiently removed cells, DNA (<50 ng/mg of tissue) and muscle fibers, preserving collagen/elastin components. The glycosaminoglycan fraction was maintained (70–98%) in the decellularized versus native tissues, while immunohistochemistry showed unchanged expression of specific ECM markers (collagen IV, laminin). The proteomic signature of acellular esophagi corroborated the retention of structural collagens, basement membrane and matrix–cell interaction proteins. Conversely, decellularization led to the loss of HLA-DR expression, producing non-immunogenic allografts. According to hydroxyproline quantification, matrix collagen was preserved (2–6 µg/mg of tissue) after decellularization, while Second-Harmonic Generation imaging highlighted a decrease in collagen intensity. Based on uniaxial tensile tests, decellularization affected tissue stiffness, but sample integrity/manipulability was still maintained. Finally, the cytotoxicity test revealed that no harmful remnants/contaminants were present on acellular esophageal matrices, suggesting allograft biosafety. Despite the different outcomes showed by the three decellularization methods (regarding, for example, tissue manipulability, DNA removal, and glycosaminoglycans/hydroxyproline contents) the ultimate validation should be provided by future repopulation tests and in vivo orthotopic implant of esophageal scaffolds. Full article

Human and animal pericardia are among the most widely exploited materials suitable to repair damaged tissues in the cardiovascular surgery context. Autologous, xenogeneic (chemically treated) and homologous pericardia are largely utilized, but they do exhibit some crucial drawbacks. Any tissue treated with glutaraldehyde is known to be prone to calcification in vivo, lacks regeneration potential, has limited durability, and can result in cytotoxicity. Moreover, autologous tissues have limited availability. Decellularized biological tissues represent a promising alternative: decellularization removes cellular and nuclear components from native tissues and makes them suitable for repopulation by autologous cells upon implantation into the body. The present work aims to assess the effects of a new detergent, i.e., Tergitol, for decellularizing bovine and porcine pericardia. The decellularization procedure successfully removed cells, while preserving the histoarchitecture of the extracellular matrix. No cytotoxic effect was observed. Therefore, decellularized pericardia showed potential to be used as scaffold for cardiovascular tissue regeneration. Full article

The most common aortic valve diseases in adults are stenosis due to calcification and regurgitation. In pediatric patients, aortic pathologies are less common. When a native valve is surgically replaced by a prosthetic one, it is necessary to consider that the latter has a limited durability. In particular, current bioprosthetic valves have to be replaced after approximately 10 years; mechanical prostheses are more durable but require the administration of permanent anticoagulant therapy. With regard to pediatric patients, both mechanical and biological prosthetic valves have to be replaced due to their inability to follow patients’ growth. An alternative surgical substitute can be represented by the acellular porcine aortic valve that exhibits less immunogenic risk and a longer lifespan. In the present study, an efficient protocol for the removal of cells by using detergents, enzyme inhibitors, and hyper- and hypotonic shocks is reported. A new detergent (Tergitol) was applied to replace TX-100 with the aim to reduce toxicity and maximize ECM preservation. The structural integrity and efficient removal of cells and nuclear components were assessed by means of histology, immunofluorescence, and protein quantification; biomechanical properties were also checked by tensile tests. After decellularization, the acellular scaffold was sterilized with a standard protocol and repopulated with bone marrow mesenchymal stem cells to analyze its biocompatibility profile. Full article

Bladder cancer (BC) is among the most common malignancies in the world and a relevant cause of cancer mortality. BC is one of the most frequent causes for bladder removal through radical cystectomy, the gold-standard treatment for localized muscle-invasive and some cases of high-risk, non-muscle-invasive bladder cancer. In order to restore urinary functionality, an autologous intestinal segment has to be used to create a urinary diversion. However, several complications are associated with bowel-tract removal, affecting patients’ quality of life. The present study project aims to develop a bio-engineered material to simplify this surgical procedure, avoiding related surgical complications and improving patients’ quality of life. The main novelty of such a therapeutic approach is the decellularization of a porcine small intestinal submucosa (SIS) conduit to replace the autologous intestinal segment currently used as urinary diversion after radical cystectomy, while avoiding an immune rejection. Here, we performed a preliminary evaluation of this acellular product by developing a novel decellularization process based on an environmentally friendly, mild detergent, i.e., Tergitol, to replace the recently declared toxic Triton X-100. Treatment efficacy was evaluated through histology, DNA, hydroxyproline and elastin quantification, mechanical and insufflation tests, two-photon microscopy, FTIR analysis, and cytocompatibility tests. The optimized decellularization protocol is effective in removing cells, including DNA content, from the porcine SIS, while preserving the integrity of the extracellular matrix despite an increase in stiffness. An effective sterilization protocol was found, and cytocompatibility of treated SIS was demonstrated from day 1 to day 7, during which human fibroblasts were able to increase in number and strongly organize along tissue fibres. Taken together, this in vitro study suggests that SIS is a suitable candidate for use in urinary diversions in place of autologous intestinal segments, considering the optimal results of decellularization and cell proliferation. Further efforts should be undertaken in order to improve SIS conduit patency and impermeability to realize a future viable substitute. Full article

The history of biomaterials dates back to the mists of time: human beings had always used exogenous materials to facilitate wound healing and try to restore damaged tissues and organs. Nowadays, a wide variety of materials are commercially available and many others are under investigation to both maintain and restore bodily functions. Emerging clinical needs forced the development of new biomaterials, and lately discovered biomaterials allowed for the performing of new clinical applications. The definition of biomaterials as materials specifically conceived for biomedical uses was raised when it was acknowledged that they have to possess a fundamental feature: biocompatibility. At first, biocompatibility was mainly associated with biologically inert substances; around the 1970s, bioactivity was first discovered and the definition of biomaterials was consequently extended. At present, it also includes biologically derived materials and biological tissues. The present work aims at walking across the history of biomaterials, looking towards the scientific literature published on this matter. Finally, some current applications of biomaterials are briefly depicted and their future exploitation is hypothesized. Full article