Search Results (4,082)

Background/Objectives: The development of new materials incorporating bioactive molecules for tissue regeneration is a growing area of interest. The objective of this study was to develop a new complex specifically designed for bone and skin tissue engineering, combining chitosan, ascorbic acid-2-magnesium phosphate (ASAP), and β-tricalcium phosphate (β-TCP). Methods: Chitosan and the complexes chitosan/ASAP and chitosan/ASAP/β-TCP were prepared in membrane form, macerated to a particulate format, and then subjected to characterization through Fourier transform infrared (FTIR) spectroscopy, optical and scanning electron microscopy (SEM), zeta potential, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). Cell viability was evaluated through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and with fluorescein diacetate (FDA) and propidium iodide (PI) staining in stem cells obtained from deciduous teeth. Statistical analyses were performed using analysis of variance (ANOVA), followed by Tukey’s test. Results: The FTIR results indicated the characteristic bands in the chitosan group and the complexation between chitosan, ASAP, and β-TCP. Microscopic characterization revealed a polydisperse distribution of micrometric particles. Zeta potential measurements demonstrated a reduction in surface charge upon the addition of ASAP and β-TCP to the chitosan matrix. TGA and DSC analyses further indicated complexation between the three components and the successful formation of a cross-linked structure in the chitosan matrix. Stem cells cultured with the particulate biomaterials demonstrated their biocompatibility. Statistical analysis revealed a significant increase in cell viability for the chitosan/ASAP and chitosan/ASAP/β-TCP groups compared to the chitosan control. Conclusions: Therefore, the chitosan/ASAP complex demonstrated potential for skin regeneration, while the chitosan/ASAP/β-TCP formulation showed promise as a biomaterial for bone regeneration due to the presence of β-tricalcium phosphate. Full article

(1) Background: Collagen, a natural polymer, is widely used in the fabrication of membranes for guided bone regeneration (GBR). These membranes are sourced from various tissues, such as skin, pericardium, peritoneum, and tendons, which exhibit differences in regenerative outcomes. Therefore, this study aimed to evaluate the morphological and chemical properties of porcine collagen membranes from five different tissue sources: skin, pericardium, dermis, tendons, and peritoneum. (2) Methods: The membrane structure was analyzed using energy-dispersive X-ray spectrometry (EDX), variable pressure scanning electron microscopy (VP-SEM), Fourier transform infrared spectroscopy (FTIR), and thermal stability via thermogravimetric analysis (TGA). The absorption capacity of the membranes for GBR was also assessed using an analytical digital balance. (3) Results: The membranes displayed distinct microstructural features. Skin- and tendon-derived membranes had rough surfaces with nanopores (1.44 ± 1.24 µm and 0.46 ± 0.1 µm, respectively), while pericardium- and dermis-derived membranes exhibited rough surfaces with macropores (78.90 ± 75.89 µm and 64.89 ± 13.15 µm, respectively). The peritoneum-derived membrane featured a rough surface of compact longitudinal fibers with irregular macropores (9.02 ± 3.70 µm). The thickness varied significantly among the membranes, showing differences in absorption capacity. The pericardium membrane exhibited the highest absorption, increasing by more than 10 times its initial mass. In contrast, the skin-derived membrane demonstrated the lowest absorption, increasing by less than 4 times its initial mass. Chemical analysis revealed that all membranes were primarily composed of carbon, nitrogen, and oxygen. Thermogravimetric and differential scanning calorimetry analyses showed no significant compositional differences among the membranes. FTIR spectra confirmed the presence of collagen, with characteristic peaks corresponding to Amide A, B, I, II, and III. (4) Conclusions: The tissue origin of collagen membranes significantly influences their morphological characteristics, which may, in turn, affect their osteogenic properties. These findings provide valuable insights into the selection of collagen membranes for GBR applications. Full article

Staphylococcus aureus is a human pathogen responsible for a wide range of diseases, such as skin and soft tissue infections, pneumonia, toxic shock syndrome, and urinary tract infections. Methicillin-resistant S. aureus (MRSA) is a well-known pathogen with consistently high mortality rates. Detecting the mecA resistance gene and phenotypical profile to β-lactams allows for the differentiation of MRSA from methicillin-susceptible S. aureus (MSSA) isolates. In this study, we characterized 57 S. aureus clinical isolates for β-lactam susceptibility and mecA presence. We classified 52.63% as MRSA and 45.61% as MSSA. However, some isolates evidenced different oxacillin resistance profiles, such as borderline oxacillin-resistant or modified S. aureus (BORSA/MODSA). The cefazolin inoculum effect (CzIE) was established for these samples, emphasizing the relevance of these isolates as a source of therapeutic failure. We also performed the detection of the Panton-Valentine Leucocidin virulence genes as well as the S. aureus spa-type clonality. As expected, spa-types t002 and t008 were the most prevalent clones, demonstrating the success of well-established clones. These findings emphasize the importance of establishing sensitivity profiles, especially in isolates with poor resistance mechanisms, to determine their prevalence and their impact on public health. Full article

The development of artificial skin that accurately mimics the mechanical properties of human skin is crucial for a wide range of applications, including surgical training for burn injuries, biomechanical testing, and research in sports injuries and ballistics. While traditional materials like gelatin, polydimethylsiloxane (PDMS), and animal skins (such as porcine and bovine skins) have been used for these purposes, they have inherent limitations in replicating the intricate properties of human skin. In this work, we conducted uniaxial tensile tests on freshly obtained cadaveric skin to analyze its mechanical properties under various loading conditions. The stress–strain data obtained from these tests were then replicated using advanced skin simulants. These skin simulants were specifically formulated using a cost-effective and moldable multi-part silicone-based polymer. This material was chosen for its ability to accurately replicate the mechanical behavior of human skin while also addressing ethical considerations and biosafety concerns. In addition, the non-linear mechanical behavior of the developed skin simulants was characterized using three different hyperelastic curve-fit models (i.e., Neo-Hookean, Mooney–Rivlin, and Yeoh models). Moreover, these innovative simulants offer an ethical and practical alternative to cadaveric skin for use in laboratory and clinical settings. Full article

Accurate replication of soft tissue properties is essential for the development of car crash test dummy skin to ensure the precision of biomechanical injury data. However, the intricacy of multi-layer soft tissue poses challenges in standardizing the development and testing of dummy skin materials to emulate soft tissue properties. This study presents a comprehensive testing and analysis of the compressive mechanical properties of both single and multi-layered soft tissues and car crash dummy skin materials, aiming to enhance the biofidelity of dummy skin. We presented one-term Ogden hyperelastic models and generalized Maxwell viscoelastic models for single-layer and multi-layer soft tissues, as well as dummy skin materials. The comparative analysis results indicate that the existing dummy skin material fails to fully consider the strain-rate-dependent characteristic of soft tissue. Furthermore, dummy skin materials exhibited ~3 times shorter relaxation times and ~2–3 times lower stress decay rates compared to soft tissues, suggesting a less viscous nature. This study provides an accurate representation of the mechanics of soft tissue and dummy skin under quasi-static compressive loading. The findings are instrumental for the development of novel bionic skin materials or structures to more precisely replicate the biomechanical properties of soft tissues, thereby enhancing the accuracy and reliability of car crash test dummies. Full article

A double-blind, randomized, and controlled clinical trial with therapeutic intervention was performed at a university hospital in Rio de Janeiro to evaluate whether the addition of Copaifera multijuga Hayne oleoresin to a carboxypolymethylene hydrogel is more effective in skin tear healing than standard treatment. The sample consisted of 84 patients, predominantly men, with a mean age of 67.37 years. These participants were divided into three groups (29 in the intervention group, which received 10% Copaifera oleoresin; 28 in the intervention group, which received 2% Copaifera oleoresin; and 27 in the control group, which received carboxypolymethylene hydrogel). Data were tabulated and analyzed according to the relevant protocols and included only patients who had completed the treatment, while losses were excluded. Weekly follow-ups were conducted to monitor progress. The average healing time differed among the three groups (p > 0.05). There was also a significant difference in healing time between the two intervention groups. Ultimately, CopaibaPolyHy-2 led to significantly faster wound healing than CopaibaPolyHy-10 (p < 0.05). A high increase in granulation and epithelial tissue and a decrease in exudate quantity were observed in the CopaibaPolyHy-2 group. It was not possible to infer whether the wound size reduction differed between the treatments (p > 0.05). At the end of the study, 100% of wounds were healed, with 47,6% healing in week 2 (n = 40). No participants experienced local or serious adverse effects throughout the study period. The current study shows that CopaibaPolyHy-2 is effective, offering a statistically significantly faster healing time, better-quality tissue, and safe treatment for skin tears. Full article

Background: Lymphedema represents a frequent cause of disability for patients undergoing oncological treatments and, being a chronic, non-reversible pathology, requires targeted and continuous rehabilitation treatments. To date, the studies available on the use of ultrasound in patients with lymphedema mainly report descriptive data; therefore, with this study, we wanted to describe in a more objective way the typical ultrasound alterations found in these patients, measuring the thickness of the different superficial structures, and defining subcutis echogenicity. Methods: 14 patients affected by secondary lymphedema of the upper limbs were enrolled in this cross-sectional observational study (12 had breast cancer and 2 with melanoma as their primary diagnosis). All patients were classified as stage II according to the ISL classification. Patients were examined between March and July 2023 with a clinical and an ultrasound evaluation. Ultrasound evaluation was performed following a protocol and took into consideration thickness of the cutis, subcutis, superficial and deep fascia, and subcutis echogenicity. Results: The cutis of the affected limbs was thicker in the distal anterior region of the arm and throughout the anterior region of the forearm. The subcutaneous tissue was thicker in the posterior region of the distal arm and throughout the forearm, including the dorsum of the hand and excluding only the proximal posterior region of the forearm. Fascial structures did not demonstrate statistically significant differences in thickness between pathological and healthy limbs, despite undergoing significant changes from a qualitative point of view (loss of the trilaminar skin appearance and the development of anechoic areas due to fluid accumulation around the hyperechoic adipose lobule). A statistically significant difference in the echogenicity of subcutaneous tissue was found at the distal anterior region of the arm and at the entire anterior forearm. Conclusions: High-resolution ultrasound has been confirmed to be a tool capable of supporting the diagnosis of lymphedema and identifying the most compromised regions of the limb. A tailored rehabilitation plan can be developed based on the non-uniform alterations in subcutaneous tissue, where some areas are affected earlier than others. This compartmentalization should be considered in lymphedema staging and management. Ultrasound may provide early detection of these changes, guiding a more precise therapeutic approach. Full article

Psoriasis and obesity, while distinct, are inter-related inflammatory conditions. Adipose tissue (AT)-derived mediators could be pathogenically active in triggering and/or amplifying psoriatic skin inflammation and, vice versa, skin inflammation could drive increased adiposity that triggers the development of several chronic conditions. Gaining insight into their intricate relationship could be essential for effective management and treatment. The aim of this study was to determine (i) the pathogenic role of psoriasis-signature cytokines in contributing to AT metabolism and (ii) the role of AT-derived mediators in triggering and/or amplifying skin inflammation. For this reason, firstly, whole AT was treated with IL-17 and TNF-α, alone or in combination, to investigate their effects on the expression and production of adipokines and inflammatory factors. IL-17 and TNF-α were able to induce an additive or synergistic effect on AT-derived mediators. In order to assess the effects on the skin of inflamed AT by psoriasis-signature cytokines, ex vivo skin organ culture was performed and an increase in several inflammatory mediators was observed. These findings confirm that psoriasis and obesity amplify each other’s inflammatory processes and understanding this mutual exacerbation could lead to more effective therapeutic strategies that address both skin inflammation and AT metabolism. Full article

Objective: Staphylococcus aureus (SA), including methicillin-resistant strains (MRSAs), is a major cause of skin and soft tissue infections (SSTIs) in military populations. This study investigated SSTI incidence and SA carriage in a military training site over 16 weeks using a prospective observational cohort design. Methods: Two training cohorts provided pre- and post-training self-collected swabs for bacterial carriage, and environmental swabs from accommodations, personal items, and training facilities. Hygiene awareness and practices were assessed through questionnaires. Bacteria were identified using culture, mass spectrometry (MALDI-TOF), and genomic sequencing. Results: Nasal carriage of SA increased from 19% to 49% by the end of training. SSTIs requiring treatment occurred in 16% of participants. Steam cleaning reduced but did not eliminate SA on personal bed linen. Additionally, 40% of participants had poor knowledge of antibacterial cleaning practices and wound management. Conclusions: Increased SA carriage was linked to human-to-human transmission in close-quarter military training environments. Implications for Public Health: Improved personal hygiene training, wound management education, and monitored cleaning protocols are essential to mitigate SSTI risks in communal military training environments. Full article

Cutaneous squamous cell carcinoma (CSCC) in dogs is a locally invasive tumor that typically occurs in areas of poorly pigmented skin due to sun exposure. Identifying new biomarkers, such as syndecan-1 (CD138) and E-cadherin, is fundamental for tumor diagnosis and prognosis. Dysregulation of syndecan-1, expressed in epithelial tissue, fibroblasts, and plasma cells, is associated with poor prognosis in several types of cancer. Similarly, E-cadherin, which plays a crucial role in cell adhesion and epithelial functionality, is also linked to adverse outcomes. This study evaluated the expression of syndecan-1 and E-cadherin in 47 cases of canine cutaneous squamous cell carcinoma. The results showed that the intensity of syndecan-1 decreased with increasing tumor aggressiveness, and its presence in the stroma was significantly associated with tumor grade. E-cadherin also demonstrated a decrease in intensity with increasing malignancy. However, the association between syndecan-1 and E-cadherin was not statistically significant. E-cadherin reduction and stromal syndecan-1 positivity seem to be associated with tumor aggressiveness in canine cutaneous squamous cell carcinoma. Further studies are needed to explore their roles in tumor progression. Full article

Background: Burns and chronic ulcers may cause severe skin loss, leading to critical health issues like shock, infection, sepsis, and multiple organ failure. Effective healing of full-thickness wounds may be challenging, with traditional methods facing limitations due to tissue shortage, infection, and lack of structural support. Methods: This study explored the combined use of gene transfection and dermal substitutes to improve wound healing. We used the DGTM (genes: DNP63A, GRHL2, TFAP2A, and MYC) factors to transfect adipose-derived stem cells (ADSCs), inducing their differentiation into keratinocytes. These transfected ADSCs were then incorporated into Pelnac^® dermal substitutes to enhance vascularization and cellular proliferation for better healing outcomes. Results: Gene transfer using DGTM factors successfully induced keratinocyte differentiation in ADSCs. The application of these differentiated cells with Pelnac^® dermal substitute to dermal wounds in mice resulted in the formation of skin tissue with a normal epidermal layer and proper collagen organization. This method alleviates the tediousness of the multiple transfection steps in previous protocols and the safety issues caused by using viral transfection reagents directly on the wound. Additionally, the inclusion of dermal substitutes addressed the lack of collagen and elastic fibers, promoting the formation of tissue resembling healthy skin rather than scar tissue. Conclusion: Integrating DGTM factor-transfected ADSCs with dermal substitutes represents a novel strategy for enhancing the healing of full-thickness wounds. Further research and clinical trials are warranted to optimize and validate this innovative approach for broader clinical applications. Full article

Bruck syndrome is a rare autosomal recessive disorder characterized by increased bone fragility and joint contractures similar to those in arthrogryposis and is known to be associated with mutations in the FKBP10 (FKBP prolyl isomerase 10) and PLOD2 (Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 2) genes. These genes encode endoplasmic reticulum proteins that play an important role in the biosynthesis of type I collagen, which in turn affects the structure and strength of connective tissues and bones in the body. Mutations are associated with disturbances in both the primary collagen chain and its post-translational formation, but the mechanism by which mutations lead to Bruck syndrome phenotypes has not been determined, not only because of the small number of patients who come to the attention of researchers but also because of the lack of disease models. In our work, we investigated the cellular effects of two forms of the wild-type PLOD2 gene, as well as the PLOD2 gene with homozygous mutation c.1885A>G (p.Thr629Ala). The synthesized genetic constructs were transfected into HEK293 cell line and human skin fibroblasts (DF2 line). The localization of PLOD2 protein in cells and the effects caused by the expression of different isoforms—long, short, and long with mutation—were analyzed. In addition, the results of the transcriptome analysis of a patient with Bruck syndrome, in whom this mutation was detected, are presented. Full article

Background and objectives: Slit1 is a secreted protein that is closely related to cell movement and adhesion. Few studies related to fibrosis exist, and the preponderance of current research is confined to the proliferation and differentiation of neural systems. Hypertrophic scars (HTSs) are delineated by an overproduction of the extracellular matrix (ECM) by activated fibroblasts, leading to anomalous fibrosis, which is a severe sequela of burns. However, the functionality of Slit1 in HTS formation remains unknown. We aimed to investigate whether Slit1 regulates fibroblasts through a fibrosis-related mechanism derived from post-burn HTS tissues and normal patient tissues. Methods: Human normal fibroblasts (HNFs) and hypertrophic scar fibroblasts (HTSFs) were extracted from normal skin and post-burn HTS tissues, with settings grouped according to the patient of origin. Cell proliferation was evaluated using a CellTiter-Glo Luminescent Cell Viability Assay Kit. Cell migration experiments were carried out using a μ-Dish insert system. Protein and mRNA expression levels were quantified by Western blot and quantitative real-time polymerase chain reaction. Results: We found increased expressions of Slit1 in HTS tissues and HTSFs compared to normal tissues and HNFs. The treatment of human recombinant Slit1 protein (rSlit1) within HNFs promoted cell proliferation and differentiation, leading to an upregulation in ECM components such as α-SMA, type I and III collagen, and fibronectin. The treatment of rSlit1 in HNFs facilitated cell migration, concurrent with enhanced levels of N-cadherin and vimentin, and a diminished expression of E-cadherin. Treatment with rSlit1 resulted in the phosphorylation of SMAD pathway proteins, including SMAD2, SMAD3, and SMAD1/5/8, and non-SMAD pathway proteins, including TAK1, JNK1, ERK1/2, and p38, in HNFs. Conclusions: Exogenous Slit1 potentiates the epithelial–mesenchymal transition and upregulates SMAD and non-SMAD signaling pathways in HNFs, leading to the development of HTS, suggesting that Slit1 is a promising new target for the treatment of post-burn HTS. Full article

Agrimonia eupatoria L. (AE) has a rich tradition of use in wound healing improvement across various cultures worldwide. In previous studies, we revealed that Agrimonia eupatoria L. water extract (AE) possesses a rich polyphenolic composition, displaying remarkable antioxidant properties. Our investigations also demonstrated that lipophosphonoxin (LPPO) exhibited antibacterial efficacy in vitro while preserving the proliferation and differentiation of fibroblasts and keratinocytes. Building upon our prior findings, in this study, we intended to examine whether a combination of AE and LPPO could enhance skin wound healing while retaining antibacterial attributes. The antibacterial activity of AE/LPPO against Staphylococcus aureus was evaluated, alongside its effects on fibroblast-to-myofibroblast transition, the formation of extracellular matrix (ECM), and endothelial cells and keratinocyte proliferation/phenotype. We also investigated AE/LPPO’s impact on TGF-β1 and VEGF-A signaling in keratinocytes/fibroblasts and endothelial cells, respectively. Additionally, wound healing progression in rats was examined through macroscopic observation and histological analysis. Our results indicate that AE/LPPO promotes myofibroblast-like phenotypic changes and augments ECM deposition. Clinically relevant, the AE/LPPO did not disrupt TGF-β1 and VEGF-A signaling and accelerated wound closure in rats. Notably, while AE and LPPO individually exhibited antibacterial activity, their combination did not lead to synergism, rather decreasing antibacterial activity, warranting further examination. These findings underscore substantial wound healing improvement facilitated by AE/LPPO, requiring further exploration in animal models closer to human physiology. Full article

Feline injection-site sarcomas (FISSs) are malignant skin tumors of mesenchymal origin arising at local post-vaccination (or injection) sites. In recent years, a fluorescence imaging technique based on probes targeting α_vβ₃ integrin has been effectively applied for the surgical complete resection of the tumor. In our study, we investigated the utility of a commercially available anti-α_v integrin polyclonal antibody for the histopathological evaluation of FISS’s surgical excision margins. We collected 10 formalin-fixed paraffin-embedded (FFPE) feline excisional biopsies with a histopathological diagnosis of FISS (7 fibrosarcomas and 3 pleomorphic sarcomas) and wide margin tissue, along with one subcutaneous injection-site granuloma and 6 osteosarcomas. Samples were processed for histology, and slides were stained for IHC with the anti-α_v integrin antibody. Immunostained slides were evaluated for the cellular localization and intensity of the staining in different neoplastic and non-neoplastic cell populations. Neoplastic and non-neoplastic spindle cells had cytoplasmic positivity in all fibrosarcomas. Inflammatory cells, including macrophages of the injection-site granuloma, were negative. Multinucleated giant cells in the pleomorphic sarcomas had an intense membranous positivity. Although the anti-α_v integrin antibody was ineffective for the histopathological evaluation of surgical excision margins, the membranous localization of α_v integrin in multinucleated giant cells of pleomorphic sarcomas suggests that it plays a role in the oncogenesis of this FISS variant. Full article