Engineering models of head and neck and oral cancers on-a-chip.

Head and neck cancers (HNCs) rank as the sixth most common cancer globally and result in over 450 000 deaths annually. Despite considerable advancements in diagnostics and treatment, the 5-year survival rate for most types of HNCs remains below 50%. Poor prognoses are often attributed to tumor heterogeneity, drug resistance, and immunosuppression. These characteristics are difficult to replicate using in vitro or in vivo models, culminating in few effective approaches for early detection and therapeutic drug development. Organs-on-a-chip offer a promising avenue for studying HNCs, serving as microphysiological models that closely recapitulate the complexities of biological tissues within highly controllable microfluidic platforms. Such systems have gained interest as advanced experimental tools to investigate human pathophysiology and assess therapeutic efficacy, providing a deeper understanding of cancer pathophysiology. This review outlines current challenges and opportunities in replicating HNCs within microphysiological systems, focusing on mimicking the soft, glandular, and hard tissues of the head and neck. We further delve into the major applications of organ-on-a-chip models for HNCs, including fundamental research, drug discovery, translational approaches, and personalized medicine. This review emphasizes the integration of organs-on-a-chip into the repertoire of biological model systems available to researchers. This integration enables the exploration of unique aspects of HNCs, thereby accelerating discoveries with the potential to improve outcomes for HNC patients.

In-vitro models of biocompatibility testing for restorative dental materials: From 2D cultures to organs on-a-chip.

Dental caries is a biofilm-mediated, diet-modulated, multifactorial and dynamic disease that affects more than 90% of adults in Western countries. The current treatment for decayed tissue is based on using materials to replace the lost enamel or dentin. More than 500 million dental restorations are placed annually worldwide, and materials used for these purposes either directly or indirectly interact with dentin and pulp tissues. The development and understanding of the effects of restorative dental materials are based on different in-vitro and in-vivo tests, which have been evolving with time. In this review, we first discuss the characteristics of the tooth and the dentin-pulp interface that are unique for materials testing. Subsequently, we discuss frequently used in-vitro tests to evaluate the biocompatibility of dental materials commonly used for restorative procedures. Finally, we present our perspective on the future directions for biological research on dental materials using tissue engineering and organs on-a-chip approaches. STATEMENT OF SIGNIFICANCE: Dental caries is still the most prevalent infectious disease globally, requiring more than 500 million restorations to be placed every year. Regrettably, the failure rates of such restorations are still high. Those rates are partially based on the fact that current platforms to test dental materials are somewhat inaccurate in reproducing critical components of the complex oral microenvironment. Thus, there is a collective effort to develop new materials while evolving the platforms to test them. In this context, the present review critically discusses in-vitro models used to evaluate the biocompatibility of restorative dental materials and brings a perspective on future directions for tissue-engineered and organs-on-a-chip platforms for testing new dental materials.

Vascular inflammation exposes perivascular cells to SARS-CoV-2 infection.

Pericytes stabilize blood vessels and promote vascular barrier function. However, vessels subjected to pro-inflammatory conditions have impaired barrier function, which has been suggested to potentially expose perivascular cells to SARS-CoV-2. To test this hypothesis, we engineered pericyte-supported vascular capillaries on-a-chip, and determined that the extravasation and binding of spike protein (S1) on perivascular cells of inflamed vessels to be significantly higher that in healthy controls, indicating a potential target to understand COVID-19 vascular complications.

Histological and biochemical effects of preventive and therapeutic vascular photobiomodulation on rat muscle injury.

The intravascular or transcutaneous application of photobiomodulation (PBM) over blood vessels (vascular photobiomodulation, VPBM) has been used for the treatment of inflammatory and chronic conditions with promising systemic results. This study evaluated the VPBM effects on a model of muscle regeneration after acute injury and compared the outcomes of preventive and therapeutic VPBM. Transcutaneous VPBM was administered over the rat's main tail vein. Serum levels of creatine kinase (CK), aspartate aminotransferase (AST), and lactate were evaluated and muscles were processed for macroscopic and microscopic analysis. Preventive and therapeutic VPBM led to decreased inflammatory infiltrate, edema, and myonecrosis but with an increase in immature muscle fibers. CK, AST, and lactate levels were lower in the groups treated with VPBM (lowest concentrations in preventive VPBM application). Preventive and therapeutic VPBM were capable of exerting a positive effect on acute muscle injury repair, with more accentuated results when preventive VPBM was administered.

A dual-ink 3D printing strategy to engineer pre-vascularized bone scaffolds in-vitro.

A functional vascular supply is a key component of any large-scale tissue, providing support for the metabolic needs of tissue-remodeling cells. Although well-studied strategies exist to fabricate biomimetic scaffolds for bone regeneration, success rates for regeneration in larger defects can be improved by engineering microvascular capillaries within the scaffolds to enhance oxygen and nutrient supply to the core of the engineered tissue as it grows. Even though the role of calcium and phosphate has been well understood to enhance osteogenesis, it remains unclear whether calcium and phosphate may have a detrimental effect on the vasculogenic and angiogenic potential of endothelial cells cultured on 3D printed bone scaffolds. In this study, we presented a novel dual-ink bioprinting method to create vasculature interwoven inside CaP bone constructs. In this method, strands of a CaP ink and a sacrificial template material was used to form scaffolds containing CaP fibers and microchannels seeded with vascular endothelial and mesenchymal stem cells (MSCs) within a photo-crosslinkable gelatin methacryloyl (GelMA) hydrogel material. Our results show similar morphology of growing vessels in the presence of CaP bioink, and no significant difference in endothelial cell sprouting was found. Furthermore, our initial results showed the differentiation of hMSCs into pericytes in the presence of CaP ink. These results indicate the feasibility of creating vascularized bone scaffolds, which can be used for enhancing vascular formation in the core of bone scaffolds.

Engineering pericyte-supported microvascular capillaries in cell-laden hydrogels using stem cells from the bone marrow, dental pulp and dental apical papilla.

Engineered tissue constructs require the fabrication of highly perfusable and mature vascular networks for effective repair and regeneration. In tissue engineering, stem cells are widely employed to create mature vascularized tissues in vitro. Pericytes are key to the maturity of these vascular networks, and therefore the ability of stem cells to differentiate into pericyte-like lineages should be understood. To date, there is limited information regarding the ability of stem cells from the different tissue sources to differentiate into pericytes and form microvascular capillaries in vitro. Therefore, here we tested the ability of the stem cells derived from bone marrow (BMSC), dental pulp (DPSC) and dental apical papilla (SCAP) to engineer pericyte-supported vascular capillaries when encapsulated along with human umbilical vein endothelial cells (HUVECs) in gelatin methacrylate (GelMA) hydrogel. Our results show that the pericyte differentiation capacity of BMSC was greater with high expression of α-SMA and NG2 positive cells. DPSC had α-SMA positive cells but showed very few NG2 positive cells. Further, SCAP cells were positive for α-SMA while they completely lacked NG2 positive cells. We found the pericyte differentiation ability of these stem cells to be different, and this significantly affected the vasculogenic ability and quality of the vessel networks. In summary, we conclude that, among stem cells from different craniofacial regions, BMSCs appear more suitable for engineering of mature vascularized networks than DPSCs or SCAPs.

3D Printing of Microgel-Loaded Modular Microcages as Instructive Scaffolds for Tissue Engineering.

Biomaterial scaffolds have served as the foundation of tissue engineering and regenerative medicine. However, scaffold systems are often difficult to scale in size or shape in order to fit defect-specific dimensions, and thus provide only limited spatiotemporal control of therapeutic delivery and host tissue responses. Here, a lithography-based 3D printing strategy is used to fabricate a novel miniaturized modular microcage scaffold system, which can be assembled and scaled manually with ease. Scalability is based on an intuitive concept of stacking modules, like conventional toy interlocking plastic blocks, allowing for literally thousands of potential geometric configurations, and without the need for specialized equipment. Moreover, the modular hollow-microcage design allows each unit to be loaded with biologic cargo of different compositions, thus enabling controllable and easy patterning of therapeutics within the material in 3D. In summary, the concept of miniaturized microcage designs with such straight-forward assembly and scalability, as well as controllable loading properties, is a flexible platform that can be extended to a wide range of materials for improved biological performance.

The effects of photodynamic therapy with blue light and papain-based gel associated with Urucum, on collagen and fibroblasts: a spectroscopic and cytotoxicity analysis.

Papacarie Duo™ is clinically used and has proven effectiveness; however, it is necessary to improve its antimicrobial action. The combined treatment of Papacarie Duo™ with Urucum (Bixa Orellana) could create a potential tool for dental caries treatment; its extract obtained from the seeds' pericarp contains a water-soluble primary pigment (cis-bixin) with smaller amounts of other carotenoids. The dicarboxylic acid salts of cis-norbixin and trans-norbixin occur in heated alkaline solutions. To analyze the absorption spectra and cytotoxicity (with human dermal fibroblasts) in different concentrations of Urucum, associated or not with Papacarie Duo™, we performed this in vitro study. The effects of pure Urucum, Papacarie Duo™, and PapaUrucum™ on the microstructure of collagen were also analyzed. The application of papain-based gel with Urucum did not present cytotoxicity, its exhibit UV absorption spectrum peak around 460 ± 20 nm. Also, it showed that the compound used did not alter the chemical structure of collagen. Consequently, this product could be used as a chemomechanical method to remove dentin caries as well as being a potential product for antimicrobial photodynamic therapy (aPDT) application.

The tooth on-a-chip: a microphysiologic model system mimicking the biologic interface of the tooth with biomaterials.

The tooth has a unique configuration with respect to biomaterials that are used for its treatment. Cells inside of the dental pulp interface indirectly with biomaterials via a calcified permeable membrane, formed by the dentin matrix and several thousands of dentinal tubules (∼2 µm in diameter). Although the cytotoxic response of the dental pulp to biomaterials has been extensively studied, there is a shortage of in vitro model systems that mimic the dentin-pulp interface and enable an improved understanding of the morphologic, metabolic and functional influence of biomaterials on live dental pulp cells. To address this shortage, here we developed an organ-on-a-chip model system which integrates cells cultured directly on a dentin wall within a microfluidic device that replicates some of the architecture and dynamics of the dentin-pulp interface. The tooth-on-a-chip is made out of molded polydimethylsiloxane (PDMS) with a design consisting of two chambers separated by a dentin fragment. To characterize pulp cell responses to dental materials on-chip, stem cells from the apical papilla (SCAPs) were cultured in odontogenic medium and seeded onto the dentin surface, and observed using live-cell microscopy. Next, to evaluate the tooth-on-a-chip as a platform for materials testing, standard dental materials used clinically (2-hydroxyethylmethacrylate - HEMA, phosphoric acid - PA, and Adper-Scotchbond - SB) were tested for cytotoxicity, cell morphology, and metabolic activity on-chip, and compared against standardized off-chip controls. All dental materials had cytotoxic effects in both on-chip and off-chip systems in the following order: HEMA > SB > PA (p < 0.05), and cells presented consistently higher metabolic activity on-chip than off-chip (p < 0.05). Furthermore, the tooth-on-a-chip enabled real-time tracking of gelatinolytic activity in a model hybrid layer (HL) formed in the microdevice, which suggests that dental pulp cells may contribute to the proteolytic activity in the HL more than endogenous proteases. In conclusion, the tooth-on-a-chip is a novel platform that replicates near-physiologic conditions of the pulp-dentin interface and enables live-cell imaging to study dental pulp cell response to biomaterials.

3D-Imaging of Whole Neuronal and Vascular Networks of the Human Dental Pulp via CLARITY and Light Sheet Microscopy.

Direct visualization of the spatial relationships of the dental pulp tissue at the whole-organ has remained challenging. CLARITY (Clear Lipid-exchanged Acrylamide Tissue hYdrogel) is a tissue clearing method that has enabled successful 3-dimensional (3D) imaging of intact tissues with high-resolution and preserved anatomic structures. We used CLARITY to study the whole human dental pulp with emphasis on the neurovascular components. Dental pulps from sound teeth were CLARITY-cleared, immunostained for PGP9.5 and CD31, as markers for peripheral neurons and blood vessels, respectively, and imaged with light sheet microscopy. Visualization of the whole dental pulp innervation and vasculature was achieved. Innervation comprised 40% of the dental pulp volume and the vasculature another 40%. Marked innervation morphological differences between uni- and multiradicular teeth were found, also distinct neurovascular interplays. Quantification of the neural and vascular structures distribution, diameter and area showed that blood vessels in the capillary size range was twice as high as that of nerve fibers. In conclusion whole CLARITY-cleared dental pulp samples revealed 3D-morphological neurovascular interactions that could not be visualized with standard microscopy. This represents an outstanding tool to study the molecular and structural intricacies of whole dental tissues in the context of disease and treatment methods.

Photodynamic therapy with Bixa orellana extract and LED for the reduction of halitosis: study protocol for a randomized, microbiological and clinical trial.

BACKGROUND: Halitosis is an unpleasant breath odour that can interfere with the professional life, social life and quality of life of people who suffer from it. A modality of treatment that has been increasing in dentistry is antimicrobial photodynamic therapy (aPDT). Bixa orellana, popularly known as "urucum" is a plant native to Brazil. The seeds are used to produce a dye that is largely used in the food, textile, paint and cosmetic industries. The aim of this study is to verify whether aPDT with Bixa orellana extract and blue light-emitting diodes (LEDs) is effective in reducing halitosis. This method will also be compared with tongue scraping, the most commonly used conventional method for tongue coating removal, and the association of both methods will be evaluated. METHODS/DESIGN: A randomized clinical trial will be conducted at the dental clinic of the Universidade Nove de Julho. Thirty-nine patients will be divided by block randomization into three groups (n = 13) according to the treatment to be performed. In Group 1, tongue scraping will be performed by the same operator in all patients for analysis of the immediate results. Patients will also be instructed on how to use the scraper at home. Group 2 will be treated with aPDT with Bixa orellana extract and the LED light curing device: Valo Cordless Ultradent®. Six points in the tongue dorsum with a distance of 1 cm between them will be irradiated. The apparatus will be pre-calibrated at wavelength 395-480 nm for 20 s and 9.6 J per point. In Group 3, patients will be submitted to the tongue scraping procedure, as well as to the previously explained aPDT. Oral air collection with the Oral Chroma™ and microbiological collections of the tongue coating shall be done before, immediately after and 7 days after treatment for comparison. DISCUSSION: Halitosis treatment is a topic that still needs attention. The results of this trial could support decision-making by clinicians regarding aPDT using blue LEDs for treating halitosis on a daily basis, as most dentists already have this light source in their offices. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03346460 . Registered on 17 November 2017.

Antimicrobial photodynamic therapy as a new approach for the treatment of vulvovaginal candidiasis: preliminary results.

In this work, we present the efficacy of photodynamic therapy against yeast cells in an animal model. We tested two photosensitizers, methylene blue and protoporphyrin IX. Thirty-seven female BALB-c mice with a body mass of 20-25 g were used. To achieve persistent vaginitis, estrus was induced by subcutaneous injection of 0.1 mg/mL estradiol valerate applied weekly. Three days after pseudo-estrus, intravaginal inoculation with Candida albicans was performed. Mice were anesthetized with ketamine (80 mg/kg) and xylazine (10 mg/kg) by intraperitoneal injection before inoculation, and antimicrobial photodynamic therapy (aPDT) was performed 5 days after fungal inoculation. Two photosensitizers were tested, methylene blue (MB; 100 µM) and protoporphyrin IX (PpNetNI; 10 µM). Two custom-made LEDs emitting light at 660 and 630 nm at approximately 800 mW each were used for irradiation. The aPDT treatment reduced the fungal colony-forming units (CFUs) by one order of magnitude for the MB (p = 0.020) and PpNetNI (p = 0.018) photosensitizers. Seven days after the treatment, there were significantly fewer CFUs compared to the control group (p = 0.041 and p = 0.035 for MB and PpNetNI, respectively), but this was not increased compared to the initial number immediately after aPDT. Using aPDT as a therapeutic option to decrease fungal infection in a vaginal candidiasis model resulted in a significant reduction in the C. albicans population. Both photosensitizers were effective for preventing reinfection within 7 days. The aPDT also had no effect on the vaginal mucosa at the ultrastructural level. In addition to the fungicide effect, we observed reduced swelling and lack of the formation of abscesses, microabscesses coating the cornified epithelial layer, and the accumulation of neutrophils in the submucosa.

Engineering Microvascular Networks in LED Light-Cured Cell-Laden Hydrogels.

The success of tissue engineering inevitably depends on the fabrication of tissue constructs that can be vascularized and that anastomose with the host vasculature. In this report, we studied the effects of light-emitting diode (LED) photopolymerized gelatin methacryloyl hydrogels (GelMA), encapsulated with stem cells from the apical papilla (SCAP) and human umbilical vein endothelial cells (HUVECs), in promoting vasculature network formation as a function of hydrogel physical and mechanical properties, as well as total cell density. Lithium acylphosphinate (LAP) was used as the photoinitiator in concentrations of 0.05, 0.075, 0.1% (w/v). GelMA hydrogel precursors of 5% (w/v) were encapsulated with cocultures of SCAPs and HUVECs at different cell densities (1×, 5×, and 10 × 106 cells/mL) and photo-cross-linked for 5 s. Results suggested that the compressive modulus of GelMA hydrogels increased as a function of LAP concentration, and had a maximum stiffness of 3.2 kPa. GelMA hydrogels photopolymerized using 0.05 or 0.075% LAP, which had an average of 1.5 and 1.6 kPa of elastic modulus respectively, had the most efficient vasculature formation after 5 days, and these results were further enhanced when the highest cell density (10 × 106 cells/mL) was used. Immunofluorescence images showed that SCAP cells spread in close contact with endothelial networks and expressed alpha smooth muscle actin (αSMA), which is suggestive of their differentiation into pericyte-like cells. αSMA expression was also apparently higher in hydrogels polymerized with 0.05% LAP and 10 × 106 cells/mLl. In conclusion, photopolymerization of GelMA hydrogels using an LED-light source can be an effective method for potential chair-side/in situ procedures for engineering of vascularized tissue constructs in regenerative medicine.

Modulating effect of low intensity pulsed ultrasound on the phenotype of inflammatory cells.

AIMS: The purpose of this study was toclarify the effect of low intensity pulsed ultrasound (LIPUS) on the phenotype of the inflammatory infiltrate in muscle tissue following acute injury. MAIN METHODS: Forty Wistar rats were submitted to cryoinjury of the tibialis anterior muscle and only half were treated with LIPUS. After 1, 2, 3 and 7 days macrophages and neutrophils were quantified. KEY FINDINGS: With one day, LIPUS led to reductions in the number of neutrophils and M1 macrophages. After two days, muscles treated with LIPUS had fewer total macrophages and M1 macrophages, but a greater number of M2 macrophages. Muscles treated with LIPUS showed fewer macrophages after three and seven days. SIGNIFICANCE: As the permanence of cells with pro-inflammatory and anti-inflammatory action can lead to the perpetuation of inflammation with consequent tissue damage and tissue fibrosis, respectively, the ability of LIPUS to modulate the occurrence of these cells demonstrates the therapeutic potential of this resource.

Effects of periodontitis on the development of asthma: The role of photodynamic therapy.

To evaluate whether periodontitis modulates lung inflammation in an experimental model of asthma as well as the photodynamic therapy (PDT) is associated with a reduction of lung inflammation. Seventy-two BALB/c male mice (~2 months) were randomly divided into 8 groups (n = 9): Basal, Periodontitis (P), P+PT, P+PT+PDT, Asthma (A), A+P, A+P+PT, and A+P+PT+PDT. Periodontitis was induced by using the ligature technique and asthma was induced by ovalbumin (OVA). PT was performed with curettes and PDT with methylene blue (0.005%), λ = 660nm, with a radiant exposure of 318J/cm2. After 43 days, euthanasia was carried out prior to lung and mandible morphological analyzes. All of the manipulations of the animals were performed by only one operator. The total and differential cell counts and cytokines IL-4, IL-5, IL-10, IFN-γ, TNF-α, IL-1ß, and IL-6 were evaluated in the bronchoalveolar lavage (BAL) and in the serum. Mucus and alkaline phosphatase were also quantified. Statistical analyzes were performed by a blinded statistician. One-way analysis of variance (ANOVA) was employed, followed by the Student-Newman-Keuls test. Periodontitis group (P) increased alkaline phosphatase and bone resorption (p<0.05), validating the experimental model of periodontitis. The A group and the P group increased the total amount of cells (p <0.05) in the BAL. However, in the A+P group, there was a decrease in these cells, except for in the A+P+PT+PDT group (p<0.05). The asthma group increased the Th2 cytokines and P group increased the Th1 cytokine profile, and A+P+PT+PDT group increased IL-10 cytokine. Mucus was increased for the A and P groups. In conclusion, periodontitis in the asthmatic mice reduced the inflammatory migrated cells in the BAL (eosinophils, lymphocytes, macrophages). In addition, it reduced the levels of the IL-4 and TNF-α cytokines, which was also accompanied by a decreased mucus production. After PDT treatment the total cell count increased however, this increase was not accompanied by a pro-inflammatory cytokines release. Only in PDT group the anti-inflammatory IL-10 was increased. Further studies are needed to understand this mechanism of action.

Cholinergic Stimulation Improves Oxidative Stress and Inflammation in Experimental Myocardial Infarction.

We previously reported that cholinergic stimulation with pyridostigmine (PY) induces anti-inflammatory cell recruitment soon after myocardial infarction (MI). In this study, we evaluated the anti-inflammatory effects of PY during the proliferative phase of cardiac repair by analyzing the infiltration of macrophages, Treg lymphocytes, oxidative stress and inflammatory cytokines. Wistar rats underwent control sham surgery or ligation of the left coronary artery and were randomly allocated to remain untreated (untreated infarcted group, I) or to receive PY (30 mg·kg(-1)·day(-1)) in the supplied water (infarcted treated group, I + PY). Blood pressure and heart rate variability were registered at day 5 post-MI. The animals were euthanized 7 days after thoracotomy, when the hearts were removed and processed for immunohistochemistry (CD68, CD206, FOXP3), cytokines (IL-1ß, IL-6, IL-10, TNF-α) and oxidative stress (superoxide dismutase, catalase, glutathione peroxidase, lipidic and protein peroxidation). PY treatment increased parasympathetic modulation, M2 macrophages and the anti-oxidant enzyme activity but reduced protein oxidation (carbonyls) and the concentration of IL-1ß, IL-6, TNF-α and IL-10. Cholinergic stimulation induces parasympathetic neuro-immune modulation and anti-inflammatory cell enrollment as well as prevents oxidative stress and cytokine production after MI.

Experimental burns: Comparison between silver sulfadiazine and photobiomodulation.

OBJECTIVE: To analyze morphological characteristics and organization of the collagen fibers of third degree burns from scalding compared to laser therapy and silver sulfadiazine, the latter considered as the gold standard. METHOD: Were selected 12 animals (Rattus norvegicus) also divided into three groups (control group [CG] - untreated burns; sulfadiazine group [SG] - burns were treated with silver sulfadiazine at 1%; laser group [LG] - burns were treated with photobiomodulation). The scald burns were carried out by using PVC mold, and the material collected on the 14th day after burn was prepared for morphological and optical retardation analysis for evaluation of inflammatory infiltrates and collagen organization, respectively. RESULTS: On the 14th day, the laser and sulfadiazine groups had mild inflammatory response, while the control group showed an intense inflammatory process, with statistical significance between laser and control groups, but not between sulfadiazine and control groups. Laser and sulfadiazine groups no longer had granulation tissue, opposite to what was seen in the control group. The presence of hair follicles and ulcer did not significantly differ between groups. The optical retardation of collagen fibers was higher in sulfadiazine group, followed by laser and control groups. As for systemic effect, we were able to identify it by simply analyzing the presence or absence of granulation tissue. CONCLUSION: Morphologically, the laser or silver sulfadiazine treatments were similar and both provided better organization of collagen fibers in relation to the untreated group. However, the sulfadiazine group modulated the deposition of collagen fibers more efficiently than the laser group.

Experimental burns: Comparison between silver sulfadiazine and photobiomodulation / Queimadura experimental: comparativo entre sulfadiazina de prata e fotobiomodulação

Summary Objective: To analyze morphological characteristics and organization of the collagen fibers of third degree burns from scalding compared to laser therapy and silver sulfadiazine, the latter considered as the gold standard. Method: Were selected 12 animals (Rattus norvegicus) also divided into three groups (control group [CG] - untreated burns; sulfadiazine group [SG] - burns were treated with silver sulfadiazine at 1%; laser group [LG] - burns were treated with photobiomodulation). The scald burns were carried out by using PVC mold, and the material collected on the 14th day after burn was prepared for morphological and optical retardation analysis for evaluation of inflammatory infiltrates and collagen organization, respectively. Results: On the 14th day, the laser and sulfadiazine groups had mild inflammatory response, while the control group showed an intense inflammatory process, with statistical significance between laser and control groups, but not between sulfadiazine and control groups. Laser and sulfadiazine groups no longer had granulation tissue, opposite to what was seen in the control group. The presence of hair follicles and ulcer did not significantly differ between groups. The optical retardation of collagen fibers was higher in sulfadiazine group, followed by laser and control groups. As for systemic effect, we were able to identify it by simply analyzing the presence or absence of granulation tissue. Conclusion: Morphologically, the laser or silver sulfadiazine treatments were similar and both provided better organization of collagen fibers in relation to the untreated group. However, the sulfadiazine group modulated the deposition of collagen fibers more efficiently than the laser group.

Resumo Objetivo: Analisar características morfológicas e organização das fibras colágenas de queimaduras de terceiro grau provocadas por escaldo em relação à terapia com laser e àquela considerada padrão-ouro, a sulfadiazina de prata. Método: Foram selecionados 12 animais (Rattus norvegicus), divididos igualmente em três grupos (grupo controle [GC] - queimaduras não tratadas; grupo sulfadiazina [GS] - queimaduras tratadas com sulfadiazina de prata 1%; grupo laser [GL] - queimaduras tratadas com fotobiomodulação). As queimaduras foram realizadas por escaldo com a utilização de molde de PVC, e o material coletado no 14º dia pós-queimadura foi preparado para análise morfológica e de retardo óptico, para avaliação do infiltrado inflamatório e da organização do colágeno, respectivamente. Resultados: No 14º dia, os grupos laser e sulfadiazina apresentaram resposta inflamatória leve, enquanto o grupo controle apresentou processo inflamatório intenso, havendo significância estatística entre os grupos laser e controle, mas não entre os grupos sulfadiazina e controle. Enquanto os grupos laser e sulfadiazina não apresentavam mais tecido de granulação, o grupo controle ainda apresentava. A presença de folículo piloso e de úlcera não diferiu significantemente entre os grupos. O retardo óptico das fibras colágenas foi maior no grupo sulfadiazina, seguido dos grupos laser e controle. Apenas a análise da presença ou ausência de tecido de granulação permitiu identificar o efeito sistêmico. Conclusão: Morfologicamente, os tratamentos com laser ou sulfadiazina de prata foram similares e ambos proporcionaram maior organização das fibras colágenas em relação ao grupo não tratado. Entretanto, o grupo sulfadiazina modulou a deposição das fibras colágenas mais eficientemente que o grupo laser.

Orofacial evaluation in patients with multiple sclerosis using Nordic Orofacial Test-Screening.

OBJECTIVES: The aim of this study is to investigate whether patients with multiple sclerosis (MS) have more orofacial dysfunctions than the general population, using the Nordic Orofacial Test-Screening (NOT-S). MATERIALS AND METHODS: The NOT-S instrument was applied in 34 patients with MS, who went to the MS Reference Center, Universidade Metropolitana de Santos and 34 healthy patients, matched for gender and age. NOT-S results were compared between patients with MS and control subjects. Disability and disease duration were assessed among the patients, in order to establish whether these parameters might affect the results from NOT-S. RESULTS: There was no significant difference in orofacial function between patients with MS and control subjects. There was no statistically significant correlation between disability and NOT-S or between disease duration and NOT-S. However, the correlation between disease duration and the degree of disability was statistically significant, thus suggesting that the results are in accordance with what would be expected regarding MS. CONCLUSIONS: These results indicate that there was no correlation between orofacial dysfunction and MS, although there were some differences in the affected domains. CLINICAL RELEVANCE: This study points out the orofacial dysfunctions which health professionals should be aware in this population.