Spinal Biomechanical Alterations, Neurogenic Inflammation (CGRP), Dermatitis

[eng] Dermatitis is a chronic inflammatory skin disease, described by intensive pruritus and eczematous lesions of skin. In most of the patients with Dermatitis, a long-lasting cycle of itch-scratch roots produces substantial morbidities and discomforts. For instance, sleeping problems, compromised quality of life, and psychosocial problems, as well as appearance-related complications including skin infections resulting to a loss of self-confidence. The purpose of treatment in dermatitis is to decrease symptoms, cure superinfection, avoid exacerbations, lessen the risk of treatment, and bring back the integrity of the skin. In most patients with mild Dermatitis, treatment goals can be accomplished with topical therapies, however, in patients with moderate to severe Dermatitis, treatment is still a challenge. At present, a guideline-based method for treating Dermatitis is lacking and the pathogenesis of Dermatitis remains unknown. However, there is evidence that neuropeptides such as Calcitonin gene- related peptide (CGRP) influence the development and course of Dermatitis. Likewise, there are studies investigating spinal neurotransmitters in accordance with itching in dermatitis and it is reported that a species of neuropeptides is released from chloroquine-sensitive pruriceptors within the spine to arbitrate histamine-independent itch in Dermatitis. Moreover, a correlation between spine biomechanical alteration and Dermatitis is reported in numerous studies. Therefore, the main objective of this work is to carry out a prospective study to determine the relationship between alterations in the spine and Dermatitis by focusing on the level of CGRP in patients’ plasma. Furthermore, in this study we set out to investigate whether chiropractic can be an effective treatment for dermatitis. 73 patients suffering from dermatitis participated in this study. 51 of these patients were randomly assigned to the treatment group and 22 patients were also randomly assigned to the control group. All patients in both, treatment and control groups, were prescribed a topical compound cream, containing emollient corticosteroid-indomethacin, and antioxidants. However, only patients in the treatment group underwent chiropractic treatment while patients in the control group only received the above- mentioned topical treatment. In order to accomplish our objectives, the following data was analyzed in patients of the treatment group: (1) Dermatological examination quantified using the Eczema Area and Severity Index (EASI) score method, (2) Radiographic description and quantification of the severity level of spinal biomechanical alterations (SBA), hereinafter referred to as (spinal) severity score. (3) Biological data including blood tests and measurement of plasma calcitonin gene-related peptide (CGRP) level in all the patients and (4) chiropractic spinal examination and treatment (SMT) and on a 3-month weekly plan. All data was compared and analyzed before and after the treatment in the 73 study patients. The results presented in this study would be indicative of a correlation between the altered biomechanics of different spinal segments and the altered state of the skin. In this study we found that the EASI levels in the patients suffering from Dermatitis were significantly correlated with SBA in the Atlas- Axis (AT- AX) (p< 0.001; r=0.82), in the cervical spine (r=0.91), in the sagittal balance of the spine (SBS) (p< 0.001; r=0.88), in Spondylolisthesis (p< 0.001; r=0.85), in Thoracic 10 (p< 0.001; r=0.87), in Lumbar 1 (p< 0.001; r=0.81), and Lumbar 2 (p< 0.001; r=0.70). Overall, the results of this study indicated that improvement in the plasma CGRP level correlates with the improvement in the EASI level and the improvement in the SBA severity score. It suggests that spinal biomechanical alterations may contribute to the release of neuropeptides, including CGRP, from sensory nerves endings. Increase of plasma CGRP results in neurogenic inflammation of the skin and contributes to dermatological disorders such as dermatitis. In addition, our results indicated a significant reduction in the CGRP level in patients of the treatment group (who underwent chiropractic spinal treatment) and following that a significant reduction in EASI scores (improvement of skin´s situation). On the other hand, although the EASI level of the patients in control group decreased after 2 weeks of using compound cream, the CGRP level remained altered and consequently, the dermatitis symptoms showed up in those patients after 3 months. As a conclusion, the result of our study suggesting that there may be a strong correlation between the spine biomechanical alteration, CGRP level, and neurogenic inflammation of skin (in the form of Dermatitis of the skin). We also strongly suggest further investigations with bigger sample population.[spa] La dermatitis es una enfermedad inflamatoria crónica de la piel, descrita por prurito intensivo y lesiones cutáneas eccematosas. En la mayoría de los pacientes con dermatitis, un ciclo prolongado de raíces con picazón y rascado produce morbilidades y malestares sustanciales. Por ejemplo, problemas para dormir, calidad de vida comprometida y problemas psicosociales, así como complicaciones relacionadas con la apariencia, incluidas infecciones de la piel que provocan una pérdida de la confianza en uno mismo. El propósito del tratamiento de la dermatitis es disminuir los síntomas, curar la superinfección, evitar las exacerbaciones, disminuir el riesgo del tratamiento y devolver la integridad de la piel. En la mayoría de los pacientes con dermatitis leve, los objetivos del tratamiento se pueden lograr con terapias tópicas, sin embargo, en pacientes con dermatitis moderada a grave, el tratamiento sigue siendo un desafío. En la actualidad, se carece de un método basado en directrices para el tratamiento de la dermatitis y se desconoce la patogenia de la dermatitis. Sin embargo, existe evidencia de que los neuropéptidos como el péptido relacionado con el gen de la calcitonina (CGRP) influyen en el desarrollo y el curso de la dermatitis. Asimismo, hay estudios que investigan los neurotransmisores espinales de acuerdo con la picazón en la dermatitis y se informa que una especie de neuropéptidos se libera de los pruriceptores sensibles a la cloroquina dentro de la columna vertebral para arbitrar la picazón independiente de histamina en la dermatitis. Además, en numerosos estudios se informa de una correlación entre la alteración biomecánica de la columna y la dermatitis. Por tanto, el principal objetivo de este trabajo es realizar un estudio prospectivo para determinar la relación entre las alteraciones de la columna y la dermatitis centrándose en el nivel de CGRP en el plasma de los pacientes. Además, en este estudio nos propusimos investigar si la quiropráctica puede ser un tratamiento eficaz para la dermatitis. En este estudio participaron 73 pacientes que padecían dermatitis. 51 de estos pacientes fueron asignados al azar al grupo de tratamiento y 22 pacientes también fueron asignados al azar al grupo de control. A todos los pacientes de los grupos de tratamiento y control se les prescribió una crema compuesta tópica que contenía corticosteroide-indometacina emoliente y antioxidantes. Sin embargo, solo los pacientes del grupo de tratamiento se sometieron a un tratamiento quiropráctico, mientras que los pacientes del grupo de control solo recibieron el tratamiento tópico mencionado anteriormente. Para lograr nuestros objetivos, se analizaron los siguientes datos en pacientes del grupo de tratamiento: (1) Examen dermatológico cuantificado mediante el Índice de Severidad y Área de Eczema (EASI) método de puntuación, (2) Descripción radiográfica y cuantificación del nivel de gravedad de las alteraciones biomecánicas espinales (SBA), en lo sucesivo denominado puntuación de gravedad (espinal). (3) Datos biológicos que incluyen análisis de sangre y medición del nivel de péptido relacionado con el gen de calcitonina en plasma (CGRP) en todos los pacientes y (4) examen y tratamiento espinal quiropráctico (SMT) y en un plan semanal de 3 meses. Todos los datos se compararon y analizaron antes y después del tratamiento en los 73 pacientes del estudio. Los resultados presentados en este estudio serían indicativos de una correlación entre la biomecánica alterada de diferentes segmentos espinales y el estado alterado de la piel. En este estudio encontramos que los niveles de EASI en los pacientes que padecían Dermatitis se correlacionaron significativamente con SBA en el Atlas-Eje (AT-AX) (p <0,001; r = 0,82), en la columna cervical (r = 0,91), en el balance sagital de la columna SBS (p <0.001; r = 0.88), en Espondilolistesis (p <0.001; r = 0.85), en T10 (p <0.001; r = 0.87), en L1 (p <0.001; r = 0,81) y L2 (p <0,001; r = 0,70). En general, los resultados de este estudio indicaron que la mejora en el nivel de CGRP en plasma se correlaciona con la mejora en el nivel de EASI y la mejora en la puntuación de gravedad de la SBA. Sugiere que las alteraciones biomecánicas espinales (SBA) pueden contribuir a la liberación de neuropéptidos, incluido el CGRP, de las terminaciones de los nervios sensoriales. El aumento de CGRP en plasma da como resultado una inflamación neurogénica de la piel y contribuye a trastornos dermatológicos como la dermatitis. Además, nuestros resultados indicaron una reducción significativa en el nivel de CGRP en los pacientes del grupo de tratamiento (que se sometieron a tratamiento espinal quiropráctico) y luego una reducción significativa en los puntajes EASI (mejora de la situación de la piel). Por otro lado, aunque el nivel de EASI de los pacientes del grupo de control disminuyó después de 2 semanas de uso de la crema compuesta, el nivel de CGRP permaneció alterado y, en consecuencia, los síntomas de dermatitis aparecieron en esos pacientes después de 3 meses. Como conclusión, el resultado de nuestro estudio sugiere que puede haber una fuerte correlación entre la alteración biomecánica de la columna, el nivel de CGRP y la inflamación neurogénica de la piel (en forma de dermatitis de la piel). También recomendamos encarecidamente que se realicen más investigaciones con una muestra de población más grande

Evaluation of a single-shot of a high-density viscoelastic solution of hyaluronic acid in patients with symptomatic primary knee osteoarthritis: the no-dolor study

Background: pronolis®HD mono 2.5% is a novel, one-shot, high-density sterile viscoelastic solution, recently available in Spain, which contains a high amount of intermediate molecular weight hyaluronic acid (HA), highly concentrated (120 mg in 4.8 mL solution: 2.5%). The objective of the study was to analyze the efficacy and safety of this treatment in symptomatic primary knee osteoarthritis (OA). Methods: this observational, prospective, multicenter, single-cohort study involved 166 patients with knee OA treated with a single-shot of Pronolis®HD mono 2.5% and followed up as many as 24 weeks. Results: compared with baseline, the score of the Western Ontario and McMaster Universities Arthritis Osteoarthritis Index (WOMAC) pain subscale reduced at the 12-week visit (primary endpoint, median: 9 interquartile range [IQR]: 7-11 versus median: 4; IQR: 2-6; p 50% improvement in the pain subscale increased progressively from 37.9% (at 2 weeks) to 66.0% (at 24 weeks). Similarly, WOMAC scores for pain on walking, stiffness subscale, and functional capacity subscale showed significant reductions at the 12-week visit which were maintained up to the 24-week visit. The EuroQol visual analog scale score increased after 12 weeks (median: 60 versus 70). The need for rescue medication (analgesics/nonsteroidal anti-inflammatory drugs) also decreased in all post-injection visits. Three patients (1.6%) reported local adverse events (joint swelling) of mild intensity. Conclusions: in conclusion, a single intra-articular injection of the high-density viscoelastic gel of HA was associated with pain reduction and relief of other symptoms in patients with knee OA

Application of 3D, 4D, 5D, and 6D bioprinting in cancer research: what does the future look like?

The application of three- and four-dimensional (3D/4D) printing in cancer research represents a significant advancement in understanding and addressing the complexities of cancer biology. 3D/4D materials provide more physiologically relevant environments compared to traditional two-dimensional models, allowing for a more accurate representation of the tumor microenvironment that enables researchers to study tumor progression, drug responses, and interactions with surrounding tissues under conditions similar to in vivo conditions. The dynamic nature of 4D materials introduces the element of time, allowing for the observation of temporal changes in cancer behavior and response to therapeutic interventions. The use of 3D/4D printing in cancer research holds great promise for advancing our understanding of the disease and improving the translation of preclinical findings to clinical applications. Accordingly, this review aims to briefly discuss 3D and 4D printing and their advantages and limitations in the field of cancer. Moreover, new techniques such as 5D/6D printing and artificial intelligence (AI) are also introduced as methods that could be used to overcome the limitations of 3D/4D printing and opened promising ways for the fast and precise diagnosis and treatment of cancer

Biosensor integrated brain-on-a-chip platforms: Progress and prospects in clinical translation

Because of the brain's complexity, developing effective treatments for neurological disorders is a formidable challenge. Research efforts to this end are advancing as in vitro systems have reached the point that they can imitate critical components of the brain's structure and function. Brain-on-a-chip (BoC) was first used for microfluidics-based systems with small synthetic tissues but has expanded recently to include in vitro simulation of the central nervous system (CNS). Defining the system's qualifying parameters may improve the BoC for the next generation of in vitro platforms. These parameters show how well a given platform solves the problems unique to in vitro CNS modeling (like recreating the brain's microenvironment and including essential parts like the blood-brain barrier (BBB)) and how much more value it offers than traditional cell culture systems. This review provides an overview of the practical concerns of creating and deploying BoC systems and elaborates on how these technologies might be used. Not only how advanced biosensing technologies could be integrated with BoC system but also how novel approaches will automate assays and improve point-of-care (PoC) diagnostics and accurate quantitative analyses are discussed. Key challenges providing opportunities for clinical translation of BoC in neurodegenerative disorders are also addressed.A.B.O acknowledges the support from the Scientific and Techno- logical Research Council of Turkey (TUBITAK) (221M724) . E.M. would like to acknowledge the support from the National Institute of Biomedical Imaging and Bioengineering (5T32EB009035) . O.Y.C. ac- knowledges the support from the Research Fund of Ege University, In- ternational Research Cooperation Project under grant number FUA- 2020-22187.Scientific and Technological Research Council of Turkey (TUBITAK) [221M724]; National Institute of Biomedical Imaging and Bioengineering [5T32EB009035]; Research Fund of Ege University, International Research Cooperation Project [FUA- 2020-22187

MXene-based nano(bio)sensors for the detection of biomarkers: a move towards intelligent sensors

MXene-based nano(bio)sensors have emerged as promising tools for detecting different biomarkers. These sensors utilize MXene materials, a class of two-dimensional transition metal carbides, nitrides, and carbonitrides, to enable highly sensitive and selective detection. One of the key advantages of MXene-based materials is their high surface area, allowing for efficient immobilization of biomolecules. They also exhibit excellent electrical conductivity, enabling rapid and sensitive detection of biomarkers. The combination of high surface area and conductivity makes MXene-based sensors ideal for detecting biomarkers at low concentrations. Furthermore, MXene-based materials possess unique mechanical properties, ensuring the durability of the sensors. This durability enables repeated use without compromising the sensor performance, making MXene-based sensors suitable for continuous monitoring applications. Despite their advantages, MXene-based nano(bio)sensors face certain challenges for practical biomedical and clinical applications. One challenge lies in the synthesis of MXene materials, which can be complex and time-consuming. Developing scalable synthesis methods is crucial to enable large-scale production and widespread use of MXene-based sensors. In addition, ensuring the stability of MXene layers under various environmental conditions remains a challenge for their practical application. Another limitation is the specificity of MXene-based sensors towards targeted biomarkers. Interfering substances or cross-reactivity with similar biomolecules can lead to false-positive or false-negative results. Enhancing the selectivity of MXene-based sensors through optimization and functionalization is essential to improve their reliability and accuracy. The integration of these sensors with emerging technologies, such as artificial intelligence (AI) and internet of things, opens up new possibilities in biomarker detection. The combination of MXene sensors with AI algorithms can enable real-time monitoring, remote data analysis, and personalized healthcare solutions. Herein, the significant challenges and future prospects of MXene-based nano(bio)sensors for the detection of biomarkers are deliberated. The key obstacles have been highlighted, such as ensuring the stability and biocompatibility of MXene-based sensors, as well as addressing scalability issues. The promising future prospects of these sensors have also been explored, including their potential for high sensitivity, selectivity, and rapid response

Antimicrobial ionic liquid‐based materials for biomedical applications

International audienceExcessive and unwarranted administration of antibiotics has invigorated the evolution of multidrug-resistant microbes. There is, therefore, an urgent need for advanced active compounds. Ionic liquids with short-lived ion-pair structures are highly tunable and have diverse applications. Apart from their unique physicochemical features, the newly discovered biological activities of ionic liquids have fascinated biochemists, microbiologists, and medical scientists. In particular, their antimicrobial properties have opened new vistas in overcoming the current challenges associated with combating antibiotic-resistant pathogens. Discussions regarding ionic liquid derivatives in monomeric and polymeric forms with antimicrobial activities are presented here. The antimicrobial mechanism of ionic liquids and parameters that affect their antimicrobial activities, such as chain length, cation/anion type, cation density, and polymerization, are considered. The potential applications of ionic liquids in the biomedical arena, including regenerative medicine, biosensing, and drug/biomolecule delivery, are presented to stimulate the scientific community to further improve the antimicrobial efficacy of ionic liquids

Biomedical applications of engineered heparin-based materials

Heparin is a negatively charged polysaccharide with various chain lengths and a hydrophilic backbone. Due to its fascinating chemical and physical properties, nontoxicity, biocompatibility, and biodegradability, heparin has been extensively used in different fields of medicine, such as cardiovascular and hematology. This review highlights recent and future advancements in designing materials based on heparin for various biomedical applications. The physicochemical and mechanical properties, biocompatibility, toxicity, and biodegradability of heparin are discussed. In addition, the applications of heparin-based materials in various biomedical fields, such as drug/gene delivery, tissue engineering, cancer therapy, and biosensors, are reviewed. Finally, challenges, opportunities, and future perspectives in preparing heparin-based materials are summarized

Engineered Vasculature for Cancer Research and Regenerative Medicine

Engineered human tissues created by three-dimensional cell culture of human cells in a hydrogel are becoming emerging model systems for cancer drug discovery and regenerative medicine. Complex functional engineered tissues can also assist in the regeneration, repair, or replacement of human tissues. However, one of the main hurdles for tissue engineering, three-dimensional cell culture, and regenerative medicine is the capability of delivering nutrients and oxygen to cells through the vasculatures. Several studies have investigated different strategies to create a functional vascular system in engineered tissues and organ-on-a-chips. Engineered vasculatures have been used for the studies of angiogenesis, vasculogenesis, as well as drug and cell transports across the endothelium. Moreover, vascular engineering allows the creation of large functional vascular conduits for regenerative medicine purposes. However, there are still many challenges in the creation of vascularized tissue constructs and their biological applications. This review will summarize the latest efforts to create vasculatures and vascularized tissues for cancer research and regenerative medicine.</jats:p

Noninvasive and Continuous Monitoring of On-Chip Stem Cell Osteogenesis Using a Reusable Electrochemical Immunobiosensor

Noninvasive monitoring of biofabricated tissues during the biomanufacturing process is needed to obtain reproducible, healthy, and functional tissues. Measuring the levels of biomarkers secreted from tissues is a promising strategy to understand the status of tissues during biofabrication. Continuous and real-time information from cultivated tissues enables users to achieve scalable manufacturing. Label-free biosensors are promising candidates for detecting cell secretomes since they can be noninvasive and do not require labor-intensive processes such as cell lysing. Moreover, most conventional monitoring techniques are single-use, conducted at the end of the fabrication process, and, challengingly, are not permissive to in-line and continual detection. To address these challenges, we developed a noninvasive and continual monitoring platform to evaluate the status of cells during the biofabrication process, with a particular focus on monitoring the transient processes that stem cells go through during in vitro differentiation over extended periods. We designed and evaluated a reusable electrochemical immunosensor with the capacity for detecting trace amounts of secreted osteogenic markers, such as osteopontin (OPN). The sensor has a low limit of detection (LOD), high sensitivity, and outstanding selectivity in complex biological media. We used this OPN immunosensor to continuously monitor on-chip osteogenesis of human mesenchymal stem cells (hMSCs) cultured 2D and 3D hydrogel constructs inside a microfluidic bioreactor for more than a month and were able to observe changing levels of OPN secretion during culture. The proposed platform can potentially be adopted for monitoring a variety of biological applications and further developed into a fully automated system for applications in advanced cellular biomanufacturing