Search Results (14,294)

Background: Chronic wounds are a growing clinical challenge due to their prolonged healing time and associated healthcare burden. Combined therapeutic approaches, including topical oxygen therapy (TOT) and negative-pressure wound therapy (NPWT), have shown promise in enhancing wound healing. This pilot exploratory study aimed to assess the clinical effectiveness of combined TOT and NPWT in chronic wound treatment and to explore the prognostic value of selected laboratory and thermographic markers. Methods: Eighteen patients with chronic wounds due to type 2 diabetes mellitus or chronic venous insufficiency were treated with either TOT alone (control group) or TOT combined with NPWT (intervention group). Wound characteristics, thermographic data, and laboratory parameters (NLR, MLR, PLR, CRP, and total protein) were collected at baseline and during therapy. The primary endpoints were the total treatment duration and complete wound closure. Statistical analyses were exploratory and used non-parametric tests, correlation analyses, and simple linear regression. Results: Ulcer duration was significantly associated with the wound surface area. Lower serum total protein levels correlated negatively with ulcer duration, wound size, and granulation tissue area. A significant reduction in treatment duration was observed in the intervention group compared to the controls. One strong correlation was found between MLR and peripheral wound temperature on day 7 in the control group. No significant group differences were observed in wound size or thermographic measures after one week of treatment. Conclusions: Combining TOT and NPWT may reduce treatment duration in chronic wound management. Selected laboratory and thermographic markers show promise as prognostic tools. These exploratory findings require confirmation in larger, randomized trials. Full article

Developing a rapidly gel-forming, in situ sprayable hydrogel with wound dressing functionality is essential for enhancing the wound healing process. In this study, a novel sprayable hydrogel-based wound dressing was developed by combining thermo- and pH- responsive polymers including Pluronic F127 (PF127) and N-succinyl chitosan (NSC). NSC was prepared by modifying chitosan with succinic anhydride, as confirmed by Fourier-transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The NSC synthesized using a succinic anhydride-to-chitosan molar ratio of 5:1 exhibited the highest degree of substitution, resulting in a water-soluble polymer effective over a broad pH range. The formulation process of the PF127:NSC sprayable hydrogel was optimized and evaluated based on its sol–gel phase transition behavior, clarity, gelation time, liquid and moisture management, stability, and cytotoxicity. These properties can be suitably tailored by adjusting the concentrations of PF127 and NSC. Moreover, the antioxidant capacity of the hydrogels was enhanced by incorporating Azadirachta indica (neem) extract, a bioactive compound, into the optimized sprayable hydrogel. Both neem release and antioxidant activity increased in a dose-dependent manner. Overall, the developed sprayable hydrogel exhibited favorable sprayability, appropriate gelation properties, controlled drug release, and antioxidant activity, underscoring its promising translational potential as a wound dressing. Full article

Total knee replacement (TKR) is a common procedure for pain relief and restoration of the mobility of the knee joint in patients with severe knee joint problems. Despite this, some patients still suffer from stiffness, instability, or pain caused by soft tissue imbalance, malalignment, or implant-related issues. Previously, surgeons have had to use their experience and visual judgment to balance the knee, which has resulted in variability of outcomes. Smart knee implants are addressing these issues by using sensor technology to provide real-time feedback on joint motion, pressure distribution, and loading forces. This enables more accurate intra-operative adjustment, enhancing implant positioning and soft tissue balance and eliminating post-operative adjustment. These implants also enable post-operative monitoring, simplifying the ability to have more effective individualized rehabilitation programs directed at optimizing patient mobility and minimizing complications. While the patient pool for smart knee implantation remains not commonly documented, it was found in a study that 83.6% of the patients would opt to have the monitoring device implemented, and nearly 90% find reassurance in monitoring their healing indicators. As the number of knee replacements is likely to rise due to aging populations and the rising prevalence of joint disease, smart implants are a welcome development in orthopedics, optimizing long-term success and patient satisfaction. Smart knee implants are built with embedded sensors such as force, motion, temperature, and pressure detectors placed within the implant structure. These sensors provide real-time data during surgery and recovery, allowing earlier detection of complications and supporting tailored rehabilitation. The design aims to improve outcomes through better monitoring and personalized care. Full article

Healing large bone defects remains challenging. Gelatin scaffolds are biocompatible and biodegradable, but lack osteoinductive activity. Plant-derived exosomes carry miRNAs, growth factors, and proteins that modulate osteogenesis, but free exosomes suffer from poor stability, limited targeting, and low bioavailability in vivo. We developed a 3D GelMA hydrogel loaded with Epimedium-derived exosomes (“GelMA@Exo”) to improve exosome retention, stability, and sustained release. Its effects on MC3T3-E1 preosteoblasts—including proliferation, osteogenic differentiation, migration, and senescence—were evaluated via in vitro assays. Angiogenic potential was assessed using HUVECs. Underlying mechanisms were examined at transcriptomic and protein levels to elucidate GelMA@Exo’s therapeutic osteogenesis actions. GelMA@Exo exhibited sustained exosome release, enhancing exosome retention and cellular uptake. In vitro, GelMA@Exo markedly boosted MC3T3-E1 proliferation, migration, and mineralized nodule formation, while reducing senescence markers and promoting angiogenesis in HUVECs. Mechanistically, GelMA@Exo upregulated key osteogenic markers (RUNX2, TGF-β1, Osterix, COL1A1, ALPL) and activated the PI3K/Akt pathway. Transcriptomic data confirmed global upregulation of osteogenesis-related genes and bone-regeneration pathways. This study presents a GelMA hydrogel functionalized with plant-derived exosomes, which synergistically provides osteoinductive stimuli and structural support. The GelMA@Exo platform offers a versatile strategy for localized delivery of natural bioactive molecules and a promising approach for bone tissue engineering. Our findings provide strong experimental evidence for the translational potential of plant-derived exosomes in regenerative medicine. Full article

CD26 (dipeptidyl peptidase-4) is a marker of colorectal cancer stem cells with high metastatic potential and resistance to therapy. Although CD26 expression is known to be associated with tumor progression, its functional involvement in epithelial-mesenchymal transition (EMT) and metastasis remains to be fully elucidated. In this study, we aimed to investigate the effects of a monoclonal anti-CD26 antibody on EMT-related phenotypes and metastatic behavior in colorectal cancer cells. We evaluated changes in EMT markers by quantitative PCR and Western blotting, assessed cell motility and invasion using scratch wound-healing and Transwell assays, and examined metastatic potential in vivo using a splenic injection mouse model. Treatment with the anti-CD26 antibody significantly increased the expression of the epithelial marker E-cadherin and reduced levels of EMT-inducing transcription factors, including ZEB1, Twist1, and Snail1, at the mRNA and protein levels. Functional assays revealed that the antibody markedly inhibited cell migration and invasion in vitro without exerting cytotoxic effects. Furthermore, systemic administration of the anti-CD26 antibody significantly suppressed the formation of liver metastases in vivo. These findings suggest that CD26 may contribute to the regulation of EMT and metastatic behavior in colorectal cancer. Our data highlight the potential therapeutic utility of CD26-targeted antibody therapy for suppressing EMT-associated phenotypes and metastatic progression. Full article

Background/Objectives: Scars are formed from trauma to the dermis and more specifically during the wound-healing phase. Skin needling is a technique used in scar therapy which stimulates the skin to regenerate. The aim of this study was to objectively and subjectively evaluate the degree of scar reduction after skin needling treatments based on visible changes using specialized measuring devices—ultrasound, Courage & Khazaka, and standardized questionnaires. Methods: Six patients were enrolled. Participants were given a series of three skin needling treatments. Before and after the treatment, the participants were examined for selected skin parameters with the help of specialized measuring devices such as Courage & Khazaka and skin ultrasound. Skin firmness and elasticity and MEP and HEP skin echogenicity were taken into account. Each patient completed POSAS questionnaires on satisfaction, pain, and adverse effects. Results: Based on the results of the POSAS questionnaire, a significant improvement in patients’ scar evaluation was observed after the treatment. Patients reported the most noticeable improvements in parameters such as color (p = 0.035), stiffness (p = 0.009), thickness (p = 0.041), and irregularity (0.007). An improvement in scar elasticity was observed in all subjects after treatment. Conclusions: Skin needling treatment combined with the skin needling technique and post-treatment skincare is an effective method of scar therapy, and the risk of side effects or complications after a series of treatments is low. Full article

Sinus augmentation provides a well-established model for investigating the three-dimensional morphometry and macromolecular dynamics of bone regeneration, particularly when using biphasic calcium phosphate (BCP) graft substitutes. This case series included six biopsies from patients who underwent maxillary sinus augmentation using BCP granules composed of 30% hydroxyapatite (HA) and 70% β-tricalcium phosphate (β-TCP). Bone core biopsies were obtained at healing times of 6 months, 9 months, and 12 months. Histological evaluation yielded qualitative and quantitative insights into new bone distribution, while micro-computed tomography (micro-CT) and Raman microspectroscopy (RMS) were employed to assess the three-dimensional architecture and macromolecular composition of the regenerated bone. Micro-CT analysis revealed progressive maturation of the regenerated bone microstructure over time. At 6 months, the apical regenerated area exhibited a significantly higher mineralized volume fraction (58 ± 5%) compared to the basal native bone (44 ± 11%; p = 0.0170), as well as significantly reduced trabecular spacing (Tb.Sp: 187 ± 70 µm vs. 325 ± 96 µm; p = 0.0155) and degree of anisotropy (DA: 0.37 ± 0.05 vs. 0.73 ± 0.03; p < 0.0001). By 12 months, the mineralized volume fraction in the regenerated area (53 ± 5%) was statistically comparable to basal bone (44 ± 3%; p > 0.05), while Tb.Sp (211 ± 20 µm) and DA (0.23 ± 0.09) remained significantly lower (Tb.Sp: 395 ± 41 µm, p = 0.0041; DA: 0.46 ± 0.04, p = 0.0001), indicating continued structural remodelling and organization. Raman microspectroscopy further revealed dynamic macromolecular changes during healing. Characteristic β-TCP peaks (e.g., 1315, 1380, 1483 cm⁻¹) progressively diminished over time and were completely absent in the regenerated tissue at 12 months, contrasting with their partial presence at 6 months. Simultaneously, increased intensity of collagen-specific bands (e.g., Amide I at 1661 cm⁻¹, Amide III at 1250 cm⁻¹) and carbonate peaks (1065 cm⁻¹) reflected active matrix formation and mineralization. Overall, this case series provides qualitative and quantitative evidence that bone regeneration and integration of BCP granules in sinus augmentation continues beyond 6 months, with ongoing maturation observed up to 12 months post-grafting. Full article

Introduction: Finger injuries are common in pediatric patients and typically heal well with conservative management. However, rare fracture patterns involving significant displacement and physeal injury, such as the one described in this case, require specialized surgical intervention to ensure proper healing and prevent long-term complications. Case Presentation: A 12-year-old left-hand-dominant female presented with pain, swelling, and deformity at the distal interphalangeal (DIP) joint following hyperextension of the left fifth digit. Initial radiographs revealed a volar displaced intra-articular fracture with physis involvement, confirmed by computed tomography (CT) imaging. Conservative management with closed reduction and splinting failed to achieve adequate alignment. Surgical intervention was performed via a dorsal approach, utilizing ORIF with K-wire fixation to restore joint congruity and ensure anatomic alignment. Outcomes: Postoperative follow-up demonstrated satisfactory healing, maintained reduction, and resolution of pain with no complications. The patient regained functional use of the digit with minimal stiffness, and the growth plate remained uninvolved during the recovery period. Discussion: This case underscores the importance of advanced imaging, early referral, and tailored surgical intervention for rare mallet fractures involving volar displacement and physeal injury. ORIF provided reliable stabilization and optimal outcomes in this complex case. Conclusions: Volar displaced Salter–Harris III fractures of the DIP joint are rare and challenging injuries in pediatric patients. This case highlights the role of ORIF in achieving successful outcomes and emphasizes the importance of precise reduction and stabilization to prevent long-term complications. Full article

This study presents a comparison of the mechanical properties of selected high-performance concrete mixtures, some of which contained a proportion of recycled concrete aggregate (15% or 30%) as a substitute for natural aggregate. A reference mixture without recycled concrete aggregate was used for comparison. Initially, the properties of concrete containing both the natural and recycled aggregate types were characterized. This was followed by a series of mechanical tests investigating the compressive strength, flexural strength, and chemical resistance (including resistance to de-icing agents and sulfuric acid). The structural performance of reinforced concrete (RC) beams produced from the mixtures was assessed, and surface morphology was evaluated using a digital microscope. The results confirmed that the use of recycled aggregate had a measurable yet limited effect on the properties of hardened concrete. While the compressive strength tended to decrease slightly with an increasing degree of replacement, the flexural strength remained stable in all the mixtures. The tested mixtures demonstrated adequate resistance to de-icing agents and sulfuric acid. Interestingly, specimens subjected to a frost-resistance test showed improved flexural strength, potentially due to ongoing hydration or microcrack healing. In addition, the RC beams with partial aggregate replacement achieved a higher load-bearing capacity compared to the reference beams. The optical surface evaluation method proved to be a valuable tool, complementary to conventional strength testing. This research enhances the current understanding of recycled aggregate concrete and supports its potential for structural applications. Full article

Background: Since the outbreak of war in Ukraine, countless forcibly displaced individuals facing not only material loss, but also deep psychological distress, have sought refuge across Europe. For those traumatized by war, the absence of a shared language in therapy can hinder healing and exacerbate suffering. While cultural diversity in psychotherapy has gained recognition, the role of native-language communication—especially from a person-centered perspective—remains underexplored. Methods: This narrative review with a thematic analysis examines whether and how psychotherapy in the mother tongue facilitates access to therapy and enhances therapeutic efficacy. Four inter-related clusters emerged: (1) the psychosocial context of trauma and displacement; (2) language as a structural gatekeeper to care (RQ1); (3) native-language therapy as a mechanism of change (RQ2); (4) potential risks such as over-identification or therapeutic mismatch (RQ2). Results: The findings suggest that native-language therapy can support the symbolic integration of trauma and foster the core conditions for healing. The implications for multilingual therapy formats, training in interpreter-mediated settings, and future research designs—including longitudinal, transnational studies—are discussed. Conclusions: In light of the current crises, language is not just a tool for access to therapy, but a pathway to psychological healing. Full article

Grafting serves as a crucial propagation technique for superior Camellia oleifera varieties, where rootstock–scion compatibility significantly determines survival and growth performance. To systematically evaluate grafting compatibility in this economically important woody oil crop, we examined 15 rootstock–scion combinations using ‘Xianglin 210’ as the scion, assessing growth traits and conducting physiological assays (enzymatic activities of SOD and POD and levels of ROS and IAA) at multiple timepoints (0–32 days post-grafting). The results demonstrated that Comb. 4 (Xianglin 27 rootstock) exhibited superior compatibility, characterized by systemic antioxidant activation (peaking at 4–8 DPG), rapid auxin accumulation (4 DPG), and efficient sugar allocation. Transcriptome sequencing and WGCNA analysis identified 3781 differentially expressed genes, with notable enrichment in stress response pathways (Hsp70, DnaJ) and auxin biosynthesis (YUCCA), while also revealing key hub genes (FKBP19) associated with graft-healing efficiency. These findings establish that successful grafting in C. oleifera depends on coordinated rapid redox regulation, auxin-mediated cell proliferation, and metabolic reprogramming, with Comb. 4 emerging as the optimal rootstock choice. The identified molecular markers not only advance our understanding of grafting mechanisms in woody plants but also provide valuable targets for future breeding programs aimed at improving grafting success rates in this important oil crop. Full article

Objectives: Topical lubricants are the fundamental treatment for dry eye disease (DED). However, the molecular mechanisms underlying their efficacy remain unknown. Here, the protective effects of Thealoz^® Duo with 3% trehalose and 0.15% hyaluronic acid are investigated in DED patients by a longitudinal clinical study and subsequent elucidation of the tear proteome and cell signaling changes. Methods: Participants were classified as moderate to severe DED (DRY, n = 35) and healthy (CTRL, n = 23) groups. Specific DED subgroups comprising evaporative (DRYlip) and aqueous-deficient with DRYlip (DRYaqlip) were also classified. Only DED patients received Thealoz^® Duo. All participants were clinically examined before (day 0, T1) and after the application of Thealoz^® Duo at day 28 (T2) and day 56 (T3). Next, 174 individual tear samples from all groups at three time-points were subjected to proteomics analysis. Results: Clinically, Thealoz^® Duo significantly improved the ocular surface disease index at T2 vs. T1 (DRY, p = 1.4 × 10⁻²; DRYlip, p = 9.2 × 10⁻³) and T3 vs. T1 (DRY, p = 2.1 × 10⁻⁵; DRYlip, p = 1.2 × 10⁻⁴), and the tear break-up time at T3 vs. T1 (DRY, p = 3.8 × 10⁻²; DRYlip, p = 1.4 × 10⁻²). Thealoz^® Duo significantly ameliorated expression of inflammatory response proteins (p < 0.05) at T3, which was observed at T1 (DRY, p = 3.4 × 10⁻⁴; DRYlip, p = 7.1 × 10⁻³; DRYaqlip, p = 2.7 × 10⁻⁸). Protein S100-A8 (S100A8), Alpha-1-antitrypsin (SERPINA1), Annexin A1 (ANXA1), and Apolipoprotein A-I (APOA1) were found to be significantly reduced in all the DED subgroups. The application of Thealoz^® Duo showed the therapeutic characteristic of the anti-inflammatory mechanism by promoting the expression of (Metalloproteinase inhibitor 1) TIMP1 in all the DED subgroups. Conclusions: Thealoz^® Duo substantially improved the DED symptoms and restored the functionality of the tear lipid layer to near normal in DRYlip and DRY patients by ameliorating inflammation. Notably, this study unravels the novel mechanistic alterations underpinning the healing effects of Thealoz^® Duo in DED subgroups in a time-dependent manner, which supports the improvement in corresponding clinical attributes. Full article

Mesenchymal stem cells (MSCs), i.e., adult stem cells with immunomodulatory and secretory properties, contribute to tissue growth and regeneration, including healing processes. Some metal nanoparticles (NPs) are known to exhibit antimicrobial activity and may further potentiate tissue healing. We studied the effect of Ag, CuO, and ZnO NPs after in vitro exposure of mouse MSCs at the transcriptional level in order to reveal the potential toxicity as well as modulation of other processes that may modify the activity of MSCs. mRNA–miRNA interactions were further investigated to explore the epigenetic regulation of gene expression. All the tested NPs mediated immunomodulatory effects on MSCs, generation of extracellular vesicles, inhibition of osteogenesis, and enhancement of adipogenesis. Ag NPs exhibited the most pronounced response; they impacted the expression of the highest number of mRNAs, including those encoding interferon-γ-stimulated genes and genes involved in drug metabolism/cytochrome P450 activity, suggesting a response to the potential toxicity of Ag NPs (oxidative stress). Highly interacting MiR-126 was upregulated by all NPs, while downregulation of MiR-92a was observed after the ZnO NP treatment only, and both effects might be associated with the improvement of MSCs’ healing potency. Overall, our results demonstrate positive effects of NPs on MSCs, although increased oxidative stress caused by Ag NPs may limit the therapeutical potential of the combined MSC+NP treatment. Full article

Casein, the main phosphoprotein in milk, has a multifaceted molecular structure and unique physicochemical properties that make it a viable candidate for biomedical use, particularly in wound healing. This review presents a concise analysis of casein’s structural composition that comprises its hydrophobic and hydrophilic nature, calcium phosphate nanocluster structure, and its response to different pH, temperature, and ionic conditions. These characteristics have direct implications for its colloidal stability, including features such as gelation, swelling capacity, and usability as a biomaterial in tissue engineering. This review also discusses industrial derivatives and recent advances in casein biomaterials based on different fabrication types such as hydrogels, electrospun fibres, films, and advanced systems. Furthermore, casein dressings’ functional and biological attributes have shown remarkable exudate absorption, retention of moisture, biocompatibility, and antimicrobial and anti-inflammatory activity in both in vivo and in vitro studies. The gathered evidence highlights casein’s versatile bioactivity and dynamic molecular properties, positioning it as a promising platform to address advanced wound dressing challenges. Full article

Autologous therapies are currently being studied to determine if they can modulate the course of knee osteoarthritis symptoms and/or disease progression. One potential therapeutic target is the polarization of pro-inflammatory M1 macrophages to pro-healing M2 macrophages. The autologous therapy, Autologous Protein Solution (APS), was incubated with donor-matched human peripheral-derived macrophages for 10 days. M1 pro-inflammatory macrophages were determined by the percentage of CD80+ and M2 pro-healing macrophages were determined by CD68+ and CD163+ by epifluorescent microscopy. To determine clinical effectiveness, an APS-specific minimal clinically important improvement (MCII) using an anchor-based method was calculated in a randomized controlled trial of APS (n = 46) and then applied to a real-world registry study (n = 78) to determine the percentage of pain responders. Compared to control media, APS statistically increased the percentage of M2 macrophages and decreased the percentage of M1 macrophages, while platelet-poor plasma had no effect on polarization. In the randomized controlled trial (RCT), the MCII at the 12-month follow-up visit was calculated as 2.0 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale and 7.5 points on the WOMAC function scale. Applying this MCII to the real-world registry data, 62.5% of patients met the MCII with an average of 4.7 ± 2.5 points of improvement in pain. Autologous therapies can influence macrophage polarization and have demonstrated clinical effectiveness in a real-world patient setting. Full article