Search Results (180)

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

The article presents a new AM (Additive Manufacturing) process development, necessary to repair parts made from Aluminum 6061 material, with T6 treatment. The laser Directed Energy Deposition (DED) and Extreme High-Speed Directed Energy Deposition (EHLA) capabilities are evaluated for repairing Al large components. To optimize the process parameters, single-track depositions were analyzed for both laser-powder DED (feed rate of 2 m/min) and EHLA (feed rate 20 m/min) for AlSi10Mg and Al6061 powders. The cross-sections of single tracks revealed the bonding characteristics and provided laser-powder DED, a suitable parameter selection for the repair. Three damage types were identified on the Al component to define the specification of the repair process and to highlight the capabilities of laser-powder DED and EHLA in repairing intricate surface scratches and dents. Our research is based on variation of the powder mass flow and beam power, studying the influence of these parameters on the weld bead geometry and bonding quality. The evaluation criteria include bonding defects, crack formation, porosity, and dilution zone depth. The bidirectional path planning strategy was applied with a fly-in and fly-out path for the hatching adjustment and acceleration distance. Samples were etched for a qualitative microstructure analysis, and the HV hardness was tested. The novelty of the paper is the new process parameters for laser-powder DED and EHLA deposition strategies to repair large Al components (6061 T6), using AlSi10Mg and Al6061 powder. Our experimental research tested the defect-free deposition and the compatibility of AlSi10Mg on the Al6061 substrate. The readers could replicate the method presented in this article to repair by laser-powder DED/EHLA large Al parts and avoid the replacement of Al components with new ones. Full article

The titanium matrix composites (TMCs) fabricated via Directed Energy Deposition (DED) effectively overcome the issue of coarse columnar grains typically observed in additively manufactured titanium alloys. In this study, systematic annealing heat treatments were applied to in situ (TiB + TiC)/Ti-6Al-4V composites to refine the microstructure and tailor mechanical properties. The results reveal that the plate-like α phase in the as-deposited composites gradually transforms into an equiaxed morphology with increasing annealing temperature and holding time. Notably, when the annealing temperature exceeds 1000 °C, significant coarsening of the TiC phase is observed, while the TiB phase remains morphologically stable. Annealing promotes decomposition of acicular martensite and stress relaxation, leading to a reduction in hardness compared to the as-deposited state. However, the reticulated distribution of the TiB and TiC reinforcement phases contributes to enhanced tensile performance. Specifically, the as-deposited composite achieves a tensile strength of 1109 MPa in the XOY direction, representing a 21.6% improvement over the as-cast counterpart, while maintaining a ductility of 2.47%. These findings demonstrate that post-deposition annealing is an effective strategy to regulate microstructure and achieve a desirable balance between strength and ductility in DED-fabricated titanium matrix composites. Full article

Dry eye disease (DED) is a hallmark of primary Sjögren’s disease (SjD) and often resists conventional treatments like lubricant eye drops. Insulin nanoemulsions offer a potential solution by improving drug penetration and retention on the ocular surface. In animal models, insulin has shown benefits in promoting tear secretion and corneal healing. This study evaluated the safety and efficacy of insulin nanoemulsion eye drops (20 IU/mL, three times daily for 30 days) in patients with SjD. Thirty-two patients were randomized in a double-masked design to receive either insulin or placebo drops. Symptoms (assessed by OSDI questionnaire) and objective measures (tear film breakup time, corneal and conjunctival staining, and Schirmer Test) were recorded at baseline, after 4 weeks of treatment, and at a 4-week follow-up. Twenty-three participants completed the study. Both groups showed significant improvement in symptoms and objective signs after treatment (p < 0.05), but no significant differences were found between the insulin and placebo groups. No clinically relevant adverse effects were reported. Insulin nanoemulsion eye drops are safe for SjD patients, but their therapeutic advantage remains unclear. Further studies with larger samples, extended follow-up, and dose adjustments are needed to better understand their potential. Full article

Background/Objectives: Dry eye disease (DED) is a multifactorial condition with complex pathophysiology involving tear film instability, ocular surface inflammation, and nerve dysfunction. This review summarizes current evidence on the different available therapies targeting these mechanisms. Methods: A review of clinical studies evaluating treatment outcomes for therapies targeting aqueous tear deficiency, Meibomian gland dysfunction, ocular surface inflammation, and ocular pain was conducted, with an emphasis on randomized controlled trials and meta-analyses where available. Results: Artificial tears provide symptomatic relief with limited impact on tear film stability. Punctal plugs improve tear retention but show variable efficacy across studies. Treatments targeting MGD—such as lipid-based lubricants, eyelid hygiene, thermal pulsation (LipiFlow, iLux), and intense pulsed light (IPL)—demonstrate improvements in gland function, though outcomes vary. Anti-inflammatory agents including cyclosporine, lifitegrast, and short-term corticosteroids improve ocular surface signs, with mixed symptom relief. Biologic therapies like autologous serum tears and platelet-rich plasma show promise for both signs and symptoms, but data remain inconsistent. Nerve-targeted therapies, including oral neuromodulators (gabapentin, antidepressants), botulinum toxin, and transcutaneous nerve stimulation, have shown potential for managing neuropathic ocular pain, although randomized data are limited. Overall, variability in study designs, patient populations, and outcome measures highlights the need for more rigorous research. Conclusions: Personalized, mechanism-based treatment strategies are essential for optimizing outcomes in DED. Future research should prioritize well-designed, controlled studies to clarify the role of emerging therapies and guide the individualized management of this heterogeneous condition. Full article

The direct energy deposition (DED) metal additive manufacturing process enables rapid deposition and repair, providing an efficient approach to producing durable tool steel components. Here, 5 wt% Cr cold-work tool steel (Caldie) was developed by reducing carbon and chromium to suppress coarse carbide formation and by increasing molybdenum and vanadium to enhance dimensional stability. In this study, Caldie tool steel was fabricated via DED for the first time, and the effects of post-heat treatment on its hierarchical microstructure and mechanical properties were investigated and compared with those of wrought (reference) material. The as-built sample exhibited a mixed microstructure comprising lath martensite, retained austenite, polygonal ferrite, and carbide networks, which transformed into full martensite with fine carbides after heat treatment (DED-HT). The tensile strength of the DED Caldie material increased from 1340 MPa to 1949 MPa after heat treatment, demonstrating superior strength compared to other heat-treated, DED-processed high-carbon tool steels. Compared to DED-HT, the wrought material exhibited finer martensite, a more uniform Bain group distribution, and finer carbides, resulting in higher strength. This study provides insights into the effects of heat treatment on the hierarchical microstructure and mechanical behavior of Caldie tool steel manufactured by DED. Full article

Background/Objectives: Additive manufacturing (AM) enables the production of cementless acetabular cups with porous surfaces that facilitate early osseointegration. Directed energy deposition (DED), a form of AM, allows the direct welding of porous structures onto metal substrates without requiring a vacuum environment, offering advantages over conventional powder bed fusion methods. Despite growing interest in DED, no prospective clinical studies evaluating DED-based acetabular components have been published to date. This study assessed short-term outcomes of a DED-based 3D-printed acetabular cup in total hip arthroplasty (THA). Methods: A total of 120 patients who underwent primary cementless THA using the Corentec Mirabo Z^® acetabular cup were prospectively enrolled. Among them, 124 hips from 100 patients who had completed a minimum of 24 months of follow-up were included in the analysis. Clinical outcomes were assessed using the Harris hip score (HHS), WOMAC, EQ-5D-5L, and pain NRS. Radiographic evaluation included measurements of cup position, osseointegration, and detection of interfacial or polar gaps on CT and plain radiographs. Implant-related complications were also recorded. Results: At a mean follow-up of 34.6 months, the implant survival rate was 99.3%, with one revision due to suspected osseointegration failure. The HHS improved from 56.6 to 91.4 at 24 months, and the NRS decreased from 6.2 to 1.1 (both p < 0.001). Interfacial gaps were observed in 58.1% of cases on CT, though most were <1 mm and not clinically significant. Common postoperative issues included greater trochanteric pain syndrome, squeaking, and iliotibial band tightness, all of which were resolved with conservative treatment. Conclusions: DED-based 3D-printed acetabular cups demonstrated favorable short-term clinical and radiographic outcomes, with high survivorship and reliable early osseointegration in cementless THA. Full article

Dry eye disease (DED) is characterized by tear film instability and oxidative stress-induced epithelial damage. This study was conducted to compare the therapeutic effects of 2% rebamipide (REB) and 3% diquafosol (DQS) on oxidative stress-related apoptotic damage of the ocular surface in DED. Human corneal epithelial cells (HCECs) were exposed to hyperosmotic stress in vitro and treated with REB or DQS. Cell viability and cleaved caspase-3 expression were evaluated using the MTT assay and Western blotting. DED was induced in vivo in C57BL/6 mice using subcutaneous scopolamine injection. Thereafter, the mice were assigned to normal control (NC), dry eye (DE), DQS-treated (DQS), or REB-treated (REB) groups. Clinical evaluations, including measurement of tear film break-up time, corneal smoothness, and the lipid layer, were performed on days 7 and 14. In addition, CD4⁺ IFN-γ⁺ T cells, inflammatory cytokines, reactive oxygen species (ROS), lipid peroxidation markers, and corneal apoptosis were analyzed on day 14. Glycocalyx integrity and goblet cell density were also evaluated. The results indicate that REB improved HCEC survival and suppressed cleaved caspase-3 expression more effectively than DQS (p < 0.05). Both treatments improved clinical outcomes in the murine dry eye model; however, REB showed superior efficacy in reducing ROS levels, lipid peroxidation, and apoptosis, and in preserving corneal glycocalyx integrity and conjunctival goblet cell density. These findings highlight the therapeutic potential and protective effects of REB against oxidative stress-related damage and apoptosis in DED. Full article

The ocular surface is susceptible to a wide spectrum of inflammatory, degenerative, and neurotrophic diseases that can impair vision. The complex pathophysiology and limited therapeutic options associated with these conditions continue to pose significant clinical challenges. Nerve Growth Factor (NGF), a neurotrophin initially recognized for its role in neuronal survival and differentiation, has emerged as a key regulator of ocular surface homeostasis and repair. Beyond its neurotrophic functions, NGF is suggested to influence epithelial proliferation, immune responses, tear secretion, and angiogenesis. Experimental and clinical studies have implicated NGF in both the pathogenesis and potential treatment of various ocular surface diseases, including allergic conjunctivitis, neurotrophic keratopathy (NK), immune-mediated and herpetic keratitis, and dry eye disease (DED), as well as post-surgical corneal wound healing. Notably, recombinant human NGF (rhNGF, cenegermin) has been approved as the first topical biologic therapy for NK. Despite encouraging clinical outcomes, challenges such as high treatment costs, limited long-term data, and potential proangiogenic effects remain. This review consolidates current evidence on the role of NGF in ocular surface health and disease, highlighting its biological mechanisms, clinical applications, and future therapeutic potential. Full article

The rapid progress in additive manufacturing (AM) has unlocked significant possibilities for producing 316/316L stainless steel components, particularly in industries requiring high precision, enhanced mechanical properties, and intricate geometries. However, the widespread adoption of AM—specifically Directed energy deposition (DED), selective laser melting (SLM), and electron beam melting (EBM) remains challenged by inherent process-related defects such as residual stresses, porosity, anisotropy, and surface roughness. This review critically examines these AM techniques, focusing on optimizing key manufacturing parameters, mitigating defects, and implementing effective post-processing treatments. This review highlights how process parameters including laser power, energy density, scanning strategy, layer thickness, build orientation, and preheating conditions directly affect microstructural evolution, mechanical properties, and defect formation in AM-fabricated 316/316L stainless steel. Comparative analysis reveals that SLM excels in achieving refined microstructures and high precision, although it is prone to residual stress accumulation and porosity. DED, on the other hand, offers flexibility for large-scale manufacturing but struggles with surface finish and mechanical property consistency. EBM effectively reduces thermal-induced residual stresses due to its sustained high preheating temperatures (typically maintained between 700 °C and 850 °C throughout the build process) and vacuum environment, but it faces limitations related to resolution, cost-effectiveness, and material applicability. Additionally, this review aligns AM techniques with specific defect reduction strategies, emphasizing the importance of post-processing methods such as heat treatment and hot isostatic pressing (HIP). These approaches enhance structural integrity by refining microstructure, reducing residual stresses, and minimizing porosity. By providing a comprehensive framework that connects AM techniques optimization strategies, this review serves as a valuable resource for academic and industry professionals. It underscores the necessity of process standardization and real-time monitoring to improve the reliability and consistency of AM-produced 316/316L stainless steel components. A targeted approach to these challenges will be crucial in advancing AM technologies to meet the stringent performance requirements of various high-value industrial applications. Full article

Dry eye disease (DED) is a common, multifactorial disorder of the ocular surface. Although DED can affect individuals at any age, its prevalence, clinical manifestations, underlying mechanisms, and optimal management strategies differ considerably across the lifespan. In children, symptoms are frequently associated with atopy and allergic disorders and environmental factors, whereas in young adults, digital device usage and contact lens wear are the predominant contributors. In older adults, systemic diseases and polypharmacy significantly elevate the risk of DED. Across all age groups, tear film instability, decreased tear production, and chronic inflammation are central pathogenic features. Key tear biomarkers, such as pro-inflammatory cytokines, have been widely linked to disease development. Cathepsin S and tumor necrosis factor-alpha have recently been implicated in age-related DED. A nuanced understanding of these age-related differences is crucial for improving diagnostic accuracy and tailoring interventions to specific patient populations. This review synthesizes current evidence on DED across age groups, focusing on prevalence, risk factors, pathophysiology, molecular mechanisms, coexisting conditions, biomarkers, and treatment options. Finally, it highlights critical unmet clinical needs in the management of age-related DED. Full article

This study explores the feasibility of manufacturing martensitic stainless steel turbine blades via a directed energy deposition (DED) process using a powder precursor. Five different blade geometries were fabricated using AISI 431 L martensitic stainless steel deposited onto an AISI 304 L austenitic stainless steel substrate. The produced components were characterized in terms of microstructure, surface roughness, porosity, hardness, and residual stresses in both the as-processed condition and after heat treatment at 260 and 593 °C. Optical and scanning electron microscopy (SEM) analyses revealed a predominantly martensitic microstructure with well-defined grain boundaries. Heat treatment influenced the phase distribution and grain size, but did not have a significant impact on the surface roughness or modulus of elasticity. Tomographic assessments confirmed the absence of aligned or coalesced pores, which are critical sites for crack initiation. Residual stress analysis indicated the presence of compressive stresses in all blade geometries, which were effectively relieved by heat treatment. In addition, salt spray corrosion tests demonstrated that the corrosion resistance of the manufactured blades was similar to that of the base material. These findings suggest that DED is a viable technique for producing and repairing turbine blades, providing structural integrity and mechanical properties suitable for high-performance applications. Full article

Background: The extracellular matrix (ECM), primarily composed of collagen and elastin synthesized by dermal fibroblasts, is critical for mesenchymal tissue integrity. Fibroblast phenotypes vary significantly with the anatomical location and developmental stage. Fetal skin, particularly prior to 14 weeks of gestation, exhibits a simplified structure compared to adult skin, characterized by a thin, loose dermal matrix and a single-layered epithelium. Objectives: This study aimed to characterize and functionally compare homogenous progenitor fetal fibroblast (PFF) populations derived from 14-week-old fetal skin with fibroblasts isolated from adult burn patients. Methods: We evaluated the proliferative capacity, collagen synthesis, and differentiation potential (adipogenesis and osteogenesis) of PFF and adult burn patient fibroblasts. Furthermore, we assessed their ability to support skin regeneration using a de-epidermized dermis (DED) model seeded with both PFF and patient-derived keratinocytes. The stability of PFF characteristics was monitored across multiple passages (P5–P12). Results: PFF demonstrated a 2–4-fold increase in proliferation rate and a 30–50% enhancement in collagen production in vitro compared to adult fibroblasts. Notably, PFF exhibited a consistent lack of adipogenic and osteogenic differentiation, an attribute distinct from adult fibroblasts. In the DED model, PFF, even at a low fibroblast-to-keratinocyte ratio (1:5), effectively facilitated the formation of well-organized skin structures, including rete ridges, surpassing the performance of adult fibroblasts and adipose-derived cells. These properties remained stable over multiple passages. Conclusions: The unique attributes of PFF, likely attributable to the simplified microenvironment (i.e., collagen organization) of developing fetal tissue, positions them as a promising source for cell-based therapies. Their inherent high collagen synthesis capacity is particularly advantageous for wound healing applications. Consequently, PFF represent a consistent and readily available resource for developing “off-the-freezer” cutaneous cell therapies, potentially enabling accelerated and improved treatment of severe burn injuries. Full article

Background/Objectives: Dry eye disease (DED), also known as “keratoconjunctivitis sicca”, is a common chronic ocular surface disease accompanied by inflammation and diminished tear production. Bovine Lactoferrin (BLF), a multi-functional iron-binding glycoprotein found in tears, decreased significantly in patients with DED, used for the treatment of dry eye, conjunctivitis, and ocular inflammation. BLF has limited therapeutic efficacy due to poor ocular bioavailability. Methods: This study developed and optimized a BLF-loaded nanosuspension (BLF-NS) using the Box–Behnken Design (BBD). Optimized BLF-NS was then incorporated with polyvinyl pyrrolidone (PVP) and hydroxypropyl methyl cellulose (HPMC) dissolving microneedles (MNs). The formulations were characterized by Scanning and transmission microscopy, DSC, FTIR, ex vivo studies in corneal tissue from sheep and tested for its antibacterial and antifungal efficacy against Methicillin-Resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, and Aspergillus niger, respectively. Moreover, they were tested for their Benzalkonium chloride (BCL) dry eye in a rabbit model. Results: The optimized nanosuspension showed a vesicle size of (215 ± 0.45) nm, a Z.P (zeta potential) of (−28 ± 0.34) mV, and an Entrapment Efficiency (EE%) of (90 ± 0.66) %. The MNs were fabricated using a ratio of biodegradable polymers, PVP/HPMC. The resulting BLF-NS-MNs exhibited sharp pyramidal geometry with high mechanical strength, ensuring ocular insertion. In vitro release showed 95% lactoferrin release over 24 h, while ex vivo permeation achieved 93% trans-corneal delivery. In vivo, BLF-NS-MNs significantly reduced pro-inflammatory cytokines (TNF-α, IL-6, MMP-9, IL-1β, MCP-1) and upregulated antioxidant and anti-inflammatory genes (PPARA, SOD 1), restoring their levels to near-normal (p < 0.001). Conclusions: The nanosuspension combined with MNs has shown higher ocular tolerance against DED ensured by the Draize and Schirmer Tear Test. Full article

Background/Objectives: Dry eye disease (DED) is a multifactorial inflammatory disease that disrupts the ocular surface, causing tear film instability, epithelial damage, and chronic inflammation. Mesenchymal stem cell-derived exosomes (MSC-exos) are promising therapeutics with immunomodulatory and regenerative properties. This study investigates the therapeutic effects of umbilical cord MSC-derived exosomes (UCMSC-exos) in a severe dry eye model, induced by a surgical resection of the infra-orbital (ILG) and extra-orbital lacrimal gland (ELG) in rats. Methods: Clinical evaluations, including tear volume measurement, slit lamp biomicroscopy, fluorescein staining, and spectral domain optical coherence tomography (SD-OCT), were performed to assess corneal neovascularization, corneal abrasion, and epithelial/stromal thickness. Histopathological analysis, immunohistochemistry, and mRNA gene expression were conducted to evaluate corneal tissue changes and inflammatory marker expression. Results: The results show that the treatment group exhibited significantly reduced corneal neovascularization compared to the control group (p = 0.030). During the first month, the Exo group also had a significantly lower corneal fluorescein staining area (p = 0.032), suggesting accelerated wound healing. SD-OCT analysis revealed that the corneal epithelial thickness in the treatment group was closer to normal levels compared to the control group (p = 0.02 and p = 0.006, respectively). UCMSC-exos treatment also modulated the expression of α-SMA and apoptosis in the cornea. Additionally, the gene expression of inflammatory cytokines (IL-1β and TNF-α) were downregulated. Conclusions: These findings suggest that MSC-exosome therapy offers a novel, cell-free regenerative approach for managing severe DED, modulating inflammatory response. Full article