Hyaluronic acid-mediated epithelial-mesenchymal transition of human lens epithelial cells via CD44 and TGF-β2

ABSTRACT Purpose: The epithelial-mesenchymal transition of human lens epithelial cells plays a role in posterior capsule opacification, a fibrotic process that leads to a common type of cataract. Hyaluronic acid has been implicated in this fibrosis. Studies have investigated the role of transforming growth factor (TGF)-β2 in epithelial-mesenchymal transition. However, the role of TGF-β2 in hyaluronic acid-mediated fibrosis of lens epithelial cell remains unknown. We here examined the role of TGF-β2 in the hyaluronic acid-mediated epithelial-mesenchymal transition of lens epithelial cells. Methods: Cultured human lens epithelial cells (HLEB3) were infected with CD44-siRNA by using the Lipofectamine 3000 transfection reagent. The CCK-8 kit was used to measure cell viability, and the scratch assay was used to determine cell migration. Cell oxidative stress was analyzed in a dichloro-dihydro-fluorescein diacetate assay and by using a flow cytometer. The TGF-β2 level in HLEB3 cells was examined through immunohistochemical staining. The TGF-β2 protein level was determined through western blotting. mRNA expression levels were determined through quantitative real-time polymerase chain reaction. Results: Treatment with hyaluronic acid (1.0 μM, 24 h) increased the epithelial-mesenchymal transition of HLEB3 cells. The increase in TGF-β2 levels corresponded to an increase in CD44 levels in the culture medium. However, blocking the CD44 function significantly reduced the TGF-β2-mediated epithelial-mesenchymal transition response of HLEB3 cells. Conclusions: Our study showed that both CD44 and TGF-β2 are critical contributors to the hyaluronic acid-mediated epithelial-mesenchymal transition of lens epithelial cells, and that TGF-β2 in epithelial-mesenchymal transition is regulated by CD44. These results suggest that CD44 could be used as a target for preventing hyaluronic acid-induced posterior capsule opacification. Our findings suggest that CD44/TGF-β2 is crucial for the hyaluronic acid-induced epithelial-mesenchymal transition of lens epithelial cells.

Assessing the therapeutic role of trehalose and hyaluronic acid: implications for patient care.

OBJECTIVE: This Systematic review aims to assess the efficacy of trehalose and hyaluronic acid in enhancing ocular recovery post-cataract surgery, focusing on their impact on tear film stability, ocular surface integrity, and patient-reported outcomes. METHODS: A comprehensive search was conducted across MEDLINE, PubMed, and Cochrane Library databases to identify randomized controlled trials investigating the efficacy of trehalose, hyaluronic acid, or their combination in post-cataract surgery care. The inclusion criteria focused on peer-reviewed studies in English, detailing outcomes relevant to ocular recovery such as tear film stability, ocular surface integrity, patient-reported discomfort, or visual acuity (VA). The quality of the included studies was assessed using the Cochrane Risk of Bias Tool and synthesized the data qualitatively. RESULTS: Four qualitative investigations met the inclusion criteria. The studies collectively assessed the efficacy of a 3% trehalose and 0.15% hyaluronic acid eye drop solution in reducing postoperative eye symptoms compared to various control solutions. Parameters measured included tear break-up time (TBUT), Fluorescein staining, tear production (Schirmer test), and Ocular Surface Disease Index (OSDI) scores. The results indicated significant improvements in tear film stability and ocular surface health for the treatment groups compared to controls, with a notable decrease in patient-reported discomfort. The study showed an improvement of - 18 (± 14.6) in the treatment group compared to - 7 (± 8.0) in the control group for OSDI. For TBUT, the treatment group improved by 3 (± 1.2) s, whereas the control group improved by 0.3 (± 0.71) s. VA, measured on a scale of 0-100, increased to 17 (± 0.7) in the treatment group compared to 15 (± 1.1) in the control group. CONCLUSIONS: Trehalose and hyaluronic acid may be beneficial in the postoperative period by enhancing tear film stability and ocular surface health. While the results are promising, further research is needed to confirm these findings, understand the mechanisms of action, and explore broader applications.

The Effect of Polynucleotide-Hyaluronic Acid Hydrogel in the Recovery After Mechanical Skin Barrier Disruption.

BACKGROUND: The epidermal barrier acts as a defense against external agents as well as helps to maintain body homeostasis. Polynucleotides (PN), exogenous DNA fragments, promote wound repair through their stimulatory and anti-inflammatory effects. Recent findings indicate a synergistic effect of PN and hyaluronic acid (HA) combinations in regulating inflammation and promoting cell proliferation. This study aims to elucidate the effects of PN and HA on repairing the epidermal barrier following its disruption by tape stripping (TS) in a mouse model. MATERIALS AND METHODS: After disrupting the epidermal barrier using TS, a formulation containing PN (14 mg/mL) and HA (6 mg/mL) was applied. Trans-epidermal water loss (TEWL) was measured at 0, 3, 6, 24, 48, and 72 h. Mice were euthanized after the final application at 72 h, and tissue samples were analyzed for epidermal/dermal thickness, neutrophil infiltration, and filaggrin expression. RESULTS: We observed a significant reduction in TEWL in the PN+HA group compared to that in the control group (20.8 ± 0.5 vs. 43.7 ± 0.5 g/m2h at 72 h, p < 0.05), indicating an improvement in barrier function. Histological evaluation showed decreased epidermal and dermal thickening in the PN+HA group compared to that in the control group (epidermal: 29.4 ± 2.2 vs. 57.9 ± 3.5 µm; dermal: 464.8 ± 25.9 vs. 825.9 ± 44.8 µm, both p < 0.05). Additionally, neutrophil infiltration in the dermis was significantly reduced, and filaggrin protein levels were significantly higher in the PN+HA group compared to those in the control group (4.8 ± 0.4 vs. 21.1 ± 3.3 for neutrophils; 0.84 ± 0.04 vs. 0.42 ± 0.03 for filaggrin, both p < 0.05). CONCLUSION: These results suggest that PN+HA may be an effective therapeutic strategy for repairing skin barrier damage.

Evaluating the Effectiveness of Commercially Available Antiadhesion Tendon Protector Sheets in Tendon Repair Surgery Versus Tendon Repair Surgery Alone: A Preclinical Model Study.

PURPOSE: Adhesion formation is the major complication after tendon repairs that halts functional restoration and causes disability in patients. This study aimed to compare the antiadhesion efficacy of two tendon protector sheets using a previously established turkey flexor tendon model. METHODS: Twenty-four adult Bourbon Red turkeys were randomized into three groups: (1) control, (2) type I collagen-glycosaminoglycan (Collagen-GAG), and (3) hyaluronic acid. In each group, the flexor digitorum profundus tendon of the middle digit was sharply lacerated at the proximal interphalangeal joint level. All operated feet were immobilized until sacrifice 6 weeks after the surgery. After sacrifice, the repaired and normal digits were collected for biomechanical testing, adhesion scores, histological examination, and adhesion-related gene expression analysis. RESULTS: At 42 days after tendon repair, the normalized work of flexion of the repaired digit was the lowest in the Collagen-GAG group. The Collagen-GAG group also had the lowest gross adhesion score, indicating minimal adhesion. The hyaluronic acid group showed lower adhesion scores compared with the control, but the difference was not statistically significant. Microscopically, the Collagen-GAG group had a significantly lower histological adhesion score than the control group. In the Collagen-GAG group, the gene expression levels of WNT3A, WNT5A, and WNT7A were suppressed. CONCLUSIONS: In an avian model of flexor tendon repair, the application of tendon protector sheets reduces peritendinous fibrotic tissue formation histologically. CLINICAL RELEVANCE: There are currently limited commercially available products to reduce postoperative peritendinous adhesions. Further validation is needed to confirm the effectiveness of tendon protector sheets in improving surgical outcomes following tendon repairs.

Injection therapy in professional footballers.

BACKGROUND: Injection therapy offers a minimally invasive approach for symptomatic relief that allows concurrent training, limiting time loss and providing a faster recovery. However, there is a lack of scientific evidence to support it, and there are controversies about its use. The present narrative review aims to present the available scientific literature on injection therapies in professional footballers (PF), highlighting the advantages and disadvantages of its use in the most common injuries. METHODS: The authors searched and reviewed contemporary literature on injection therapies in PF in electronic databases, summarizing them in a narrative review. RESULTS: Injection therapies such as hyaluronic acid and PRP have shown an adequate safety profile that allows their use. Current evidence suggests that hyaluronic acid injections are a valid option for managing symptomatic cartilage injuries. At the same time, PRP injections have failed to prove beneficial in treating muscle injuries and should be avoided until further evidence proves the opposite. Yet, PRP may have potential use in partial ACL injuries, anterior inferior tibiofibular ligament injuries (ankle syndesmosis), and fifth metatarsal fractures and needs further study. Due to the long-term health repercussions, other injection therapies should be preferred over corticosteroids in PF. CONCLUSIONS: There is a paucity of evidence on the use and benefits of injection therapies in PF despite its extensive use among physicians. Viscosupplementation may have a role in improving symptomatic cartilage injuries. In contrast, PRP injection therapy needs further high-quality clinical trials to assess its role in PF sports injuries.

Non-surgical treatment of residual periodontal pockets using sodium hypochlorite/amino acid gel and cross-linked hyaluronic acid-a 9-month pilot randomized controlled clinical trial.

OBJECTIVES: This pilot randomized controlled clinical trial compares the clinical outcome obtained in persistent periodontal pockets during 9-month follow-up of supportive periodontal step 4 treatment performed by either combining subgingival instrumentation with adjunctively used sodium hypochlorite/amino acid gel and crosslinked hyaluronic acid (xHyA) or subgingival instrumentation alone. MATERIALS AND METHODS: Study protocol is registered under NCT06438354 at Clinicaltrials.gov. Patients seeking further therapy after completed step 2 non-surgical periodontal treatment underwent either repeated subgingival instrumentation with adjunctive application of sodium hypochlorite/amino acid gel and crosslinked hyaluronic acid (group A) or repeated subgingival instrumentation alone (group B). One calibrated investigator performed the treatment sequence in both groups accordingly. Subgingival instrumentation of the residual pockets was carried out under local anaesthesia using hand- and ultrasonic instruments, as well as air polishing in both groups. Patients were instructed to continue oral hygiene without any restriction. At 3-month re-evaluation treatment was repeated accordingly at sites with persistent 5 mm probing depth and BoP + . Clinical attachment level (CAL), pocket probing depth (PPD), gingival recession (GR), and bleeding on probing (BoP) were recorded at baseline (T1), 3- (T2) and 9-month (T3) post-op, with CAL as a primary outcome measure. RESULTS: In total 52 patients (20 females and 32 males, mean age 58.4 ± 2.4 years) presenting with 1448 sites which required further periodontal treatment were enrolled. Both groups exhibited homogeneity in terms of age, gender, smoking habit, initial number of sites, and BOP. At 9-month evaluation, PD reduction and CAL gain showed significant differences between the test and control group, favouring the adjunctive treatment. GR tended to exhibit more recovery in the test group compared to the control group. Although BOP frequency effectively reduced in both groups, there was no statistically significant difference between the two groups. CONCLUSION: Within the limits of the study, the present data indicates that, during subgingival instrumentation of persistent pockets, the adjunctive usage of sodium hypochlorite/amino acid gel and xHyA sufficiently improves the clinical outcomes. The continuous improvement of CAL in association with the GR scores observed in group A, indicates that sites subjected to adjunctive treatment may indicate a tendency for a regenerative response to treatment within the 9-month follow-up period.

Turn Your AART into a HIT Using a Complete Range of Aesthetic Injectables: Methodology for Combining Products to Maximise Patient Outcomes.

Purpose: Optimizing outcomes of aesthetic treatments with injectable products usually requires a consideration of the entire face to ensure balance, along with combination treatments that align with the patient's goals. To help injectors, a method of assessing the patient and developing an individualized, holistic treatment plan was developed. This methodology is termed Assessment, Anatomy, Range, and Treatment (AART™) and Holistic Individualized Treatments (HITs™). This article aims to describe and evaluate the novel and systematic AART-HIT™ methodology. Methods: The AART-HIT™ methodology, including its associated diagnostic tool the Facial Assessment Scale (FAS™), were developed to aid injectors in completing a patient assessment in which the entire face is evaluated, the relevant anatomy is considered, the science behind the available range of products is understood, and the treatment plan is individualised for the patient. Specifically, the HITs™ are methodologic tools for practitioners to perform a standardized, full facial assessment and to create an individualized treatment approach to holistically address a patient's aesthetic concerns. The use of this methodology in clinical practice was assessed via a survey, deployed to twenty-eight clinicians. Results: Over 85% of participants agreed that the AART-HIT™ methodology was adequate for their needs. Additionally, 100% of participants agreed that the temporal sequencing of HITs™ and the FAS™ diagnostic tool was useful in clinical practice. Furthermore, over 70% of participants agreed that the anatomical locations identified in each HIT™ were sufficient, while over 80% responded that the HITs™ adequately represented the range of products. Finally, over 85% of participants agreed that the HITs™ covered different ethnic skin types and various patient ages and, over 80% of participants responded that they would not add additional elements to any of the 5 HITs™. Conclusion: The AART-HIT™ methodology, including the FAS™ were comprehensive enough for clinical use in providing a personalised treatment plan for individual patients.

A New TGF-ß Mimetic, XEP™-716 Miniprotein™, Exhibiting Regenerative Properties Objectivized by Instrumental Evaluation.

INTRODUCTION: Skin aging, which results from intrinsic and extrinsic factors, is characterized by a rough, uneven and wrinkled appearance of the skin at the macroscopic level. At the microscopic level, aging shows lowered keratinocyte turnover, flattened dermal-epidermal junction and reduced collagen fiber density; however, use of skin biopsies to evaluate characteristic properties of these microscopic changes is too limiting for panelists and rarely used. The development of non-invasive techniques is an opportunity to be considered for such evaluations. Our objective was to demonstrate the rejuvenating effects of XEP™-716 Miniprotein™ on skin, a miniprotein having TGF-ß beta-like properties, in vitro on normal human fibroblasts and at the clinical level. METHODS: In vitro, the skin rejuvenation properties of XEP™-716 Miniprotein™ were studied by quantification of well-known dermal components such as collagen type I, hyaluronic acid and elastin. At the clinical level, we used a non-invasive technique, the confocal laser scanning microscopy (CLSM) system, which enabled non-invasive morphological characterization of skin structures (stratum corneum thickness, viable epidermis, full epidermis, dermal-epidermal junction, papillae, dermal collagen density) and high-frequency ultrasonography to quantify the dermal density and thickness, which are useful parameters for quantifying rejuvenating effects on skin. Lastly, a cutometer was used to assess the skin's biomechanical properties, mainly firmness and elasticity. This monocentric double-blind, split-face, randomized, placebo-controlled clinical trial compared the active ingredient XEP™-716 Miniprotein™ in a vehicle on one hemiface versus vehicle alone on the other (placebo) and enrolled panelists aged 40 to 60 years old. All measurements were carried out on the malar area before and after 28 and 56 days of twice daily application of a cosmetic cream formulation containing either 2.5% or 5% XEP™-716 Miniprotein™. The skin rejuvenating properties were demonstrated by studying dermo-epidermal junction (DEJ) flattening reduction using the measure of two parameters by CLSM: the DEJ length and number of edged papillae. Dermis rejuvenation was assessed by measuring the collagen fiber perimeters (CLSM), dermal density and dermal thickness (ultrasonography). RESULTS: The in vitro results confirmed the ability of XEP™-716 Miniprotein™ to stimulate the key extracellular macromolecules, namely collagen type I, hyaluronic acid and elastin, at a level comparable to that induced by TGF beta growth factor. The clinical data showed that after 28 and 56 days of topical XEP™-716 Miniprotein™ application, there was a statistically significant increase of DEJ length, number of edged papillae and collagen fiber perimeters. At the same time point, the B-scan images of facial skin showed a statistically significant increase of dermal density and thickness. These results reveal that the DEJ became more undulated and tightly attached to the dermis, while the papillary dermis was densified, both traits being typical characteristic of younger skin. Rejuvenation was also confirmed by an improvement of skin firmness and elasticity. CONCLUSION: The in vitro and clinical results presented in this article show that XEP™-716 Miniprotein™ is a potent ingredient to rejuvenate the DEJ and dermis of mature skin.

SARS-CoV-2 infection induces hyaluronan production in vitro and hyaluronan levels in COVID-19 patients relate to morbidity and long-term lung impairment: a prospective cohort study.

We previously demonstrated that the lungs of deceased COVID-19 patients were filled with a clear hydrogel consisting of hyaluronan (HA). In this translational study, we investigated the role of HA at all stages of COVID-19 disease to map the consequences of elevated HA on morbidity and identify the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced HA production. A reduced alveolar surface area was observed in the lungs of deceased COVID-19 patients compared to healthy controls, as visualized by a 3D rendering of lung morphology using light-sheet fluorescence microscopy. We confirmed the presence of HA in lung biopsies and found large quantities of proinflammatory fragmented HA. The association of systemic HA in blood plasma and disease severity was assessed in patients with mild (WHO Clinical Progression Scale, WHO-CPS, 1-5) and severe COVID-19 (WHO-CPS, 6-9) during the acute and convalescent phases and related to lung function. We found that systemic levels of HA were high during acute COVID-19 disease, remained elevated during convalescence, and were associated with a reduced diffusion capacity. In vitro 3D-lung models, differentiated from primary human bronchial epithelial cells, were used to study the effects of SARS-CoV-2 infection on HA metabolism, and transcriptomic analyses revealed a dysregulation of HA synthases and hyaluronidases, both contributing to increased HA in apical secretions. Furthermore, corticosteroid treatment reduced the inflammation and downregulated HA synthases. Our findings demonstrate that HA plays a role in COVID-19 morbidity and that sustained elevated HA concentrations may contribute to long-term respiratory impairment.IMPORTANCEThis study provides insights into the role of hyaluronan (HA) in the severity and long-term impact of COVID-19 on lung function. Through extensive morphological examination of lung tissues and a multicenter study, we identified that HA levels are significantly elevated in COVID-19 patients, correlating with a reduced lung diffusion capacity during convalescence. Using a 3D-lung model, we further uncovered how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 infection causes a dysregulated HA metabolism, leading to increased HA production. Our findings provide valuable insights into the pathogenesis of SARS-CoV-2 and suggest that targeting HA metabolism could offer new therapeutic avenues for managing COVID-19, particularly to prevent long-term lung impairment. Additionally, HA holds potential as a biomarker for predicting disease severity, which could guide personalized treatment strategies.

Excipient-free nanotransformation of hydrophilic macromolecules using aqueous counter collision for enhanced bioavailability.

The demand for sustainable, eco-friendly biopolymer transdermal delivery systems has increased owing to growing environmental awareness. In this study, we used aqueous counter collision (ACC), a nontoxic nanotransformation method, to convert high- and ultrahigh-molecular-weight hydrophilic macromolecules into their corresponding nanoparticles (NPs). Hyaluronic acid (HA) and crosslinked HA (CLHA) were chosen as the model compounds. Their NPs exhibited particle sizes in the range of 10-100 nm and negative zeta potentials (-20 to -30 mV). Transmission electron microscopy revealed that the NPs were nearly spherical with smooth surfaces. Fourier-transform infrared and proton nuclear magnetic resonance spectroscopy and agarose gel electrophoresis confirmed that the structures and molecular weights of HA and CLHA remained unaltered after ACC. However, the storage and loss moduli of HANPs and CLHANPs were significantly lower than those of HA and CLHA, respectively. Furthermore, the permeation of HANPs and CLHANPs in reconstructed human skin and human cadaver skin was visualized and quantified. HANPs and CLHANPs penetrated deeper into the skin, whereas HA and CLHA were mainly found in the stratum corneum. The total skin absorption (permeation and deposition) of HANPs and CLHANPs was approximately 2.952 and 5.572 times those of HA and CLHA, respectively. Furthermore, HANPs and CLHANPs exhibited resistance to enzyme and free radical degradation. Our findings reveal ACC as a promising, sustainable hydrophilic macromolecule delivery system compared with the chemical hydrolysis of HA.

Development of dual drug loaded-hydrogel scaffold combining microfluidics and coaxial 3D-printing for intravitreal implantation.

Treating diabetic retinopathy (DR) effectively is challenging, aiming for high efficacy with minimal discomfort. While intravitreal injection is the current standard, it has several disadvantages. Implantable systems offer an alternative, less invasive, with long-lasting effects drug delivery system (DDS). The current study aims to develop a soft, minimally invasive, biodegradable, and bioadhesive material-based hydrogel scaffold to prevent common issues with implants. A grid-shaped scaffold was created using coaxial 3D printing (3DP) to extrude two bioinks in a single filament. The scaffold comprises an inner core of curcumin-loaded liposomes (CUR-LPs) that prepared by microfluidics (MFs) embedded in a hydrogel of hydroxyethyl cellulose (HEC), and an outer layer of hyaluronic acid-chitosan matrix with free resveratrol (RSV), delivering two Sirt1 agonists synergistically activating Sirt1 downregulated in DR. Optimized liposomes, prepared via MFs, exhibit suitable properties for retinal delivery in terms of size (<200 nm), polydispersity index (PDI) (<0.3), neutral zeta potential (ZP), encapsulation efficiency (∼97 %), and stability up to 4 weeks. Mechanical studies confirm scaffold elasticity for easy implantation. The release profiles show sustained release of both molecules, with different patterns related to different localization of the molecules. RSV released initially after 30 min with a total release more than 90 % at 336 h. CUR release starts after 24 h with only 4.78 % of CUR released before and gradually released thanks to its internal localization in the scaffold. Liposomes and hydrogels can generate dual drug-loaded 3D structures with sustained release. Microscopic analysis confirms optimal distribution of liposomes within the hydrogel scaffold. The latter resulted compatible in vitro with human retinal microvascular endothelial cells up to 72 h of exposition. The hydrogel scaffold, composed of hyaluronic acid and chitosan, shows promise for prolonged treatment and minimally invasive surgery.

Response to: Correction of Tear Trough Deformity with Minced Orbital Fat Grafts During Transconjunctival Lower Blepharoplasty.

Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Influence of buffer on colloidal stability, microstructure, and rheology of cellulose nanocrystals in hyaluronic acid suspensions.

Hyaluronic acid (HA) is a natural biopolymer found in various human tissues, while cellulose nanocrystals (CNCs) extracted from pulp fibers have unique rheological properties and biocompatibility. Due to the superior biomechanical properties of CNC and HA, a CNC-based HA suspension may be useful in biomedical applications. While buffers are an essential constituent of any suspension used for biomedical applications to maintain the desired pH level, they can significantly affect the properties of the suspension, including colloidal stability, microstructure, and rheological characteristics. To our knowledge, this is the first study analyzing the influence of buffer solutions on the suspension characteristics of HA/CNC systems, integrating both theoretical and experimental approaches. The results revealed an alignment between predictions of the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory and results from experiments characterizing a buffer-specific trend in colloidal stability. Suspensions with a higher energy barrier showed higher colloidal stability, with a lower tendency for phase separation and agglomerate formations. The microstructural analysis of CNC tactoids in the suspension revealed the existence of the hedgehog defect when dispersed in different buffer solutions. The defect is predicted to be caused by the pH-dependent protonation and deprotonation of HA. Furthermore, steady shear viscometry showed a microstructural-dependent shear viscosity trend, which, in turn, depends on the buffer solution. The study provides novel insights into the microstructural and bulk properties of HA and CNC suspensions in various buffer solutions. The results highlight the importance of solvent choice in tailoring the properties of the suspension for specific biomedical applications. These findings may be helpful in formulating HA and CNC suspensions for different biomedical applications, including drug delivery systems and viscosupplement injections.

Magnetically induced anisotropic structure in an injectable hydrogel for skeletal muscle regeneration.

Skeletal muscle integrity and its intrinsic aligned architecture are crucial for locomotion, postural support, and respiration functions, impacting overall quality of life. However, volumetric muscle loss (VML) can exceed intrinsic regenerative potential, leading to fibrosis and impairments. Autologous muscle grafting, the current gold standard, is constrained by tissue availability and success rates. Therefore, innovative strategies like cell-based therapies and scaffold-based approaches are needed. Our minimally invasive approach involves a tunable injectable hydrogel capable of achieving an aligned architecture post-injection via a low-intensity static magnetic field (SMF). Our hydrogel formulation uses gellan gum as the backbone polymer, enriched with essential extracellular matrix components such as hyaluronic acid and collagen type I, enhancing bio-functionality. To achieve an aligned architectural biomimicry, collagen type I is coupled with iron oxide magnetic nanoparticles, creating magnetic collagen bundles (MagC) that align within the hydrogel when exposed to a SMF. An extensive study was performed to characterize MagC and assess the hydrogel's stability, mechanical properties, and biological response in vitro and in vivo. The proposed system, fully composed of natural polymers, exhibited mechanical properties similar to human skeletal muscle and demonstrated effective biological performances, supporting its potential as a safe and patient-friendly treatment for VML.

Viscoelasticity of Hyaluronic Acid Hydrogels Regulates Human Pluripotent Stem Cell-derived Spinal Cord Organoid Patterning and Vascularization.

Recently, it has been recognized that natural extracellular matrix (ECM) and tissues are viscoelastic, while only elastic properties have been investigated in the past. How the viscoelastic matrix regulates stem cell patterning is critical for cell-ECM mechano-transduction. Here, this study fabricated different methacrylated hyaluronic acid (HA) hydrogels using covalent cross-linking, consisting of two gels with similar elasticity (stiffness) but different viscoelasticity, and two gels with similar viscoelasticity but different elasticity (stiffness). Meanwhile, a second set of dual network hydrogels are fabricated containing both covalent and coordinated cross-links. Human spinal cord organoid (hSCO) patterning in HA hydrogels and co-culture with isogenic human blood vessel organoids (hBVOs) are investigated. The viscoelastic hydrogels promote regional hSCO patterning compared to the elastic hydrogels. More viscoelastic hydrogels can promote dorsal marker expression, while softer hydrogels result in higher interneuron marker expression. The effects of viscoelastic properties of the hydrogels become more dominant than the stiffness effects in the co-culture of hSCOs and hBVOs. In addition, more viscoelastic hydrogels can lead to more Yes-associated protein nuclear translocation, revealing the mechanism of cell-ECM mechano-transduction. This research provides insights into viscoelastic behaviors of the hydrogels during human organoid patterning with ECM-mimicking in vitro microenvironments for applications in regenerative medicine.

Clinical validation of preoperative serum markers for liver fibrosis in living donor liver transplantation recipients.

PURPOSE: To validate the reliability of fibrosis markers as predictors of graft survival in living donor liver transplantation (LDLT) recipients. METHODS: We reviewed data retrospectively, from 163 patients who underwent adult LDLT with preoperative measurements of type IV collagen (CIV), Mac-2 binding protein glycosylation isomer (M2BPGi), and hyaluronic acid (HA). Patients were divided into high and low groups for each biomarker, based on optimal cutoff values, and graft loss within 6 months was evaluated in each group. RESULTS: The high CIV level group showed significantly lower 6-month graft survival rates and significantly higher rates of postoperative sepsis and sepsis from pneumonia. However, the groups with high and low M2BPGi levels and those with high and low HA levels did not show significant differences in 6-month graft survival rates or rates of postoperative sepsis. Multivariate analysis revealed that a CIV level ≥ 590 was a significant predictor of graft loss within 6 months, postoperative sepsis, and sepsis from pneumonia. CONCLUSION: Unlike other fibrosis markers, preoperative CIV levels can predict graft survival, postoperative sepsis, and sepsis from pneumonia after LDLT.

A Practical Guide to Injection Therapy in Hand Tendinopathies: A Systematic Review of Randomized Controlled Trials.

Hand tendinopathies represent a pathological condition associated with significant disability. However, due to this high heterogeneity of the treatments and their efficacy, there is still a lack of consensus on the infiltrative therapy of the hand. This systematic review aimed to investigate the efficacy of injection techniques in the treatment of pain related to the main hand tendinopathies. We searched online medical databases (PubMed, Pedro, Cochrane Library, Scopus, and WoS). Only RCTs published in the last 10 years (up to 5 August 2024), written in English, and related to infiltrative treatment in wrist and hand tendinopathies were evaluated. The risk of bias in RCTs was assessed with Version 2 of the Cochrane Risk of Bias tool for randomized trials (RoB 2). Out of 641 articles identified, 23 were included in the final synthesis: 14 RCTs on trigger finger, and 9 RCTs on de Quervain's tenosynovitis. The present systematic review showed that infiltrative therapy of trigger finger and de Quervain's tenosynovitis constitutes a fundamental element in the treatment of these pathological conditions, in terms of pain reduction and improvement in the functionality of the hand.

Polycaprolactone Hybrid Scaffold Loaded With N,O-Carboxymethyl Chitosan/Aldehyde Hyaluronic Acid/Hydroxyapatite Hydrogel for Bone Regeneration.

Hydrogels have emerged as potential materials for bone grafting, thanks to their biocompatibility, biodegradation, and flexibility in filling irregular bone defects. In this study, we fabricated a novel NAH hydrogel system, composed of N,O-carboxymethyl chitosan (NOCC), aldehyde hyaluronic acid (AHA), and hydroxyapatite (HAp). To improve the mechanical strength of the fabricated hydrogel, a porous polycaprolactone (PCL) matrix was synthesized and used as a three-dimensional (3D) support template for NAH hydrogel loading, forming a novel PCL/NAH hybrid scaffold. A mixture of monosodium glutamate (M) and sucrose (S) at varied weight ratios (5M:5S, 7M:3S, and 9M:1S) was used for the fabrication of 3D PCL matrices. The morphology, interconnectivity, and water resistance of the porous PCL scaffolds were investigated for optimal hydrogel loading efficiency. The results demonstrated that PCL scaffolds with porogen ratios of 7M:3S and 9M:1S possessed better interconnectivity than 5M:5S ratio. The compressive strength of the PCL/NAH hybrid scaffolds with 9M:1S (561.6 ± 6.1 kPa) and 7M:3S (623.8 ± 6.8 kPa) ratios are similar to cancellous bone and all hybrid scaffolds were biocompatible. Rabbit models with tibial defects were implanted with the PCL/NAH scaffolds to assess the wound healing capability. The results suggest that the PCL/NAH hybrid scaffolds, specifically those with porogen ratio of 7M:3S, exhibit promising bone healing effects.

Overview of 37 Tear Substitutes in Europe Based on Various Physicochemical Parameters.

INTRODUCTION: Dry eye disease (DED) is one of the most prevalent eye conditions worldwide, with artificial tears serving as a primary treatment option. Despite their wide availability on the European market, there is a lack of established classifications based on their physicochemical properties. The aim of our study was therefore (i) to develop an analytical method that measures the concentration and the molecular weight (MW) of the hyaluronic acid (HA) in commercialized products, and (ii) to propose an overview based on their various physicochemical parameters. METHODS: The intrinsic viscosity and MW of the HA, as well as osmolarity, pH, rheological profile, and viscosity, were measured or determined. A specific method was developed to measure the average intrinsic viscosity and HA content using a liquid size-exclusion chromatography system. The MW was determined using the Mark-Houwink equation. RESULTS: Thirty-seven products commercialized in Europe were analyzed, with 21 of them containing HA. The HA MW was lowest (300 kDa) for Thealose®, Thealoz Duo® Gel, and Hyabak®, and highest (1300 kDa) for Vismed® Multi, Vismed® Gel, and Neovis® Gel. The pH values varied between 5.94 for Treovis® and 8.06 for Systane® Ultra. Osmolarity ranged between 148 mOsm/L and 325 mOsm/L for Neovis® and Treovis®, respectively. Viscosity was highly variable, ranging from 0.38 mPas·s for Hylolipid® to 337.47 mPas·s for Thealoz® Duo Gel. Finally, rheological profile analysis revealed different shear-thinning behaviors. CONCLUSION: While the perfect eye drop does not exist, a multitude of options are available to choose from. This study improves our understanding of the major tear substitutes available on the European market based on several physicochemical properties. A better understanding and awareness of these parameters is crucial in order to offer the best treatment for patients with DED.