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Introduction: KOA, a chronic degenerative joint disease, is commonly treated with intra-articular HA and PRP, used alone or in combination. However, the efficacy and safety of combination therapy (PRP + HA) remain unclear. Aim: The aim of this systematic review and meta-analysis is to assess the clinical effectiveness and safety profile of PRP + HA versus PRP monotherapy for KOA. Material and methods: A systematic search was conducted using four electronic databases (PubMed, EMBASE, Scopus, and Cochrane Library) to select publications published in peer-reviewed journals. The mean difference (MD) and risk ratio (RR) was calculated, along with their 95% confidence intervals. We assessed heterogeneity using Cochrane Q and I2statistics and the appropriate p-value. The analysis used RevMan 5.4. GRADE system was used for evidence assessment for each outcome parameter. Results: This meta-analysis of 11 RCTs (n = 1023 KOA patients) revealed that PRP + HA has substantial effectiveness than PRP alone in reducing OMAC total scores [MD -1.77 (95% CI -2.20 to − 1.34); I2 = 10%, and p < 0.001], VAS scores [MD -4.27 (95% CI -4.96 to − 3.58); I2 = 13%, and p < 0.001], and Lequesne index score [MD -5.48 (95% CI -6.56 to − 4.40); I2 = 16%, and p < 0.001], while increasing IKDC scores [MD -2.10 (95% CI -3.70 to − 0.50); I2 = 9%, and p = 0.01], with low risk of adverse events [RR 0.41 (95% CI 0.35 to 0.48); I2 = 12%, and p < 0.001]. Conclusion: This meta-analysis reveals that, for patients with KOA, PRP + HA therapy is safe and yields better outcomes in pain relief and functional improvement compared to PRP monotherapy. [ABSTRACT FROM AUTHOR]

This study presents the development of thiol–maleimide/thiol–thiol double self-crosslinking hyaluronic acid-based (dscHA) hydrogels for use as dermal fillers. Hyaluronic acid with varying degrees of maleimide substitution (10%, 20%, and 30%) was synthesized and characterized, and dscHA hydrogels were fabricated using two molecular weights of four-arm polyethylene glycol (PEG10K/20K)–thiol as crosslinkers. The six resulting dscHA hydrogels demonstrated solid-like behavior with distinct physical and rheological properties. SEM analysis revealed a decrease in porosity with higher crosslinker MW and maleimide substitution. The swelling ratios of the six hydrogels reached equilibrium at approximately 1 h and ranged from 20% to 35%, indicating relatively low swelling. Degradation rates decreased with increasing maleimide substitution, while crosslinker MW had little effect. Higher maleimide substitution also required greater injection force. Elastic modulus (G′) in the linear viscoelastic region increased with maleimide substitution and crosslinker MW, indicating enhanced firmness. All hydrogels displayed similar creep-recovery behavior, showing instantaneous deformation under constant stress. Alternate-step strain tests indicated that all six dscHA hydrogels could maintain elasticity, allowing them to integrate with the surrounding tissue via viscous deformation caused by the stress exerted by changes in facial expression. Ultimately, the connection between the clinical performance of the obtained dscHA hydrogels used as dermal filler and their physicochemical and rheological properties was discussed to aid clinicians in the selection of the most appropriate hydrogel for facial rejuvenation. While these findings are promising, further studies are required to assess irritation, toxicity, and in vivo degradation before clinical use. Overall, it was concluded that all six dscHA hydrogels show promise as dermal fillers for various facial regions. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Chin augmentation by hyaluronic acid filler injection rarely causes abnormal bone resorption in the mentum. Thus, when taking the history of a patient with jaw deformity, it is imperative to check the history of treatment of the mentum. Hyaluronic acid (HA) filler injection is a common procedure in nonsurgical cosmetic chin augmentation. Due to its high biocompatibility and simple injection technique, HA filler injection is a popular procedure. However, adverse events such as allergic reactions and foreign body reactions have been reported in some cases. In this study, we report a case of skeletal Class II jaw deformity in which bone resorption was observed in the mentum after HA filler injection. The purpose of this study is to discuss the indications for HA filler injection in skeletal Class II cases that require orthognathic surgery. The patient was a 30‐year‐old woman. To improve retrusion of the mentum, she has been receiving HA filler injections in the mentum three times every 6 months in the cosmetic surgery clinic since 2015. However, the retrusion of the mentum did not improve, which prompted here to visit the orthodontic clinic. Radiographs and CT revealed bowl‐shaped bone resorption surrounding the foreign bodies in the mentum. She was diagnosed with maxillary protrusion, vertical maxillary excess, mandibular retrusion, and bilateral condylar resorption. Bimaxillary orthognathic surgery (BOGS) and removal of residual HA fillers were planned after completion of the preoperative orthodontic treatment. After BOGS, the foreign bodies were completely removed, and the resorption cavities were filled with excess bone segments from the surgical sites. X‐ray photoelectron spectroscopy analysis of the foreign bodies suggested the presence of HA. One year after the BOGS, no progression of condylar resorption occurred, and bone healing at the mentum had a good prognosis. Therefore, the patient underwent reduction and advancement genioplasty. She was satisfied with her facial profile and occlusal function. Unexpected bone resorption in the mentum caused by HA filler injection is often discovered incidentally. Although, patients may feel hesitant to confess their history of treatment of the mentum, it is important to ensure that they are carefully interviewed. [ABSTRACT FROM AUTHOR]

Abstract Background Premature ejaculation (PE) is the most common self-reported sexual disorder among men, affecting up to 20% of the population. Recently, the injection of hyaluronic acid (HA) as a bulking agent into the glans of the penis was proposed as a promising modality for PE. It is believed to act as a barrier between the skin and nerve terminals, leading to decreased sensation of the glans penis, indirectly improving the outcome of PE. This scoping review aims to provide an overview of the techniques, efficacy, and safety of the injection of HA for PE derived from the existing scientific literature. Main body A literature search was conducted using PubMed, Scopus, and Web of Science databases and the keywords “hyaluronic acid” and “premature ejaculation.” Original articles were selected for further evaluation, while both case reports and case series were excluded. After the screening, ten relevant studies were included, with two main methods of injection, the Fanning technique and multiple puncture techniques, which were applied in the previous studies. All studies showed compelling improvements in both the intravaginal ejaculation latency time (IELT) and patients’ satisfaction. IELT increments may reach up to 8.54-fold even in the first month and sustain significantly up to 12 months. The complications reported, such as bleeding, pain, swelling, and discoloration, were mild and self-limited, which then resolved between 2 weeks and 1 month. No serious adverse events were reported. Conclusions With adequate surgical training and proper patient selection, penile augmentation using hyaluronic acid is a safe and effective method in the management of premature ejaculation.

Lung diseases are one of the leading causes of global mortality. Advances in induced pluripotent stem cell (iPSC) differentiation have enabled the creation of bronchiolar and alveolar lung organoids, advancing research on lung conditions. Traditional Matrigel encapsulation, reliant on the spontaneous assembly and propagation of cells with limited external intervention, often results in variability and low reproducibility. The absence of hyaluronic acid (HA) in Matrigel, a key lung extracellular matrix component, limits bronchiolar and alveolar cell differentiation, reducing the efficacy and reproducibility of iPSC‐derived organoid generation. To address this, a novel hybrid hydrogel combining HA and 23% Matrigel, inspired by the natural lung environment, is developed. This hydrogel offers improved biochemical support and viscoelastic properties, significantly accelerating organoid development. Within eight days, the hydrogel produces uniformly sized organoids containing both bronchiolar and alveolar epithelial cells. Increased levels of active mechanosensors and transducers, including PIEZO1, Integrin, and Myosin, suggest that the hydrogel's altered viscoelasticity triggers a mechanotransduction cascade. This bioinspired hydrogel provides a robust, fast model for biomedical research, facilitating rapid drug screening, respiratory disease treatment studies, and surfactant trafficking investigations. Furthermore, it enables the exploration of underlying biomechanical mechanisms to enhance the controllability of organoid generation and maturation. [ABSTRACT FROM AUTHOR]

Over the last few decades, scientists have recognized the critical role that various components of the extracellular matrix (ECM) play in maintaining homeostatic immunity. Besides, dysregulation in the synthesis or degradation levels of these components directly impacts the mechanisms of immune response during tissue injury caused by tumor processes or the regeneration of the tissue itself in the event of damage. ECM is a complex network of protein compounds, proteoglycans and glycosaminoglycans (GAGs). Hyaluronic acid (HA) is one of the major GAGs of this network, whose metabolism is strictly physiologically regulated and quickly altered in injury processes, affecting the behavior of different cells, from stem cells to differentiated immune cells. In this revision we discuss how the native or chemically modified HA interacts with its specific receptors and modulates intra and intercellular communication of immune cells, focusing on cancer and tissue regeneration conditions. [ABSTRACT FROM AUTHOR]

As one major problem after tendon rupture repair, surgeons are confronted with fibrotic adhesion formation of the healing tendon to the surrounding tissue. Although early active motion is recommended during rehabilitation, adhesions may lead to joint stiffness and a restricted range of motion. One viable option to counteract adhesion formation is to add a thin elastic tube that is placed over the conventionally sutured repair site. Such a tube reduces adhesion formation because it acts as a physical barrier. Additionally, such barriers can be optimized by adding a biolubricant.We here present adhesion data of rabbit Achilles tendons that were fully transsected, repaired with a 4-strand suture and received a) no implant; b) an electrospun DegraPol tube and c) a bi-layered tube with one electrospun DegraPol layer and one high molecular weight hyaluronic acid (HA)/polyethylene oxide (PEO) electrospun layer. Based on Picrosirius red stained tendon cross-sections three weeks post-operation, the percentage of adhesion data is presented. Moreover, mechanical data of the implant materials are presented as a further dataset, with the following readouts: fracture strain [%], ultimate tensile stress [MPa] and Young's modulus [MPa]. They are presented in axial and transverse stretching directions, respectively.The adhesion data can be reused for comparison to other implant materials, drugs or anti-adhesive strategies that are applied in similar pre-clinical models like the rabbit Achilles tendon model. The mechanical data of the implant materials offer the possibility to compare electrospun meshes based on other polymers to the materials used here or for computational models of such materials.

Purpose of Review: The aim of this review, is to present an updated revision of topical management of SAC and PAC, based on the available scientific evidence and focused on the impact of ophthalmic solution formulations on eye surface. Recent Findings: Physicians treating ocular allergy should be aware of tear film and tear film disruption in SAC and PAC, and how eye drop composition and additives affect the physiology of the allergic eye. Summary: Seasonal and perennial allergic conjunctivitis (SAC and PAC) are the most frequent causes of ocular allergy (OA), and both conditions are underdiagnosed and undertreated. SAC and PAC are immunoglobulin E (IgE)-mediated hypersensitivity reactions. The additional tear film disruption caused by the release of inflammatory mediators increases and exacerbates the impact of signs and symptoms and may trigger damage of the ocular surface. Comorbidities are frequent, and dry eye disease in particular must be considered. Clinical guidelines for the management of SAC and PAC recommend topical therapy with antihistamines, mast cells stabilizers or dualaction agents as first-line treatment, but care should be taken, as many medications contain other compounds that may contribute to ocular surface damage. [ABSTRACT FROM AUTHOR]

A comprehensive overview of CD44 (CD44 Molecule (Indian Blood Group)), a cell surface glycoprotein, and its interaction with hyaluronic acid (HA) in drug resistance mechanisms across various types of cancer is provided, where CRISPR/Cas9 gene editing was utilized to silence CD44 expression and examine its impact on cancer cell behavior, migration, invasion, proliferation, and drug sensitivity. The significance of the HA-CD44 axis in tumor microenvironment (TME) delivery and its implications in specific cancer types, the influence of CD44 variants and the KHDRBS3 (KH RNA Binding Domain Containing, Signal Transduction Associated 3) gene on cancer progression and drug resistance, and the potential of targeting HA-mediated pathways using CRISPR/Cas9 gene editing technology to overcome drug resistance in cancer were also highlighted. [ABSTRACT FROM AUTHOR]

Abstract Lung diseases are one of the leading causes of global mortality. Advances in induced pluripotent stem cell (iPSC) differentiation have enabled the creation of bronchiolar and alveolar lung organoids, advancing research on lung conditions. Traditional Matrigel encapsulation, reliant on the spontaneous assembly and propagation of cells with limited external intervention, often results in variability and low reproducibility. The absence of hyaluronic acid (HA) in Matrigel, a key lung extracellular matrix component, limits bronchiolar and alveolar cell differentiation, reducing the efficacy and reproducibility of iPSC‐derived organoid generation. To address this, a novel hybrid hydrogel combining HA and 23% Matrigel, inspired by the natural lung environment, is developed. This hydrogel offers improved biochemical support and viscoelastic properties, significantly accelerating organoid development. Within eight days, the hydrogel produces uniformly sized organoids containing both bronchiolar and alveolar epithelial cells. Increased levels of active mechanosensors and transducers, including PIEZO1, Integrin, and Myosin, suggest that the hydrogel's altered viscoelasticity triggers a mechanotransduction cascade. This bioinspired hydrogel provides a robust, fast model for biomedical research, facilitating rapid drug screening, respiratory disease treatment studies, and surfactant trafficking investigations. Furthermore, it enables the exploration of underlying biomechanical mechanisms to enhance the controllability of organoid generation and maturation.

Through the formation of covalent connections with hyaluronic acid (HA), the inter-α-trypsin inhibitor (IαI) family collaborates to preserve the stability of the extracellular matrix (ECM). The five distinct homologous heavy chains (ITIH) and one type of light chain make up the IαI family. ITIH alone or in combination with bikunin (BK) has been proven to have important impacts in a number of earlier investigations. This implies that BK and ITIH might be crucial to both physiological and pathological processes. The functions of BK and ITIH in various pathophysiological processes are discussed independently in this paper. In the meanwhile, this study offers suggestions for further research on the roles of BK and ITIH in the course of disease and summarizes the plausible mechanisms of the previous studies.

Abstract Background With the aging of human society, more and more elderly patients have to undergo surgery and anesthesia. Clinical observations have indicated from time to time that spinal anesthesia in the elderly appears to last longer than in young people, although there is limited research in this area and the mechanism is unclear at present time. This research work is expected to help understand the decline of local anesthetic metabolism in cerebrospinal fluid of elderly patients so as to help them with precise anesthesia and rapid rehabilitation. Methods Twenty patients with spinal anesthesia in orthopedic lower limb surgery were selected to study the rate of drug metabolism in cerebrospinal fluid in two age groups, i.e.,18–30 years old and 75–90 years old. Ropivacaine in peripheral blood is used as a probe to reflect the speed of drug metabolism in cerebrospinal fluid. The contents of total Aβ protein and hyaluronic acid in the cerebrospinal fluid were investigated as well. Results The equivalent dose of ropivacaine anesthetizes the elderly group for a longer time. The metabolism rate of ropivacaine in an elderly patient was slower than that of a young patient. No significant difference in total Aβ protein between the two groups was observed while hyaluronic acid in the elderly group was significantly higher than that in the young group. Conclusions This study shows that the dose of ropivacaine should be reduced when used for anesthesia in elderly patients. The cumulation of ropivacaine and HA appears to imitate the degeneration of central lymphatic circulation metabolism in elderly people.

Abstract Remarkable resistance of bacterial biofilms to high doses of antimicrobials and antibiotics is one of their main challenges. Encapsulation of proteolytic enzymes is one of the suggested strategies to tackle this problem. In this regard, the antibacterial and anti-biofilm activity of biocompatible hyaluronic acid- Lysine nanogels containing serratiopeptidase (SRP-loaded HA-Lys nanogel) was assessed against P. aeruginosa and S. aureus strains. SRP-loaded HA-Lys nanogel was prepared using dropping method and optimized by Box-Behnken experimental design. These formulations were studied for physical characterization, release profile, stability, bioactivity, and anti-biofilm effects. The particle size, polydispersity index (PDI), and surface charge were measured by Zetasizer Nano ZS. The average particle size and zeta potential of the optimum sample were 156 nm and -14.1 mV, respectively. SRP release showed an initial burst followed by sustained release and the highest release was around 77%. Enzyme biological activity data revealed the higher efficiency of free SRP compared to SRP-loaded HA-Lys nanogel. The time-kill assay showed that both forms of SRP-loaded HA-Lys nanogel and blank HA-Lys nanogel showed significant antimicrobial activity against examined bacteria in comparison to the free enzyme. The obtained results demonstrated improved anti-biofilm efficacy and down regulation of tested biofilm genes for both SRP-loaded HA-Lys nanogel 100% and blank HA-Lys nanogel 100% compared to SRP 100%.

This study presents the development of thiol–maleimide/thiol–thiol double self-crosslinking hyaluronic acid-based (dscHA) hydrogels for use as dermal fillers. Hyaluronic acid with varying degrees of maleimide substitution (10%, 20%, and 30%) was synthesized and characterized, and dscHA hydrogels were fabricated using two molecular weights of four-arm polyethylene glycol (PEG10K/20K)–thiol as crosslinkers. The six resulting dscHA hydrogels demonstrated solid-like behavior with distinct physical and rheological properties. SEM analysis revealed a decrease in porosity with higher crosslinker MW and maleimide substitution. The swelling ratios of the six hydrogels reached equilibrium at approximately 1 h and ranged from 20% to 35%, indicating relatively low swelling. Degradation rates decreased with increasing maleimide substitution, while crosslinker MW had little effect. Higher maleimide substitution also required greater injection force. Elastic modulus (G′) in the linear viscoelastic region increased with maleimide substitution and crosslinker MW, indicating enhanced firmness. All hydrogels displayed similar creep-recovery behavior, showing instantaneous deformation under constant stress. Alternate-step strain tests indicated that all six dscHA hydrogels could maintain elasticity, allowing them to integrate with the surrounding tissue via viscous deformation caused by the stress exerted by changes in facial expression. Ultimately, the connection between the clinical performance of the obtained dscHA hydrogels used as dermal filler and their physicochemical and rheological properties was discussed to aid clinicians in the selection of the most appropriate hydrogel for facial rejuvenation. While these findings are promising, further studies are required to assess irritation, toxicity, and in vivo degradation before clinical use. Overall, it was concluded that all six dscHA hydrogels show promise as dermal fillers for various facial regions.

Background: With the aging of human society, more and more elderly patients have to undergo surgery and anesthesia. Clinical observations have indicated from time to time that spinal anesthesia in the elderly appears to last longer than in young people, although there is limited research in this area and the mechanism is unclear at present time. This research work is expected to help understand the decline of local anesthetic metabolism in cerebrospinal fluid of elderly patients so as to help them with precise anesthesia and rapid rehabilitation. Methods: Twenty patients with spinal anesthesia in orthopedic lower limb surgery were selected to study the rate of drug metabolism in cerebrospinal fluid in two age groups, i.e.,18–30 years old and 75–90 years old. Ropivacaine in peripheral blood is used as a probe to reflect the speed of drug metabolism in cerebrospinal fluid. The contents of total Aβ protein and hyaluronic acid in the cerebrospinal fluid were investigated as well. Results: The equivalent dose of ropivacaine anesthetizes the elderly group for a longer time. The metabolism rate of ropivacaine in an elderly patient was slower than that of a young patient. No significant difference in total Aβ protein between the two groups was observed while hyaluronic acid in the elderly group was significantly higher than that in the young group. Conclusions: This study shows that the dose of ropivacaine should be reduced when used for anesthesia in elderly patients. The cumulation of ropivacaine and HA appears to imitate the degeneration of central lymphatic circulation metabolism in elderly people. [ABSTRACT FROM AUTHOR]

Fluorescent graphitic carbon nitride (g-C3N4) doped with various heteroatoms, such as B, P, and S, named Bg-C3N4, Pg-C3N4, and Sg-C3N4, were synthesized with variable band-gap values as diagnostic materials. Furthermore, they were embedded within hyaluronic acid (HA) microgels as g-C3N4@HA microgel composites. The g-C3N4@HA microgels had a 0.5–20 μm size range that is suitable for intravenous administration. Bare g-C3N4 showed excellent fluorescence ability with 360 nm excitation wavelength and 410–460 emission wavelengths for possible cell imaging application of g-C3N4@HA microgel composites as diagnostic agents. The g-C3N4@HA-based microgels were non-hemolytic, and no clotting effects on blood cells or cell toxicity on fibroblasts were observed at 1000 μg/mL concentration. In addition, approximately 70% cell viability for SKMEL-30 melanoma cells was seen with Sg-C3N4 and its HA microgel composites. The prepared g-C3N4@HA and Sg-C3N4@HA microgels were used in cell imaging because of their excellent penetration capability for healthy fibroblasts. Furthermore, g-C3N4-based materials did not interact with malignant cells, but their HA microgel composites had significant penetration capability linked to the binding function of HA with the cancerous cells. Flow cytometry analysis revealed that g-C3N4 and g-C3N4@HA microgel composites did not interfere with the viability of healthy fibroblast cells and provided fluorescence imaging without any staining while significantly decreasing the viability of cancerous cells. Overall, heteroatom-doped g-C3N4@HA microgel composites, especially Sg-C3N4@HA microgels, can be safely used as multifunctional theragnostic agents for both diagnostic as well as target and treatment purposes in cancer therapy because of their fluorescent nature. [ABSTRACT FROM AUTHOR]

Abstract Background Hyaluronic acid (HA) has gained significant attention due to its unique physical, chemical, and biological properties, making it widely used in various industries. This study aimed to screen bacterial isolates for HA production, characterize favorable fermentation conditions, and evaluate the inhibitory effect of bacterial HA on cancer cell lines. Results A total of 108 bacterial isolates from diverse sources were screened for HA production using HPLC, turbidimetric, and carbazole determination methods. Among the HA-producing isolates, Klebsiella pneumoniae H15 isolated from an animal feces sample, was superior in HA production. The strain was characterized based on its morphological, cultural, and biochemical characteristics. Molecular identification using 16S rDNA sequencing and phylogenetic analysis confirmed its identity. Fermentation conditions, including pH, temperature, time, and agitation rate, were optimized to maximize HA production. The basal medium, comprising sucrose (7.0%) as carbon source and combined yeast extract with peptone (1.25% each) as nitrogen substrate, favored the highest HA production at pH 8.0, for 30 h, at 30 °C, under shaking at 180 rpm. The average maximized HA concentration reached 1.5 g L−1. Furthermore, bacterial HA exhibited a significant inhibitory effect on three cancer cell lines (MCF-7, HepG-2 and HCT), with the lowest concentration ranging from 0.98–3.91 µg mL−1. Conclusions K. pneumoniae H15, isolated from animal feces demonstrated promising potential for HA production. The most favorable fermentation conditions led to a high HA production. The inhibitory effect of bacterial HA on cancer cell lines highlights its potential therapeutic applications. These findings contribute to a broader understanding and utilization of HA in various industries and therapeutic applications.

Background: Knee osteoarthritis (KOA) is one of the most prevalent forms of OA and causes pain, joint instability, and functional limitations. The management of KOA involves a wide range of therapies, including surgical interventions, medications, exercise prescription, physical agent modalities, and patient education. While knee arthroplasty is an effective treatment for severe KOA, it is not suitable for younger patients or those with non-end-stage disease due to its cost and potential complications. Pharmacological therapy options for KOA include analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), and corticosteroid injections, but they can have significant adverse effects. In recent years, platelet-rich plasma (PRP) and hyaluronic acid (HA) have emerged as promising treatments for KOA. Methods: We conducted a literature review to explore the effectiveness of both PRP and HA in treating knee osteoarthritis. We compared some studies to know their effectiveness in patients, when given alone and with combination. Conclusion: PRP injections have consistently outperformed HA injections in treating knee osteoarthritis, offering pain relief and improved function, but the potential benefits of combining PRP with HA remain inconclusive, necessitating further research to ascertain their effectiveness and safety in combination treatment. This narrative review serves as a guide to evidence-based treatment.

Background: Excessive inflammation may cause tissue damage and disrupt the function of the skin barrier. Hyaluronic acid (HA), an endogenous component, was found to regulate multiple inflammatory factors for skin health. This work aims to further enhance its efficacy by grafting amino acid onto its molecule. Methods: Glutamic acid (Glu) was selected as the ligand to react with low‐molecular‐weight HA. Fibroblast tests and a 3D skin model were used to investigate the anti‐inflammation efficacy of HA‐Glu. Results: For IL‐1α, IL‐6 and TNF‐α, the grafted compound presents stronger inhibition ability versus native HA. Moreover, HA‐Glu could promote the repair of damaged skin by improving the compactness of the stratum corneum and increasing the thickness of the living cell layer. Conclusion: The application of HA‐Glu compound in skin care formulas would be effective to alleviate inflammation‐induced skin symptoms and skin aging. [ABSTRACT FROM AUTHOR]

Objective: This systematic review aimed to investigate and examine whether intra‐articular injections of platelet‐rich plasma (PRP) after arthrocentesis are beneficial for the treatment of temporomandibular disorders, when compared to other treatments, such as injections of hyaluronic acid (HA) or saline after arthrocentesis. Methods: An electronic search on PubMed was performed using combinations of the terms 'temporomandibular' and 'platelet rich plasma', to identify studies reported in English and published up until 2017. The initial screening identified 222 records, of which only seven fulfilled the inclusion criteria and were included in this review. Of these studies, three compared injection of PRP after arthrocentesis with the injection of HA after arthrocentesis, while two compared injection of PRP after arthrocentesis with Ringer's lactate after arthrocentesis and one compared injection of PRP after arthrocentesis to sodium chloride. Results: Five of the studies found that PRP injections have led to significant improvements in mandibular range of motion and pain intensity up to 12 months after treatment, while the remaining two studies found similar results for the different treatments. Conclusion: However, a standardized protocol for PRP preparation and application needs to be established. [ABSTRACT FROM AUTHOR]

Vascular complications from soft tissue fillers can have catastrophic consequences for patients. Adverse events are rare, but they are increasing, and their appearance may be the result of intravascular injection. A comprehensive understanding of the 2-dimensional anatomy (distribution) and 3-dimensional anatomy (depth) of the facial vasculature is fundamental for the safe delivery of nonsurgical cosmetic procedures. The purpose of this review is to provide an illustrated approach to examine surgical anatomy specific to the facial vascular system and the anatomical considerations clinicians need to give in specific danger during injectable cosmetic procedures. A grounding in safety and anatomy will help the new injector to mitigate the risk of vascular complications.

Background: Hyaluronic acid (HA) has gained significant attention due to its unique physical, chemical, and biological properties, making it widely used in various industries. This study aimed to screen bacterial isolates for HA production, characterize favorable fermentation conditions, and evaluate the inhibitory effect of bacterial HA on cancer cell lines. Results: A total of 108 bacterial isolates from diverse sources were screened for HA production using HPLC, turbidimetric, and carbazole determination methods. Among the HA-producing isolates, Klebsiella pneumoniae H15 isolated from an animal feces sample, was superior in HA production. The strain was characterized based on its morphological, cultural, and biochemical characteristics. Molecular identification using 16S rDNA sequencing and phylogenetic analysis confirmed its identity. Fermentation conditions, including pH, temperature, time, and agitation rate, were optimized to maximize HA production. The basal medium, comprising sucrose (7.0%) as carbon source and combined yeast extract with peptone (1.25% each) as nitrogen substrate, favored the highest HA production at pH 8.0, for 30 h, at 30 °C, under shaking at 180 rpm. The average maximized HA concentration reached 1.5 g L−1. Furthermore, bacterial HA exhibited a significant inhibitory effect on three cancer cell lines (MCF-7, HepG-2 and HCT), with the lowest concentration ranging from 0.98–3.91 µg mL−1. Conclusions: K. pneumoniae H15, isolated from animal feces demonstrated promising potential for HA production. The most favorable fermentation conditions led to a high HA production. The inhibitory effect of bacterial HA on cancer cell lines highlights its potential therapeutic applications. These findings contribute to a broader understanding and utilization of HA in various industries and therapeutic applications. [ABSTRACT FROM AUTHOR]

Background and Objectives: Tamarind-seed polysaccharide (TSP) and hyaluronic acid (HA) have mucoadhesive properties that improve drug absorption and delay in drug elimination from the ocular surface. We aimed to evaluate TSP/HA-containing formulation for its efficiency in dry-eye symptoms induced by adverse environments and the interaction between mucomimic polymer and tear-film parameters. Materials and Methods: The participants were exposed to 5% relative humidity (RH) in a Controlled Environment Chamber (CEC) under constant room temperature (21 °C). Tear-film parameters were assessed at 40% RH and 5% RH. Rohto Dry Eye Relief drops were used in the two treatment modalities, protection (drops instilled before exposure to the dry environment) and relief (drops instilled after exposure to the dry environment). The HIRCAL grid, Servomed EP3 Evaporimeter, and Keeler's TearScope-Plus were used to screen for non-invasive tear break-up time (NITBUT), tear evaporation rate, and lipid-layer thickness (LLT) using protection and relief treatment methodology. Results: LLT was found to be significantly thinner at 5% RH compared with at 40% RH (p = 0.007). The median LLT dropped from 50–70 nm (grade 3) at 40% RH to 10–50 nm (grade 2) at 5% RH. TSP/HA eye drops significantly augment LLT in both treatment modalities, protection (p = 0.01) and relief (p = 0.004) at 5% RH. The mean evaporation rate doubled from 40.93 at 40% RH to 82.42 g/m2/h after exposure to 5% RH. In protection mode, the TSP/HA allowed the average evaporation rate to be much lower than when no TSP/HA was used at 5% RH (p < 0.008). No alteration in evaporation rate was recorded when the TSP/HA drop was used after exposure (relief). The mean NITBUT was reduced from 13 s in normal conditions to 6 s in the dry environment. Instillation of TSP/HA eye drops resulted in significant improvement (p = 0.006) in tear stability, where the NITBUT increased to 8 s in both protection (before exposure) and relief (after exposure) (p = 0.001). Although improved, these values were still significantly lower than NITBUT observed at 40% RH. Conclusions: Significant protection of tear-film parameters was recorded post instillation of TSP/HA eye drop under a desiccating environment. Both treatment methods (protection and relief) were shown to be effective. The presence of TSP/HA enhances the effectiveness of teardrops in protecting the tear-film parameters when exposed to adverse environments. [ABSTRACT FROM AUTHOR]

In this review, a compilation of articles in databases on the extraction methods and applications of hyaluronic acid (HA) was carried out. HA is a highly hydrated component of different tissues, including connective, epithelial, and neural. It is an anionic, linear glycosaminoglycan (GAG) primarily found in the native extracellular matrix (ECM) of soft connective tissues. Included in the review were studies on the extraction methods (chemical, enzymatical, combined) of HA, describing advantages and disadvantages as well as news methods of extraction. The applications of HA in food are addressed, including oral supplementation, biomaterials, medical research, and pharmaceutical and cosmetic industry applications. Subsequently, we included a section related to the structure and penetration routes of the skin, with emphasis on the benefits of systems for transdermal drug delivery nanocarriers as promoters of percutaneous absorption. Finally, the future trends on the applications of HA were included. This final section contains the effects before, during, and after the application of HA-based products. [ABSTRACT FROM AUTHOR]

Background: Gingival recession is defined as the apical migration of gingival margin to the cementoenamel junction. Recently, amnion membrane, the third-generation membrane which is a placental-derived tissue, has been introduced. Materials and Methods: Study included 45 subjects with age group of 20–60 years of both genders. Patients with Miller's Class I and Class II gingival recession were selected for the study. The progress was assessed at baseline one, three, and six months observation interval through clinical parameters RD, RW, PD, and CAL at the end of six months. Results: Recession depths in the first, third, and sixth month were 1.82 ± 0.442, 1.31 ± 0.47 mm, and 0.91 ± 0.29, respectively, which showed a significant reduction from the baseline. Recession widths in the first, second, and third weeks were 3.04 ± 0.442 mm, 1.31 ± 0.47 mm, and 1.49 ± 0.59 mm, respectively. There was a statistically significant reduction (P > 0.005) when compared to the baseline. Pocket depths in the first, third, and sixth month were 0.93 ± 0.447, 0.42 ± 0.50, and 0.24 ± 0.43 (P > 0.005) which is significant when compared to baseline. Clinical attachment levels in the first, third, and sixth month were 2.73 ± 0.751, 1.78 ± 0.70, and 1.18 ± 0.53 (P > 0.005) which is significant compared to six months. Conclusion: Within the limitations of the present study, the data obtained by periodic assessment of the clinical parameters indicate the use of amnion membrane and hyaluronic acid, and proper technique may thus be the panacea for root coverage procedure.

Background: Gingival recession is defined as the apical migration of gingival margin to the cementoenamel junction. Recently, amnion membrane, the third-generation membrane which is a placental-derived tissue, has been introduced. Materials and Methods: Study included 45 subjects with age group of 20--60 years of both genders. Patients with Miller's Class I and Class II gingival recession were selected for the study. The progress was assessed at baseline one, three, and six months observation interval through clinical parameters RD, RW, PD, and CAL at the end of six months. Results: Recession depths in the first, third, and sixth month were 1.82 ± 0.442, 1.31 ± 0.47 mm, and 0.91 ± 0.29, respectively, which showed a significant reduction from the baseline. Recession widths in the first, second, and third weeks were 3.04 ± 0.442 mm, 1.31 ± 0.47 mm, and 1.49 ± 0.59 mm, respectively. There was a statistically significant reduction (P > 0.005) when compared to the baseline. Pocket depths in the first, third, and sixth month were 0.93 ± 0.447, 0.42 ± 0.50, and 0.24 ± 0.43 (P > 0.005) which is significant when compared to baseline. Clinical attachment levels in the first, third, and sixth month were 2.73 ± 0.751, 1.78 ± 0.70, and 1.18 ± 0.53 (P > 0.005) which is significant compared to six months. Conclusion: Within the limitations of the present study, the data obtained by periodic assessment of the clinical parameters indicate the use of amnion membrane and hyaluronic acid, and proper technique may thus be the panacea for root coverage procedure. [ABSTRACT FROM AUTHOR]

The use of a controlled-release drug carrier is an innovative solution for the treatment of local infections, in particular in dentistry, skin diseases, and in open wounds. The biocompatibility, biodegradability, the possibility of a large amount of drug adsorbed (especially those with hydrophilic properties), and the ability to create structures of any shape and size are the reasons for hydrogels to be frequently studied. The main disadvantage of hydrogel carriers is the rapid rate of drug release; hence, in this study, an attempt was made to additionally chemically cross-link 1-ethyl-3-(3-dimethyl aminopropyl)-1-carbodiimide hydrochloride (EDC) with the hyaluronic acid–alginate (HA–SAL) structure. The answer to significantly reduce the mass flux typical for hydrogel structure was to surround it with a polymer layer using a dry cover. By coating the carriers with polylactide, the release time was increased by around forty times. As the carriers were designed to reduce local bacterial infections, among others in dentistry, the released antibiotics were amoxycillin, metronidazole, and doxycycline. [ABSTRACT FROM AUTHOR]

The therapeutic management of premature lifelong ejaculation (PE) ranges from behavioral therapy to pharmacological and surgical treatments. Hyaluronic Acid (HA) injection into the glans penis is a non-surgical procedure, intended to reduce glans hypersensitivity, improving the intravaginal ejaculation latency time (IELT). HA injection can be performed through different techniques that, although safe and effective, rarely can cause local complications. In this pilot uncontrolled study, we tested the effectiveness of a new technique based on a single HA injection into the frenulum of the glans, to improve IELT in a sample of patients affected by PE. We observed a significant increase of the IELT after one (median 73.3, IQR 66.2–79.9 s) and two months (66.2, 63.1–73.9) that gradually decreased at three months, remaining still significantly higher than at baseline (34.8, 30.9–37.4). PEDT and IIEF questionnaires significantly improved compared to baseline in the first two months of follow-up (p < 0.001). In conclusion, the preliminary results emerging from this pilot uncontrolled study, highlight the effectiveness of this one-shot HA injection approach, although a larger sample and longer follow-up time are needed to standardize the procedure.

OBJECTIVE: The aim of our study was to test if oral high hyaluronic acid (HMW-HA) administration was effective in contrasting induced preterm birth (PTB) in female Wistar rats. MATERIALS AND METHODS: A total of 24 pregnant rats were pretreated with placebo or low (2.5 mg/day)/high dose (5 mg/day) of HMWHA (day 15) and then induced to delivery with mifepristone plus prostaglandin E2 (PGE2) (3 mg/100 μL + 0.5 mg/animal) on the 19th day of pregnancy. The delivery time was recorded and the messenger RNA (mRNA) levels of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)1β, IL-6] were detected in the uterine tissues by real-time polymerase chain reaction (real PCR). Immunohistochemistry was performed alongside. RESULTS: Oral HMW-HA was well absorbed in the body and was able to significantly delay the timing of delivery and decrease mRNA synthesis of pro-inflammatory cytokines. CONCLUSIONS: HMW-HA, by acting in the management of PTB, may represent a new approach to protecting physiological pregnancy. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM, WHO grade IV glioma) is the most common and lethal malignant brain tumor in adults with a dismal prognosis. The extracellular matrix (ECM) supports GBM progression by promoting tumor cell proliferation, migration, and immune escape. Uridine diphosphate (UDP)-glucose 6-dehydrogenase (UGDH) is the rate-limiting enzyme that catalyzes the biosynthesis of glycosaminoglycans that are the principal component of the CNS ECM. We investigated how targeting UGDH in GBM influences the GBM immune microenvironment, including tumor-associated microglia/macrophages (TAMs) and T cells. TAMs are the main immune effector cells in GBM and can directly target tumor cells if properly activated. In co-cultures of GBM cells and human primary macrophages, UGDH knockdown in GBM cells promoted macrophage phagocytosis and M1-like polarization. In orthotropic human GBM xenografts and syngeneic mouse glioma models, targeting UGDH decreased ECM deposition, increased TAM phagocytosis marker expression, reduced M2-like TAMs and inhibited tumor growth. UGDH knockdown in GBM cells also promoted cytotoxic T cell infiltration and activation in orthotopic syngeneic mouse glioma models. The potent and in-human-use small molecule GAG synthesis inhibitor 4-methylumbelliferone (4-MU) was found to inhibit GBM cell proliferation and migration in vitro, mimic the macrophage and T-cell responses to UGDH knockdown in vitro and in vivo and inhibit growth of orthotopic murine GBM. Our study shows that UGDH supports GBM growth through multiple mechanisms and supports the development of ECM-based therapeutic strategies to simultaneously target tumor cells and their microenvironment.

As vastly modified on secreted proteins, N-glycosylation is found on milk proteins and undergo dynamic changes during lactation, characterizing milk protein glycosylation would benefit the elucidation of glycosylation pattern differences between samples. However, their low abundance required specific enrichment. Herein, through rational design and controllable synthesis, we developed a novel multi-functional polymer for the isolation of protein glycosylation. It efficiently separated glycopeptides from complex background inferences with mutual efforts of hydrophilic interaction chromatography (HILIC), metal ion affinity and ion exchange. By fine-tuning Ca2+ as regulators of aldehyde hyaluronic acid (HA) conformation, the grafting density of HA was remarkably improved. Moreover, grafting Ti4+ further enhanced the enrichment performance. Application of this material to characterize bovine milk and colostrum proteins yields 479 and 611 intact glycopeptides, respectively. Comparative analysis unraveled the distinct glycosylation pattern as well the different distribution of glycoprotein abundances between the two samples, offering insights for functional food development. • A novel functional polymer aHA-Ti for glycopeptide enrichment was prepared based on hyaluronic acid. • Ca2+ ions regulate aldehyde-hyaluronic acid conformation, enhancing aHA grafting density. • aHA-Ti enriches intact glycopeptides via hydrophilic interaction, metal ion affinity and ion exchange. • Determine distinct glycosylation patterns in bovine milk and colostrum at site-specific glycan level using the prepared material [ABSTRACT FROM AUTHOR]

Managing advanced colon cancer is challenging, requiring targeted therapies. This study presents a novel nanoconjugate system, HA-CMD@ETP-MLT-NCs, designed to deliver etoposide (ETP) specifically to colon cancer cells. The system consists of Hyaluronic Acid (HA)-Functionalized Carboxymethyl Dextran (CMD) coated with Melatonin (MLT). The nanoconjugates showed good stability, with a zeta potential of −29.90 mV and a particle size of 199.1 nm. They achieved an 80.3 % yield and a high drug entrapment efficiency of 93.4 %. In vitro release studies demonstrated pH-dependent drug release, with 73.4 % released at pH 5.5 (tumour-like environment) and 42.6 % at pH 7.4 (normal tissue) over 24 h. The nanoconjugates improved cellular uptake, induced apoptosis, and reduced reactive oxygen species (ROS) in HCT116 colon cancer cells. Flow cytometry showed a significant decrease in ROS levels, and lipid peroxidation inhibition increased to 56.67 %. These findings suggest that HA-CMD@ETP-MLT-NCs enhance etoposide delivery and reduce side effects. Further in vivo studies and clinical trials are needed to confirm its therapeutic potential. [Display omitted] • Etoposide in HA-functionalized nanoconjugates improves solubility, stability, and delivery. • HA-CMD@ETP-MLT nanoconjugates ensure sustained ETP release and enhanced cytotoxicity. • HA-CMD@ETP-MLT-NCs achieve higher cellular uptake and apoptosis in HCT116 cells. • Treatment with HA-CMD@ETP-MLT-NCs reduces reactive oxygen species (ROS) levels. • HA-CMD nanocomposites enhance etoposide efficacy for metastatic colon cancer therapy. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), a prevalent and deadly cancer, poses a significant challenge with current treatments due to limitations such as poor stability, off-target effects, and severe side effects. Extracellular vesicles (EVs), derived from tumor cells, have the remarkable ability to home back to their cells of origin and can serve as Trojan horses for drug delivery. CD44, a cell surface glycoprotein, promotes cancer stem cell-like properties and is linked to poor prognosis and resistance to chemotherapy in HCC. Therefore, targeting CD44-expressing HCC cells is of interest in the development of novel therapeutic strategies for the treatment of HCC. In this study, we developed tumor cell-derived EVs (TEVs) functionalized with hyaluronic acid (HA) to serve as natural carriers for the precise delivery of doxorubicin (Dox), which specifically targets HCC cells expressing CD44. Our results demonstrated that HA-engineered EVs (HA-EVs) significantly enhanced Dox accumulation within HCC cells. In a mouse model, HA-EVs effectively delivered Dox to tumors, suppressing their growth and progression while minimizing systemic toxicity. This study demonstrates the potential of HA-functionalized EVs as a novel and targeted therapeutic platform for HCC, offering a valuable strategy for improving drug delivery and patient outcomes. This study presents a promising strategy to advance targeted chemotherapy for HCC and address the challenges associated with conventional treatments. Engineered HA-functionalized EVs offer a tailored and efficient approach to increase drug delivery precision, underscoring their potential as a novel therapeutic platform in the realm of HCC treatment. • Tumor cell-derived EVs functionalized with HA can target CD44-expressing hepatocellular carcinoma (HCC) cells. • EVs modified with HA can effectively deliver doxorubicin (Dox) to HCC cells expressing CD44. • HA-modified EVs suppressed tumor growth while minimizing side effects compared to conventional treatment. • HA-functionalized EVs show promise as a new therapeutic platform for targeted drug delivery. [ABSTRACT FROM AUTHOR]

Abstract Introduction There is no study on the effectiveness of hyaluronic acid (HA) placement either with or without absorbable collagen sponge (ACS) in reducing or preventing bisphosphonate-related osteonecrosis of the jaws (BRONJ). This preliminary animal study examined the efficacy of this clinically important treatment. Methods For simulating BRONJ, zoledronic acid was administered to 40 rats for 5 weeks. Two weeks later, a right first molar was extracted from each rat. The rats were randomized into four groups of socket treatments: control (empty extraction socket) or with sockets filled with ACS, HA, or HA+ACS (n=4×10). After 2 weeks, 5 rats in each group were sacrificed and subjected to histopathologic and histomorphometric evaluation. Eight weeks post-surgically, the rest of rats were euthanized and histologically examined. The Kruskal-Wallis test was used to compare the four treatments at each time point (α=0.05). Results Six rats were lost overall. In the second week, vascularization was higher in ACS group (P0.05); empty lacunae were the most and fewest in control and HA+ACS groups, respectively (P0.05). In the eighth week, vascularization was not different in groups (P>0.05); the highest and lowest osteoclast activities were seen in the control and HA+ACS groups, respectively (P

Acute respiratory distress syndrome (ARDS) is accompanied by a dramatic increase in lung hyaluronic acid (HA), leading to a dose-dependent reduction of pulmonary oxygenation. This pattern is associated with severe infections, such as COVID-19, and other important lung injury etiologies. HA actively participates in molecular pathways involved in the cytokine storm of COVID-19-induced ARDS. The objective of this study was to evaluate an imaging approach of radiolabeled HA for assessment of dysregulated HA deposition in mouse models with skin inflammation and lipopolysaccharide (LPS)-induced ARDS using a novel portable intensified Quantum Imaging Detector (iQID) gamma camera system. HA of 10 kDa molecular weight (HA10) was radiolabeled with 125I and 99mTc respectively to produce [125I]I-HA10 and [99mTc]Tc-HA10, followed by comparative studies on stability, in vivo biodistribution, and uptake at inflammatory skin sites in mice with 12-O-tetradecanoylphorbol-13-acetate (TPA)-inflamed ears. [99mTc]Tc-HA10 was used for iQID in vivo dynamic imaging of mice with ARDS induced by intratracheal instillation of LPS. [99mTc]Tc-HA10 and [125I]I-HA10 had similar biodistribution and localization at inflammatory sites. [99mTc]Tc-HA10 was shown to be feasible in measuring skin injury and monitoring skin wound healing. [99mTc]Tc-HA10 dynamic pulmonary images yielded good visualization of radioactive uptake in the lungs. There was significantly increased lung uptake and slower lung washout in mice with LPS-induced ARDS than in control mice. Postmortem biodistribution measurement of [99mTc]TcHA10 (%ID/g) was 11.0 ± 3.9 vs. 1.3 ± 0.3 in the ARDS mice (n = 6) and controls (n = 6) (P < 0.001), consistent with upregulated HA expression as determined by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) staining. [99mTc]Tc-HA10 is promising as a biomarker for evaluating HA dysregulation that contributes to pulmonary injury in ARDS. Rapid iQID imaging of [99mTc]Tc-HA10 clearance from injured lungs may provide a functional template for timely assessment and quantitative monitoring of pulmonary pathophysiology and intervention in ARDS. [Display omitted] [ABSTRACT FROM AUTHOR]

This paper provides an assessment of molecular and functional changes in blood vessels, and a description of vascular patterns during preeclampsia (PE). Patients with normal pregnancy, and pregnancy complicated by PE at earlier (20–34 weeks) and later terms (≥34 weeks) underwent a 24 h monitoring of blood pressure, central hemodynamics, arterial stiffness, and myocardial function. The blood levels of the structural components of endothelial glycocalyx (eGC): syndecan-1 (SDC 1), heparan sulfate proteoglycan 2 (HSPG2), and hyaluronic acid (HA) were determined. In early-onset PE, the vascular pattern comprised changes in all structural components of eGCs, including transmembrane proteoglycans levels, and severe disorders of central hemodynamics, arterial stiffness, and myocardial changes, probably leading to more severe course of PE and the formation of morphological grounds for cardiovascular disorders. The vascular pattern in late-onset PE, including changes in HA levels, central hemodynamics, and myocardial function, may be a signal of potential cardiovascular disorder. PE may change adaptive hemodynamic responses to a pathological reaction affecting both arterial elasticity and the left ventricular myocardium, with its subsequent hypertrophy and decompensation, leading to a delayed development of cardiovascular disorders after PE. Further clinical studies of these indicators will possibly identify predictors of PE and long-term consequences of the disease. [ABSTRACT FROM AUTHOR]

Background: It remains unknown how timing of preoperative intra-articular knee hyaluronic acid (HA) injections impacts risk for developing postoperative periprosthetic joint infection (PJI) following total knee arthroplasty (TKA)., Methods: The PearlDiver Mariner database was utilized to identified patients undergoing primary TKA between 2015 and 2022 who received an HA injection without a corticosteroid injection within 12 months prior to surgery. The HA cohort was matched 1:1 to a control cohort undergoing no preoperative injections (corticosteroid or HA). Multivariable logistic regression analysis was utilized to determine the risk of preoperative HA injections on PJI at 1, 3, 6, 12, and 24 months postoperative. The following pre-operative intervals between injection and TKA were evaluated: 0-1 month, 1-2 months, 2-3 months, 4-6 months, and 7-12 months., Results: 38,546 patients (HA: n = 19,273; Control: n = 19,273) were analyzed. HA injections within 1 month prior to surgery demonstrated significant increase in rates of PJI at 3-months (OR: 3.00, 95% CI: 1.29 - 6.47; p = 0.005), 6-months (OR: 2.66, 95% CI: 1.30 - 5.46; p = 0.007), 12-months (OR: 2.37, 95% CI: 1.20 - 4.67; p = 0.013), and 24-months (OR: 2.65, 95% CI: 1.50 - 4.68; p < 0.001) postoperatively. HA injections between 1-2 months prior to surgery showed increased rates of PJI at 12-months (OR: 1.60, 95% CI: 1.06-2.41; p = 0.011) postoperatively. No difference in infection risk was demonstrated between patients receiving injections > 2 months prior to surgery relative to matched controls., Conclusions: Intra-articular hyaluronic acid injections administered within 2 months of TKA appear to increase the risk of PJI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hyaluronic acid (HA), the primary component of brain extracellular matrix, is increasingly used to model neuropathological processes, including glioblastoma (GBM) tumor invasion. While elastic hydrogels based on crosslinked low-molecular-weight (LMW) HA are widely exploited for this purpose and have proven valuable for discovery and screening, brain tissue is both viscoelastic and rich in high-MW (HMW) HA, and it remains unclear how these differences influence invasion. To address this question, hydrogels comprised of either HMW (1.5 MDa) or LMW (60 kDa) HA are introduced, characterized, and applied in GBM invasion studies. Unlike LMW HA hydrogels, HMW HA hydrogels relax stresses quickly, to a similar extent as brain tissue, and to a greater extent than many conventional HA-based scaffolds. GBM cells implanted within HMW HA hydrogels invade much more rapidly than in their LMW HA counterparts and exhibit distinct leader-follower dynamics. Leader cells adopt dendritic morphologies similar to invasive GBM cells observed in vivo. Transcriptomic, pharmacologic, and imaging studies suggest that leader cells exploit hyaluronidase, an enzyme strongly enriched in human GBMs, to prime a path for followers. This study offers new insight into how HA viscoelastic properties drive invasion and argues for the use of highly stress-relaxing materials to model GBM., (© 2024 Wiley‐VCH GmbH.)

Liver fibrosis poses a significant global health burden, in which hepatic stellate cells (HSCs) play a crucial role. Targeted nanomedicine delivery systems directed at HSCs have shown immense potential in the treatment of liver fibrosis. Herein, a bioinspired material, engineered therapeutic miR-181a-5p (a miRNA known to inhibit fibrotic signaling pathways) and targeted moiety hyaluronic acid (HA) co-functionalized extracellular vesicles (EVs) are developed. HA is incorporated onto the surface of EVs using DSPE-PEG as a linker, allowing preferential binding to CD44 receptors, which are overexpressed on activated HSCs. Our results confirmed enhanced cellular uptake and improved payload delivery, as evidenced by the increased intracellular abundance of miR-181a-5p in activated HSCs and fibrotic livers. HA-equipped EVs loaded with miR-181a-5p (DPH-EVs@miR) significantly reduce HSC activation and extracellular matrix (ECM) deposition by inhibiting the TGF-β/Smad signaling pathway, thus alleviating the progression of liver fibrosis. Additionally, DPH-EVs@miR improves liver function, ameliorates inflammatory infiltration, and mitigates hepatocyte apoptosis, demonstrating superior hepatic protective effects. Collectively, this study reports a prospective nanovesicle therapeutic platform loaded with therapeutic miRNA and targeting motifs for liver fibrosis. The biomarker-guided EV-engineering technology utilized in this study provides a promising tool for nanomedicine and precision medicine., (© 2024 Wiley‐VCH GmbH.)

Background and Objectives: Tamarind-seed polysaccharide (TSP) and hyaluronic acid (HA) have mucoadhesive properties that improve drug absorption and delay in drug elimination from the ocular surface. We aimed to evaluate TSP/HA-containing formulation for its efficiency in dry-eye symptoms induced by adverse environments and the interaction between mucomimic polymer and tear-film parameters. Materials and Methods: The participants were exposed to 5% relative humidity (RH) in a Controlled Environment Chamber (CEC) under constant room temperature (21 °C). Tear-film parameters were assessed at 40% RH and 5% RH. Rohto Dry Eye Relief drops were used in the two treatment modalities, protection (drops instilled before exposure to the dry environment) and relief (drops instilled after exposure to the dry environment). The HIRCAL grid, Servomed EP3 Evaporimeter, and Keeler’s TearScope-Plus were used to screen for non-invasive tear break-up time (NITBUT), tear evaporation rate, and lipid-layer thickness (LLT) using protection and relief treatment methodology. Results: LLT was found to be significantly thinner at 5% RH compared with at 40% RH (p = 0.007). The median LLT dropped from 50–70 nm (grade 3) at 40% RH to 10–50 nm (grade 2) at 5% RH. TSP/HA eye drops significantly augment LLT in both treatment modalities, protection (p = 0.01) and relief (p = 0.004) at 5% RH. The mean evaporation rate doubled from 40.93 at 40% RH to 82.42 g/m2/h after exposure to 5% RH. In protection mode, the TSP/HA allowed the average evaporation rate to be much lower than when no TSP/HA was used at 5% RH (p < 0.008). No alteration in evaporation rate was recorded when the TSP/HA drop was used after exposure (relief). The mean NITBUT was reduced from 13 s in normal conditions to 6 s in the dry environment. Instillation of TSP/HA eye drops resulted in significant improvement (p = 0.006) in tear stability, where the NITBUT increased to 8 s in both protection (before exposure) and relief (after exposure) (p = 0.001). Although improved, these values were still significantly lower than NITBUT observed at 40% RH. Conclusions: Significant protection of tear-film parameters was recorded post instillation of TSP/HA eye drop under a desiccating environment. Both treatment methods (protection and relief) were shown to be effective. The presence of TSP/HA enhances the effectiveness of teardrops in protecting the tear-film parameters when exposed to adverse environments.

The use of a controlled-release drug carrier is an innovative solution for the treatment of local infections, in particular in dentistry, skin diseases, and in open wounds. The biocompatibility, biodegradability, the possibility of a large amount of drug adsorbed (especially those with hydrophilic properties), and the ability to create structures of any shape and size are the reasons for hydrogels to be frequently studied. The main disadvantage of hydrogel carriers is the rapid rate of drug release; hence, in this study, an attempt was made to additionally chemically cross-link 1-ethyl-3-(3-dimethyl aminopropyl)-1-carbodiimide hydrochloride (EDC) with the hyaluronic acid–alginate (HA–SAL) structure. The answer to significantly reduce the mass flux typical for hydrogel structure was to surround it with a polymer layer using a dry cover. By coating the carriers with polylactide, the release time was increased by around forty times. As the carriers were designed to reduce local bacterial infections, among others in dentistry, the released antibiotics were amoxycillin, metronidazole, and doxycycline.

We previously found that modified citrus pectin (MCP), an inhibitor of pro-inflammatory factor Galectin-3 (Gal-3), has significant anti-inflammatory and chondroprotective effects. In this study, a hyaluronate (HA) gel-based sustained release system of MCP (MCP-HA) was developed as an anti-inflammatory agent for chronic inflammation for osteoarthritis (OA) treatment. The MCP-HA gel was injected into the knee joint cavities of OA rabbit models induced by anterior cruciate ligament transection (ACLT) or modified Hulth method once a week for five weeks. We found that MCP-HA could improve the symptoms and signs of OA, protect articular cartilage from degeneration, suppress synovial inflammation, and therefore alleviate OA progression. Proteomic analysis of the synovial fluid obtained from the knee joints of OA rabbits revealed that MCP-HA synergistically regulated the levels of multiple inflammatory mediators and proteins involved in metabolic pathways. Taken together, our results demonstrate that the MCP-HA shows a synergistic effect of HA and MCP by modulating both inflammation and metabolic processes, thereby alleviating OA progression. The MCP-HA sustained release system has promising potential for long-term use in OA treatment. [Display omitted] • Injectable modified citrus pectin and hyaluronate gel (MCP-HA) was prepared. • MCP-HA could be used in local delivery and release MCP in a sustained way. • MCP-HA could alleviate osteoarthritis (OA) progression, had potential in OA treatment. • MCP-HA could regulate both inflammatory and metabolic pathways in OA treatment. [ABSTRACT FROM AUTHOR]

Objectives: We previously reported, based on a multicenter randomized-control study, that the efficacy of intra-articular injections of hyaluronic acid (IA-HA) was not inferior to that of oral non-steroidal anti-inflammatory drugs (NSAIDs) in patients with knee osteoarthritis (OA). However, the molecular effects on the pathophysiology of knee OA remain unclear. C-terminal telopeptides of type II collagen (CTX-II) is reported to primarily originate from the interface between articular cartilage and subchondral bone, which is a site of potential remodeling in OA. We performed a predefined sub-analysis of the previous study to compare the changes of urinary CTX-II (uCTX-II) in response to IA-HA to those in response to NSAID for knee OA.Design: A total of 200 knee OA patients were registered from 20 hospitals and randomized to receive IA-HA (2,700 kDa HA, 5 times at 1-week intervals) or NSAID (loxoprofen sodium, 180 mg/day) for 5 weeks. The uCTX-II levels were measured before and after treatment.Results: The uCTX-II levels were significantly increased by IA-HA treatment (337.7 ± 193.8 to 370.7 ± 234.8 ng/μmol Cr) and were significantly reduced by NSAID treatment (423.2 ± 257.6 to 370.3 ± 250.9 ng/μmol Cr). The %changes of uCTX-II induced by IA-HA (11.6 ± 29.5%) and NSAID (-9.0 ± 26.7%) was significantly different (between-group difference: 20.6, 95% confidence intervals: 10.6 to 30.6).Conclusions: While both IA-HA and NSAID improved symptoms of knee OA, uCTX-II levels were increased by IA-HA and reduced by NSAIDs treatment, suggesting these treatments may improve symptoms of knee OA through different modes of action. [ABSTRACT FROM AUTHOR]