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Objective To compare the clinical effectiveness of sodium polynucleotide, classic hyaluronic acid, and crosslinked hyaluronic acid for the management of painful knee osteoarthritis. Design Randomized, double-blind, parallel-group clinical trial. Setting Multicenter study. Subjects Patients with chronic painful knee osteoarthritis. Methods Ninety patients were selected and randomized into polynucleotide, classic hyaluronic acid, and crosslinked hyaluronic acid groups (30 per group). Intra-articular injections of the viscosupplement for each group were administered to the patients three times at one-week intervals. The primary outcome was differences in changes of weight-bearing pain scores at 16 weeks between the groups. The secondary outcomes were changes in the intensity of knee pain during weight-bearing, walking, and rest, and functional disability, quality of life, and adverse events during the 16-week follow-up period. Results At 16 weeks, the polynucleotide group showed a higher reduction in pain score using a Visual Analog Scale score (0–100) than the classic hyaluronic acid (−17.6 [95% CI = −35.1 to −0.1]; P = .048) and crosslinked hyaluronic acid (−22.4 [95% CI = −41.5 to −3.3]; P = .016) groups. The polynucleotide and crosslinked hyaluronic acid groups showed an early-onset reduction in knee pain during weight-bearing, walking, and rest. All three groups showed reductions in functional disability and improved quality of life at 16 weeks without inter-group differences. No severe adverse events were reported throughout the study period. Conclusion Polynucleotide significantly relieves pain more and relieves pain faster in patients with knee osteoarthritis than classic and crosslinked hyaluronic acid, with improved health-related quality of life.

Knee osteoarthritis (KOA) is a common degenerative joint disease that primarily affects the elderly individuals. Traditional treatments include medications and physical therapy, but recent attention has turned to platelet-rich plasma (PRP) and hyaluronic acid (HA) injection therapies. This meta-analysis aimed to evaluate the efficacy and safety of PRP combined with HA versus PRP alone in the treatment of KOA. We conducted a comprehensive literature search of the PubMed, Embase, and Cochrane Library databases, which included covering publications from their inception to July 2024. Studies comparing PRP+HA with PRP alone were selected. Data on visual analog scale (VAS) scores, WOMAC total scores, Lequesne scores, and adverse events were extracted. Statistical analysis was performed via Review Manager 5.3.5. This meta-analysis included 16 studies involving a total of 1,384 patients. The VAS score comparison indicated that, in the long term, PRP combined with HA was more effective in reducing knee pain than PRP alone was (SMD: -0.30, 95% CI: -0.53 to -0.06, P =  0.01). The combined PRP and HA treatment achieved better results in terms of the WOMAC total score (MD =  -6.58, 95% CI: -10.65 to -2.52, P <  0.001). At the 6-month follow-up, the Lequesne index score comparison revealed that PRP combined with HA significantly improved knee pain scores compared with PRP alone (MD =  -1.38, 95% CI: -1.91 to -0.86, P <  0.001). In terms of adverse events, PRP+HA was associated with a lower risk of adverse events than PRP alone was (OR =  0.54, 95% CI: 0.33 to 0.85, P =  0.009). PRP combined with HA offers significant long-term benefits in pain relief and functional improvement over PRP alone for knee osteoarthritis, with better safety. The sequence of injection may influence treatment outcomes. PROSPERO CRD42024598691.

Purpose: To investigate the clinical effect of sodium hyaluronate eye drops combined with tobramycin, dexamethasone, and pranoprofen eye drops in the treatment of dry eye after phacoemulsification. Methods: Medical records of 188 patients with dry eye after phacoemulsification, treated in our hospital from August 2020 to August 2021, were included and divided into groups based on the type of dry eye treatment. Patients in the control group (n = 90) were treated with tobramycin, dexamethasone, and pranoprofen eye drops. Patients in the test group (n = 98) were treated with sodium hyaluronate, tobramycin, dexamethasone, and pranoprofen eye drops. The tear secretion test (TST), film rupture time (BUT), corneal fluorescence staining (FS) score, levels of interleukin (IL)-6, and tumor necrosis factor (TNF)-α before the treatment and at 1 month follow-up, the overall total effective rate and the number of completely cured cases were compared between the two groups. Multiple linear regression was used to calculate coefficients for predicting clinical variables. Ordinal logistic regression was used to compute coefficients and odds ratios for predicting effective scores. Results: The total effective rate in the observation group (99%) was significantly higher than that in the control group (80.00%). After the treatment, the TST and BUT indexes of the observation group were higher compared to the control group, and the FS score of the observation group was lower than that of the control group. TNF-α and IL-6 levels of the observation group were lower compared to the control group. Logistic regression analysis demonstrated that the differences in the effective rate and clinical variables between the two groups remained significant after adjusting for the effect of age. Conclusion: A combination of sodium hyaluronate, tobramycin, dexamethasone, and pranoprofen eye drops for the treatment of dry eye after phacoemulsification can improve the curative effect, reduce corneal fluorescein staining and inflammatory factor index levels compared to the treatment regimen lacking sodium hyaluronate eye drops.

Oral hyaluronan has been reported to improve various aspects of skin physiology, but existing trials often lack methodological rigor, comprehensive outcome assessment, and diverse populations. This randomized, double-blind, placebo-controlled trial evaluated the effects of sodium hyaluronate (SH) supplementation at two daily doses on skin parameters in healthy Caucasian adults. A total of 150 participants were randomized to receive SH (1.8 MDa) at 60 mg/day (SH60), 120 mg/day (SH120), or placebo for 12 weeks. Facial hydration, transepidermal water loss (TEWL), sebum, elasticity, wrinkle depth, skin gloss, colorimetric parameters, epidermal thickness, dermal density, red areas, and pore size were assessed at baseline and monthly. Subjective skin condition was evaluated every two weeks, and components of natural moisturizing factor (NMF) in forearm skin were quantified by LC-MS/MS. SH120 significantly enhanced skin hydration and elasticity, while reducing TEWL, sebum, and periorbital wrinkle depth versus placebo. It also improved skin structure by increasing epidermal thickness, dermal density, and NMF levels. SH60 showed similar but more modest effects. No changes were observed for colorimetric parameters, red areas, pore size, or gloss. In conclusion, oral SH supplementation improved multiple aspects of skin physiology, supporting its use as a functional food ingredient with measurable benefits for skin health and healthy aging. Trial registration: ClinicalTrials.gov, NCT07065110 (retrospectively registered on 15 Jul 2025); EFSA (European Food Safety Authority) registry: EFSA202400027979 (prospectively filed on 06 Jun 2024).

Dry eye disease (DED) is a common ocular surface disorder. Esculin and digitalis possess anti-inflammatory and anti-oxidant properties, which may benefit patients with DED. This study aimed to assess the therapeutic efficacy of esculin and digitalis glycosides (EAD) eye drops, either alone or in combination with 0.3% sodium hyaluronate (SH) eye drops, in treating DED. In this randomized controlled trial, 78 participants with DED (78 eyes) were included and divided into three groups: Group A received 0.3% SH, Group B received EAD, and Group C received 0.3% SH combined with EAD eye drops for 4 weeks. The efficacy of the treatments was assessed at 2 and 4 weeks using the Ocular Surface Disease Index (OSDI), tear break-up time (TBUT), Schirmer I test (SIt), and corneal fluorescein staining (CFS) as primary evaluation metrics. After 4 weeks of treatment, Group A showed a decrease in OSDI and an increase in SIT ( p  < 0.05). Group B showed a decrease in OSDI score ( P  < 0.05) and a significant improvement in SIt ( P  < 0.01). Group C demonstrated a significant increase in both TBUT and SIt values at the 2-week mark. Improvements were noted across all parameters, including OSDI score, TBUT, SIt, and CFS score after 4 weeks of treatment ( P  < 0.05). The total effective rate for participants in Group C was 88.46%, significantly higher than Group A’s rate of 65.38% ( P  < 0.05). In conclusion, the combination of EAD eye drops with 0.3% SH eye drops proved more effective than either treatment alone.

Purpose Prospective, randomised, open-label, comparative study to evaluate efficacy of trehalose/sodium hyaluronate eye drops for post-operative discomfort and tear film stability in patients undergoing cataract surgery. Methods Patients with healthy ocular surface, subclinical, or mild dry eye were enrolled. Tear breakup time (TBUT), Schirmer test, dry eye symptoms, corneal fluorescein staining (CFS), and ocular surface disease (OSDI) evaluation were performed pre-operatively and at two and four weeks after surgery. Patients were assigned to receive trehalose/sodium hyaluronate eye drops b.i.d (Group A), or 0.9% unpreserved sodium chloride eye drops b.i.d for 4 weeks (Group B). Results One hundred and thirty-five patients were randomised, 66 patients in Group A (73.2 ± 4.5 years) and 69 patients in Group B (74.3 ± 3.8 years), 60.8% females. Fifteen patients (8 Group A) were lost at follow-up. Pre-operatively, no between-group differences were observed, and TBUT increased in Group A between the pre-operative and 2 and 4 week evaluations and was higher in group A than in Group B at 4 weeks. Schirmer test and CFS showed an improvement only in Group A four weeks post-operatively. In Group A an improvement was observed after two and four weeks in foreign body and puncture sensation, whilst a difference in blinking discomfort was observed after four weeks. In Group B we observed an improvement in puncture sensation two and four weeks after surgery. Mean OSDI scores differences between the two groups were significant at four weeks. Conclusions Trehalose/sodium hyaluronate eye drops were effective in reducing signs and symptoms of dry eye and improving tear film stability

PurposeZona pellucida-free (ZP-free) embryos often fail to achieve good developmental outcomes and are routinely discarded in assisted reproductive laboratories. Existing attempts to rescue ZP-free embryos are not widely used due to operational complexity and high technical requirements. To handle cases with missing ZP, we applied modified sodium hyaluronate gel (MSHG) to embryo culture to determine if it can function as a substitute for human zona pellucida.MethodsThe developmental process and the blastocyst formation rate of embryos were analyzed in both mouse and human. The first clinical application of MSHG was reported, and the pregnancy outcome was continuously followed up.ResultsHuman and mouse ZP-free embryos cultured with MSHG showed a blastocyst formation rate similar to ZP-intact embryos. MSHG improves blastocysts formation rate by maintaining blastomere spatial arrangement at early stages. Compared to ZP-free embryos, the proportion of tetrahedrally arranged blastomeres at the 4-cell stage increased significantly in embryos cultured with MSHG in humans. A ZP-free blastocyst cultured in MSHG with the highest score was successfully implanted after day 5 transplantation and developed normally.ConclusionThese data demonstrate that MSHG can substitute the function of zona pellucida and rescue human ZP-free embryos during assisted reproductive technology.

Background Intrauterine adhesions (IUAs) can easily cause female infertility or recurrent abortion, but there is still no effective treatment to improve the pregnancy and live birth rates in patients with IUAs. In recent years, great advances have been made in stem cell therapy; however, additional clarity is needed on the clinical efficacy of endometrial stem cells in the treatment of IUAs. Materials and methods Fifteen patients with moderate-to-severe IUAs were included in the study at Xiangtan Central Hospital from 2018 to 2020. Patients were treated with endometrial stem cells and sodium hyaluronate gel by intrauterine perfusion in combination with estrogen and acetylsalicylic acid support therapy. Then, data on the pregnancy and live birth status was collected within two years after treatment. To explore the underlying mechanism, primary endometrial stem cells from healthy individuals and IUA patients, as well as fifth-generation endometrial stem cells from IUA patients, were further conducted with RNA sequencing to screen for differentially expressed genes, which were subsequently used for functional enrichment analysis. Results After endometrial stem cell transplantation into the uterine cavity, the American Fertility Society scores of all patients decreased, and hysteroscopy revealed an improvement in the uterine condition and a reduction in adhesion symptoms. The total pregnancy rate of the 15 patients was 60.0% and the live birth rate was 53.3%. In addition, RNA sequencing analysis revealed that the cytokine − cytokine receptor interaction was associated with endometrial repair by endometrial stem cells. Conclusions Intrauterine infusion of autologous endometrial stem cells is highly effective for patients with moderate-to-severe IUA, and is a promising treatment strategy. Trial registration Chinese Clinical Trial Registry, CHICTR1800016769, Registered 22 June 2018- Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=27042 .

Abstract Injectable sodium hyaluronate (NaHA) is extensively utilized in aesthetic medicine as a dermal hydrating agent. However, there are few standardized, human-relevant preclinical methods that can reliably evaluate the moisturizing performance of those products. Existing animal and simplified cell-based models show restricted physiological relevance and insufficient sensitivity. To address this gap, we established a depot-mimicking reconstructed human full-thickness skin (RhFS) platform incorporating an inclusion-based intradermal delivery strategy. Instead of conventional mixing, this strategy mimics the clinical ‘depot effect’ of intradermal injection, allowing for the simultaneous assessment of cellular responses and tissue-level hydration dynamics. It forms a localized NaHA depot within the dermal compartment of RhFS and preserves spatial hydration gradients, which are lost when NaHA is mixed homogenously. The platform integrates physicochemical characterization of polymer-bound water states with cellular and tissue-level functional readouts. By quantifying key biomarkers, including CD44, aquaporin-3 (AQP3) and natural moisturizing factors (NMFs), our results demonstrate that the inclusion-based delivery strategy significantly outperforms conventional mixing approaches in activating epidermal hydration pathways. Crucially, this platform effectively distinguished the moisturizing efficacy of multiple commercial NaHA formulas, thereby revealing a structure-activity relationship between water-binding states and biological outcomes. Overall, this study presents a reproducible, mechanism-informed and human-relevant framework for preclinical performance evaluation of NaHA-based injectable biomaterials and provides a sensitive alternative to conventional animal-based approaches. Graphical abstract For image description, please refer to the figure legend and surrounding text.

Background: Using hydrogels for the controlled release of drugs is beneficial for patients, who then receive the proper dose of the medicinal substance. In addition, the formulation can provide more consistent drug absorption while reducing the frequency of dosing. Objectives: The aim of this investigation is to propose a novel HA (sodium hyaluronate)-based hydrogel for intra-articular injection doped with synthetic polymers and incorporated with bupivacaine hydrochloride (Bu) as a local anesthetic. The other aim of this study is to reveal the effects of the formulation’s ingredients on its viscosity and the relationship between the hydrogel’s viscosity and drug release. Methods: First, HA-based hydrogels doped with synthetic polymers and incorporated with Bu were prepared. A study of the hydrogels’ viscosities was performed using a rotational viscometer. Release tests were carried out by employing a paddle-over-disk apparatus following the USP/Ph.Eur guidelines. The drug concentrations in the acceptor fluid were analyzed spectrophotometrically. Results: It was found that the viscosity of the hydrogels doped with synthetic polymers was higher than the viscosity of the hydrogels made with only HA. The viscosity of the hydrogels doped with AX (ammonium acryloyldimethyltaurate/VP copolymer) was the highest, measuring 6750 ± 160 cP and 12623 ± 379 cP with and without Bu, respectively. The results of the kinetic experiment indicate that the Higuchi and Korsmeyer–Peppas models best described the drug release. Bu was released the most slowly from the formulation doped with AX. The release rate constants obtained from the Higuchi and Korsmeyer–Peppas models were kH = 4.4 ± 0.2 mg × min−1/2 and kK-P = 3.4 ± 0.2 × 10−2 min–N, respectively. The half-release time, calculated using the Higuchi model, was the longest for the formulation doped with AX, at 199.5 ± 17.6 min. Conclusions: This indicates that the incorporation of AX into the hydrogel may prolong the drug dissolution. The hydrogel doped with AX was the optimal formulation for the controlled release of Bu.