Hyaluronic Acid (Oral)

BACKGROUND: Hyaluronic acid (HA) is a key component naturally present in the skin and is commonly used in skincare formulations and dermal fillers. Recently, there has been growing interest in oral HA supplementation for maintaining skin health and preventing aging due to its potential systemic benefits. OBJECTIVE: This study aims to provide a comprehensive analysis of the efficacy of oral HA supplementation on various skin parameters, including hydration, elasticity, firmness, wrinkle reduction, and transepidermal water loss. METHOD: Electronic databases (PubMed and Google Scholar) were searched for relevant articles. A total of 7 randomized controlled trials (RCTs) on the use of oral HA as a supplement were identified. A meta-analysis was performed to compare the standardized mean differences between the treatment (HA) and control (placebo) groups. RESULTS: The meta-analysis revealed statistically significant improvements in skin hydration, elasticity, and wrinkle depth following oral HA supplementation. Although the effects of oral HA on skin firmness, wrinkle volume, and transepidermal water loss were not statistically significant, a general trend of improvement was observed in these parameters. CONCLUSION: The findings of this analysis align with existing literature, underscoring the potential of oral HA supplementation as a valuable component in anti-aging and skincare regimens. However, the study's limited sample size and heterogeneity among included studies call for larger, more robust trials to confirm these findings and further explore the effects of oral HA on skin health.

Background Ageing is a degenerative process that affects the entire body. Skin ageing is characterised by a decrease in the levels of collagen, elastin fibre, and hyaluronic acid (HA), resulting in a loss of skin elasticity and hydration. Prior studies suggest that oral collagen supplements can help increase collagen, elastin, and HA levels, ultimately improving skin health. Objective To assess the impact of collagen-based supplements on the signs of skin ageing and determine the effective dosage. Methods This systematic review and meta-analysis utilized PubMed, Clinical Key, ProQuest, and Cochrane Library databases to identify studies published from 2010 to 2021. It includes ten randomised controlled trials (RCTs) with a total of 646 participants. Results The findings indicate that collagen supplements were statistically effective in increasing skin hydration (SMD 1.25 (CI: 0.77-1.74)) and elasticity (SMD 0.61 (CI: 0.21-1.02)). The most commonly administered dose was 4 g/day, with a median dose of 3.5 g/ day. Limitations Most of the studies could not control for weather-related factors. The findings are more applicable to females. Moderate heterogeneity (I2 = 55.5-56.5%) may limit generalisability. The risk of bias was generally unclear, and publication bias could not be assessed due to the small number of studies. Conclusion Oral administration of collagen supplement in a dose ranging from 1-10 g/day was statistically effective in increasing the skin hydration and elasticity.

BACKGROUND: Stem cells are specialised precursor cells that can replace aged or damaged cells and thereby maintain healthy tissue function. Stem cell therapy is increasingly used as a treatment for knee osteoarthritis, despite the lack of clarity around the mechanism by which stem cell therapy may slow down disease progression in osteoarthritis, and uncertainty regarding its benefits and harms. OBJECTIVES: To assess the benefits and harms of stem cell injections for people with osteoarthritis of the knee. A secondary objective is to maintain the currency of the evidence, using a living systematic review approach. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase on 15 September 2023, unrestricted by date or language of publication. We also searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) for relevant trial protocols and ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs), or trials using quasi-randomised methods of participant allocation, comparing stem cell injection with placebo injection, no treatment or usual care, glucocorticoid injection, other injections, exercise, drug therapy, surgical interventions, and supplements and complementary therapies in people with knee osteoarthritis. DATA COLLECTION AND ANALYSIS: Two review authors selected studies for inclusion, extracted trial characteristics and outcome data, assessed risk of bias and assessed the certainty of evidence using the GRADE approach. The primary comparison was stem cell injection compared with placebo injection. The primary time point for pain, function and quality of life was three to six months, and the end of the trial period for participant-reported success, joint structure changes and adverse event outcomes. Major outcomes were pain, function, quality of life, global assessment of success, radiographic joint progression, withdrawals due to adverse events and serious adverse events. MAIN RESULTS: We found 25 randomised trials (1341 participants) comparing stem cell injections with placebo injection (eight trials), no treatment or usual care (analgesia, we

BACKGROUND: Treatment of gingival recessions through surgical approaches is a common periodontal intervention. There is a rise in using biologics in root coverage procedures. As it has been shown that hyaluronic acid (HA) promotes wound healing, this review aimed to assess its efficacy in the treatment of gingival recessions. METHODS: An electronic search was conducted across several databases (Medline/ PubMed, Embase, Scopus, Web of Science) supplemented by manual searching. The effectiveness of using HA was evaluated using various outcome measures, with the primary indicators being complete and mean coverage, recession depth, and recession width. Meta-analysis was performed to estimate the differences between test and control sites. RESULTS: A total of 9 studies were eligible for inclusion. The overall analysis showed no significant difference between coronally advanced flap (CAF) + HA and control groups (CAF alone or CAF + sub-epithelial connective tissue graft) in terms of mean root coverage with a mean difference of 8.23 (95% confidence interval -3.06 to 19.53) and p = 0.12. CONCLUSIONS: The current evidence suggests that the local application of HA may have some slight benefits over CAF alone in certain parameters. Nevertheless, its application does not add significant benefits to connective tissue graft. Given the high heterogeneity among the studies, further research with extended follow-up periods is necessary to better understand the clinical implications of using hyaluronic acid in this context. TRIAL REGISTRATION: CRD42024580649. © 2025. The Author(s).

Temporomandibular joint osteoarthritis (TMJ-OA) is a progressive degenerative disorder, for which therapeutic interventions remain limited. The disruption of metabolic homeostasis plays a critical role in the pathogenesis and advancement of TMJ-OA. However, it remains unclear whether extracellular vesicles (EVs) as cellular metabolites are correlated with the pathogenesis, treatment and diagnosis of TMJ-OA. In this study, we demonstrated that autologous circulating extracellular vesicles (C-EVs) possessed significant therapeutic potential for TMJ-OA through the targeted removal of senescent chondrocytes. In a randomized clinical trial (ChiCTR2200063153), C-EV administration was found to significantly enhance condylar bone regeneration and alleviate symptoms relative to hyaluronic acid controls, without eliciting any adverse effects. Comparative analysis revealed that joint cavity-derived EVs from TMJ-OA patients (OA-EVs) exhibited structural abnormalities, diminished expression of canonical EV markers, and pro-inflammatory characteristics. In contrast, C-EVs were significantly enriched with functional proteins C1q binding protein (C1QBP). And the level of C1QBP-positive EVs was positively correlated with therapeutic outcomes, thereby establishing C1QBP as a potential predictive biomarker for TMJ-OA. Furthermore, C-EVs reestablished joint homeostasis by regulating the immune microenvironment and tissue regeneration capacity. Mechanistically, C1QBPhigh C-EVs upregulated the expression of membrane C1q on senescent chondrocytes, thereby initiating C1q-C1QBP binding, p14ARF translocation to mitochondria, and subsequent cytochrome C/caspase-3-dependent apoptosis. Our findings demonstrate that C-EVs serve a dual therapeutic role by facilitating the clearance of senescent cells via the C1QBP/C1q/p14ARF axis, while promoting tissue regeneration and regulating metabolites homeostasis, offering a novel biological strategy for TMJ-OA treatment. © 2026 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.

OBJECTIVE: Temporomandibular joint disorders (TMDs) are a common source of orofacial pain and dysfunction. Arthrocentesis of the temporomandibular joint (TMJ) is a minimally invasive treatment that can be augmented with intra-articular injections. This study aimed to compare the clinical efficacy of platelet-rich plasma (PRP) versus hyaluronic acid (HA) injections following TMJ arthrocentesis in patients with TMDs unresponsive to conservative therapy. METHODS: Sixty patients (72 joints) were randomized into three equal groups. Group A underwent arthrocentesis with Ringer's lactate (RL) alone (control), Group B received PRP injection post-arthrocentesis, and Group C received HA injection post-arthrocentesis. Pain intensity (VAS), maximum mouth opening (MMO), and TMJ sounds were evaluated at baseline, 1 week, 12 weeks, and 24 weeks. Repeated-measures ANOVA and chi-square tests were used for analysis (p < 0.05). RESULTS: All groups showed significant improvements in pain and MMO over time. Mean VAS pain scores decreased from ~ 4.8 to < 1.0 at 24 weeks (p < 0.001), while MMO increased from ~ 32 mm to ~ 40 mm (p < 0.001). No significant differences were found between the PRP and HA groups in pain or function at any follow-up point, nor between either treatment group and the control group. TMJ clicking resolved or improved in > 95% of joints across all groups. No adverse events were recorded. CONCLUSION: TMJ arthrocentesis alone provides substantial pain relief and functional gains. PRP and HA did not confer additional benefit over lavage alone within the 6-month timeframe. Further studies are required to assess any potential long-term differences. © 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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). © 2025. The Author(s).

BACKGROUND: Lips are prone to dehydration and aging. Effective noninvasive hyaluronic acid (HA) delivery remains challenging. AIM: To evaluate topical Replenishing Lip Filler-Tiered Release Vesicles (RLF-TRV) in filler-naïve and previously-augmented lips. METHODS: Two single-center trials evaluated efficacy and tolerability of RLF-TRV Serum. Study 1 included filler-naïve subjects or those without lip filler for 12 months. Study 2 enrolled subjects with prior HA lip augmentation (3-9 months earlier) in a double-blind, placebo-controlled design. Participants applied RLF-TRV or placebo twice daily for 3 weeks, followed by a 2-week regression period. Outcomes included grading of shine, texture, and vermilion border, Investigator and Subject Global Aesthetic Improvement Scale (I-GAIS, S-GAIS), and satisfaction. Imaging and tolerability assessments were conducted throughout the study. RESULTS: RLF-TRV significantly improved lip aesthetics (shine, texture, and vermilion border), with high satisfaction across both studies. In Study 1, 94% of treated participants were "Improved" on I-GAIS (p < 0.001), and 81% were "Much-Improved" on S-GAIS (p < 0.05). In Study 2, 88% of treated participants were "Improved" on both I-GAIS and S-GAIS. RLF-TRV was well tolerated, with no recorded adverse events. CONCLUSIONS: RLF-TRV significantly improved lip aesthetics, offering a noninvasive alternative or complementary treatment to injectable procedures. © 2025 Ourself. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.

OBJECTIVES: For treating stage II grade B periodontitis in controlled type 2 diabetes, this study compared the clinical and microbiological effectiveness of adjunctive 2% minocycline and 0.2% hyaluronan gels in combination with subgingival instrumentation versus subgingival instrumentation alone. METHODS: Twenty patients were divided into two groups: group I (hyaluronan and minocycline gel with subgingival instrumentation vs. placebo with subgingival instrumentation) and group II (hyaluronan and minocycline gel alone vs. placebo with subgingival instrumentation ). Using a split-mouth design, subgingival plaque samples were analysed for Porphyromas gingivalis (P gingivalis) and Prevotella intermedia (P intermedia) at baseline and one month after treatment. Clinical parameters such as plaque index (PI), gingival index (GI), bleeding on probing (BOP), periodontal pocket depth (PPD), and clinical attachment level (CAL) were evaluated at baseline and three months after treatment. RESULTS: In Group I, the clinical improvements were significant in sites treated with subgingival instrumentation and the hyaluronan-minocycline gel than with subgingival instrumentation and placebo, with a mean decrease in PPD 2.1 ± 0.4 mm versus 1.2 ± 0.3 mm and a mean increase in CAL 1.9 ± 0.3 mm versus 1.0 ± 0.2 mm (p < 0.01 for both). Microbiologically, these sites also showed a 63% greater reduction in the level of P. gingivalis (p < 0.01). In Group II, the use of subgingival instrumentation and placebo yielded better clinical outcome measures for PPD and CAL (p < 0.05) than for gel monotherapy, although gel-only sites showed a minor but significant reduction in the level of P. gingivalis (p < 0.05). CONCLUSION: The adjunctive application of hyaluronan-minocycline gel with subgingival instrumentation showed significant short-term improvements in periodontal outcomes compared with subgingival instrumentation alone, indicating a beneficial supportive effect for type 2 diabetics with Stage II, Grade B periodontitis. In contrast, gel monotherapy showed limited clinical efficacy, despite some microbiological reduction, underscoring that mechanical debridement remains essential and that loca

OBJECTIVE: The current trial assessed for the first time radiographic and histological alterations, following alveolar ridge preservation (ARP), using autogenous demineralized dentin graft carried in 0.2% high molecular weight sodium hyaluronate (ADDG+HA; test group) versus autogenous demineralized dentin graft (ADDG, control group) alone. MATERIAL AND METHODS: Thirty patients (n = 30) with non-restorable single-rooted teeth were randomly assigned into two groups (n = 15/group). Following extraction, ARP was performed using either ADDG solely or ADDG+HA. Bucco-lingual alveolar ridge width (BLRW; primary outcome), buccal (BRH) and lingual ridge height (LRH), percentage of newly formed bone, soft tissue and residual graft in human biopsies histologically, as well as patients' pain and discomfort (all secondary outcomes) were assessed after 6 months at the time of implant placement. Sample bone core biopsies were further collected, processed, and histomorphometrically and SEM analyzed. RESULTS: For the ADDG and ADDG+HA groups, the alveolar ridge dimensional changes were comparable, being -1.21 ± 0.77 mm and -1.18 ± 0.86 mm in BLRW, -0.89 ± 0.74 and -0.83 ± 0.85 mm in BRH, and -0.9 ± 0.76 mm and -1.05 ± 1.18 mm in LRH respectively (p > 0.05). Clinically, no complications, pain, or inflammatory responses were reported. Histologically, all samples demonstrated bone growth and socket bone fill, while the ADDG+HA group showed a significantly greater presence of mineralized mature bone, which accounted for 33% ± 8.1% of the specimen after 6 months. CONCLUSIONS: Both ADDG and ADDG+HA demonstrated comparable outcomes in terms of ARP. HA amalgamation with ADDG appears to enhance bone mineralization and maturation, yet without a significant impact on dimensional changes during ARP procedures. TRIAL REGISTRATION: NCT05613075. © 2025 The Author(s). Clinical Implant Dentistry and Related Research published by Wiley Periodicals LLC.

BACKGROUND: A major factor influencing the outcome of primary molar pulpotomy is the pulp-dressing material used. This study aimed to evaluate the clinical and radiographic outcomes of primary molar pulpotomies using hyaluronic acid (HA) gel and mineral Trioxide Aggregate (MTA) as pulpotomy medicaments at 6 and 12 months follow-up. MATERIALS AND METHODS: A total of 28 children aged 4-8 years were included. Thirty-two primary molar teeth with deep carious lesions, with no history of spontaneous pain or signs of irreversible pulpitis, were treated by pulpotomy by a single operator using either HA or MTA as the pulp-dressing material. All teeth were restored using glass-ionomer cement, followed by a stainless steel crown. Clinical and radiographic assessments were performed at the 3, 6, and 12 months by two independent evaluators. Statistical comparative analyses were performed using the Chi-square test, and Kaplan-Meier plots were synthesized. Statistical significance was determined when P < 0.05 was obtained. RESULTS: In each group, 15 teeth were analyzed after 12 months. The clinical success rates were 93% and 100%, while the radiographic success rates were 80% and 60% for the MTA and HA groups, respectively. Most radiographic failures in the HA group were seen at the 6th-month follow-up. CONCLUSION: HA was comparable to MTA as a pulp-dressing material when evaluated clinically and radiographically at the 3, 6, and 12 months' follow-up.

OBJECTIVES: This study aimed to compare the effects of locally applied hyaluronic acid (HA) and injectable platelet-rich fibrin (I-PRF) on patient morbidity, oral health-related quality of life (OHRQoL), and healing of palatal donor sites, palatal tissue consistency, complete epithelization (CE), and color match (CM). MATERIALS AND METHODS: Sixty-seven patients undergoing free gingival grafting (FGG) were randomly assigned to three groups in an examiner-masked clinical trial. Test group 1 received a 0.8% HA gel-impregnated gelatin sponge, test group 2 received an I-PRF-impregnated sponge, and the control group received a sterile sponge. Pain and burning were assessed via a visual analog scale (VAS) on days 3, 7, 14, and 21. CM was evaluated on days 3, 7, 14, 21, 28, and at months 1 and 3. CE and Landry Wound Healing Index (WHI) were recorded on days 3, 7, 14, 21, and 28. RESULTS: Topical application of hyaluronic acid (HA) and injectable platelet-rich fibrin (I-PRF) significantly reduced postoperative discomfort and improved complete epithelization (CE) compared to the control group (p < 0.05). HA showed better outcomes than I-PRF in wound healing and morbidity, while I-PRF also significantly reduced postoperative pain (p < 0.05). Palatal tissue thickness at the 1st and 3rd months differed significantly among groups (p = 0.001), and OHRQoL scores decreased significantly from day 7 to day 14 in all groups (p < 0.05). CONCLUSION: The adjunctive use of HA or I-PRF with gelatin sponge is more effective in minimizing discomfort and enhancing healing at palatal donor sites than sponge use alone. CLINICAL RELEVANCE: Optimizing healing and minimizing patient discomfort at palatal donor sites are crucial for improving outcomes in free gingival grafting procedures. This study demonstrates that the adjunctive application of HA or I-PRF significantly enhances soft tissue healing and reduces postoperative morbidity. Particularly, HA was found to be more effective in promoting wound healing and comfort. These findings support the clinical use of HA or I-PRF as simple, biocompatible adjuncts to improve patient experience and surgical outcomes in periodontal procedures. CLINICA

OBJECTIVE: The aim was to evaluate the impact of cross-linked hyaluronic acid (HA) gel on the clinical outcomes of gingival depigmentation using scalpel or diode laser techniques. METHOD AND MATERIALS: In this single-blinded, prospective, randomized clinical trial, 44 patients who had maxillary gingival pigmentation were allocated into a test group (HA+) that had HA gel applied, and a control group (HA-). Depigmentation was performed using a scalpel or a 940-nm diode laser (0.8 W) in a split-mouth design. The follow-up visits were at 3, 7, 14, and 30 days. Clinical measurements included the Wound Healing Index (WHI), digital measurement of the non-healed remaining area (NRA), pigmentation, pain, and Bleeding Index. RESULTS: At 30 days, WHI and NRA showed similar results in both HA- and HA+ groups (P > .05). In contrast, the diode laser had significantly improved mean WHI by day 7 and 14, and mean NRA by day 3 and 7 (WHI = 1.55 and 1.02; NRA = 28.7% and 2.1%, respectively) in comparison to the scalpel (WHI = 1.70 and 1.14; NRA = 52.6% and 5.0%, respectively). The decrease in pigmentation intensity and distribution was highly significant (P .001) and similar between the HA-, HA+, scalpel, and laser groups at 1 month (P > .05). The pain did not differ significantly between HA- and HA+ groups (P > .05). However, pain was significantly less with the diode laser than the scalpel (P .05). Significantly less bleeding occurred with the diode laser than the scalpel (P .001). CONCLUSION: HA did not confer additional benefits to promote wound healing and reduce pain in depigmentation. Diode laser is a convenient method of depigmentation that improves initial healing and decreases initial pain, with reduced bleeding. Gingival hyperpigmentation is a major esthetic issue for many individuals. Laser and scalpel treatments produce equivalent esthetic outcomes.

BACKGROUND: Midface volume deficiency is a common aesthetic concern that can be addressed with dermal fillers. YVOIRE Y-Solution 720 (YYS720) is a hyaluronic acid (HA)-based filler designed for midface augmentation. This study aimed to evaluate the effectiveness and safety of YYS720 in improving midface volume. METHODS: Asian participants with mild to severe midface volume loss were randomly assigned to receive either YYS720 injection (n = 173) or no treatment (control, n = 65). Midface volume was evaluated at 4, 14, and 26 weeks using Midface Volume Deficit Severity Rating Scale for Asian Faces (MFVDA-SRS) for both YYS720 and control groups. Additionally, for YYS720, midface volume was evaluated 52 weeks after the last injection. RESULTS: At Week 26, the proportion of participants with ≥ 1-grade reduction on the MFVDA-SRS score was 82.0% (137/167 participants) for YYS720 and 5.1% (3/59 participants) for control with difference (95% confidence interval, CI) between the groups of 77.0% (66.8, 84.0), demonstrating the statistically significant improvement of YYS7720 in midface augmentation. At Week 52, the proportion of participants with ≥1-grade reduction on the MFVDA-SRS score was 76.2% for YYS720 group. Global Aesthetic Improvement Scale (GAIS) responder rates by participants were consistently high in YYS720 group across all time points up to Week 26. No specific safety concern was detected. Common treatment site responses included swelling, tenderness, and pain, which were generally mild and transient. CONCLUSIONS: This study supports that YVOIRE Y-Solution 720 is an effective and safe option for midface volume augmentation. LEVEL OF EVIDENCE I: 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 . © 2025. The Author(s).

Curcumin (CUR) has been reported to enhance the chemotherapeutic efficacy of oxaliplatin (OXA) in colorectal cancer (CRC) and inhibit OXA-induced side effects. However, shortcomings, including poor solubility and sensitivity to metabolic transformation, have greatly undermined its value in clinical applications. In this study, the potential of CUR-encapsulated hyaluronic acid (HA)-zein composite nanoparticles (HZ-CUR) as an oral adjuvant for OXA-based chemotherapy was assessed in representative CRC models in mice. Cell viability and colony formation assays in three human CRC cell lines showed that HZ-CUR had a stronger anti-CRC effect than free CUR when given alone and a stronger synergistic effect when combined with OXA, especially in HCT116 and HT29 cell lines. Western blotting, cellular uptake, and RNA interference assays revealed that OXA-induced upregulation of CD44 likely contributed to enhanced cellular uptake of HZ-CUR and thus the enhanced anticancer effect. The significantly improved anti-CRC effects and potential underlying mechanism of HZ-CUR alone and in combination with OXA were further validated in a subcutaneous xenograft and an in situ CRC model in mice. These findings support that HZ-CUR may be an effective oral adjuvant for OXA-based CRC chemotherapy that would not only improve its efficacy but also help reduce the associated side effects.

Osteoarthritis (OA) progression is associated with joint pain and stiffness. Intra-articular hyaluronic acid (IAHA) injection in knee OA restores the viscoelasticity of the joint and prevents cartilage damage. Shea nut oil extract (SNO) was shown to provide chondroprotection on surgically-induced OA progression in rats. Here we aim to examine IAHA injection supplemented with SNO diet for a synergetic evaluation on the disease progression in OA rats. We employed an anterior cruciate ligament transection plus medial meniscectomy-induced knee OA rat model with up to 12 weeks of sign/behavior observation (knee width, weight-bearing) and histological assessments of joint damage. We found both IAHA and SNO alone significantly attenuated histological changes of cartilage degeneration and synovial reactions in these knee OA rats. Nonetheless, oral SNO alone mitigated OA pain and inflammation while IAHA alone had no significant impact on the weight-bearing test and knee joint swelling. Moreover, with IAHA-treated rats fed with oral SNO diet, additional anti-inflammatory and anti-nociceptive effects were found, which further enhanced and maintained IAHA protection. Given the differential phenotype of oral SNO vs. IAHA, a regimen of IAHA coupled with SNO supplement provides a long-term effect of IAHA treatment. Taken together, the SNO supplement can be safely used as an adjuvant diet for chronic symptomatic relief of OA coupled with IAHA management.

Biphasic bone substitutes (BBS) are currently well-established biomaterials. Through their constant development, even natural components like hyaluronic acid (HY) have been added to improve both their handling and also their regenerative properties. However, little knowledge exists regarding the consequences of the addition of HY to their biocompatibility and the inflammatory tissue reactions. Thus, the present study was conducted, aiming to analyze the influence of two different amounts of high molecular weight HY (HMWHY), combined with a BBS, on in vitro biocompatibility and in vivo tissue reaction. Established in vitro procedures, using L929 cells, were used for cytocompatibility analyses under the test conditions of DIN EN:ISO 10993-5. For the in vivo part of the study, calvarial defects were created in 20 Wistar rats and subsequently filled with BBS, and BBS combined with two different HMWHY amounts, i.e., BBS + HY(L) and BBS + HY(H). As controls, empty defects were used. Established histological, immunohistochemical, and histomorphometrical methods were applied to analyze the tissue reactions to the three different materials, including the induction of pro- and anti-inflammatory macrophages and multinucleated giant cells (BMGCs). The in vitro results showed that none of the materials or compositions caused biological damage to the L929 cells and can be considered to be non-toxic. The in vivo results showed that only the addition of high doses of HY to a biphasic bone substitute significantly decreases the occurrence of pro-inflammatory macrophages (* p < 0.05), comparable to the numbers found in the control group, while no significant differences within the three study groups for M2-macrophages nor BMGCs were detected. In conclusion, the addition of different amounts of HMWHY does not seem to affect the inflammation response to BBS, while improving the material handling properties.

Proinflammatory cytokines and reactive oxygen species (ROS) are known to be involved in the initiation and progression of osteoarthritis (OA). New evidence clarifying the correlation between ROS and inflammation has indicated that oxidative stress can up-regulate inflammatory cytokines. l-Ascorbic acid (AA), an antioxidant, has been shown to have anti-inflammatory effects and improve matrix deposition in chondrocytes. The purpose of this study was to examine the effects of hyaluronic acid (HA; 100 μg/mL) supplemented with AA (50 μg/mL) on human normal and interleukin-1 beta-stimulated (IL-1β, 10 ng/mL) chondrocytes. HA, AA, and HA + AA treatment did not change cell morphology, viability, proliferation, and glycosaminoglycan production in normal chondrocytes. HA, AA, and HA + AA, by contrast, partially restored viability and morphology of hypertrophic chondrocytes, and HA and HA + AA further decreased the cytotoxicity of IL-1β. Real-time PCR revealed that AA and HA + AA had no substantial effects on unstimulated chondrocytes, except for down-regulation of matrix metalloproteinase (MMP)-9 mRNA levels. For IL-1β-stimulated chondrocytes, significant down-regulation of IL-1β, tumor necrosis factor-alpha (TNF-α), MMP-3, and MMP-9 mRNA expression was found when cells were cultured in HA-supplemented media. Moreover, HA + AA supplementation further significantly decreased MMP-3 and MMP-9 mRNA expression. The protein production of MMP-3 was decreased, with a significant difference between the HA + AA group and HA group. The antioxidant capacity and superoxide dismutases activity were also partially restored in stimulated chondrocytes. HA supplemented with AA modulates MMPs expression and antioxidant fuction in chondrocytes. AA may enhance the anticatabolic effects of HA on OA chondrocytes. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1809-1817, 2018. © 2017 Wiley Periodicals, Inc.

179. Cell Physiol Biochem. 2015;37(5):1792-806. doi: 10.1159/000438542. Epub 2015 Nov 13. Synergistic Effects of a Mixture of Glycosaminoglycans to Inhibit Adipogenesis and Enhance Chondrocyte Features in Multipotent Cells. Petrov PD, Granados N, Chetrit C, Martínez-Puig D, Palou A, Bonet ML. BACKGROUND/AIMS: Multipotent mesenchymal stem cells affect homeostasis of adipose and joint tissues. Factors influencing their differentiation fate are of interest for both obesity and joint problems. We studied the impact of a mixture of glycosaminoglycans (GAGs) (hyaluronic acid: dermatan sulfate 1:0.25, w/w) used in an oral supplement for joint discomfort (Oralvisc™) on the differentiation fate of multipotent cells. METHODS: Primary mouse embryo fibroblasts (MEFs) were used as a model system. Post-confluent monolayer MEF cultures non-stimulated or hormonally stimulated to adipogenesis were chronically exposed to the GAGs mixture, its individual components or vehicle. The appearance of lipid laden cells, lipid accumulation and expression of selected genes at the mRNA and protein level was assessed. RESULTS: Exposure to the GAGs mixture synergistically suppressed spontaneous adipogenesis and induced the expression of cartilage extracellular matrix proteins, aggrecan core protein, decorin and cartilage oligomeric matrix protein. Hormonally-induced adipogenesis in the presence of the GAGs mixture resulted in decreased adipogenic differentiation, down-regulation of adipogenic/lipogenic factors and genes for insulin resistance-related adipokines (resistin and retinol binding protein 4), and up-regulation of oxidative metabolism-related genes. Adipogenesis in the presence of dermatan sulfate, the minor component of the mixture, was not impaired but resulted in smaller lipid droplets and the induction of a more complete brown adipocyte-related transcriptional program in the cells in the adipose state. CONCLUSIONS: The Oralvisc™ GAGs mixture can tip the adipogenic/chondrogenic fate balance of multipotent cells away from adipogenesis while favoring chondrocyte related gene expression. The mixture and its dermatan sulfate component also have modulatory effects of interest on hor

For decades, evidence-based data and reported experience have warned that the common chronic oral nonsteroidal anti-inflammatory drug (NSAID) therapy for osteoarthritis (OA) in elderly patients is ultimately dangerous. Elderly patients with OA are at heightened risk for developing serious gastrointestional and cardiovascular adverse events, including gastrointestinal bleeding, myocardial infarction, and stroke. Prescribing NSAIDs, especially in an elderly population, continues to be discouraged because of these significant risks. A dilemma exists for individuals who need the established efficacy associated with oral NSAIDs but who are at increased risk for serious adverse events associated with these agents. The goal of this clinical review was to evaluate the risks versus benefits of current options in the treatment of OA. This review found that topical NSAIDs seem to be the safest choice among all options to mitigate gastrointestinal and cardiovascular risks and should be considered prior to the initiation of oral nonselective or cyclooxygenase (COX)-2-selective NSAIDs for individuals presenting with a localized expression of OA. Further research is needed to evaluate and compare these therapies in treating both pain and inflammation effectively while mitigating safety risks in high-risk populations. A role for CD44 in the production of IFN-gamma and immunopathology during infection with Toxoplasma gondii. Blass SL(1), Puré E, Hunter CA. Author information: (1)Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. The interaction of activated CD44 with its ligand, low m.w. hyaluronan, is involved in inflammation, but no role has been identified for this interaction in the regulation of an immune response to infection. In these studies, infection of C57BL/6 mice with Toxoplasma gondii resulted in increased expression of CD44 on T cells, B cells, NK cells, and macrophages, and a small percentage of CD4(+) T cells express an activated form of CD44. Administration of anti-CD44 to infected mice prevented the development of a CD4(+) T cell-dependent, infection-induced inflammatory response in the small

36. J Immunol. 2001 May 1;166(9):5726-32. doi: 10.4049/jimmunol.166.9.5726. A role for CD44 in the production of IFN-gamma and immunopathology during infection with Toxoplasma gondii. Blass SL(1), Puré E, Hunter CA. Author information: (1)Department of Pathobiology, School of Veterinary Medicine

High-molecular-weight hyaluronic acid (HA) produced by the synovium may function physiologically to aid preservation of cartilage structure and prevent arthritic pain; both the size and concentration of HA in synovial fluid are diminished in osteoarthritis (OA). Glucosamine therapy for OA can be expected to increase synovial HA production by providing rate-limiting substrate. In addition, certain sulfated glycosaminoglycans and polysaccharides - including chondroitin sulfate (CS), dermatan sulfate, and pentosan polysulfate - stimulate synovial HA production, apparently owing to a hormone-like effect triggered by the binding of these polymers to membrane proteins of synovial cells. Surprisingly, a significant proportion of orally administered CS is absorbed as intact polymers - apparently by pinocytosis. These considerations may rationalize clinical studies concluding that oral CS provides slow-onset but durable pain relief and functional improvement in OA. The possibility that oral glucosamine and CS may interact in a complementary or synergistic fashion to improve synovial fluid HA content in OA should be assessed in clinical studies, and the potential of adjunctive CS administration to improve the clinical response achievable with optimal intakes of glucosamine should likewise be evaluated. In light of the fact that the synovium virtually functions as a 'placenta' for cartilage, focusing on synovium as the target for therapeutic intervention in OA may be a rational strategy. Copyright 2000 Harcourt Publishers Ltd.

The present study was done to determine the additional influence of daily ethanol intake (15% in drinking water ad libitum) on long-term toxic effects of a single administration of dibutyltin dichloride (DBTC, 8 mg/kg b.w. i.v.) in pancreas and liver of rats. Pathohistological changes in pancreas, bile duct and liver as well as pathobiochemical parameters of pancreatitis (amylase and lipase activity), liver lesions (alkaline phosphatase activity and bilirubin) and fibrosis (hydroxyproline and hyaluronic acid) were measured 1 day and 1 to 24 weeks after DBTC- and DBTC/ethanol administration. DBTC alone induced in rats an acute interstitial pancreatitis as well as acute bile duct and liver lesions in the early experimental phase. Later on, the acute inflammatory processes in pancreas and liver took a chronic course resulting in pancreatic fibrosis and liver cirrhosis. Ethanol increased the toxic effects of DBTC on pancreas and liver during the acute and chronic course. In the acute phase lasting 1 day to 2 weeks, ethanol enhanced the DBTC toxicity on acinar cell and bilio-pancreatic duct epithelium as well as the formation of obstructive ductal plugs by necrotic cell debris. The obstruction and cholestasis in the DBTC/ethanol-group were significantly stronger as in the DBTC-group. The significant increase of hydroxyproline in urine and hyaluronic acid in serum of the DBTC/ethanol treated rats after 12 to 24 weeks was connected with a more severe chronic inflammatory fibrosis in pancreas and liver in comparison to the DBTC-treated group.

Oral administration of alcohol along with nicotine decreased all the glycosaminoglycan (GAG) fractions except hyaluronic acid in aorta and liver of rats. Decreased activity of the enzymes involved in the biosynthesis of precursors of GAG and increased activity of many of GAG hydrolysing enzymes indicate decreased biosynthesis and increased degradation of GAG. Sulphate metabolism in liver was also significantly altered by administration of both alcohol and nicotine showing considerable decrease in the concentration of sulphated GAG.

INTRODUCTION: The combination of hyaluronic acid (HA) fillers and polydioxanone (PDO) thread lifting is gaining popularity for mid-face rejuvenation, especially among the Asian population. Despite the common use of these techniques, there is a paucity of long-term studies assessing their combined efficacy and safety. This study aims to evaluate the efficacy and safety of combined HA filler and PDO thread treatment for mid-face rejuvenation over a 24-month period in a Korean population. MATERIALS AND METHODS: This prospective, blinded, single-center, open-label trial included 11 Korean subjects, aged 29-70 years, with mid-face volume loss graded 1-4 on the antero-medial cheek fullness scale. Participants were treated with crosslinked HA dermal fillers and PDO threads. Assessments were conducted using the Global Aesthetic Improvement Scale (GAIS), investigator-led clinical evaluations, and volumetric measurements using the Morpheus 3D system at baseline, 6, 12, and 24 months post-treatment. RESULTS: Quantitative analysis revealed a significant reduction in mid-face width from an average baseline of 149.27-145.00 mm at 24 months (p < 0.00001). Similarly, lower-face width decreased from 130.36 to 117.27 mm at 24 months (p < 0.00001). The GAIS scores demonstrated high levels of subject satisfaction, with 9 out of 11 patients reporting consistent satisfaction or improvement over 24 months. Minimal adverse events were reported, and no serious complications occurred. DISCUSSION: The combination of HA fillers and PDO threads was effective in achieving and maintaining long-term improvements in facial volume and contour. The Morpheus 3D system provided objective volumetric data, which supported the subjective improvements observed by patients and investigators. The study results highlight the benefits of ongoing neocollagenesis and tissue remodeling beyond the dissolution period of the materials. CONCLUSION: The combination of HA filler injections and PDO thread lifting offers a promising and minimally invasive option for long-term mid-face rejuvenation with high patient satisfaction and a favorable safety profile. Further studies are warranted to confirm these findings ac

Erratum in Nutrients. 2024 Jun 20;16(12):1961. doi: 10.3390/nu16121961. Osteoarthritis is a significant global health problem. Many patients seek more effective alternatives to nonsteroidal anti-inflammatory medicines or commercial supplements to manage joint pain and inflammation. FlexPro MD® (FP-MD) combines krill oil, astaxanthin, and lower molecular weight hyaluronic acid to support joint health. A 12-week, randomized, double-blind, placebo-controlled trial compared the efficacy and safety of FP-MD and placebo once daily in participants (n = 100) with mild osteoarthritis of the knee or hip joint. For the primary endpoint of joint pain score, per-protocol participants (n = 75) in the FP-MD group (n = 37) had a statistically significantly greater mean reduction from baseline in the Korean Visual Analog Scale (K-VAS) at week 12 compared with participants in the placebo group (n = 38) (20.8 ± 16.16 mm vs. 10.6 ± 17.58, p = 0.0105). The Korean Western Ontario and McMaster Universities Osteoarthritis Index (K-WOMAC) total score was also significantly improved in the FP-MD group at week 12 compared with placebo (-13.0 ± 13.62 vs. -5.5 ± 18.08, p = 0.0489), especially an improvement in pain score (-2.5 ± 2.92 vs. -1.3 ± 3.94, p = 0.02635). FP-MD group had greater improvement in joint function scoring by investigator assessment (p = 0.0127) and by group participants (p = 0.0070). A statistically significantly greater number of patients reported adverse events in the placebo group compared with the FP-MD group (16% vs. 4%, p = 0.0455), most commonly gastrointestinal disorders in both of the groups. These findings suggest that FP-MD is well tolerated and can be effectively used to address joint pain in patients diagnosed with mild osteoarthritis, the main symptom of this condition.

BACKGROUND: Hyaluronic acid is the most popular dermal filler in the treatment of nasolabial folds. Injection methods vary among physicians. METHODS: A randomized, two-center, double-blind, intraindividual trial was designed to compare a new method of injecting ART FILLER® UNIVERSAL using the retaining ligament with the traditional method (linear threading and bolus injection) in moderate to severe nasolabial folds. Forty patients with moderate to severe nasolabial folds were randomized into groups A and B. Group A received injections via the traditional method on the left side and the ligament method on the right side, while group B received the reverse. Clinical efficacy and patient safety were independently assessed by a blinded evaluator, the injector, using the Wrinkle Severity Rating Scale (WSRS), the Global Aesthetic Improvement Scale (GAIS), and the Medicis Midface Volume Scale (MMVS) at 4 weeks (before and after the touch-up injection), 8 weeks, 12 weeks, and 24 weeks after the baseline injection. RESULTS: From the perspective of the blinded evaluator, the improvements in WSRS scores from baseline did not differ significantly between the ligament method (0.73 ± 0.61) and the traditional method (0.89 ± 0.61) at week 24 (p > 0.05). The mean GAIS score at week 24 was 1.41 ± 0.49 for the traditional method and 1.32 ± 0.47 for the ligament method (p > 0.05). CONCLUSIONS: The efficacy and safety of the ligament method for the management of nasolabial folds are comparable to those of the traditional method in terms of WSRS and GAIS score improvement in the long run. The ligament method is superior to the traditional method in that it improves midface deficits with fewer adverse events. LEVEL OF EVIDENCE II: 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 . CLINICAL TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry under the registration number ChiCTR2100041702. © 2023. Springer Science+Business Media, LLC, part of Springer Nature a

Oral hyaluronic acid has been shown to reduce inflammation and pain in humans with osteoarthritis. Eight Asian small-clawed otters (Aonyx cinerea) and two African spot-necked otters (Hydrictis maculicolis) with varying degrees of osteoarthritic changes identified on radiographs were selected for a randomized, double-blinded, placebo-controlled clinical trial. Animal husbandry staff completed otter mobility assessment (OMA) questionnaires for each animal prior to study commencement and following either oral hyaluronic acid at a loading dose of 4 mg/kg PO SID for 10 d followed by a maintenance dose of 2 mg/kg PO SID for 20 d, or placebo for 30 d. Four veterinarians with experience assessing otters watched randomized videos of otter gaits and assigned a clinical lameness score. Two additional evaluators watched the videos: an experienced veterinarian in small animal practice and a final-year veterinary student. All evaluators for OMA and clinical lameness score were blinded to treatment group. Radiographs performed prior to, and following, the study were assessed by a board-certified radiologist (Dennison). The OMA questionnaire had high reliability coefficients and correlated strongly with clinical gait scores and radiographic assessment. Although hyaluronic acid appears to be safe for use in otters at the dose described, there was no observed significant effect of hyaluronic acid on clinical lameness scores, OMA scores, or radiographic assessment of the limbs. The development of the OMA questionnaire is a promising tool for evaluating lameness in managed-care otters and may be further validated in future studies investigating therapeutics or incorporated as a component of animal welfare assessment.

BACKGROUND: Oral mucositis is a serious complication radiation therapy for cancer. This is a major complication during radiation therapy of the head and neck tumors in approximately all patients. Therefore, this study was conducted to evaluate the effect of Mucosamin on treatment of radiation induced oral mucositis during and after radiotherapy amongst patients with oral cavity squamous cell carcinoma. MATERIALS AND METHODS: In this prospective clinical trial, eligible patients who referred to radiation oncology department of Namazi Hospital, Shiraz, Iran from Jan 2018 till Jan 2019 were evaluated. The cases with confirmed pathologic diagnosis of squamous cell carcinoma of the oral cavity underwent 6,000 cGy radiation therapy and were randomly divided into two groups: 1- Intervention group; Mucosamin spray for 3-4 times a day (n = 40); 2 - Control group; standard medications (3 times a day) (n = 40). Oral mucositis was evaluated weekly based on RTOG scoring scale. Grade of mucositis was recorded during treatment and after radiation therapy. RESULTS: A total of 80 patients were divided in two groups of Mucosamin and control. From week 3 until the end of radiotherapy (week 6) and after radiotherapy (week 8), there was a significant difference in the severity of oral mucositis between the Mucosamin and the control groups (P <0.05). CONCLUSION: The results of this study showed that Mucosamin spray was able to significantly improved radiation-induced oral mucositis in patients with oral squamous cell carcinoma.<br />.

We evaluated and compared the effectiveness of intra-articular injection of hip joint using hyaluronic acid and steroid in patients with femoroacetabular impingement (FAI). Thirty patients with FAI clinically and radiologically were enrolled and underwent hip injection using steroid (TA) or hyaluronic acid (HA) at 0-weeks with cross-over injection at 2-weeks in patients without clinical response of decrease of pain intensity less than 2-point. Patients were followed up to 12-weeks for pain intensity (Numeric rating scale, NRS: 0-10), hip disability score (HOOS), oral medication and adverse events. In 17 patients without cross-over, HOOS at 2-weeks was improved significantly in patients with HA injection (mean increase of HOOS = 13.8 with HA vs. -2.2 with TA, P = 0.031) without difference of NRS (P = 0.943). In 13 patients with cross-over, NRS was significantly improved at 2-weeks with first TA injection (mean decrease of NRS= 1.7 with first TA vs. 0.3 with first HA, P = 0.036), without difference of HOOS (P = 0.431). At 4-weeks, NRS and HOOS were significantly different according to injection drugs (NRS: 0.9 with TA first and HA later vs. 2.7 with HA first and TA later, P = 0.001; mean increase of HOOS: 5.3 with TA first and HA later vs. 10.2 with HA first and TA later, P = 0.032). Intra-articular hip injection may be effective in FAI, with faster effect of pain improvement by TA and more delayed effect of function improvement by HA.