Hyaluronic Acid Group Research Articles

Tunnel Technique and Subepithelial Connective Tissue Graft, With or Without Cross-Linked Hyaluronic Acid, in the Treatment of Multiple Gingival Recessions: Prognostic Parameters for Clinical Treatment Outcomes of Randomized Controlled Trial

Objectives: This study aimed to investigate factors that influence the 12-month outcomes after the treatment of multiple gingival recessions (GRs) with a modified coronally advanced tunnel (MCAT) and a subepithelial connective tissue graft (SCTG), with cross-linked hyaluronic acid (HA, tests) or without (controls). Materials and Methods: Twenty-four patients with 266 GRs were treated. A logistic regression model was set to identify the baseline parameters that could predict the 12-month outcomes. The study protocol was registered at ClinicalTrials.gov (ID No. NCT05045586). Results: The evaluated clinical and esthetic parameters showed marked improvement in both groups without any statistically significant differences between the groups, with the exception of the soft tissue texture (STT). The STT was in favor of the HA group (0.96 versus 0.73, p = 0.0091). The likelihood of an MRC > 85%, of achieving CRC, and of gaining an RES = 10 was the highest for the incisors (reference group) and the lowest for the molars (OR = 0.046, p = 0.005). With each 1 mm increase in the baseline clinical attachment level, the odds of failure (MRC < 85%, not achieving CRC) increased, whereas each 1 mm increase in the baseline keratinized tissue width (KTW) improved the chances of an MRC > 85%, of achieving CRC, and of gaining an RES = 10. The application of HA increased the likelihood of a perfect RES more than twofold (OR = 2.683, p = 0.001). Conclusions: The application of HA improved the 12-month esthetic outcomes after the treatment of GRs with the MCAT technique. The baseline CAL, KTW, and tooth type predicted the 12-month MRC, CRC, and RES. An evaluation of the baseline characteristics of the surgical area might help clinicians develop individualized treatment plans.

Effect of Hyaluronic Acid Mucoadhesives on Palatal Wound Healing and Postoperative Discomfort in Free Gingival Graft Surgery: A Clinical Trial

Objectives: This study aimed to assess the effect of hyaluronic acid (HA) mucoadhesives with two different concentrations on palatal epithelial wound healing and postoperative discomfort following free gingival graft (FGG) surgery. Materials and Methods: In this triple-blind, randomized, controlled clinical trial, 39 patients undergoing FGG surgery were randomly allocated to three groups (N=13). Following palatal graft harvesting, the two experimental groups received mucoadhesives containing 0.8% and 0.2% HA, while the control group received mucoadhesives without HA. In all groups, the donor site was protected with periodontal dressing. Epithelization, color match, contour, and distortion were assessed at 3, 7, 14, 21, and 42 days, postoperatively using the Landry's healing index and modified Manchester Scar Proforma (mMSP) index. Pain level and response to thermal stimuli were evaluated after 3, 7, 14, and 21 days using a visual analog scale (VAS). Data were analyzed by the Chi-square, Kruskal-Wallis, Mann-Whitney, Friedman, and Wilcoxon signed-rank tests (alpha=0.05). Results: Significant differences were observed in the mMSP index scores among the groups at 3, 7, 14, and 42 days, favoring HA groups (P<0.05). The Landry's healing index score was significantly higher in 0.8% HA group on day 21 (P=0.023), compared to the control group. No significant differences were found in pain score or thermal stimulus responses among the groups (P>0.05). Conclusion: Mucoadhesives containing HA were found to enhance palatal wound healing, leading to improved outcomes in terms of epithelization, color match, contour, and distortion reduction.

Bovine pulp extracellular matrix hydrogel for regenerative endodontic applications: in vitro characterization and in vivo analysis in a necrotic tooth model

BackgroundRegenerative endodontic procedures (REPs) offer the promise of restoring vitality and function to a previously necrotic and infected tooth. However, the nature of regenerated tissues following REPs remains unpredictable and uncontrollable. Decellularized extracellular matrix scaffolds have gained recent attention as scaffolds for regenerative endodontics.ObjectivesPreparation and characterization of a bovine dental pulp-derived extracellular matrix (P-ECM) hydrogel for regenerative endodontic applications. Biocompatibility and regenerative capacity of the prepared scaffold were evaluated in vivo in a canine animal model.MethodsFifteen freshly extracted bovine molar teeth were used to prepare P-ECM hydrogels following approval of the institutional review board of the faculty of dentistry, Alexandria University. Decellularization and lyophilization of the extracted pulp tissues, DNA quantification and histological examination of decellularized P-ECM were done. P-ECM hydrogel was prepared by digestion of decellularized pulps. Prepared scaffolds were evaluated for protein content and release as well as release of VEGF, bFGF, TGF-β1 and BMP2 using ELISA. Rabbit dental pulp stem cells’ (rDPSCs) viability in response to P-ECM hydrogels was performed. Finally, proof-of-concept of the regenerative capacity of P-ECM scaffolds was assessed in an infected mature canine tooth model following REPs versus blood clot (BC), injectable platelet-rich fibrin (i-PRF) or hyaluronic acid (HA). Statistical analysis was done using independent t test, the Friedman test and chi-square tests (p value ≤ 0.05).ResultsDNA was found to be below the cut-off point (50 ng/mg tissue). Histological evaluation revealed absence of nuclei, retention of glycosaminoglycans (GAGs) and collagen content, respectively. P-ECM hydrogel had a total protein content of (493.12 µg/µl) and protein release was detected up to 14 days. P-ECM hydrogel also retained VEGF, bFGF, TGF-β1 and BMP2. P-ECM hydrogel maintained the viability of rDPSCs as compared to cells cultured under control conditions. P-ECM hydrogel triggered more organized tissues compared to BC, i-PRF and HA when used in REPs for necrotic mature teeth in dogs. Periapical inflammation was significantly less in HA and P-ECM groups compared to blood-derived scaffolds.ConclusionBovine dental pulp-derived extracellular matrix (P-ECM) hydrogel scaffold retained its bioactive properties and demonstrated a promising potential in regenerative endodontic procedures compared to conventional blood-derived scaffolds.

Influence of High-Altitude Residential History on Optimal HbA1c Cutoff for Detecting Abnormal Glucose Metabolism.

Aims: To explore the influence of recent high-altitude residential history on the optimal cutoff of glycosylated hemoglobin (HbA1c) for detecting abnormal glucose metabolism. Methods: The study included 505 self-reported healthy Han participants of age 18-65 years, recruited in Chengdu and categorized based on recent (within 3 months) high-altitude (>2,500 m) residential history. The 1999 WHO criteria was used as the gold standard for defining prediabetes and diabetes. HbA1c test performance was assessed using receiver operating characteristic curve, with the optimal cutoff determined by Maximum Youden index. Propensity score matching with 0.02 calipers and nearest neighbor method was used to balance confounding factors between groups. Results: Of the participants, 238 (47.13%) were populations with recent high-altitude residential history (HA group), and 267 (52.87%) were low-altitude dwellers (LA group). The HA group had slightly higher HbA1c levels (p > 0.05) and higher erythrocyte and hemoglobin levels (p < 0.05), compared to the LA group. Weak correlations between prediabetes and HbA1c levels were observed in the HA group (rs = 0.21, p < 0.05) and the LA group (rs = 0.07, p = 0.25). The optimal cutoff for the detection of diabetes was 6.5% (area under the curve [AUC] 0.94) in the HA group and 5.9% (AUC 0.97) in the LA group, which remained unchanged after adjustment for confounders. Conclusions: The optimal cutoff of HbA1c for the detection of diabetes in populations with recent history of living at high altitude was higher than that in general populations living at low altitude, and the diagnostic value of HbA1c for prediabetes was also inadequate.

Ultrasound-guided infiltration with hyaluronic acid compared with corticosteroid for the treatment of Morton's neuroma.

A local injection may be used as an early option in the treatment of Morton's neuroma, and can be performed using various medications. The aim of this study was to compare the effects of injections of hyaluronic acid compared with corticosteroid in the treatment of this condition. A total of 91 patients were assessed for this trial, of whom 45 were subsequently included and randomized into two groups. One patient was lost to follow-up, leaving 22 patients (24 feet) in each group. The patients in the hyaluronic acid group were treated with three ultrasound-guided injections (one per week) of hyaluronic acid (Osteonil Plus). Those in the corticosteroid group were treated with three ultrasound-guided injections (also one per week) of triamcinolone (Triancil). The patients were evaluated before treatment and at one, three, six, and 12 months after treatment. The primary outcome measure was the visual analogue scale for pain (VAS). Secondary outcome measures included the American Orthopaedic Foot and Ankle Society (AOFAS) score, and complications. Both groups showed significant improvement in VAS and AOFAS scores (p < 0.05) after 12 months. The corticosteroid group had a significantly greater reduction in VAS and increase in AOFAS scores compared with the hyaluronic acid group, at one, three, and six months, but with no significant difference at 12 months. There were no complications in the hyaluronic acid group. There were minor local complications in six patients (six feet) (25.0%) in the corticosteroid group, all with discolouration of the skin at the site of the injection. These minor complications might have been due to the three weekly injections of a relatively high dose of corticosteroid. No patient subsequently underwent excision of the neuroma. An ultrasound-guided corticosteroid injection showed statistically significantly better functional and pain outcomes than an ultrasound-guided injection of hyaluronic acid for the treatment of a Morton's neuroma at many timepoints. Thus, a corticosteroid injection should be regarded as a primary option in the treatment of these patients, and the only indication for an injection of hyaluronic acid might be in patients in whom corticosteroid is contraindicated.

The Impact of Hydrogen Sulfide in the Paraventricular Nucleus on the MAPK Pathway in High Salt-Induced Hypertension.

The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure. We administered hydroxylamine hydrochloride (HA), a cystathionine-β-synthase inhibitor, into the PVN to suppress endogenous hydrogen sulfide and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt (HS)-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the normal salt (NS) + PVN vehicle group, the NS + PVN HA group, the HS + PVN vehicle group, and the HS + PVN HA group, with 10 rats in each group. The rats in the NS groups were fed a NS diet containing 0.3% NaCl, while the HS groups were fed a HS diet containing 8% NaCl. The mean arterial pressure was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H 2 S in the PVN and plasma norepinephrine using enzyme linked immunosorbent assay. In addition, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time polymerase chain reaction. In this study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of HS-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system.

A retrospective claims data analysis of health care utilization and cost among patients receiving multi-injection intraarticular hyaluronic acid.

With the rising costs for knee arthroplasty, therapies that allow patients to avoid or delay surgery following knee osteoarthritis (KOA) may help in reducing overall health care costs. Multiple intraarticular hyaluronic acid (HA) products are available on the market, varying by formulation, molecular weight, and number of injections, but clinical and economic benefits may differ by product. OBJECTIVES: To evaluate the all-cause and KOA-related health care resource utilization (HCRU) and costs among newly diagnosed patients with KOA treated with multi-injection HA. A retrospective cohort study using a large commercial claims database (Merative MarketScan database) to identify patients with KOA treated with high molecular weight (HMW) (n = 11,200), medium molecular weight (MMW) (n = 10,225), or low molecular weight (LMW) HAs (n = 8,473) between 2016 and 2019. KOA-related and all-cause HCRU and costs were compared within 12 months after the index HA treatment date. The association between outcomes and HA treatments was evaluated using a doubly robust method to adjust for confounding factors. HCRU and costs among the propensity score-weighted HA groups were compared using generalized linear models. HMW HA patients were found to have lower adjusted KOA-related medical costs by $265.37 (P < 0.001) and pharmacy costs by $19.90 (P < 0.001) compared with LMW HA patients, as well as lower all-cause total medical costs by $130.42 (P = 0.013) and pharmacy costs by $63.33 (P < 0.001). HMW HA patients also had a lower adjusted KOA-related medical cost by $205.74 (P < 0.001) and pharmacy cost by $14.39 (P < 0.001) compared with MMW HA patients, as well as lower all-cause medical by $1,195.66 (P < 0.001) and pharmacy by $196.99 (P < 0.001). Three-injection treatment patients (HMW HA, 84%; MMW HA, 82%) had high completion rate, compared with the 5-injection treatment cohort (LMW HA, 48%). HMW HA patients had statistically significantly lower adjusted all-cause and KOA-related medical and pharmacy costs at 1 year follow-up compared with MMW HA and LMW HA patients. It is unclear if this is related to differences in molecular weight or specific mechanism of actions.

Effect of Vinyl Acetate, Glass Fibers Contents, and Buffer Space on EVA's Mechanical Property and Shock Absorption Ability.

The aim of the study was to evaluate the mechanical properties and impact absorption capacity of prototype materials comprising ethylene vinyl acetate (EVA) of different hardness reinforced using different amounts of glass fibers (GFs), considering a buffer space. Six prototype materials were made by adding E-GFs (5 and 10 wt%) to EVA with vinyl acetate (VA) contents of 9.4 wt% ("hard" or HA) and 27.5 wt% ("soft" or SO). Durometer hardness and tensile strength tests were performed to evaluate the mechanical properties of the materials. Moreover, an impact test was conducted using a customized pendulum impact tester to assess the impact absorption capacity (with or without a buffer space) of the specimens. The mechanical properties of the prototypes, namely, durometer hardness, Young's modulus, and tensile strength, were significantly higher in the HA group than in the SO group, regardless of the presence or added amount of GFs. The addition of GFs, particularly in a large amount (10 wt%), significantly increased these values. In terms of the impact absorption capacity, the original hardness of the EVA material, that is, its VA content, had a more substantial effect than the presence or absence of GFs and the added amount of GFs. Interestingly, the HA specimens with the buffer space exhibited significantly higher impact absorption capacities than the SO specimens. Meanwhile, the SO specimens without the buffer space exhibited significantly higher impact absorption capacities than the HA specimens. Moreover, regardless of the sample material and impact distance, the buffer space significantly improved impact absorption. In particular, with the buffer space, the impact absorption capacity increased with the added amount of GFs. The basic mechanical properties, including durometer hardness, Young's modulus, and tensile strength, of the EVA prototype were significantly increased by reducing the amount of VA regardless of the presence or added amount of GFs. Adding GFs, particularly in large amounts, significantly increased the values of aforementioned mechanical properties. Impact absorption was significantly affected by the hardness of the original EVA material and enhanced by the addition of the buffer space. The HA specimen had a high shock absorption capacity with the buffer space, and the SO specimen had a high shock absorption capacity without the buffer space. With the buffer space, impact absorption improved with the amount of added GFs.

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

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

Effectiveness of Intra-articular Botulinum Toxin Type A with Hyaluronic Acid Compared to Intra-articular Platelet-rich Plasma with Hyaluronic Acid in Improving Pain and Functional Limitation in Knee Osteoarthritis

Abstract Background: Knee osteoarthritis (KOA) is the most common cause of chronic knee pain causing functional disability and dependency. Multiple interventions have been used in reducing pain and improving functionality. We intend to compare the efficacy of intra-articular platelet-rich plasma (PRP) and hyaluronic acid (HA) with botulinum toxin type A and HA in bilateral Grade 3 and 4 KOA. Methods: Prospective single-blinded randomized controlled trial conducted for 6 months. Among 54 participants, 27 received intra-articular botulinum toxin type A with HA (Group A), and the other 27 received intra-articular PRP with HA (Group B), single session. Pain (Numerical Rating Scale [NRS]) and functional limitation (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) were assessed at 2, 4, 12, and 24 weeks postintervention. Effect of weight and physiotherapy on NRS and WOMAC score were assessed. P &lt;0.05 was considered statistically significant. Data were analyzed by statistical software R version 4.2.3. Results: Fifty-four participants were enrolled. There was no loss to follow-ups. Except for age (P &lt; 0.001) and mean height (P = 0.013), other demographic data were insignificant. Preprocedural NRS was significantly high in Group A (P = 0.04). Overall NRS postprocedure was significantly lesser in Group B, P &lt; 0.001. The mean WOMAC score postprocedure was significantly low in Group B, P &lt; 0.001. Group B had increased heart rate which was statistically significant (P = 0.051). The mean reduction in WOMAC score was observed with regular physiotherapy in Group B (P = 0.023). Reduction in weight was directly proportional to reduction in NRS (P = 0.015). Conclusion: Intra-articular PRP with HA, single session, is effective in improving pain, functionality, and safe in Grade 3 and 4 KOA.

Does the Use of Injectable Platelet-Rich Fibrin Following Arthrocentesis for Disc Displacement Without Reduction Alleviate Pain?

The role of adjunctive injection agents at the end of temporomandibular joint (TMJ) arthrocentesis remains controversial. This study aims to compare pain reduction in patients with disc displacement without reduction treated with arthrocentesis alone (AO), arthrocentesis with injectable platelet-rich fibrin (iPRF), and arthrocentesis with hyaluronic acid (HA). A single-center, retrospective cohort study was conducted at the affiliated hospital of Health Sciences University, Hamidiye Faculty of Dentistry. Inclusion criteria were female subjects aged 18-65, who underwent TMJ unilateral arthrocentesis, and diagnosed with disc displacement without reduction. Exclusion criteria were prior use of occlusal splints, accompanying diagnosis of myalgia and bilateral arthralgia which both of the joints exceeds or equal to 50mm visual analogue scale for pain (pVAS) value. The primary predictor variable was the adjunctive injection agent: iPRF, HA, or no injection (AO as control). Primary and secondary outcomes were measured preoperatively (T0), and at 1month (T1) and 6months (T2) postoperatively. The primary outcome was pain (pVAS) at T2. Secondary outcomes were pVAS at T1 and maximum interincisal opening at T1 and T2. Demographics, preoperative and perioperative data were collected. Descriptive, bivariate, and multivariate analyses were conducted. The P value was set at ≤.05. A total of 88 subjects completed the study. The mean age of the subjects in the AO (n=30), HA (n=29) and iPRF (n=29) groups was 36.8 (±10.2), 34.8 (±8.9) and 37.6 (±11.6) respectively (P>.05). The mean pVAS scores at T0 for the AO, HA and iPRF groups were 63.2 (±8.7), 66.7 (±9.6) and 66.2 (±9.6) respectively (P>.05). The mean pVAS scores at T1 were 36.5 (±10.8), 29.0(±11.5) and 35.9 (±9.8) respectively (P<.05). The mean pVAS scores at T2 were 34.8 (±16.3), 24.7 (±12.7) and 25.3 (±13.4) respectively (P<.05). There were no differences in maximum interincisal opening between the groups at any timepoint (P>.05). iPRF and HA injections are associated with greater pain relief compared to AO. No significant difference was observed between iPRF and HA, suggesting that the choice between them can be based on cost-effectiveness.

Effectiveness of a Single Intra-articular Injection of High-Molecular-Weight Hyaluronic Acid Versus NSAIDs on the Visual Analog Pain Scale and Western Ontario and McMaster Universities Osteoarthritis Index Scores in Patients With Knee Osteoarthritis.

This study aimed to determine the effectiveness of a single intra-articular injection of high-molecular-weight (HMW) hyaluronic acid (HA) at a dose of 4 mL/60 mg to reduce pain in people with knee osteoarthritis (OA) over 12 months. This retrospective study was conducted after obtaining ethical approval from Dhaka Medical College and Hospital, Bangladesh. From July 2020 to June 2021, a medical professional conducted the investigation. The investigation encompassed patients aged 40 to 70 hospitalized at our facility and diagnosed with Grade 2 or Grade 3 knee OAaccording to the Kellgren-Lawrence grading method. We divided the patients into two categories based on the treatments they received. Patients in Group A received a single injection of HMW HA (60 mg/4 mL) into the joint, along with instructions on activities of daily living, exercise, and painkillers. Group B patients received conservative therapy, which involved the use of nonsteroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, therapeutic exercises, and a knee brace during physical activity. This study compared the efficacy of a single injection of HMW HA in the joint versus NSAIDs for managing OA-related symptoms over 12 weeks. The HA group initially scored similarly to the comparison group. By week three, however, the group receiving HA had considerably higher Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (p=0.019). This pattern continued through weeks 6 (p=0.044), 9 (p=0.016), and 12 (p<0.001). Similarly, by week 3 (p=0.029), the visual analog scale (VAS) scores, which were initially identical (p=0.120), demonstrated a significant preference for HA, and this preference persisted through weeks 6, 9, and 12 (all p<0.001). The results show that by the third week, HA is more effective than NSAIDs at relieving pain and improving symptoms. The study's results indicated that over 12 weeks, the use of HMW HA led to statistically significant reductions in pain intensity, as measured by the VAS. Furthermore, HMW HA demonstrated a more significant improvement in WOMAC ratings, which assess physical function, stiffness, and pain, compared to NSAIDs. The findings suggest that administering HMW HA injections can significantly reduce symptoms and improve functionality in individuals with knee OA.

The Mid-Term Effect of Preservative-Free Artificial Tears Containing Hyaluronic Acid on Dry Eye Incidence after Cataract Surgery: A Retrospective Cohort Study.

The aim of this study is to survey the effectiveness of preservative-free artificial tears containing hyaluronic acid (HA) on post-cataract surgery dry eye disease (DED) prevention. A retrospective cohort study was performed, and patients that received cataract surgeries were divided into either an HA group or non-HA group depending on the artificial tear they used. A total of 37 and 74 eyes were enrolled into the HA and non-HA groups, respectively, after the selection. The primary outcomes are postoperative superficial keratitis and multiple (>3) DED symptoms. The generalized linear model was utilized to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) of primary outcomes between the two groups. There were 10 and 2 episodes of superficial keratitis in the non-HA group and HA group, respectively, and the HA group demonstrated a significantly lower incidence of superficial keratitis (p < 0.001). Moreover, 13 and 5 patients developed multiple DED symptoms in the non-HA and HA groups, and the HA group illustrated fewer multiple DED symptoms (p = 0.024). The lower preoperative tear break-up time (TBUT) was correlated with superficial keratitis in the HA group (p = 0.043), while old age, low preoperative TBUT and ocular surface staining were associated with superficial keratitis in the non-HA group (all p < 0.05). Lower preoperative TBUT was correlated with multiple DED symptoms in the HA group (p = 0.020), while female sex, low preoperative TBUT and any DED symptoms were associated with multiple DED symptoms in the non-HA group (all p < 0.05). In conclusion, the usage of preservative-free artificial tears containing HA is associated with lower postoperative DED events.

Effects of supplementing extracorporeal shockwave therapy (ESWT) to hyaluronic acid (HA) injection among patients with rotator cuff lesions without complete tear: A prospective double-blinded randomized study.

The study investigates the combined efficacy of subacromial hyaluronic acid (HA) injections and extracorporeal shockwave therapy (ESWT) in managing rotator cuff lesions without complete tears. Eligible patients were randomized into three groups: 3 HA injections combined with 2 sham ESWT (HA), 3 HA injections combined with 1 ESWT and 1 sham ESWT (HA + 1 ESWT), or 3 HA injections combined with 2 ESWT (HA + 2 ESWT) with an allocation ratio of 1:1:1. Visual Analogue Scale (VAS), Constant-Murley Score (CMS), range of motion (ROM), and muscle power of shoulder abduction (MP) were assessed pre-intervention and at 1, 3, 6, and 12 months post-initial HA injection. Shoulder magnetic resonance imaging (MRI) was conducted before and twelve months after the intervention. All pertinent parameters showed no significant between-group differences at baseline but demonstrated significant within-group improvement throughout the study. The HA + 1 ESWT group demonstrated superior improvements in MP (P=0.011) and CMS (P=0.018) at 1 month, and in MP (P=0.014) and CMS (P=0.005) at 6 months, compared to the HA group. The HA + 2 ESWT group showed greater improvements in FF (P=0.027), IR (P=0.019), and SROM (P=0.025) at 1 month, and in ABD (P=0.022) at 6 months, compared to the HA group. Notably, the HA + 2 ESWT group exhibited greater improvements in FF (P=0.013), IR (P=0.019), and SROM (P=0.025) at 1 month, and in FF (P=0.007) at 3 months, than the HA + 1 ESWT group. Moreover, no deterioration in tendinopathy grading or tear status occurred in the HA + 1 ESWT group on MRI scans. ESWT provides additional benefits when combined with HA injections for patients with rotator cuff lesions lacking complete tears.

Comprehensive evaluation of xylometazoline hydrochloride formulations: Ex-vivo and in-vitro studies

Xylometazoline is a well-established nasal decongestant that has been used alone and in combination with dexpanthenol as an over the counter (OTC) medicine. Considering the possibility of further improvement of xylometazoline nasal formulations, hyaluronic acid (HA) was evaluated as an additional ingredient. The aim of this study was to investigate the permeation, mucosal retention, and mucoadhesion properties of a new xylometazoline-HA [Xylo-HA] formulation ex vivo and to explore the potential benefits of incorporating HA in the formulation in vitro. Sheep nasal mucosa was used in the ex vivo study, where Xylo-HA was compared with xylometazoline alone [Xylo-Mono], and in combination with dexpanthenol [Xylo-Dex] to understand the impact of formulation changes. The permeation of xylometazoline was generally low (Xylo-Mono 11.14 ± 4.75 %, Xylo-HA 14.57 ± 5.72 % and Xylo-Dex 11.00 ± 3.05 % of the applied dose). The steady state fluxes of xylometazoline were determined as 12.64 ± 3.52 μg/cm2h, 14.94 ± 3.38 μg/cm2h and 12.19 ± 2.05 μg/cm2h for Xylo-Mono, Xylo-HA and Xylo-Dex, respectively. No significant differences were observed between the formulations in the permeation nor mucosal retention studies (p > 0.05 for all), while Xylo-HA exhibited superior mucoadhesive proprieties (p < 0.05 for all). The effects on wound healing and barrier integrity of the three xylometazoline formulations were tested in vitro on HaCaT cells. To better elucidate the role of HA, an additional HA formulation without xylometazoline was prepared (HA-Mono). A scratch test was performed to evaluate wound healing, revealing that the test formulations did not achieve complete wound closure within 72 h and demonstrated a similar effect at the end of the testing period. To assess the effect on barrier integrity, cells were treated for 5 days with daily measurements of transepithelial electrical resistance (TEER). At the end of the experiment, Xylo-Dex showed a moderate 14 % increase in TEER, while Xylo-Mono did not significantly affect this parameter. TEER rose by 951 % in the Xylo-HA, and by 10497 % in the HA group, suggesting that incorporating HA led to enhanced barrier function. Further clinical studies are recommended to better understand the clinical implications and efficacy of the Xylo-HA formulation, with particular focus on the role of HA.

An injectable hyaluronic acid-Polydeoxyribonucleotides (HA-PDRN) crosslinked hydrogel as a dermal filler

Injectable hydrogels, commonly utilized as dermal fillers, show great potential for increasing tissue volume and correcting wrinkles. HA (hyaluronic acid), extensively used in dermal fillers, requires considerable modifications to meet commercial demands for effectiveness and functionality. PDRN (polydeoxyribonucleotides), DNA extracted from salmon sperm cells, offer several therapeutic benefits, including anti-inflammatory and collagen stimulation. This work presents a new crosslinked hydrogel based on HA and PDRN. HA-PDRN crosslinked hydrogels were fabricated via covalent interactions between the carboxyl groups of HA and amino groups of PDRN, resulting in desirable properties such as viscoelasticity, appearance, hydration, degradation, injectability, and biocompatibility. In vivo studies on mice revealed that these hydrogels maintain volume for over 24 weeks, with reduced inflammation and enhanced collagen synthesis, as well as exhibiting durability, safety, and supportability.

The Usage of Different Hyaluronic-Acid-Containing Artificial Tears and the Treatment Outcome of Intense Pulsed Light Therapy for Dry Eye Disease: A Retrospective Cohort Study.

In this study, we aimed to investigate the effect of different hyaluronic acid (HA)-containing artificial tears on dry eye disease (DED) treatment in combination with intense pulsed light (IPL) therapy. A retrospective cohort study was conducted, and the participants received IPL therapy and HA-containing artificial tears. There were 42 and 40 eyes in the 0.10% and 0.15% HA groups after selection, respectively. The main outcomes were the postoperative non-invasive tear break-up time (NITBUT), Schirmer II test results, ocular surface stain, and numbers of DED-related symptoms. A generalized linear model was utilized to produce the adjusted odds ratio (aOR) and 95% confidence interval (CI) of the main outcomes between groups. At the three-month follow-up, the NITBUT was significantly higher in the 0.15% HA group (p = 0.023), and the NITBUT recovery was also significantly better in the 0.15% HA group compared to the 0.10% HA group (p = 0.039). The multiple DED-related symptoms significantly correlated with no DED symptom improvement in both the 0.10% and 0.15% HA groups (both p < 0.05), while the low pre-treatment NITBUT was marginally related to no DED symptom improvement in the 0.10% HA group (p = 0.047). A low NITBUT and Schirmer II test result correlated with no DED symptom improvement in both the groups (all p < 0.05). In conclusion, the application of 0.10% and 0.15% HA-containing artificial tears revealed similar effects to IPL therapy for DED.

Macrophage-Targeted GSH-Depleting Nanocomplexes for Synergistic Chemodynamic Therapy/Gas Therapy/Immunotherapy of Intracellular Bacterial Infection.

Intracellular pathogens can survive inside the macrophages to protect themselves from eradication by the innate immune system and conventional antibiotics, resulting in severe bacterial infections. In this work, an antibiotic-free nanocomplex (HA/GA-Fe@NO-DON), exhibiting macrophage-targeted synergistic gas therapy (nitric oxide, NO)/chemodynamic therapy/immunotherapy, was reported. HA/GA-Fe nanoparticles were synthesized by the strong coordination interactions among carboxyl groups of hyaluronic acid (HA), polyphenol groups of gallic acid (GA), and Fe(II) ions. The hydrophobic glutathione (GSH)-responsive NO donor (NO-DON) was encapsulated in HA/GA-Fe nanoparticles to form the final nanocomplexes (HA/GA-Fe@NO-DON). HA on the nanocomplexes guides the macrophage-specific uptake and intracellular accumulation. After the uptake, HA/GA-Fe@NO-DON nanocomplexes could not only generate highly toxic hydroxyl radicals (•OH) by the Fenton reaction and GSH depletion but also release NO when stimulated by intracellular GSH. Meanwhile, the nanocomplexes could trigger an efficient proinflammation immune response to reinforce the antibacterial activity. This work presents the development of antibiotic-free macrophage-targeted HA/GA-Fe@NO-DON nanocomplexes as an effective adjuvant nanomedicine with synergistic gas therapy/chemodynamic therapy/immunotherapy for eliminating intracellular bacterial infection.

Early Vocal Development in Toddlers With Simultaneous Bilateral Cochlear Implants

Background and Objectives The purpose of this study is to investigate the vocal development in toddlers with simultaneous bilateral cochlear implants (bilateral CI group) and to compare their progress to that of chronological age-matched (CA group) and hearing agematched (HA group) toddlers who have normal hearing and typical development.Subjects and Method Thirteen toddlers who received bilateral CIs simultaneously before 18 months of age participated in this study. Twenty-six toddlers participated as the control groups (CA group and HA group). The spontaneous utterances were collected from each toddler during free play with their parents in the laboratory. A total of 2324 spontaneous utterances of 39 toddlers (13 toddlers in each of the three groups) were classified as either canonical vocalizations or noncanonical vocalizations.Results The bilateral CI group produced significantly fewer canonical vocalizations than the CA group. However, there was not a significant difference in the ratio of canonical vocalizations between the CI and the CA groups. There were no significant differences in the frequency and ratio of canonical vocalization between the CI and HA groups. In the CI group, the frequency of canonical and noncanonical vocalizations was significantly correlated with receptive and expressive language scores.Conclusion The findings of this study showed that toddlers with bilateral CIs make good advancements in vocal development compared to toddlers with normal hearing. However, toddlers with bilateral CIs seem to produce an insufficient quantity of canonical vocalizations compared to age-matched hearing toddlers. Information about vocal development following simultaneous bilateral CI helps speech therapists and parents recognize speech development before the use of intelligible speech in communication.

The results of preventing postoperative achilles tendon adhesion using cross-linked and non-cross-linked hyaluronic acid, a study with rat model

BackgroundThere are many adhesion barrier materials, cross-linked or non-cross-linked hyaluronic acid (HA), used during surgeries.PurposeThis study investigates the efficacy of cross-linked and non-cross-linked HA in preventing Achilles tendon adhesions. We hypothesized that non-cross-linked HA may be more effective than cross-linked HA in preventing Achilles tendon adhesions following injury and repair.MethodsTwenty male Sprague Dawley rats, totaling 40 legs, underwent Achilles tendon transection and repair. Following the surgery, they were treated simultaneously with cross-linked and non-cross-linked HA formulations. The rats were divided into four groups: a positive control group, a group treated with BMC non-cross-linked HA gel, a group treated with DEFEHERE cross-linked HA gel, and a group treated with ANIKA cross-linked HA gel. Four weeks after surgery, macroscopic evaluation of peritendinous adhesion and histological analysis were conducted to assess the effectiveness of the treatments.ResultsNon-cross-linked BMC HA demonstrated superior efficacy in preventing tendon adhesions compared to cross-linked HA and control groups. Histological analysis confirmed reduced adhesion severity in the non-cross-linked HA group (P < 0.05). The findings support the potential of non-cross-linked HA as a treatment to inhibit tendon adhesions. Further research, including clinical trials, is warranted to validate these results in human subjects.ConclusionsNon-cross-linked BMC HA had significantly lower tendon adhesions parameters and better healing scores in histological analysis than cross-linked HA and control group did. Non-cross-linked HA holds promise as a potential treatment to inhibit the formation of such adhesions.