Addition Of Hyaluronic Acid Research Articles

Hyaluronic Acid as a Carrier Supports the Effects of Glucocorticoids and Diminishes the Cytotoxic Effects of Local Anesthetics in Human Articular Chondrocytes In Vitro.

The current study aimed to investigate the cytotoxicity of co-administrating local anesthetics (LA) with glucocorticoids (GC) and hyaluronic acid (HA) in vitro. Human articular cartilage was obtained from five patients undergoing total knee arthroplasty. Chondrocytes were isolated, expanded, and seeded in 24-well plates for experimental testing. LA (lidocaine, bupivacaine, ropivacaine) were administered separately and co-administered with the following substances: GC, HA, and GC/HA. Viability was confirmed by microscopic images, flow cytometry, metabolic activity, and live/dead assay. The addition of HA and GC/HA resulted in enhanced attachment and branched appearance of the chondrocytes compared to LA and LA/GC. Metabolic activity was better in all LA co-administered with HA and GC/HA than with GC and only LA. Flow cytometry revealed the lowest cell viability in lidocaine and the highest cell viability in ropivacaine. This finding was also confirmed by live/dead assay. In conclusion, HA supports the effect of GC and reduces chondrotoxic effects of LA in vitro. Thereby, the co-administration of HA to LA and GC offers an alternative less chondrotoxic approach for treating patients with symptomatic osteoarthritis of the knee.

Biomolecules in Dental Applications: Randomized, Controlled Clinical Trial Evaluating the Influence of Hyaluronic Acid Adjunctive Therapy on Clinical Parameters of Moderate Periodontitis.

The biological activity of hyaluronic acid (HA) has been well-researched during the past decades; however, there are few randomized, controlled trials of its clinical effects in periodontal therapy. The purpose of this study was to evaluate the effect of hyaluronic acid on the principal parameters of periodontal healing. A specific, commercially available formulation designed and registered for professional dental application, composed of 16 mg/mL of cross-linked and 2 mg/mL of non-cross-linked HA, was used as an adjunctive to non-surgical periodontal therapy, and clinical parameters were evaluated after 3 months. The addition of HA to periodontal therapy demonstrated more favorable clinical results regarding reduction in inflammation, measured by bleeding on probing (−6% compared to the control group) and gain in periodontal attachment (1 mm more than control group), while it had no effect on probing depth reduction. No side effects were reported. Our study demonstrated that HA is a safe and easy-to-use biological agent; due to its wide array of properties, it may significantly improve the results of periodontal therapy. However, more long-term studies are needed to investigate whether these favorable effects remain over time.

Evaluation of the Efficacy of IALUSET VITAL® Cream in Helping the Improvement of the Atopic Dermatitis Symptoms in Adults: A Randomized, Double Blind, Vehicle-Controlled Clinical Trial

Atopic dermatitis (AD) is a chronic relapsing skin disease, associated with impaired skin barrier function and characterized by poorly defined pruritic, erythematous lesions. In this study, the efficacy of a new topical cream (IALUSET VITAL®), containing hyaluronic acid and the extract of Salvia haenkei, in reducing symptoms of moderate AD in adults was investigated. This study was a randomized, double blind, vehicle-controlled clinical study. Treatment efficacy was evaluated considering both objective parameters (Scoring Atopic Dermatitis, SCORAD) and subjective pa-rameters (Patient Oriented Eczema Measure, POEM, and an itching sensation) and through non-invasive bioengineering techniques to measure skin moisturization and Trans Epidermal Water Loss (TEWL). Under the experimental conditions of the study, IALUSET VITAL® significantly reduced AD severity, as shown by the SCORAD index, and was revealed to be effective in alleviating the most common signs and symptoms of moderate AD, suppressing itch and improving skin moisturization, and to have a good safety profile, being well-tolerated by patients. However, statistically significant differences between active and vehicle group were not found in the other parameters analyzed, likely because the basic formulation of IALUSET VITAL® guarantees good emollient properties and the addition of hyaluronic acid and extract of Salvia haenkei as active ingredients results in a great increase in effectiveness.

Efficacy of sodium hyaluronate in relieving nasal symptoms of children with intermittent allergic rhinitis: a randomized controlled trial.

Nasal irrigation is recommended as add-on therapy in patients with intermittent allergic rhinitis (AR). We aimed to evaluate the clinical efficacy of adding hyaluronic acid (HA) or normal saline solution (NSS) to nasal corticosteroid (NC) therapy as add-on therapy in improving quality of life and reducing nasal symptom scores of children with intermittent AR compared to NC therapy. In this 28-day long, open-label, randomized controlled trial, one puff of NC was administered once a day through both nostrils of 76 children with SAR (6-12years old), whose Total Nasal Symptom Score (TNSS) was ≥ 4. Twenty-six patients received NC only (Group 1); 24 patients received NSS (Group 2), and 26 patients received HA (Group 3) twice a day by means of nasal douche device. Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and TNSS were measured as subjective parameters, and nasal eosinophil count (NEC) in nasal cytology, nasal airflow (NAF), and resistance were measured as objective parameters. No significant difference was found in post-treatment between groups in terms of TNSS, PRQLQ, and NEC values. Mean values of post-treatment left NAF of the groups were significantly different (p = 0.030), and the mean value of Group 3 was the highest (mean ± SD = 247.62 ± 155.8 ccm/sn). In comparing pre- and post-treatment intragroup mean total NAR (TNAR) values, a statistically significant decrease was recorded only in group three (p = 0.025). The addition of HA to NC as an adjunct therapy in children with intermittent AR has limited beneficial effects in our study and deserves further investigation. The clinical trial registration number ID:NCT04752956.

Synthesis of a Lubricant to Mimic the Biorheological Behavior of Osteoarthritic and Revision Synovial Fluid

The rheological properties of synovial fluid (SF) are essential for the friction behavior and wear performance of total joint replacements. Standardized in vitro wear tests for endoprosthesis recommend diluted calf serum, which exhibits substantial different rheological properties compared to SF. Therefore, the in vitro test conditions do not mimic the in vivo conditions. SF samples from osteoarthritis knee patients and patients undergoing knee endoprosthesis revision surgery were compared biochemically and rheologically. The flow properties of SF samples were compared to synthetic fluid constituents, such as bovine serum albumin (BSA) and hyaluronic acid (HA). Interestingly, HA was identified as a significant contributor to shear-thinning. Using the acquired data and mathematical modelling, the flow behavior of human SF was modelled reliably by an adapted adjustment of biorelevant fluid components. Friction tests in a hard/soft bearing (ceramic/UHMWPE) demonstrated that, in contrast to serum, the synthetic model fluids generate a more realistic friction condition. The developed model for an SF mimicking lubricant is recommended for in vitro wear tests of endoprostheses. Furthermore, the results highlight that simulator tests should be performed with a modified lubricant considering an addition of HA for clinically relevant lubrication conditions.

Elucidating the role of hyaluronic acid in the structure and morphology of calcium oxalate crystals

Recent surge in reports describing new additives that inhibiting the growth and nucleation of calcium oxalate (CaOx), the most common component of renal calculi or kidney stones, have rekindled interest in CaOx crystallization. In this in vitro study, the effect of hyaluronic acid (HA), a protein commonly found in urine, on the morphology and phase of the CaOx crystals is investigated. CaOx crystals were crystallized at pH 5.8 and 37 °C with a [Ca2+]:[C2O42-] ratio of 20:1, which is close to physiological conditions, in aqueous solution and artificial urine media. The obtained crystals were characterized structurally, morphologically and in terms of their surface charge. The crystals precipitated in aqueous solution without the HA additive were pure phase calcium oxalate monohydrate (COM) crystals with typical hexagonal morphology. The addition of HA partially promotes the transformation of COM into calcium oxalate dihydrate (COD) in aqueous solution. However, the only solid phase to form in artificial urine media with and without HA was identified as COD with tetragonal bipyramidal morphology. The results of this investigation will contribute to the understanding of the role HA plays on the morphology, structure, and thermal characteristics of CaOx and ultimately facilitate the development of effective treatments for kidney stones.

Sulforaphane-loaded hyaluronic acid-poloxamer hybrid hydrogel enhances cartilage protection in osteoarthritis models

Sulforaphane (SFN) is an isothiocyanate with anti-arthritic and immuno-regulatory activities, supported by the downregulation of NF-κB pathway, reduction on metalloproteinases expression and prevention of cytokine-induced cartilage degeneration implicated in OA progression. SFN promising pharmacological effects associated to its possible use, by intra-articular route and directly in contact to the site of action, highlight SFN as promising candidate for the development of drug-delivery systems. The association of poloxamers (PL) and hyaluronic acid (HA) supports the development of osteotrophic and chondroprotective pharmaceutical formulations. This study aims to develop PL-HA hybrid hydrogels as delivery systems for SFN intra-articular release and evaluate their biocompatibility and efficacy for osteoarthritis treatment. All formulations showed viscoelastic behavior and cubic phase organization. SFN incorporation and drug loading showed a concentration-dependent behavior following HA addition. Drug release profiles were influenced by both diffusion and relaxation of polymeric chains mechanisms. The PL407-PL338-HA-SFN hydrogel did not evoke pronounced cytotoxic effects on either osteoblast or chondrosarcoma cell lines. In vitro/ex vivo pharmacological evaluation interfered with an elevated activation of NF-κB and COX-2, increased the type II collagen expression, and inhibited proteoglycan depletion. These results highlight the biocompatibility and the pharmacological efficacy of PL-HA hybrid hydrogels as delivery systems for SFN intra-articular release for OA treatment.

Anisotropic Truncated Octahedral Au with Pt Deposition on Arris for Localized Surface Plasmon Resonance-Enhanced Photothermal and Photodynamic Therapy of Osteosarcoma.

The multifunctional combined nanoplatform has a wide application prospect in the synergistic treatment of cancer. Nevertheless, the traditional treatment of phototherapy is limited by the catalytic nanomaterial itself, so the effect is not satisfactory. Here, the arris of the anisotropic truncated octahedral Au (TOh Au) was coated with noble metal Pt to form a spatial separation structure, which enhanced the local surface plasmonic resonance and thus boosted the photocatalytic effect. In this system, the highly efficient photocatalysis provides a strong guarantee for oncotherapy. On the one hand, the structure of arris deposition adequately improves the efficiency of photothermal conversion, which substantially improves the effectiveness of photothermal therapy. On the other hand, in situ oxygen production of Pt ameliorates tumor hypoxia, and through the O2 self-production and sales mode, the growth and development of tumor were inhibited. Meanwhile, under the enhanced photocatalysis, more O2 were produced, which greatly evolved the treatment effect of photodynamic therapy. In the end, the addition of hyaluronic acid can specifically target osteosarcoma cells while improving the retention time and biocompatibility of the material in the body. Thus, the nanocomposite shows superexcellent synergistic enhancement of photothermal conversion efficiency and photodynamic capability in vitro and in vivo, which provides a potential possibility for osteosarcoma cure.

Hyaluronic-benzydamine oromucosal films outperform conventional mouth rinse in ulcer healing

Oral mucositis is an ulcerative inflammation that is commonly encountered in patients receiving radio- and chemotherapy as an acute side effect. Local benzydamine (Bnz) application suppresses inflammation, while hyaluronic acid (HA) aids ulcer healing. In this study, Bnz-HA, a triple-layer oromucosal film, was developed for fast localized treatment of oral mucositis, compared to conventional formulations, with the aim to prolong Bnz retention onto the affected area and enhance its therapeutic efficacy by HA incorporation. The Bnz-HA films comprised a mucoadhesive-layer, containing HA and HPMC 4000, that adheres to the oral mucosa and controls Bnz release from the middle drug-layer, which was, in turn, adhered to a backing-layer containing Eudragit RS and allowing unidirectional drug release. Similarly, Bnz films were prepared omitting the HA addition. The films were characterized for their mucoadhesion, swelling capacity and in vitro drug release. The extent and duration of ulcer healing after 5 days film application were recorded in vivo using oral ulcer rabbit model. Bnz-HA and Bnz films showed strong mucoadhesion, maximum swelling after 2 h and a controlled drug release over 12 h. However, the incorporation of HA in Bnz-HA films significantly enhanced ulcer healing, outperforming the Bnz film and Tantum-Verde® mouth rinse. Conclusively, Bnz-HA films control Bnz release, reduce the dosing frequency and achieve rapid ulcer healing, hence being a promising delivery system outperforming conventional oral rinse.

Asymmetric serpentine microchannel based impedance cytometer enabling consistent transit and accurate characterization of tumor cells and blood cells

A consistent cell transit position is essential for accurately characterize cellular impedance signature. In this paper, we integrated asymmetric serpentine structure and elasto-inertial focusing methods to manipulate cells’ special transit position horizontally and vertically, and minimize the fluctuation of impendence responses at multiple excitation frequencies. The asymmetric serpentine structure is capable to rapidly align randomly distributed particles into a single stream horizontally, and the addition of hyaluronic acid (HA) in the sample fluid enables cells to focus in a single train in a wide range of flow rate. In the experiment section, we evaluated the alignment accuracy of asymmetric serpentine microchannel using standard particles ranging from 7 to 20 μm to mimic tumor cells. Compared with randomly distributed and dually aligned particles, the coefficient of variation (CV) of the impedance of particles is markedly reduced. To further prove this device can differentiate various cells, we tested breast tumor cells (MCF7), non-small lung tumor cells (A549) and white blood cells. Based on their electrical impedance signature including opacity and phase shift, a machine learning algorithm was used to identify cell types. This device is able to differentiate MCF7 cells with an accuracy of 95 % and differentiate A549 cells with an accuracy of 92.3 %. This device is able to efficiently focus tumor cells without sheath flow and accurately detect tumor cells, it has a great potential to discriminate, count and phenotype rare circulating tumor cells in patients’ blood.

Development, characterization and sterilisation of Nanocellulose-alginate-(hyaluronic acid)- bioinks and 3D bioprinted scaffolds for tissue engineering

3D-bioprinting is an emerging technology of high potential in tissue engineering (TE), since it shows effective control over scaffold fabrication and cell distribution. Biopolymers such as alginate (Alg), nanofibrillated cellulose (NC) and hyaluronic acid (HA) offer excellent characteristics for use as bioinks due to their excellent biocompatibility and rheological properties. Cell incorporation into the bioink requires sterilisation assurance, and autoclave, β-radiation and γ-radiation are widely used sterilisation techniques in biomedicine; however, their use in 3D-bioprinting for bioinks sterilisation is still in their early stages. In this study, different sterilisation procedures were applied on NC-Alg and NC-Alg-HA bioinks and their effect on several parameters was evaluated. Results demonstrated that NC-Alg and NC-Alg-HA bioinks suffered relevant rheological and physicochemical modifications after sterilisation; yet, it can be concluded that the short cycle autoclave is the best option to sterilise both NC-Alg based cell-free bioinks, and that the incorporation of HA to the NC-Alg bioink improves its characteristics. Additionally, 3D scaffolds were bioprinted and specifically characterized as well as the D1 mesenchymal stromal cells (D1-MSCs) embedded for cell viability analysis. Notably, the addition of HA demonstrates better scaffold properties, together with higher biocompatibility and cell viability in comparison with the NC-Alg scaffolds. Thus, the use of MSCs containing NC-Alg based scaffolds may become a feasible tissue engineering approach for regenerative medicine.

Surface Treatment of the Dental Implant with Hyaluronic Acid: An Overview of Recent Data.

Recently, interest has grown by focusing on the evaluation of a molecule already produced in the human body such as hyaluronic acid (HA), as an application to the surface of the titanium implant. Its osteo-conductive characteristics and positive interaction with the progenitor cells responsible for bone formation, consequently, make it responsible for secondary stability. The aim of this work was to analyze the various surface treatments in titanium implants, demonstrating that the topography and surface chemistry of biomaterials can correlate with the host response; also focusing on the addition of HA to the implant surface and assessing the biological implications during early stages of recovery. Used as a coating, HA acts on the migration, adhesion, proliferation and differentiation of cell precursors on titanium implants by improving the connection between implant and bone. Furthermore, the improvement of the bioactivity of the implant surfaces through HA could therefore facilitate the positioning of the dental prosthesis precisely in the early loading phase, thus satisfying the patients’ requests. It is important to note that all the findings should be supported by further experimental studies in animals as well as humans to evaluate and confirm the use of HA in any field of dentistry.

Wound Healing Promotion by Hyaluronic Acid: Effect of Molecular Weight on Gene Expression and In Vivo Wound Closure.

Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1β), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds.

Encapsulation and Characterization of Nanoemulsions Based on an Anti-oxidative Polymeric Amphiphile for Topical Apigenin Delivery.

Apigenin (Apig) is used as a model drug due to its many beneficial bio-activities and therapeutic potentials. Nevertheless, its poor water solubility and low storage stability have limited its application feasibility on the pharmaceutical field. To address this issue, this study developed nanoemulsions (NEs) using an anti-oxidative polymeric amphiphile, d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), hydrogenated soy lecithin (HL), black soldier fly larvae (BSFL) oil, and avocado (AV) oil through pre-homogenization and ultrasonication method. Addition of TPGS (weight ratios 100 and 50% as compared to HL) into NEs effectively reduced particle size and phase transition region area of NEs with pure HL. Incorporation of Apig into NEs made particle size increase and provided a disorder effect on intraparticle molecular packing. Nevertheless, the encapsulation efficiency of NEs for Apig approached to about 99%. The chemical stability of Apig was significantly improved and its antioxidant ability was elevated by incorporation with BSFL oil and AV oil NEs, especially for NEs with single TPGS. NEs with single TPGS also exhibited the best Apig skin deposition. For future application of topical Apig delivery, NEs-gel was formed by the addition of hyaluronic acid (HA) into NEs. Their rheological characteristics were dominated by the surfactant ratios of HL to TPGS.

Supramolecular poloxamer-based in situ gels with hyaluronic acid and cyclodextrins

Mechanically enhanced poloxamer (F127)-based injectable hydrogels in the presence of hyaluronic acid (HA) and three types of cyclodextrin (CD) molecules were prepared. With the addition of HA to the F127 system, higher strain values to break down the interactions between the micelles were obtained. The formulations exhibit more frequency-dependent behavior than F127–HA gels with the inclusion of CD molecules. All the F127–HA–CD formulations containing α-, β- and γ-CD were found in the injectable range and the viscosity values increased considerably when mucin was added to the triple component formulations that prove the mucoadhesive properties of the gels.

Effects of Co-Culture of Graphene Oxide Scaffolds with Different Concentrations and Umbilical Mesenchymal Stem Cells on the Proliferation and Differentiation of Stem Cells

Background: The main role of the scaffold materials is to enable cells to survive in the scaffold binding as while as to further promote their proliferation and differentiation ability. For mesenchymal stem cell, the scaffold could provide an environment for them to maintain their phenotype, and synthesize all necessary molecules and proteins. Generally, scaffold materials for stem cell need to possess basic characteristics such as high porosity, large surface area, surface rigidity and biodeg-radability. Thus, the two-dimensional graphene oxide (GO) with oxygen-containing functional groups may be suitable scaffold materials for mesenchymal stem cell culture. In this study, the effect of GO on the value-added differentiation activity of mesenchymal stem cell was systematically investigated. Results: It was found that low concentration of GO and sufficient concentration of umbilical cord mesenchymal stem cells are suitable for the second Co-culture. Furthermore, the addition of hyaluronic acid will make this culture more evenly distributed. Conclusions: The adsorption of GO on umbilical cord mesenchymal stem cells can also make the two closely linked, which avoids the impact of animal joint activities on cells.

Study 3D Endothelial Cell Network Formation under Various Oxygen Microenvironment and Hydrogel Composition Combinations Using Upside-Down Microfluidic Devices.

Formation of 3D networks is a crucial process for endothelial cells during development of primary blood vessels under both normal and pathological conditions. In order to investigate effects of oxygen microenvironment and matrix composition on the 3D network formation, an upside-down microfluidic cell culture device capable of generating oxygen gradients is developed in this paper. In cell experiments, network formation of human umbilical vein endothelial cells (HUVECs) within fibrinogen-based hydrogels with different concentrations of hyaluronic acid (HA) is systematically studied. In addition, five different oxygen microenvironments (uniform normoxia, 5%, and 1% O2 ; oxygen gradients under normoxia and 5% O2 ) are also applied for the cell culture. The generated oxygen gradients are characterized based on fluorescence lifetime measurements. The experimental results show increased 3D cell network length when the cells are cultured under the oxygen gradients within the hydrogels with the HA addition suggesting their roles in promoting network formation. Furthermore, the formed networks tend to align along the direction of the oxygen gradients indicating the presence of gradient-driven cellular response. The results demonstrate that the developed upside-down microfluidic device can provide an advanced platform to investigate 3D cell culture under the controlled oxygen microenvironments for various biomedical studies in vitro.

Ozone exposure promotes pyroptosis in rat lungs via the TLR2/4-NF-κB-NLRP3 signaling pathway

ObjectiveOzone has become a major air pollutant in recent years, which leading to a variety of lung diseases. This study aimed to explore the mechanisms of pyroptosis and related signaling pathways in ozone-induced lung injury. MethodsWe exposed 120 Wistar rats to ozone, 20 in each group (half male and half female). Ozone exposure concentrations were 0, 0.12, 0.5, 1.0, 2.0 and 4.0 ppm for 6 h. At the same time, we isolated and cultured type I alveolar epithelial cells, then intervened with high mobility group box 1 protein (HMGB1), hyaluronic acid (HA) and Toll-like receptors 2/4 (TLR2/4) inhibitor. In animal experiments, histopathological experiments, TUNEL, ELISA and biochemical indicators were performed. RT-qPCR and western blot experiments assay were used to detect the expression changes of key factors in relevant signal pathways in vivo and in vitro. ResultsAfter acute ozone exposure, the levels of lung cell injury indicators in bronchoalveolar lavage fluid (BALF), as well as the levels of inflammatory factors in BALF, blood, and lung tissue were significantly increased. Male rats were more sensitive to ozone exposure. Low-concentration ozone exposure caused mild interstitial inflammation in rat lung tissue. Severe inflammation and pulmonary edema appeared with increases in concentration. ELISA results in BALF showed that HMGB1 and HA expressions increased gradually with the increase of ozone exposure concentration. RT-qPCR and Western blot showed that when ozone concentrations increased above 0.5 ppm, the expression of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3 (NLRP3), cleaved caspase-1, and N-gasdermin D (N-GSDMD) in the lung tissue increased significantly, suggesting that ozone exposure induces pyroptosis. At the same time, it was found that ozone exposure activated the nuclear factor kappa B (NF-κB) signal pathway, and increased the mRNA expressions of Toll-like receptors TLR2/4. The results of cell experiments showed that after the addition of HMGB1 and HA, the expression of NF-κB and pyroptosis related indexes increased in type I alveolar epithelial cells, while the corresponding expression decreased after the addition of TLR2/4 inhibitors. ConclusionOzone exposure causes lung injury in a dose- and gender-dependent manner, and is more severe in males. When injured, the levels of HMGB1 and HA in BALF increased, which interact with TLR 2/4 to activate the downstream NF-κB signaling pathway. Further activating the NLRP3 inflammasome complex and regulating the ozone-induced pyroptosis.

Maxillary sinus augmentation with three different biomaterials: Histological, histomorphometric, clinical, and patient-reported outcomes from a randomized controlled trial.

Lateral maxillary sinus augmentation (MSA) is a predictable bone regeneration technique in case of atrophy of the posterior-upper maxilla. Aimed at obtaining quantity and quality of bone suitable for receiving osseointegrated implants, its success is largely due to the skill of the surgeon, but also to the characteristics of the biomaterial used. Twenty-four patients needing MSA were included in the study. The patients were randomly allocated to three different groups: anorganic bovine bone mineral as control, tricalcium phosphate with or without hyaluronic acid (HA) as test groups. Nine months after MSA, bone biopsies were harvested for the histomorphometric analysis. Secondary outcomes were mean bone gain, intraoperative and postoperative complications, implant insertion torque, implant failure, and patient-reported outcome measures. Although the percentage of new bone was not statistically different between the three groups (P = .191), the percentages of residual biomaterial was significantly higher (P < .000) and nonmineralized tissue significantly lower (P < .000) in the control than in the test groups. Test groups did not differ significantly from each other for all histomorphometric parameters. The implant insertion torque was significantly higher in the control group (P < .0005). The rest of the secondary outcomes were not significantly different between the groups. MSA is a safe and predictable procedure in terms of histological, clinical, and PROAMs, regardless of the biomaterial used. The addition of HA did not influence the outcomes.

Efficacy of hyaluronic acid on intervertebral disc inflammation: An in vitro study using notochordal cell lines and human disc cells.

Hyaluronic acid (HA) is widely recognized as a therapeutic target and currently used in medicine. However, HA metabolism during intervertebral disc degeneration (IVDD) has not been completely elucidated. This study aimed to evaluate the efficacy of HA on intervertebral disc (IVD) inflammation and identify the main molecules modulating HA degradation in IVDs. To assess HA function in IVD cells in vitro, we treated human disc cells and U-CH1-N cells, a notochordal nucleus pulposus cell line, with HA or hyaluronidase. Real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis showed that tumor necrosis factor alpha (TNF-α)-mediated induction of the expression of TNF-α and cyclooxygenase-2 (COX2) was clearly neutralized by HA treatment, andthe expression of TNF-α and COX2 was significantly induced by hyaluronidase treatment in both cell types. Additionally, Western blot analysis showed that hyaluronidase-induced phosphorylation of p38 and Erk1/2, and that TNF-α-mediated phosphorylation of p38 and Erk1/2 was clearly reduced by HA addition. In degenerating human IVD samples, immunohistochemistry for hyaluronidase showed that the expression of hyaluronidases including HYAL1, HYAL2, and cell migration-inducing protein (CEMIP) tended to increase in accordance with IVDD. In particular, HYAL1 showed statistically significant differences. In vitro study also confirmed asimilar phenomenon that TNF-α treatment increased both messenger RNA and protein expression in both cell types. Our results demonstrated that HA could potentially suppress IVDD by regulating p38 and Erk1/2 pathways, and that the expression of HYAL1 was correlated with IVDD progression. These findings indicated that HYAL1 would be a potential molecular target for suppressing IVDD by controlling HA metabolism.