Hyaluronic Acid Formulations Research Articles

One-Year, Efficacy and Safety Open Label Study, with a Single Injection of a New Hyaluronan for Knee OA: The SOYA Trial.

PurposeTo assess the efficacy and safety of a single injection of a new formulation of hyaluronic acid (MPS-HA2%) in patients with symptomatic knee osteoarthritis after 12 months’ follow-up.Patients and MethodsProspective, single-arm, multicentre, open-label, 12-month follow-up study. Patients with Kellgren–Lawrence (KL) 2–3 and visual analogue scale (VAS) pain scores of ≥40–< 80 mm received a single injection of MPS-HA2%. The primary outcome was the reduction in VAS pain scores from baseline, and the secondary outcomes were the Western Ontario and McMaster (WOMAC) Universities Osteoarthritis Index, the minimum clinically important improvement (MCII), and patient and investigator global assessments (PGA, IGA) measured on 5-point Likert scale. Adverse events were recorded throughout the study for safety purposes.ResultsA total of 101 patients (mean age: 68 years; 74% female; and 78% overweight) were included. The mean reduction in pain at 12 months was 37.7%; the total WOMAC score improved by 36.5% and the pain, stiffness and physical function subscores returned improvements of 32.1%, 34.1% and 32.7%, respectively (p=0.0001 with respect to baseline). At 12 months, a statistically significant 62.2% of patients obtained an improvement equal to or greater than the MCII. The mean PGA score at baseline was 2.44 and 1.46 at 12 months (p<0.05), and the mean IGA scores at equivalent timepoints were 2.29 and 1.48 (p<0.05). Fourteen patients received a second injection at the 6-month follow-up visit. Eight patients reported a total of 12 treatment-related adverse events that were local, non-serious and of mild-to-moderate intensity.ConclusionWith just a single intra-articular injection, this not controlled trial suggests that MPS-HA2% is effective 12 months after the procedure in most cases. Patient tolerability and safety were both optimal (NCT03852914).

Clinical effectiveness and safety of intra-articular injection of HYALGO in the management of knee osteoarthritis symptoms: A multicenter prospective study

BackgroundThe reduced concentration of hyaluronic acid in the synovial fluid, leading to impairment of joint function and painful symptomatology during knee osteoarthritis (OA), can be restored by using injectable formulations of hyaluronic acid (HA) and chondroitin sulfate (CS), variable for relative composition, HA/CS molecular modifications, and injection protocols. The present study aims to assess the safety and performance of the intra-articular (IA) viscosupplementing agent HYALGO, a formulation combining 40 mg/mL HA (>1700 kDa) and 40 mg/mL CS, in the treatment of patients suffering from knee OA. Methods74 patients affected by knee lesions classified as grade II and III according to Kellgren and Lawrence classification were prospectively recruited and treated with three HYALGO injections (2 mL) given one week apart. Visual analogue scale (VAS) pain changes were monitored at each injection and over-time at 6, 14, and 26 weeks of follow-up. Secondary endpoints were: Western Ontario McMaster University Osteoarthritis index (WOMAC), Patient's Global Assessment (PGA) score, Clinical Observer Global Assessment (COGA) score, Outcome Measures in Rheumatology Committee (OMERACT) and Osteoarthritis Research Society International (OARSI) responders rates. Patients were also assessed for changes in their ultrasound joint scores according to the criteria of the OMERACT US Task Force Group. ResultsPain reduction was statistically significant starting from the first IA injection. Mean pain reduction from baseline to week 26 was −90.6%. At 26 weeks, WOMAC Pain was reduced by −62.7%, WOMAC Stiffness by −47.2%, WOMAC Physical Function by −54.1%; Total WOMAC by −53.8%. The VAS PGA change from baseline was −48.0 [mm] and VAS COGA -41.0 [mm]. Responders at week 26 were 78.4%. Ultrasound parameters (joint effusion, synovial thickness, and popliteal cysts) improved or remained stable from baseline to week 6. ConclusionsThree injections of HYALGO were safe and effective to manage symptomatic knee OA, with a beneficial effect that increased progressively over time, peaking 6 months after injection.

New Trends in Injection-Based Therapy for Thumb-Base Osteoarthritis: Where Are We and where Are We Going?

Thumb-base osteoarthritis (TBOA) is a common condition, mostly affecting post-menopausal women, often inducing a significant impact on quality of life and hand functionality. Despite its high prevalence and disability, the therapeutic options in TBOA are still limited and few have been investigated. Among the pharmacological strategies for TBOA management, it would be worthwhile to mention the injection-based therapy. Unfortunately, its efficacy is still the subject of debate. Indeed, the 2018 update of the European League Against Rheumatism (EULAR) recommendations for the management of hand osteoarthritis (OA) stated that intra-articular (IA) injections of glucocorticoids should not generally be used, but may be considered in patients with painful interphalangeal joints, without any specific mention to the TBOA localization and to other widely used injections agents, such as hyaluronic acid (HA) and platelet-rich plasma (PRP). Even American College of Rheumatology (ACR) experts conditionally recommended against IA HA injections in patients with TBOA, while they conditionally encouraged IA glucocorticoids. However, the recommendations from international scientific societies don’t often reflect the clinical practice of physicians who routinely take care of TBOA patients; indeed, corticosteroid injections are a mainstay of therapy in OA, especially for patients with pain refractory to oral treatments and HA is considered as a safe and effective treatment. The discrepancy with the literature data is due to the great heterogeneity of the clinical trials published in this field: indeed, the studies differ for methodology and protocol design, outcome measures, treatment (different formulations of HA, steroids, PRP, and schedules) and times of follow-up. For these reasons, the current review will provide deep insight into the injection-based therapy for TBOA, with particular attention to the different employed agents, the variety of the schedule treatments, the most common injection techniques, and the obtained results in terms of efficacy and safety. In depth, we will discuss the available literature on corticosteroids and HA injections for TBOA and the emerging role of PRP and other injection agents for this condition. We will consider in our analysis not only randomized controlled trials (RCTs) but also recent pilot or retrospective studies trying to step forward to identify satisfactory management strategies for TBOA.

Hyaluronic Acid Fillers for Midface Augmentation: A Systematic Review.

Injectable fillers represent one of the most requested minimally invasive treatments to rejuvenate the aging face, and its popularity is steadily rising. A vast majority of filler treatments are with hyaluronic acid (HA). The aim of this systematic review is to evaluate patient outcomes, safety profile, and administration techniques of various HA fillers for malar augmentation. A systematic review of the published literature was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and included PubMed, Embase, and Science Direct databases. Medical Subject Headings (MeSH) terms used were "cheek" OR "midface" OR "malar" and "filler" OR "hyaluronic acid" OR "Juvederm" OR "Restylane" OR "Perlane" OR "Belotero." The initial search identified 699 articles; 256 duplicates were removed. Additional 12 studies were identified from reference lists. A total of 455 were screened by title and abstract and 387 studies were eliminated based on criteria. Also, 68 articles underwent full-text review, and 18 articles were included in the final review and involved seven different HA formulations. Men and women from many age groups were highly satisfied with their results following HA treatment for midface augmentation up to 24 months. The most common adverse events included bruising, swelling, and tenderness, and typically lasted no more than 2 weeks. Upper cheek filler injections near the zygoma should be placed in the submuscular plane while lower cheek injections should be placed in the subcutaneous tissue. HA is an attractive choice for midface augmentation due to its high patient satisfaction, long-lasting effects, and low side-effect profile. Due to the variability in technique, level of expertise, and subjective measurements across studies, one optimal regimen could not be concluded. However, midface augmentation treatment should be personalized to each patient. Additional clinical trials are required to more conclusively determine the most appropriate approach for this procedure.

Investigation of Changes in Saliva in Radiotherapy-Induced Head Neck Cancer Patients.

The intact function of the salivary glands is of utmost importance for oral health. During radiotherapy in patients with head and neck tumors, the salivary glands can be damaged, causing the composition of saliva to change. This leads to xerostomia, which is a primary contributor to oral mucositis. Medications used for protective or palliative treatment often show poor efficacy as radiation-induced changes in the physico-chemical properties of saliva are not well understood. To improve treatment options, this study aimed to carefully examine unstimulated whole saliva of patients receiving radiation therapy and compare it with healthy unstimulated whole saliva. To this end, the pH, osmolality, electrical conductivity, buffer capacity, the whole protein and mucin concentrations, and the viscoelastic and adhesive properties were investigated. Moreover, hyaluronic acid was examined as a potential candidate for a saliva replacement fluid. The results showed that the pH of radiation-induced saliva shifted from neutral to acidic, the osmolality increased and the viscoelastic properties changed due to a disruption of the mucin network and a change in water secretion from the salivary glands. By adopting an aqueous 0.25% hyaluronic acid formulation regarding the lost properties, similar adhesion characteristics as in healthy, unstimulated saliva could be achieved.

Novel Combinatorial Dexamethasone and Hyaluronic Acid Micro Particulate Injection for the Treatment of Hip Arthritis: Assesment in Rabbit Model

The aforementioned study emphasis on formulation of Dexamethasone and Hyaluronic acid (DHA) loaded microspheres for intra-articulate injection at hip region to cure arthritic condition. DHA microspheres were formulated by solvent evaporation technique. The microspheres were found with smooth, regular surface characteristics. The loading and encapsulation efficiencies were also found higher. The in vitro release was found to be 15.12% for initial 24 hrs while 97.65% up to 25 days. Such microspheres were injected to hip region of Adult male new Zealand Rabbits (2.5–3 kg) to observe anti arthritic effect. The study result showed excellent ability of microsphere in order to treat arthritis. Therefore the results obtained concluded effectiveness of DHA microspheres in treating arthritic disease.

Association of hyaluronic acid with a deproteinized bovine graft improves bone repair and increases bone formation in critical-size bone defects.

This study is designed to evaluate the potential of different formulations of hyaluronic acid (HA) to improve new bone formation in critical-size calvaria defect (CSD) when combined with a deproteinized bovine graft (DBG) material. Thirty male rats were used. A 5-mm-diameter CSD was created and three experimental groups (n=10) were randomly assigned based on the treatments performed. Group DBG: CSD filled with a DBG; group DBG/LV: CSD filled by the combination of DBG and HA in a low-viscosity crosslinking agent; group DBG/HV: CSD filled by the combination of DBG and HA in a high-viscosity crosslinking agent. Animals were euthanized 30 days postoperatively. Histological, histometric (percentage of newly formed bone [PNFB], percentage of remaining graft particles, histochemical, and immunohistochemical (bone morphogenetic protein 2/4 [BMP2/4], osteocalcin [OCN], and tartrate-resistant acid phosphatase [TRAP]) analyses were performed. The highest PNFB was observed in DBG/HV when compared with the other groups (P ≤0.05). DBG/LV and DBG/HV presented almost no inflammatory cells. In contrast, inflammation was observed in group DBG. Extensive resorption of graft particles was observed in group DBG, which was not present in DBG/LV and DBG/HV as confirmed by the larger size of the particles (P ≤0.05). BMP2/4 and OCN immunolabeling were higher in DBG/HV when compared with group DBG (P ≤0.05). Increased number of TRAP-positive cells was observed in DBG/LV and DBG/HV (P ≤0.05). Lower percentage of mature collagen fibers was observed in DBG/HV (P ≤0.05). The combination of HA in a high-viscosity crosslinking agent with DBG improves the bone repair process and increases the amount of newly formed bone towards CSDs in rat calvaria.

Understanding the Dual Dilemma of Dry Eye and Glaucoma: An International Review.

Glaucoma-related ocular surface disease (G-OSD) is a significant, yet often underdiagnosed, ocular co-morbidity affecting 40% to 59% of glaucoma patients worldwide. Although the use of topical glaucoma medications represents a proven strategy to control the untoward effects of high intraocular pressure, this treatment can profoundly disrupt the homeostasis of the tear film. The cumulative effect of medications, preservatives, and excipients alter underlying cellular structures which results in tear film abnormalities and instability of the ocular surface. Furthermore, these chronic inflammatory changes have been shown to impact efficacy of glaucoma treatment, patient compliance with therapy and overall quality of life. The pathogenesis of G-OSD is multifactorial and involves a vicious self-perpetuating cycle of inflammatory cytokines and proteins. The diagnosis of such disease is based on similar tests used in assessing traditional dry eye, taking into consideration findings specific to this patient population. The hallmark of treatment for these patients is to minimize the ocular surface inflammatory response by choosing glaucoma therapies that spare the ocular surface such as preservative free formulations and initiating dry eye treatment early in the course of care. In summary, glaucoma affects millions of patients around the world and chronic use of topical glaucoma medications may negatively impact the patient's ocular surface, symptoms, and vision. Understanding the pathogenesis of G-OSD, recognizing its risk factors and incorporating diagnostic and therapeutic strategies that restore and maintain ocular surface homeostasis will result in improved care for our patients.

Multicentre International Study for the Prevention with Ialuril® of Radio-Induced Cystitis (MISTIC): A Randomised Controlled Study

Background: Acute and late radiation cystitis is a common adverse effect of cancer treatment with radiotherapy to the pelvic area. We hypothesised that hyaluronic acid and chondroitin sulphate may provide protection of the urothelium during radiotherapy and alleviate acute and chronic consequences of pelvic radiotherapy. Methods: This randomised, controlled, multicentre study was done across seven centres in four countries. Male patients aged ≥18 years scheduled to undergo primary intensity‐modulated radiotherapy for localised prostate cancer were enrolled. Patients were randomised to intravesical hyaluronic acid plus chondroitin sulphate plus an oral soft gel formulation of curcumin, quercetin, hyaluronic acid, and chondroitin sulphate. No masking was applied. The primary endpoint were absolute change from baseline to follow-ups in the urinary domain score of the Expanded Prostate Cancer Index Composite (EPIC), the ICIQ-Male Lower Urinary Tract Symptoms (ICIQ-MLUTS) questionnaire, and the EuroQol Group questionnaire EQ-5D-5L. Secondary outcomes was the rate of patients who stopped treatment due to intolerance or adverse events. Findings: Of 57 patients screened between January 2017 and May 2019, 49 were enrolled and randomly assigned to either active (intravesical plus oral, n=25) treatment or controls (no treatment, n=24). Three patients in the control group withdrew after randomisation. When stratified according to urinary symptoms and impact of symptoms on quality of life, sub-total scores and total score were lower from baseline to 12 months in controls (p=0.05, p=0.003, and p=0.008, respectively). There was a significant time*group interaction in favour of active treatment for incontinence symptom score (p=0.011) and bother score (p=0.017). Interpretation: Our results suggest that intravesical hyaluronic acid plus chondroitin sulphate in combination with a hyaluronic acid and chondroitin-containing oral formulation are a safe and well tolerated treatment to reduce the acute and chronic urinary adverse consequences of pelvic radiotherapy. Trial Registration: The study was registered with ClinicalTrials.gov (NCT03493997). Funding Statement: (TETI Association) IBSA SA supplied freely Ialuril and Ialuril Soft Gels Declaration of Interests: All other authors declare no competing interests. Ethics Approval Statement: The study was approved by the responsible institutions for medical research ethics for all participating centres and was conducted in compliance with the International Conference on Harmonization/Good Clinical Practice guidelines, national laws, applicable regulatory requirements, and the ethical principles of the Declaration of Helsinki. Specifically, the study was approved by the Ethics Committees of the Universidad Autonoma de Barcelona, Barcelona, Spain, the Universita Vita-Salute San Raffaele, Milan, Italy, the Ospedali Careggi, Firenze, Italy, the University of Palermo, Italy, the St. Cyril and Method University Hospital Bratislava, Slovakia, the Fakultna nemocnica s poliklinikou Presov, Slovakia, and Istanbul University, Istanbul, Turkey.

A high molecular weight hyaluronic acid biphasic dispersion as potential therapeutics for interstitial cystitis.

Interstitial cystitis (IC) is a progressive bladder disease characterized by increased urothelial permeability, inflammation of the bladder with abdominal pain. While there is no consensus on the etiology of the disease, it was believed that restoring the barrier between urinary solutes and (GAG) urothelium would interrupt the progression of this disease. Currently, several treatment options include intravesical delivery of hyaluronic acid (HA) and/or chondroitin sulfate solutions, through a catheter to restore the urothelial barrier, but have shown limited success in preclinical, clinical trials. Herein we report for the first time successful engineering and characterization of biphasic system developed by combining cross‐linked hyaluronic acid and naïve HA solution to decrease inflammation and permeability in an in vitro model of interstitial cystitis. The cross‐linking of HA was performed by 4‐arm‐polyethyeleneamine chemistry. The HA formulations were tested for their viscoelastic properties and the effects on cell metabolism, inflammatory markers, and permeability. Our study demonstrates the therapeutic effects of different ratios of the biphasic system and reports their ability to increase the barrier effect by decreasing the permeability and alteration of cell metabolism with respect to relative controls. Restoring the barrier by using biphasic system of HA therapy may be a promising approach to IC.

An injectable click-crosslinked hyaluronic acid hydrogel modified with a BMP-2 mimetic peptide as a bone tissue engineering scaffold

An injectable, click-crosslinking (Cx) hyaluronic acid (HA) hydrogel scaffold modified with a bone morphogenetic protein-2 (BMP-2) mimetic peptide (BP) was prepared for bone tissue engineering applications. The injectable click-crosslinking HA formulation was prepared from HA-tetrazine (HA-Tet) and HA-cyclooctene (HA-TCO). The Cx-HA hydrogel scaffold was prepared simply by mixing HA-Tet and HA-TCO. The Cx-HA hydrogel scaffold was stable for a longer period than HA both in vitro and in vivo, which was verified via in-vivo fluorescence imaging in real time. BP acted as an osteogenic differentiation factor for human dental pulp stem cells (hDPSCs). After its formation in vivo, the Cx-HA scaffold provided a fine environment for the hDPSCs, and the biocompatibility of the hydrogel scaffold with tissue was good. Like traditional BMP-2, BP induced the osteogenic differentiation of hDPSCs in vitro. The physical properties and injectability of the chemically loaded BP for the Cx-HA hydrogel (Cx-HA-BP) were nearly identical to those of the physically loaded BP hydrogels and the Cx-HA-BP formulation quickly formed a hydrogel scaffold in vivo. The chemically loaded hydrogel scaffold retained the BP for over a month. The Cx-HA-BP hydrogel was better at inducing the osteogenic differentiation of loaded hDPSCs, because it prolonged the availability of BP. In summary, we successfully developed an injectable, click-crosslinking Cx-HA hydrogel scaffold to prolong the availability of BP for efficient bone tissue engineering.

Nasal Powder Formulation of Tranexamic Acid and Hyaluronic Acid for the Treatment of Epistaxis.

The aim of this study was to develop a nasal powder formulation of the antifibrinolytic drug, tranexamic acid (TXA), in combination with the wound-healing agent hyaluronic acid (HA) for the local treatment of epistaxis (nose bleeding). Formulations of TXA alone and with different concentrations of HA were freeze-dried and characterised according to their physicochemical properties. Aerosol performance was assessed to ensure nasal deposition with minimal lung deposition. Nasal epithelial cells were used to assess cytotoxicity, transport across the nasal epithelium, antioxidant, wound-healing and anti-inflammatory properties of all formulations. Formulations containing TXA and HA were produced and found to be mostly deposited in the nasal cavity (more than 90%). Formulation of TXA + 0.3%HA showed wound reduction of 29.3% when assessed in ALI culture. At this concentration, formulations also reduced ROS production in RPMI 2650, and IL-8 production in primary nasal epithelial cells. Furthermore, for formulations containing HA, the higher viscosity may lead to larger residence time in the nasal cavity. Combination of TXA with HA shows promising results for the treatment of nasal epistaxis.

DoE-Assisted Development of a Novel Glycosaminoglycan-Based Injectable Formulation for Viscosupplementation.

The aim of the present work was the development of a novel glycosaminoglycan (GAG)-based injectable formulation intended for intra-articular administration that should best mimic the healthy synovial fluid. Hyaluronic acid (HA) was chosen among GAG polymers, since it is the most abundant component of the synovial fluid. A DoE (Design of Experiment) approach was used for the development of a formulation containing two HA (very high (VHMW) and low (LMW) molecular weight) grades. The rationale for this choice is that so far, no commercial product based on a single HA grade or even on binary HA mixture possesses optimal viscoelastic properties in comparison with healthy synovial fluid. A full factorial design was chosen to investigate the influence of concentration and relative fraction of the two polymer grades (retained as factors of the model) on formulation functional (viscosity and viscoelastic) properties, which are considered response variables. Thanks to the DoE approach, the composition of the optimized HA formulation was found. The addition to such formulation of an injectable grade fat-free soy phospholipid, which was rich in phosphatidylcholine (PC), resulted in improved lubrication properties. The final HA + PC formulation, packaged in pre-filled sterile syringes, was stable in long-term and accelerated ICH (International Council for Harmonisation) storage conditions. The overall results pointed out the formulation suitability for further steps of pharmaceutical developments, namely for the passage to pilot scale.

In Vivo Imaging of Click-Crosslinked Hydrogel Depots Following Intratympanic Injection.

In this study, we developed injectable intratympanic hyaluronic acid (HA) depots for the treatment of hearing loss. We prepared an injectable click-crosslinking formulation by modifying HA with tetrazine (HA-TET) and trans-cyclooctene (HA-TCO), which crosslinked to form an HA depot (Cx-HA). Preparation of the click-crosslinking HA formulation was facile, and Cx-HA depot formation was reproducible. Additionally, the Cx-HA hydrogel was significantly stiffer than HA hydrogel. To monitor the degradation pattern of hydrogels, we mixed a zwitterionic near-infrared (NIR) fluorophore (e.g., ZW800-1C) in the click-crosslinking HA formulation. Then, HA-TET and HA-TCO solutions containing ZW800-1C were loaded separately into the compartments of a dual-barrel syringe for intratympanic injection. The Cx-HA depots formed quickly, and an extended residence time in the tympanic cavity was confirmed by performing NIR fluorescence imaging. We have successfully prepared an injectable click-crosslinking HA formulation that has promise as an intratympanic drug depot.

An Injectable Click-Crosslinked Hyaluronic Acid Hydrogel Modified with a BMP-2 Mimic Peptide as a Bone Tissue Engineering Scaffold

An injectable, click-crosslinking (Cx) hyaluronic acid (HA) hydrogel scaffold modified with a bone morphogenetic protein-2 (BMP-2) mimetic peptide (BP) was prepared for bone tissue engineering applications. The injectable click-crosslinking HA formulation was prepared from HA-tetrazine (HA-Tet) and HA-cyclooctene (HA-TCO). The Cx-HA hydrogel scaffold was prepared simply by mixing HA-Tet and HA-TCO. The Cx-HA hydrogel scaffold was stable for a longer period than HA both in vitro and in vivo, which was verified via in-vivo fluorescence imaging in real time. BP acted as an osteogenic differentiation factor for human dental pulp stem cells (hDPSCs). After its formation in vivo, the Cx-HA scaffold provided an excellent environment for the hDPSCs, and the biocompatibility of the hydrogel scaffold with tissue was excellent. Like traditional BMP-2, BP induced the osteogenic differentiation of hDPSCs in vitro. The physical properties and injectability of the chemically loaded BP for the Cx-HA hydrogel (Cx-HA-BP) were nearly identical to those of the physically loaded BP hydrogels and the Cx-HA-BP formulation quickly formed a hydrogel scaffold in vivo. The chemically loaded hydrogel scaffold retained the BP for over a month. The Cx-HA-BP hydrogel was better at inducing the osteogenic differentiation of loaded hDPSCs, because it prolonged the availability of BP. In summary, we successfully developed an injectable, click-crosslinking Cx-HA hydrogel scaffold to prolong the availability of BP for efficient bone tissue engineering.

Polyanionic Hydrogels as Reservoirs for Polycationic Antibiotic Substitutes Providing Prolonged Antibacterial Activity.

Implantation of biomedical devices is often followed by bacterial infections that may seriously affect implant functionalities and lead to their failure. In the context of bacterial resistance to antibiotics, which is a growing problem worldwide, new strategies that are able to overcome these problems are needed. In this work, we introduce a new formulation of hyaluronic acid (HA)-based antimicrobial material: HA hydrogels loaded with polyarginine (PAR), a polycationic antibiotic substitute. The loading is possible through electrostatic interactions between negatively charged HA and positively charged PAR. Such hydrogels absorb high quantities of PAR, which are then gradually released from the hydrogel. This original system provides a long-lasting antibacterial effect on an in vitro model of repetitive infection, thus demonstrating a strong potential to fight multiple rounds of infections that are resistant to antibiotic treatment. In addition, HA-PAR hydrogels could be deposited onto/into medical devices such as wound dressings and mesh prostheses used in clinical applications. Finally, we performed first in vivo tests of hydrogel-coated mesh materials to verify their biocompatibility in a rat model, which show no difference between control HA hydrogel and PAR-loaded hydrogel in terms of inflammation.

Consequences on Private Insurance Coverage: The AAOS Clinical Practice Guidelines and Hyaluronic Acid Injections.

Consequences on Private Insurance Coverage: The AAOS Clinical Practice Guidelines and Hyaluronic Acid Injections.

The interaction between hyaluronidase and hyaluronic acid gel fillers - a review of the literature and comparative analysis

Hyaluronic acid (HA) is the most common component of aesthetic fillers. Many formulations exist, each exhibiting properties that are manifestations of individual molecular modifications. The enzyme hyaluronidase degrades hyaluronic acid and can therefore be injected into soft tissue to reduce suboptimally placed HA fillers or to reverse local ischemic complications. The clinically available varieties of hyaluronidase may be derived from crude animal extracts or genetically engineered from recombinant human DNA. Different HA fillers are not uniformly dissolved by a single source hyaluronidase, and hyaluronidase from different sources may have varying efficacy in the degradation of HA. Previous studies of subsets of HA fillers and hyaluronidases have provided limited and often conflicting data regarding these differences, and a more comprehensive scientific study is needed. In this review, the authors describe commonly available formulations of HA and hyaluronidase and review all studies of HA-hyaluronidase interaction available via a PubMed and Google Scholar search from 2005 to present, exploring trends in the data. Factors determined to confer increased resistance to degradation included higher concentration of HA, higher crosslinking density, and status as monophasic versus biphasic. Fillers of the Juvéderm family were generally found to be more resistant to degradation than members of the Restylane family. Results are less consistent for Belotero Balance. No variety of hyaluronidase was consistently superior at dissolving any variety of HA filler. More research is needed to clarify these clinically relevant relationships.

The use of Hyaluronic Acid as an adjuvant Therapeutic Approach to Non-Surgical Periodontal Therapy for Periodontitis

Periodontitis is a highly prevalent infectious-inflammatory disease, characterized by alveolar bone resorption. Hyaluronic acid (HA) has stood out for its anti-inflammatory and antioxidant effects. The present study evaluated, through a literature review, the use of HA as an adjunctive therapeutic approach to non-surgical periodontal therapy (NSPT) of periodontitis (PD), carried out through scaling and root planing. For this, the Pubmed and Medline databases were used with the following descriptors: Hyaluronic Acid AND Periodontitis. Among 58 manuscripts found, 11 studies were selected after analyzing their title and respective abstracts. Pre-clinical or clinical research published from 2010 to 2020, including the use of HA exclusively in the NSPT of PD, were included for this literature review. Studies using other pharmacological interventions in conjunction with HA, other literature reviews and research related to the treatment of gingivitis, periodontal or pulp regeneration, surgical periodontal therapy, apical or peri-implantitis periodontitis were excluded. The main data of the selected manuscripts were compiled in a table and, then, their results were compared and discussed among themselves. Despite a wide variety of methodological protocols carried out by prospective researches, it is noted that HA has potential healing, anti-inflammatory and antimicrobial effects, which can be interesting from the point of view of periodontal treatment, considering the infectious and inflammatory character of PD. There are also different commercial formulations of HA on the market. It is suggested, therefore, that HA can be promising as a chemical adjuvant to PD NSPT, and can be used in the form of subgingival irrigation in deep periodontal pockets.

Evaluation of the efficacy of EGF and hyaluronic acid formulation on periodontal defects named also black holes

Evaluation of the efficacy of EGF and hyaluronic acid formulation on periodontal defects named also black holes