Hyaluronic Acid Chondroitin Sulfate Research Articles

Overactive bladder: results from patients treated by hyaluronic acid-chondroitin sulphate therapy.

Overactive bladder (OAB) is a chronic condition. This study was prompted by the need to fill the gap between medical treatment and advanced therapies allowing improvement in Quality of Life. The aim of the current study was to evaluate the association between treatment type (Ialuril®; IBSA Farmaceutici, Lodi, Italy; in combination with antimuscarinic or alone after drop-out of antimuscarinic, relative to antimuscarinic alone treatment) and functional outcomes (number of micturitions, pelvic pain, urinary incontinence, nocturia, urgency). Of all patients newly diagnosed (January 2016 - January 2022) with OAB syndrome, we retrospectively identified 150 patients. They harbored three groups of 50 patients each: group 1 (antimuscarinic drug), group 2 (antimuscarinic drug + hyaluronic acid-chondroitin sulphate [HA-CS]), group 3 (antimuscarinic dropout patients). Univariable linear and logistic regression models were fitted for number and rates of incontinence, urgency, pelvic pain, nocturia, respectively. A significant mean reduction of 1.5 micturition (P=0.02) was recorded in group 2 compared to group 1. Conversely, no statistically significant mean difference was recorded in group 3 compared to group 1. Regarding pelvic pain, both group 2 and group 3 were associated with lower rate of pelvic pain (P<0.001). Regarding urgency, a statistically significant protective OR was recorded for group 2 (OR=0.39; P=0.04), compared to group 1. The combination therapy was associated with symptom improvement in antimuscarinic naïve OAB patients. Conversely in antimuscarinic dropped-out patients only pelvic pain improved with the HS-CA. No statistically significant differences were recorded for other functional outcomes, such as incontinence and nocturia.

Bioinspired collagen-gelatin-hyaluronic acid-chondroitin sulfate tetra-copolymer scaffold biomimicking native cartilage extracellular matrix facilitates chondrogenesis of human synovium-derived stem cells

The microenvironment plays a crucial role in stem cell differentiation, and a scaffold that mimics native cartilaginous extracellular components can promote chondrogenesis. In this study, a collagen–gelatin–hyaluronic acid–chondroitin sulfate tetra-copolymer scaffold with composition and architecture similar to those of hyaline cartilage was fabricated using a microfluidic technique and compared with a pure gelatin scaffold. The newly designed biomimetic scaffold had a swelling ratio of 1278 % ± 270 %, a porosity of 77.68 % ± 11.70 %, a compressive strength of 1005 ± 174 KPa, and showed a good resilience against compression force. Synovium-derived stem cells (SDSCs) seeded into the tetra-copolymer scaffold attached to the scaffold firmly and exhibited good mitochondrial activity, high cell survival with a pronounced glycosaminoglycan production. SDSCs cultured on the tetra-copolymer scaffold with chondrogenic induction exhibited upregulated mRNA expression of COL2A1, ChM-1, Nrf2, TGF-β1, and BMP-7. Ex vivo study revealed that the SDSC–tetra-copolymer scaffold regenerated cartilage-like tissue in SCID mice with abundant type II collagen and S-100 production. BMP7 and COL2A1 expression in the tetra-copolymer scaffold group was much higher than that in the gelatin scaffold group ex vivo. The tetra-copolymer scaffold thus exhibits strong chondrogenic capability and will facilitate cartilage tissue engineering.

Comparison of Intravesical Hyaluronic Acid, Chondroitin Sulfate, and Combination of Hyaluronic Acid-Chondroitin Sulfate Therapies in Animal Model of Interstitial Cystitis.

PurposeThree intravesical treatment agents were compared in an interstitial cystitis rat model: chondroitin sulfate, hyaluronic acid, and combined hyaluronic acid-chondroitin sulfate.MethodsThirty-five female rats were divided into 5 groups: control (group I), isotonic (group II), chondroitin sulfate (group III), hyaluronic acid (group IV), and hyaluronic acid-chondroitin sulfate (group V). Chemical cystitis was induced in all experimental groups by intravesical instillation of 1 mL of hydrogen peroxide (H2O2) for 15 minutes via the transurethral route. The treatment was administered every other day for 3 sessions 2 days after inducing chemical cystitis. Groups II, III, IV, and V received 1 mL of 0.9% NaCl, 1 mL of 0.2% sodium chondroitin sulfate, 1 mL of low-molecular-weight hyaluronic acid, and 1 mL of 2% sodium chondroitin sulfate+1.6% sodium hyaluronic acid, respectively. On day 7, the animals were sacrificed and the bladders were removed for histopathological and immunohistochemical assessments.ResultsSignificant between-group differences were found in vascular congestion (P=0.006). The grade of submucosal edema in groups II and IV was significantly higher than in group I (P=0.006, P=0.006, respectively). In group I, the grade of granulation tissue was lower than the other 4 groups, but no significant difference was found between the remaining groups (P=0.016). Neutrophil cell infiltration was more intense in groups II and IV than in group I (P=0.006, P=0.006, respectively). Significant differences in the leukocyte and mast cell count were detected between groups II and IV (P<0.001, P<0.001, respectively). Abnormal zonula occludens-1 and uroplakin-III immunoreactivity in group II was higher than in groups I, III, or V (P=0.002, P=0.010, respectively). Interleukin-8 expression was lower in group V than in group II (P=0.001).ConclusionA single treatment of chondroitin sulfate and combined hyaluronic acid-chondroitin sulfate treatment demonstrated efficacy by suppressing inflammation and achieving improvements in the urothelium.

Efficacy and Tolerability of Progen, a Nutritional Supplement Based on Innovative Plasma Proteins, in ACL Reconstruction: A Multicenter Randomized Controlled Trial.

Background:New biologic strategies are arising to enhance healing and improve the clinical outcome of anterior cruciate ligament (ACL) reconstruction.Purpose:To evaluate the efficacy of a new oral nutritional supplement (Progen) that contains hydrolyzed collagen peptides and plasma proteins, a hyaluronic acid–chondroitin sulfate complex, and vitamin C.Study Design:Randomized controlled trial; Level of evidence, 2.Methods:The study included patients who underwent ACL reconstruction with hamstring autografts using the same fixation method. All patients received the same analgesia and physical therapy (PT) protocol and were randomized to receive either the nutritional supplement (supplemented group) or no additional therapy (control group). Patients were followed up at days 7, 30, 60, and 90. Pain was assessed by use of a visual analog scale (VAS) and by analgesic consumption. Clinical outcome was assessed via International Knee Documentation Committee (IKDC) score and the number of PT sessions. Perceived efficacy and tolerability were rated on a 5-point Likert scale. Graft maturation was assessed by a blinded musculoskeletal radiologist using magnetic resonance imaging. The number of adverse events (AEs) was recorded.Results:The intention-to-treat analysis included 72 patients, 36 allocated to the supplemented group and 36 to the control group, with no significant differences regarding demographic and preoperative characteristics. Both groups showed significant improvement in pain and function (measured by VAS and IKDC scores) during the 90-day follow-up period (P < .001 for both), without significant differences between groups. The supplemented group had fewer patients that needed analgesics (8.5% vs 50.0%; P < .05) and attended fewer PT sessions (38.0 vs 48.4 sessions; P < .001) at 90 days and had a higher IKDC score at 60 days (62.5 vs 55.5; P = .029) compared with the control group. Patient- and physician-perceived efficacy was considered significantly higher in the supplemented group at 60 and 90 days (P < .05). Perceived tolerability of the overall intervention was better in the supplemented group at 30, 60, and 90 days (P < .05). Graft maturation showed more advanced degrees (grades 3 and 4) in the supplemented group at 90 days (61.8% vs 38.2%; P < .01). No intolerance or AEs associated with the nutritional supplement treatment were reported.Conclusion:The combination of the nutritional supplement and PT after ACL reconstruction improved pain, clinical outcome, and graft maturation. Nutritional supplementation showed higher efficacy during the second month of recovery, without causing AEs.Registration:NCT03355651 (ClinicalTrials.gov identifier).

Multifunctional Hyaluronic Acid and Chondroitin Sulfate Nanoparticles: Impact of Glycosaminoglycan Presentation on Receptor Mediated Cellular Uptake and Immune Activation.

Hyaluronic acid (HA) and chondroitin sulfate (CS) polymers are extensively used for various biomedical applications, such as for tissue engineering, drug delivery, and gene delivery. Although both these biopolymers are known to target cell surface CD44 receptors, their relative cellular targeting properties and immune activation potential have never been evaluated. In this article, we present the synthesis and characterization of novel self-assembled supramolecular HA and CS nanoparticles (NPs). These NPs were developed using fluorescein as a hydrophobic component that induced amphiphilicity in biopolymers and also efficiently stabilized anticancer drug doxorubicin (DOX) promoting a near zero-order drug release. The cellular uptake and cytotoxicity studies of these NPs in different human cancer lines, namely, human colorectal carcinoma cell line HCT116 and human breast cancer cell line MCF-7 demonstrated dose dependent cytotoxicity. Interestingly, both NPs showed CD44 dependent cellular uptake with the CS-DOX NP displaying higher dose-dependent cytotoxicity than the HA-DOX NP in different mammalian cells tested. Immunological evaluation of these nanocarriers in an ex vivo human whole blood model revealed that unlike unmodified polymers, the HA NP and CS NP surprisingly showed platelet aggregation and thrombin-antithrombin complex formation at high concentrations (0.8 mg/mL). We also observed a clear difference in early- and late-stage complement activation (C3a and sC5b-9) with CS and CS NP triggering significant complement activation at high concentrations (0.08-0.8 mg/mL), unlike HA and HA NP. These results offer new insight into designing glycosaminoglycan-based NPs and understanding their hematological responses and targeting ability.

Clinical comparision of intravesical hyaluronic acid and hyaluronic acid-chondroitin sulphate therapy for patients with bladder pain syndrome/interstitital cystitis.

Patients with a history of bladder pain syndrome/interstitial cystitis (BPS/IC) and who responded poorly or unsatisfactorily with previous treatment were compared taking intravesical hyaluronic acid (HA) or hyaluronic acid-chondroitin sulphate (HA-CS). Patients were treated with intravesical instillation with 50 mL sterile sodium hyalurinic acid (Hyacyst, Syner-Med, Surrey, UK) (n = 32) and sodium hyaluronate 1.6% sodium chondroitin sulphate 2% (Ialuril, Aspire Pharma, UK) (n = 33). Intravesical instillations were performed weekly in first month, every 15 days in the second month and monthly in third and fourth months, for a total of 8 doses. Patients were evaluated using a visual analog pain scale (VAS), interstitial cystitis symptom index (ICSI), interstitial cystitis problem index (ICPI), voiding diary for frequency/nocturia, cystometric bladder capacity and voided volume at the beginning and at 6 months. All patients had a potassium sensitivity test (PST) initially. Wilcoxon and Mann-Whitney U tests were used for statistical analysis. In total, 53 patients met the study criteria. There were 30 patients in the HA-CS group (mean age: 48.47) and 23 patients in the HA group (mean age: 49.61) (p > 0.05). The initial PST was positive in 71.7% patients (38/53) overall with no difference between groups (p > 0.05). Responses for VAS, ICCS, ICPS, 24-hour frequency/nocturia statistically improved in both groups at 6 months. There was no significant difference in symptomatic improvement (p > 0.05). Eight patients had mild adverse events. HA and HA/CS instillation can be effective in BPS/IC patients who do not respond to conservative treatment. An important limitation of our study is that the HA dosage of the 2 treatment arms were different. It would be more appropriate with same HA dosage in both groups; however, there was no commercially available glycosaminoglycan (GAG) substance with same HA dosage for single and combination therapy. Large, long-term randomized studies are required to determine if there is a difference between these treatments.

592 Nocturia related to post radiation bladder pain can be improved by hyaluronic acid chondroitin sulfate (ialuril®)

592 Nocturia related to post radiation bladder pain can be improved by hyaluronic acid chondroitin sulfate (ialuril®)

Effect of a solution of hyaluronic acid–chondroitin sulfate–N-acetyl glucosamine on the repair response of cartilage to single-impact load damage

To investigate effects of 1% hyaluronic acid-chondroitin sulfate-N-acetyl glucosamine (HCNAG) on the damage repair response in equine articular cartilage. Articular cartilage from 9 clinically normal adult horses. Full-thickness cartilage disks were harvested from the third metacarpal bone. Cartilage was single-impact loaded (SIL) with 0.175 J at 0.7 m/s and cultured in DMEM plus 1 % (vol/vol) HCNAG or fibroblastic growth factor (FGF)-2 (50 ng/mL). Histologic and immunohistochemical techniques were used to identify tissue architecture and apoptotic cells and to immunolocalize type I and II collagen and proliferating nuclear cell antigen (PCNA). Type II collagen immunoreactivity increased in SIL cartilage, compared with control samples. At days 14 and 28 (day 0 = initiation of culture), control samples had significantly fewer repair cells than did other treatment groups. In control samples and SIL + HCNAG, there was a significant decrease in apoptotic cell number, compared with results for SIL and SIL + FGF-2 samples. At days 14 and 28, there was a significant increase in chondrocytes stained positive for PCNA in the control samples. 1% HCNAG significantly affected apoptotic and repair cell numbers in an SIL damage-repair technique in adult equine articular cartilage. However, HCNAG had no effect on the number of PCNA-positive chondrocytes or on type II collagen immunohistochemical results. The inclusion of 1% HCNAG in lavage solutions administered after arthroscopy may be beneficial to cartilage health by increasing the number of repair cells and decreasing the number of apoptotic cells.

The role of sodium hyaluronate and sodium chondroitin sulphate in the management of bladder disease

Bladder epithelium is not only a simple defence against infections, but it is also a specialized tissue regulating complex bladder functions and playing an active role in the pathogenesis of many bladder diseases. There is strong evidence that different chronic inflammatory bladder diseases, such as recurrent urinary tract infection (UTI), chemical or radiation cystitis and painful bladder syndrome/interstitial cystitis (PBS/IC), can be pathophysiologically linked in the first step of the disease to the loss of the glycosaminoglycan (GAG) mucous layer independently of the original cause of the inflammatory process. The aim of this article is to review the current evidence on the clinic applications of GAGs in urology, with particular emphasis on the therapeutic use of hyaluronic acid (HA) and chondroitin sulphate (CS). A comprehensive electronic literature search was conducted in May 2011 using the Medline database. Three studies supported the decrease of the rate of recurrent UTIs by restoring the GAG layer, showing a significant reduction of UTI rates and a prolonged median time to recurrence after HA intravesical instillations in women with recurrent UTI. We provide higher level evidence by reporting a prospective, randomized, double-blind, placebo-controlled study on the use of intravesical HA and CS in women with recurrent UTIs. A significant reduction of 77% in the UTI rate per patient per year versus placebo was observed at the end of the study. Nine studies were published between 2002 and 2011 on the use of HA and CS to treat PBS/IC. Three of them evaluated the use of GAGs bladder instillation to prolong the effects of bladder hydrodistension. In the other six studies the efficacy of HA bladder instillations to reduce symptoms score was assessed. Preliminary studies support data on the role of HA-CS in detrusor overactivity, nonbacterial cystitis and urological malignancies. Few data are available regarding the mode of action of HA-CS or its effectiveness in the management of bladder diseases. The major issue in interpreting the available evidence regarding HA-CS is that most of the reported studies are nonrandomized and without a control arm. HA-CS may be considered for further studies, including randomized, controlled trials with adequate power.

Comparative study on Lewis lung tumor lines with 'low' and 'high' metastatic capacity. II. Cytochemical and biochemical evidence for differences in glycosaminoglycans.

The enhanced metastatic capacity of an in vivo selected Lewis lung tumor line (LLT-HH) was correlated with changes in cell-associated glycosaminoglycans (GAG) using ultrastructural cytochemistry, flow cytometry and biochemistry. The increase in highly sulphated GAG content on the cell membrane of LLT-HH cells compared to the parent LLT cells was demonstrated cytochemically. Using in vitro [3H]glucosamine labelling of GAG components it was shown that the LLT-HH cells were characterized by a high production of heparan sulphate while the parent LLT line had a high hyaluronic acid-chondroitin sulphate production. The high metastatic phenotype is accompanied by an altered production of cell-associated GAGs.