Tissue-engineered cartilage nanoscaffolds prepared with collagen, hyaluronic acid and chondroitin sulfate / 中华医学美学美容杂志

Objective:To explore the possibility of constructing tissue-engineered cartilage three-dimensional nanoscaffolds with collagen Ⅱ (COLⅡ), hyaluronic acid (HA) and chondroitin sulfate (CS).Methods:The tissue-engineered cartilage scaffolds were prepared by electrospinning techniques with the mixture COLⅡ-HA-CS solvent, which dissolved by 3-trifluoroethanol-water. The surface topography was observed under electron microscope (SEM). And the diameter of nanofibers, the water absorption rate, contact angle and degradation rate were also detected. Generation 2 rabbit chondrocytes were seeded into the scaffold. The cell survival rate and proliferation were evaluated by Cell Counting Kit-8.Results:When the concentration range of electrospinning was 80-120 mg/ml and the mixing ratio of Col, HA and CS was 6-8∶1∶1-2, the tissue engineered cartilage nanoscaffolds could be successfully prepared. Their diameters were mainly distributed between 126.5±23.3 nm and 374.7±14.1 nm. The scaffolds had satisfactory hydrophilicity and degradability. The chondrocytes could well adhere and proliferate on the scaffold.Conclusions:The COLⅡ-HA-CS tissue-engineered cartilage nanoscaffolds have good physical and biological properties, which suggests its promising application in tissue-engineered cartilage.

Reducción de la cobertura social para los fármacos antiartrósicos sintomáticos de acción lenta: una iniciativa de desinversión en Argentina, 2015-2017 / Reduction of social coverage for symptomatic slow-acting drugs for osteoarthritis: a disinvestment initiative in Argentina, 2015-2017

RESUMEN En abril de 2016, el Instituto Nacional de Servicios Sociales para Jubilados y Pensionados excluyó del subsidio social la cobertura al 100% de 159 fármacos, entre ellos, los antiartrósicos sintomáticos de acción lenta o symptomatic slow-acting drugs for osteoarthritis (SySADOA), por insuficiente evidencia de beneficio clínico significativo. Evaluamos el efecto de esta medida sobre la utilización de SySADOA y de los antiinflamatorios no esteroides (AINE), no afectados por la medida. Se compararon las dispensas ambulatorias de los SySADOA y los AINE de 2015 a 2017, midiendo unidades dispensadas, precio de venta al público y gasto de bolsillo del beneficiario para cada mes. Luego de la medida, descendieron un 61,6% los envases de SySADOA dispensados y un 63,4% el monto total del precio de venta al público, medido en valores constantes. La dispensa no se reorientó hacia los AINE, que descendieron un 6,1%. Disminuyó tanto la incidencia de nuevos tratamientos (de 6,4 a 3,3 tratamientos por 1.000 beneficiarios por mes) como su continuidad. El gasto de bolsillo de los beneficiarios en SySADOA aumentó un 75,8% (a valores constantes). La desinversión en intervenciones de valor terapéutico cuestionable es una herramienta valiosa para la sustentabilidad de los sistemas de salud.

ABSTRACT In April 2016, the National Institute of Social Services for Retirees and Pensioners discontinued its policy of 100% coverage for 159 drugs (the "social subsidy"), including symptomatic slow-acting drugs for osteoarthritis (SYSADOAs), due to insufficient evidence of significant clinical benefit. We evaluated the effect of this measure on the use of SYSADOAs as well as non-steroidal anti-inflammatory drugs (NSAIDs), which were unaffected by this policy change. We compared outpatient dispensations of SYSADOAs and NSAIDs from 2015 to 2017, measuring dispensed units, retail price, and out-of-pocket expenses for beneficiaries each month. After the change in coverage, there was a 61.6% total decrease in SYSADOA units dispensed, and a 63.4% decrease in the final sales price to the public, measured in constant values. Dispensation was not reoriented towards NSAIDs, which fell by 6.1%. The incidence of new treatments decreased (from 6.4 to 3.3 treatments per 1,000 beneficiaries per month), as did their continuity. Beneficiaries' out-of-pocket spending on SYSADOAs increased by 75.8% (at constant values). Disinvestment in interventions with questionable therapeutic value is an important tool in working toward the sustainability of health systems.

Hyaluronic acid has chondroprotective and joint-preserving effects on LPS-induced synovitis in horses

The intra-articular use of hyaluronic acid (HA) for the treatment of synovitis and osteoarthritis is still controversial. As a consequence, corticosteroids remain the most frequently employed therapeutic agents, despite their potential systemic and local deleterious effects. This study examined the anti-inflammatory, antioxidant, and chondroprotective activities of low and high molecular weight hyaluronic acid (LMW-HA and HMW-HA) on lipopolysaccharide (LPS)-induced synovitis in horses compared to triamcinolone acetonide (TA). LPS was injected in the metacarpophalangeal joints, which were treated intra-articularly with either TA (as control) or LMW-HA or HMW-HA. Joint clinical evaluation and synovial fluid (SF) analysis were performed at 0, 8, 24, and 48 h. The white blood cell counts (WBC), prostaglandin E2 (PGE2), interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor-α, chondroitin sulfate (CS) and HA concentrations, oxidative burst, and HA molecular weights were measured. TA reduced the lameness, swelling, and PGE2 release but increased the SF CS concentrations enormously at 24h and 48h, and decreased the SF HA modal molecular weight. These results indicate the breakdown of articular cartilage aggrecan and SF HA. In contrast, LMW-HA and HMW-HA were less effective in reducing the inflammation symptoms, but preserved the joints because only a modest increase in CS occurred at 24 h, decreasing at 48 h, and the SF HA was maintained. The HA-treatment also had anti-inflammatory actions, and LMW-HA was the most effective in reducing the release of cytokine. In summary, the HA treatment inhibited efficiently the digestion of cartilage proteoglycans and SF HA breakdown.

Glucosamine, chondroitin sulfate combined with bone health exercise can promote bone mineral density and muscle strength in postmenopausal women:a random community trial / 中国组织工程研究

BACKGROUND: Glucosamine and chondroitin sulfate are important compositions of cartilage tissues. Animal experiments have shown that glucosamine and chondroitin sulfate can treat osteoporosis synergistically, but the effect of their combinations with regular exercise on the bone and joint health of menopausal women is little reported. OBJECTIVE: To observe the effects of the combination of glucosamine, chondroitin sulfate and bone health exercises on skeletal and joint health in postmenopausal women by a random community trial. METHODS: From January to June 2016, 206 eligible postmenopausal women were selected from Bishan District of Chongqing and randomly divided into two groups by random digital method. The trial group received glucosamine and chondroitin sulfate (3 capsules/day, and bone health exercises (at least 3 times/week), while the control group did not receive special treatment. After 6 months of intervention, the bone mineral density, muscle strength of habitual knee, incidence of fracture, osteoarthritis and fall, and levels of symptom and function were compared between the two groups. The peak torque of extension and flexion of habitual knee at 0 and 60 (°) /s angular velocity was detected using Isomed 2000 Dynamometer. RESULTS AND CONCLUSION: (1) The bone mineral density and the peak torque of extension and flexion of habitual knee at 0 and 60 (°) /s angular velocity in the trial group were significantly higher than those in the control group at 6 months after treatment (P ＜ 0.05). (2) The incidence of fall in the trail group was lower than that in the control group at 6 months (17.00％ vs. 5.94％, P ＜ 0.05). The incidence of fracture and osteoarthritis had no significant difference between two groups (P＞ 0.05). (3) The self-ranking of joint pain, holding power of muscle, walking distance and joint stiff had significant differences between two groups (P ＜ 0.05). (4) These results indicate that glucosamine and chondroitin sulfate supplements combined with regular bone health exercises can improve bone mineral density and muscle strength, and prevent joint pain and stiff in postmenopausal women to some extent, thus preventing fall, fracture and osteoarthritis of postmenopausal women.

A prospective randomized controlled multicentre trial comparing intravesical DMSO and chondroïtin sulphate 2% for painful bladder syndrome/interstitial cystitis

ABSTRACT Objective To compare effectiveness of intravesical chondroïtin sulphate (CS) 2% and dimethyl sulphoxide (DMSO) 50% in patients with painful bladder syndrome/interstitial cystitis (PBS/IC). Materials and methods Patients were randomized to receive either 6 weekly instillations of CS 2% or 50% DMSO. Primary endpoint was difference in proportion of patients achieving score 6 (moderately improved) or 7 (markedly improved) in both groups using the Global Response Assessment (GRA) scale. Secondary parameters were mean 24-hours frequency and nocturia on a 3-day micturition dairy, changes from baseline in O’Leary-Sant questionnaire score and visual analog scale (VAS) for suprapubic pain. Results Thirty-six patients were the intention to treat population (22 in CS and 14 in DMSO group). In DMSO group, 57% withdrew consent and only 6 concluded the trial. Major reasons were pain during and after instillation, intolerable garlic odor and lack of efficacy. In CS group, 27% withdrew consent. Compared with DMSO group, more patients in CS group (72.7% vs. 14%) reported moderate or marked improvement (P=0.002, 95% CI 0.05-0.72) and achieved a reduction in VAS scores (20% vs. 8.3%). CS group performed significantly better in pain reduction (-1.2 vs. -0.6) and nocturia (-2.4 vs. -0.7) and better in total O’Leary reduction (-9.8 vs. -7.2). CS was better tolerated. The trial was stopped due to high number of drop-outs with DMSO. Conclusions Intravesical CS 2% is viable treatment for PBS/IC with minimal side effects. DMSO should be used with caution and with active monitoring of side effects. More randomized controlled studies on intravesical treatments are needed.

Intravesical Sodium Chondroitin Sulphate to Treat Overactive Bladder: Preliminary Result / 대한배뇨장애요실금학회지

PURPOSE: This study aimed to verify the efficacy and safety of intravesical treatment with sodium chondroitin sulfate (CS) in patients with overactive bladder (OAB) who are refractory to previous antimuscarinic treatment. METHODS: This study was performed between June 2012 and January 2015 and included 31 consecutive women (mean age, 42.10+/-7.34 years) with OAB who had been previously treated with two types of antimuscarinic drugs. The results of gynecologic and cystoscopic examinations were normal, and OAB comorbidity was absent. Treatment with intravesical instillations containing 40 mL CS (0.2%; 2 mg/mL) was administered for 6 weeks; after weekly treatments, monthly treatments were administered. The OAB-validated 8 (OAB-V8) symptom scores, nocturia, frequency, urgency, urge incontinence, and urinary volumes measured by uroflowmetry were evaluated for all the patients. The values obtained before the treatment were statistically compared with those obtained six months after the treatment. RESULTS: The duration of the symptoms was 18.36+/-6.19 months. A statistically significant improvement of the patients' conditions was observed in terms of the OAB-V8 symptom scores, nocturia, frequency, urgency, urge incontinence, and urinary volumes measured by uroflowmetry after the treatment. CONCLUSIONS: Despite the limitations of this study, the outcomes confirmed that CS therapy is safe and effective for the treatment of OAB.

Biocompatibility of Ferrara intracorneal ring segment with and without chondroitin sulfate coating: clinical and histopathological evaluation in rabbits

PURPOSE: To investigate and compare the biocompatibility of two types of Ferrara intracorneal ring segment: with and without chondroitin sulfate coating by clinical and histopathological evaluation. METHODS: A randomized experimental study was carried out on thirty right-eye corneas from 30 Norfolk albino rabbits allocated into two experimental groups: Group G1 - implanted with Ferrara intracorneal ring segment without coating (FICRS) and Group G2 - implanted with Ferrara intracorneal ring segment with chondroitin sulfate coating (FICRS-CS). Left eyes formed the control group. Clinical parameters analyzed were: presence of edema, vascularization, infection and ring extrusion one, 30, and 60 days after surgery. Histopathological parameters analyzed were: number of corneal epithelial layers over and adjacent to the ring, presence of spongiosis, hydropic degeneration, basement membrane thinning, inflammatory cells, neovascularization and pseudocapsule formation. RESULTS: At clinical examination 60 days after implant, edema, vascularization and extrusion were observed respectively in 20%, 26.7%, 6.7% of FICRS corneas and in 6.7%, 6.7%, and 0% of FICRS-CS corneas. Histopathological evaluation showed epithelial-layer reduction from 5 (5;6) to 3 (3;3) with FICRS and from 5 (5;5) to 4 (3;5) with FICRS-CS in the region over the ring. Epithelial spongiosis, hydropic degeneration, and basement membrane thinning were present in 69.2%, 53.8%, and 69.2% of FICRS and in 73.3%, 73.3%, and 46.7% with FICRS-CS, respectively. Vascularization was present in 38.5% of FICRS and 13.3% with FICRS-CS, inflammatory cells in 75% of FICRS and 33.3% with FICRS-CS, and pseudocapsule in 66.7% of FICRS and 93.3% with FICRS-CS. Giant cells occurred only in the FICRS-CS group (20%). CONCLUSION: Ferrara intracorneal rings coated with chondroitin sulfate (FICRS-CS) caused lower frequency of clinical and histopathological alterations than Ferrara intracorneal rings without the coating (FICRS), demonstrating higher biocompatibility of the FICRS-CS.

Evaluation of an Amniotic Membrane-Collagen Dermal Substitute in the Management of Full-Thickness Skin Defects in a Pig

BACKGROUND: To minimize the inflammatory reaction and improve healing, a new modified dermal substitute composed of an atelocollagen, chondroitin-6-sulfate, and amniotic membrane (AM) was applied to full-thickness skin defects in a pig. Atelocollagen was extracted from bovine skin, and two modified dermal substitutes were generated according to the cross-linking type. METHODS: The AM-collagen dermal substitutes were characterized and compared with currently used dermal substitutes in a pig skin defect model. There were five experimental groups: dehydrothermal (DHT) cross-linking atelocollagen with the AM on the top (AM-DHT), DHT and chemical cross-linking atelocollagen with the AM on the top (AM-DHT/chemical), Terudermis, Integra, and AlloDerm. After 3x3 cm full-thickness skin defects on the back of a pig were created, each dermal substitutes dermal substitutes was randomly grafted on the defects. Two weeks after grafting, autologous partial-thickness skin was over-grafted on the neodermis. The take rate of the dermal substitutes, skin, and histological sections were all assessed at 1, 2, and 4 weeks postoperatively. RESULTS: More rapid healing and a higher take rate were evident in the AM-DHT and Terudermis groups. Histological examination revealed fewer inflammatory cells and more fibroblast hyperplasia in these two groups. Four weeks after surgery, the amount of newly formed collagen was significantly more appropriate in the AM-DHT group. CONCLUSIONS: These observations provide supporting evidence that a newly developed amniotic-collagen dermal substitute may inhibit inflammatory reactions and promote wound healing.

Primary research on the changes of contents and molecular structures of chondroitin sulfate in aortic dissection / 中国现代普通外科进展

Objectives:To elucidate the changes on contents and molecular structures of chondroitin sulfate in aneurysmal wall of aortic dissection and disscuss its likely roles in the pathogenesis and progression of aortic dissection.Methods:After glycosaminoglycans in aortae being abstracted,chondroitin sulfate were separated and purified respectively through DEAE Sephacel by ion exchange chromatography and then identified by cellulose acetate electrophoresis.Chondroitin sulfate were hydrolyzed with chondroitinase ABC,and then its disaccharide compositions were analyzed by high performance capillary electrophoresis.Results:Compared with the control group, chondroitin sulfate increased significantly(P

Determination of unsaturated disaccharides produced from chondroitin sulfate in urine using high performance liquid chromatography with fluorometric post column derivatization / 中国地方病学杂志

Objective To explore the effectiveness of the unsaturated disaccharides derived from chondroitin sulfate(CS)in urine using post column derivation fluorometric method of high performance liquid chromatography (HPLC).Methods Urine samples were prepared with the centrifugal flirtation and the routine precipitation methods separately,then digest the sample with CS lyses,use the post column derivation method of HPLC to fluorometric determine the unsaturated disaecharides(△Di-0S,△Di-4S and △Di-6S),compare the recovery differences of the CS standard in the urine pretreated by the two methods.Results The HPLC system ran well,the lowest detection limit of the method was 10 ng.When the urine was pretreated by the centrifugal flirtation method,the recovery of △Di-0S,△Di-4S and △Di-6S produced from the CS standard were 86.93%,87.28%and 85.03%,respectively,while the recovery of the three disaccharides in routine precipitation method were 75.09%,72.96%and 77.70%merely.Conclusions The HPLC post column derivatization fluorometric method is comparatively sensitive,it can be used to determine unsaturated disaccharides decomposed by CS.In the pretreatment procedure of the urine,the centrifugal flirtation method was superior to the routine precipitation method,it can be used as microdetermination for the unsaturated disaccharides.

Effect of cultured chondrocyte-seeded chondroitin-sulfate conjugated type I collagen scaffold on cartilage regeneration

PURPOSE: In this study, porous type I collagen scaffolds were cross-linked using dehydrothermal(DHT) treatment and/or 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide(EDC), in the presence and absence of chondroitin-6-sulfate(CS) and cultured autologous chondrocytes(Chondro) for cartilage regeneration. METHODS: Cartilage defects were created in the proximal part of the ear of New Zealand rabbits. Four prepared types of scaffolds(n=4) were inserted. The groups included Chondro-Collagen-DHT(Group 1), Chondro- Collagen-DHT-EDC(Group 2), Chondro-CS-Collagen- DHT(Group 3), and Chondro-CS-Collagen-DHT-EDC (Group 4). Histomorphometric analysis and cartilage- specific gene expression of the reconstructed tissues were evaluated 4, 8, and 12 weeks after implantation . RESULTS: EDC cross-linked groups 2 and 4 regenerated more cartilage than other groups. However, calcification was observed in the 4th week after implantation. CS did not increase chondrogenesis in all groups. Cartilage-specific type II collagen mRNA expression increased in the course of time in all groups. CONCLUSION: EDC cross-linking methods maintain the scaffold and promote extracellular matrix production of chondrocytes.

The Effect of Various Methods of Cross-linking in Type I Collagen Scaffold on Cartilage Regeneration

PURPOSE: Collagen is the principal structural biomolecule in cartilage extracellular matrix, which makes it a logical target for cartilage engineering. In this study, porous type I collagen scaffolds were cross-linked using dehydrothermal(DHT) treatment and/or 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide(EDC), in the presence and absence of chondroitin-6-sulfate(CS) for cartilage regeneration. METHODS: Cartilage defects were created in the proximal part of the ear of New Zealand rabbits. Four types of scaffolds(n=4) were inserted. The types included DHT cross-linked(Group 1), DHT and EDC cross- linked(Group 2), CS added DHT cross-linked(Group 3), and CS added DHT and EDC cross-linked(Group 4). Histomorphometric analysis and cartilage-specific gene expression of the reconstructed tissues were evaluated respectively 4, 8, and 12 weeks after implantation. RESULTS: The largest quantity of regenerated cartilage was found in DHT cross-linked groups 1 and 3 in the 8th week and then decreased in the 12th week, while calcification increased. Calcification was observed from the 8th week and the area increased in the 12th week. Group 4 was treated with EDC cross-linking and CS, and the matrix did not degrade in the 12th week. Cartilage-specific type II collagen mRNA expression increased with time in all groups. CONCLUSION: CS did not increase chondrogenesis in all groups. EDC cross-linking may prevent chondrocyte infiltration from the perichondrium into the collagen scaffold.