scholarly journals Hybrid Hydrogel Composed of Hyaluronic Acid, Gelatin, and Extracellular Cartilage Matrix for Perforated TM Repair

2021 ◽  
Vol 9 ◽  
Author(s):  
Yili Wang ◽  
Feng Wen ◽  
Xueting Yao ◽  
Lulu Zeng ◽  
Jiaming Wu ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Cartilage Matrix ◽  
Blue Staining ◽  
Alcian Blue Staining ◽  
Hybrid Hydrogel ◽  
Composite Hydrogels ◽  
Further Development ◽  
Perforated Tympanic Membrane

A novel series of composite hydrogels, built from the three components 1), hyaluronic acid methacryloyl (HAMA); 2), gelatin methacryloyl (GelMA), and 3), extracellular cartilage matrix (ECM), was prepared and studied regarding the possible utility in the surgical repair of damaged (perforated) tympanic membrane (TM). Noteworthy is component 3), which was harvested from the ribs of α-1,3-galactosidyltransferase-knockout (α-1,3 GalT-KO) pigs. The absence of α-1,3-galactosyl glycoprotein is hypothesized to prevent rejection due to foreign-body immunogenicity. The composite hydrogels were characterized by various aspects, using a variety of physicochemical techniques: aqueous swelling, structural degradation, behavior under compression, and morphology, e.g., in vitro biocompatibility was assessed by the CCK-8 and live–dead assays and through cytoskeleton staining/microscopy. Alcian blue staining and real-time PCR (RT-PCR) were performed to examine the chondrogenic induction potential of the hydrogels. Moreover, a rat TM defect model was used to evaluate the in vivo performance of the hydrogels in this particular application. Taken together, the results from this study are surprising and promising. Much further development work will be required to make the material ready for surgical use.

scholarly journals The Study of Mechanisms of Protective Effect of Rg1 against Arthritis by Inhibiting Osteoclast Differentiation and Maturation in CIA Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Yanqing Gu ◽  
Weimin Fan ◽  
Guoyong Yin
Keyword(s):  
Articular Cartilage ◽  
Osteoclast Differentiation ◽  
Cathepsin K ◽  
Blue Staining ◽  
Alcian Blue Staining ◽  
Pathologic Analysis ◽  
Rank Signaling ◽  
K Matrix

Ginsenoside Rg1 is a natural product extracted fromPanax ginsengC.A. Although Rg1 protects tissue structure and functions by inhibiting local inflammatory reaction, the mechanism remains poorly understood.In vitro, Rg1 dose-dependently inhibited TRAP activity in receptor activator of nuclear factor-κB ligand- (RANKL-) induced osteoclasts and decreased the number of osteoclasts and osteoclast resorption area. Rg1 also significantly inhibited the RANK signaling pathway, including suppressing the expression of Trap, cathepsin K, matrix metalloproteinase 9 (MMP9), and calcitonin receptor (CTR).In vivo, Rg1 dramatically decreased arthritis scores in CIA mice and effectively controlled symptoms of inflammatory arthritis. Pathologic analysis demonstrated that Rg1 significantly attenuated pathological changes in CIA mice. Pronounced reduction in synovial hyperplasia and inflammatory cell invasion were observed in CIA mice after Rg1 therapy. Alcian blue staining results illustrated that mice treated with Rg1 had significantly reduced destruction in the articular cartilage. TRAP and cathepsin K staining results demonstrated a significant reduction of numbers of OCs in the articular cartilage in proximal interphalangeal joints and ankle joints in Rg1-treated mice. In summary, this study revealed that Rg1 reduced the inflammatory destruction of periarticular bone by inhibiting differentiation and maturation of osteoclasts in CIA mice.

Preparation and characterization of antibacterial and anti-inflammatory hyaluronic acid-chitosan-dexamethasone hydrogels for peri-implantitis repair

2021 ◽  
pp. 088532822110479
Author(s):  
Zhen Zhou ◽  
Qiang Zhang ◽  
Yamin Wang
Keyword(s):  
Hyaluronic Acid ◽  
Physicochemical Characterization ◽  
Inflammatory Drug ◽  
Composite Hydrogels ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Nih 3T3

Numerous treatment methods for peri-implantitis have been widely used including oral cleaning, traditional metal scraping means, or local antibiotic application. However, to continuously release antibacterial and anti-inflammatory drug in location in situ for effective peri-implantitis repair is still challenging. Herein, an anti-inflammatory drug dexamethasone (DE)–incorporated hyaluronic acid (HA)-chitosan (CT) composite hydrogels system was developed to repair peri-implantitis. The physicochemical characterization and biocompatibility of the hydrogel were evaluated in vitro. The in vivo hydrogels degradation and peri-implantitis repair were assessed in mice. The results showed that the prepared multifunctional hydrogels achieved sustained release, with an equilibrium swelling of 18, and promoted the growth against NIH-3T3 fibroblast cells. The in vitro antibacterial tests showed HA-CT-DE hydrogels can inhibit methicillin-resistant Staphylococcus aureus and Escherichia coli. It down-regulated the expression levels of inflammation factor IL-1β, IL-6 and, TNF-α in peri-implantitis. The prepared HA-CT-DE composite hydrogels with integrated function is promising for the treatment of peri-implantitis.

THU0055 ANTI-DEGRADATIVE AND PRO-CHONDROGENIC PROPERTIES OF LIRAGLUTIDE, A GLUCAGON-LIKE-PEPTIDE 1 RECEPTOR AGONIST: EVIDENCE FROM PRECLINICAL STUDIES AND IMPLICATION FOR OSTEOARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 239.1-239
Author(s):  
F. Berenbaum ◽  
C. Meurot ◽  
J. Breton ◽  
L. Sudre ◽  
C. Bougault ◽  
...  
Keyword(s):  
Alcian Blue ◽  
Articular Chondrocytes ◽  
Inflammatory Responses ◽  
Joint Disease ◽  
Blue Staining ◽  
Alcian Blue Staining ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Background:Osteoarthritis (OA) is a degenerative joint disease affecting millions of individuals worldwide. Its development has been reported to be associated with cartilage degradation and inflammatory responses leading to pain, swelling and reduced function. Although OA is a disorder of the whole joint, the progressive destruction of cartilage extracellular matrix is considered as its hallmark. To date, approved OA treatments are only symptomatic. Therefore, there is an urgent need to explore disease-modifying OA drugs (DMOADs) that can mitigate, stop, or even reverse the development of OA.Objectives:In this context, the objective of this study was to assess the effect of liraglutide, a Glucagon-Like-Peptide 1 Receptor (GLP-1R) agonist approved for type 2 diabetes, on chondrogenesis, catabolism/inflammation and cartilage protection inin vitroandin vivopreclinical models of OA.Methods:The capacity of liraglutide to induce chondrogenesis was evaluated using primary human mesenchymal stem cells (hMSCs). Alcian blue staining was used to assess differentiation of hMSC into chondrocyte spheroids. IL-1β-stimulated mouse articular chondrocytes were treated with different concentrations of liraglutide for 24h. Production of matrix metalloproteinase MMP-13, prostaglandin E2 (PGE2) and nitrite was measured by ELISA and Griess reaction, respectively. Exendin 9-39, a GLP-1R antagonist, was used to confirm target engagement in thein vitroexperiments. Intra-articular (IA) injections of liraglutide or vehicle were performed in the type II collagenase rat model. Histopathological analyses (OARSI scores1) were conducted blindly by one investigator.Results:Liraglutide induced the differentiation of hMSCs into chondrocytes. Indeed, 21 days after differentiation initiation, 5/6 and 4/6 alcian-blue positive spheroids were observed for 10 and 100nM liraglutide, respectively, versus 0/6 for vehicle. Liraglutide significantly reduced dose-dependently the IL-1β-induced production of PGE2 (5808±178 for vehicle vs 4560±140, 2933±171 and 2365±85 pg/ml for liraglutide 10, 100 and 500nM, respectively, p≤0.001), nitrite (24.9±0.4 for vehicle vs 20.9±1.5, 19.1±0.9 and 16.5±0.5 µM for liraglutide 10, 100 and 500nM, respectively, p≤0.001) and MMP-13 (686±9 for vehicle vs 553±3, 402±5 and 297±8 pg/ml for liraglutide 10, 100 and 500nM, respectively, p≤0.001) in murine chondrocytes. Effects of liraglutide were GLP-1R dependent since exendin 9-39 significantly counteracted both chondrogenesis and inflammation/catabolism markers expression. Histological assessment of rat collagenase-injected knee joint revealed a significant (p≤0.05) decrease of the total joint score in the IA Liraglutide treated group (8±4) compared to vehicle (11±4).Conclusion:Liraglutide induced chondrogenesis, decreased metalloproteinase and inflammatory mediators production by chondrocytes and protected cartilage inin vitroandin vivopreclinical OA models, opening the way for repositioning this drug as a potential DMOAD.References:[1]Osteoarthritis Cartilage. 2010 Oct;18 Suppl 3:S24-34Acknowledgments:All the people who contributed to the InOsteo project: the members of 4P-Pharma, INSERM UMR S938 research team, SATT Lutech and Sorbonne UniversityDisclosure of Interests:Francis Berenbaum Grant/research support from: TRB Chemedica (through institution), MSD (through institution), Pfizer (through institution), Consultant of: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Bone Therapeutics, Regulaxis, Peptinov, 4P Pharma, Paid instructor for: Sandoz, Speakers bureau: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Sandoz, Coralie Meurot Employee of: 4P-Pharma, Jerome Breton Employee of: 4P-Pharma, Laure Sudre: None declared, Carole Bougault: None declared, Revital Rattenbach Shareholder of: 4P-Pharma, Employee of: 4P-Pharma, Celine Martin Employee of: 4P-Pharma, Claire Jacques: None declared

In vitro and in vivo Evaluation of BMSC Laden RGD-Conjugated MPEG-PCL Composite Hydrogels for Bone Regeneration

2019 ◽  
Author(s):  
Hyun Joo Kim ◽  
Su Jung You ◽  
Dae Hyeok Yang ◽  
Heung Jae Chun ◽  
Hae Kwan Park ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Composite Hydrogels

scholarly journals Secreted KIAA1199 promotes the progression of rheumatoid arthritis by mediating hyaluronic acid degradation in an ANXA1-dependent manner

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei Zhang ◽  
Guoyu Yin ◽  
Heping Zhao ◽  
Hanzhi Ling ◽  
Zhen Xie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Dependent Manner ◽  
Collagen Induced Arthritis ◽  
Intracellular Degradation ◽  
Main Pathway ◽  
First Time

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

scholarly journals In vitro and in vivo effect of hyaluronic acid modified, doxorubicin and gallic acid co-delivered lipid-polymeric hybrid nano-system for leukemia therapy

2019 ◽  
Vol Volume 13 ◽  
pp. 2043-2055 ◽  
Author(s):  
Yanping Shao ◽  
Wenda Luo ◽  
Qunyi Guo ◽  
Xiaohong Li ◽  
Qianqian Zhang ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Gallic Acid

scholarly journals Diacerein-Loaded Hyaluosomes as a Dual-Function Platform for Osteoarthritis Management via Intra-Articular Injection: In Vitro Characterization and In Vivo Assessment in a Rat Model

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 765
Author(s):  
Nouran O. Abdelmageed ◽  
Nadia M. Morsi ◽  
Rehab N. Shamma
Keyword(s):  
Hyaluronic Acid ◽  
Cartilage Damage ◽  
Entrapment Efficiency ◽  
Dual Function ◽  
In Vitro Characterization ◽  
Drug Entrapment Efficiency ◽  
Formulation Parameters ◽  
Acid Gel

The application of intra-articular injections in osteoarthritis management has gained great attention lately. In this work, novel intra-articular injectable hyaluronic acid gel-core vesicles (hyaluosomes) loaded with diacerein (DCN), a structural modifying osteoarthritis drug, were developed. A full factorial design was employed to study the effect of different formulation parameters on the drug entrapment efficiency, particle size, and zeta potential. Results showed that the prepared optimized DCN- loaded hyaluosomes were able to achieve high entrapment (90.7%) with a small size (310 nm). The morphology of the optimized hyaluosomes was further examined using TEM, and revealed spherical shaped vesicles with hyaluronic acid in the core. Furthermore, the ability of the prepared DCN-loaded hyaluosomes to improve the in vivo inflammatory condition, and deterioration of cartilage in rats (injected with antigen to induce arthritis) following intra-articular injection was assessed, and revealed superior function on preventing cartilage damage, and inflammation. The inflammatory activity assessed by measuring the rat’s plasma TNF-α and IL-1b levels, revealed significant elevation in the untreated group as compared to the treated groups. The obtained results show that the prepared DCN-loaded hyaluosomes would represent a step forward in the design of novel intra articular injection for management of osteoarthritis.

Results of an experimental study of hydrogel drainage containing ranibizumab in antiglaucoma operations

2021 ◽  
pp. 63-67
Author(s):  
I.I. Khusnitdinov ◽  
Keyword(s):  
Experimental Study ◽  
Hyaluronic Acid ◽  
Key Words ◽  
Experimental Research ◽  
Experimental Studies ◽  
Glaucoma Surgery ◽  
Control Group ◽  
Morphological Studies

Purpose. Еxperimental substantiation of the effectiveness of biocompatible biodegradable hydrogels based on hyaluronic acid and chitosan succinate as a carrier of ranibizumab in antiglaucoma operations. Material and methods. Hydrogel drainage (HD) was obtained immediately before surgery. A solution of ranibizumab (0.23 ml) was mixed with a solution of hyaluronic acid dialdehyde (0.5 ml), then a solution of chitosan succinate (0.5 ml) was added. Experimental studies were performed in 12 (12 eyes) healthy rabbits. The first group consisted of 6 eyes – 0.187 ml of ranibizumab per 1 ml of gel. In the control group, HD was used intraoperatively without the addition of ranibizumab (6 eyes). Morphological studies were performed on 7th, 21st, and 42nd days. Results. In experimental studies in vitro and in vivo, it was proved that ranibizumab, administered as a part of 0.1 ml of hydrogel drainage in the antiglaucoma surgery area is released within 3 weeks and suppresses vascularization, scarring of the operating area, and preserves the intrascleral cavity. The optimal concentration of ranibizumab was selected-0.02 ml in 0.1 ml of gel. Conclusion. The safety and effectiveness of the use of hydrogel drainage with ranibizumab based on hyaluronic acid dialdehyde and chitosan succinate in anti-glaucoma operations has been proven. Key words: experimental research, hydrogel drainage, ranibizumab, glaucoma surgery.

scholarly journals Preclinical Pharmacokinetics of C118P, a Novel Prodrug of Microtubules Inhibitor and Its Metabolite C118 in Mice, Rats, and Dogs

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2883 ◽  
Author(s):  
Cang Zhang ◽  
Xiaolan Zhang ◽  
Guangji Wang ◽  
Ying Peng ◽  
Xueyuan Zhang ◽  
...  
Keyword(s):  
Clinical Development ◽  
High Dose ◽  
Protein Inhibitor ◽  
Promising Candidate ◽  
Preclinical Pharmacokinetics ◽  
Tumor Bearing ◽  
Microtubule Protein ◽  
Further Development

C118P, a phosphate prodrug of C118, which is a novel microtubule protein inhibitor, is currently under Phase I clinical development in China for treating ovarian cancer and lung cancer. The preclinical pharmacokinetics of prodrug C118P and its metabolite C118 were extensively characterized in vivo in mice, rats, and dogs and in vitro to support the further development of C118P. The preclinical tissue distribution and excretion were investigated in rats. Plasma protein binding in mice, rat, and human, and hepatic microsomal metabolic stability in mice, rat, dog, monkey, and human, were also evaluated. The (AUC0-inf) and C30s of C118P at 50 mg/kg in rats and 6 mg/kg in dogs, and the C2min of C118 at 6 mg/kg in dogs increased less than the dosage increase, suggested nonlinear pharmacokinetic occurred at high dose. As a prodrug, C118P can be quickly hydrolyzed into C118 after an intravenous administration. The unbound C118 in plasma is slightly higher than C118P. C118P can hardly penetrate the tissue, while C118 can distribute widely into tissues. In tumor-bearing nude mice, the concentration of C118 is high in lung, ovary, and tumor, with an extended half-life in tumor. C118P is a promising candidate prodrug for further clinical development.

scholarly journals Functional optical coherence tomography of retinal photoreceptors

2018 ◽  
Vol 243 (17-18) ◽  
pp. 1256-1264 ◽  
Author(s):  
Xincheng Yao ◽  
Taeyoon Son ◽  
Tae-Hoon Kim ◽  
Yiming Lu
Keyword(s):  
Vision Loss ◽  
Objective Assessment ◽  
Age Related Macular Degeneration ◽  
Retinal Stimulation ◽  
Age Related ◽  
Retinal Photoreceptors ◽  
Severe Vision Loss ◽  
Further Development

Age-related macular degeneration (AMD) is the leading cause of severe vision loss and legal blindness. It is known that retinal photoreceptors are the primary target of AMD. Therefore, a reliable method for objective assessment of photoreceptor function is needed for early detection and reliable treatment evaluation of AMD and other eye diseases such as retinitis pigmentosa that are known to cause photoreceptor dysfunctions. Stimulus-evoked intrinsic optical signal (IOS) changes promise a unique opportunity for objective assessment of physiological function of retinal photoreceptor and inner neurons. Instead of a comprehensive review, this mini-review is to provide a brief summary of our recent in vitro and in vivo optical coherence tomography (OCT) studies of stimulus-evoked IOS changes in animal retinas. By providing excellent axial resolution to differentiate individual retinal layers, depth-resolved OCT revealed rapid IOS response at the photoreceptor outer segment. The fast photoreceptor-IOS occurred almost right away (∼ 2 ms) after the onset of retinal stimulation, differentiating itself from slow IOS changes correlated with inner neural and hemodynamic changes. Further development of the functional IOS instruments and retinal stimulation protocols may provide a feasible solution to pursue clinical application of functional IOS imaging for objective assessment of human photoreceptors. Impact statement Retinal photoreceptors are the primary target of age-related macular degeneration (AMD) which is the leading cause of severe vision loss and legal blindness. An objective method for functional assessment of photoreceptor physiology can benefit early detection and better treatment evaluation of AMD and other eye diseases that are known to cause photoreceptor dysfunctions. This article summarizes in vitro study of IOS mechanisms and in vivo demonstration of IOS imaging of intact animals. Further development of the functional IOS imaging may provide a revolutionary solution to achieve objective assessment of human photoreceptors.

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