Unsulfated biotechnological chondroitin by itself as well as in combination with high molecular weight hyaluronan improves the inflammation profile in osteoarthritis in vitro model

Abstract

Several studies suggest that inflammation has a pivotal role during the progression of osteoarthritis (OA) and cytokines have been identified as the main process mediators. This study aimed to explore the ability to modulate the main OA pro‐inflammatory biomarkers of novel gels (H‐HA/BC) based on high molecular weight hyaluronan (H‐HA) and unsulfated biotechnological chondroitin (BC). For the first time, BC was tested also in combination with H‐HA on human primary cells isolated from pathological knee joints. Specifically, the experiments were performed using an OA in vitro model based on human chondrocytes and synoviocytes. To evaluate the anti‐inflammatory effects of H‐HA/BC in comparison with H‐HA and BC single gels, NF‐kB, COMP‐2, MyD88, MMP‐13 and a wide range of cytokines, known to be specific biomarkers in OA (e.g., IL‐6, IL‐8, and TNF‐α), were evaluated. In addition, cell morphology and proliferation occurring in the presence of either H‐HA/BC or single components were assessed using time‐lapse video microscopy. It was shown that synovial fluids and cells isolated from OA suffering patients, presented a cytokine pattern respondent to an ongoing inflammation status. H‐HA and BC significantly reduced the levels of 23 biomarkers associated with cartilage damage. However, H‐HA/BC decreased significantly 24 biological mediators and downregulated 19 of them more efficiently than the single components. In synoviocytes cultures, cytokine analyses proved that H‐HA/BC gels re‐established an extracellular environment more similar to a healthy condition reducing considerably the concentration of 11 analytes. Instead, H‐HA and BC significantly modulated 7 (5 only with a longer treatment) and 8 biological cytokines, respectively. Our results suggest that H‐HA/BC beyond the viscosupplementation effect typical for HA‐based gels, can improve the inflammation status in joints and thus could be introduced as a valid protective and anti‐inflammatory intraarticular device in the field of Class III medical devices for OA treatments.

Hyaluronan and Derivatives: An In Vitro Multilevel Assessment of Their Potential in Viscosupplementation

“…Primary in vitro cultures of pathological human chondrocytes and synoviocytes were obtained following the experimental protocols that are well established in our laboratories [ 15 , 44 ]. In detail, the knee cartilages specimens and synovium samples were obtained from the Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli” (Naples, Italy), from OA-affected patients who were subjected to knee surgery.…”

“…Characterization comprised hydrodynamic and rheological analyses, which aimed to quantify and characterize the water-soluble HA included in the formulas and the viscosupplentation potential along with its variation due to dilution and HA-enzymatic hydrolysis (both phenomena occur in vivo after delivery). Moreover, we compared their bioactivity in a human primary cell model of OA, analyzing the cell morphology, viability and biosynthesis of key biomarkers of cartilage, and also evaluating specific mediators to address the inflammatory status [ 43 , 44 ]. To the best of our knowledge, this is the first study directly comparing both the biophysical and biochemical features of products for intrarticular injections based on the diverse chemical forms of hyaluronan.…”

Neural Tissue Homeostasis and Repair Is Regulated via CS and DS Proteoglycan Motifs

“…However, Chn elicited a significant improvement in the anti-inflammatory profile of synoviocytes and chondrocytes in an OA model analyzed by multiplex and Western blot analysis. Chn significantly decreased the levels of several pro-inflammatory cytokines (IL-1β, IL-5, 6, 7, 9, 15, 17), anti-inflammatory cytokines (IL-4, IL-10), chemokines (IL-8, MCAF, MIP-1a, MIP-1b, RANTES) in synovial fluid samples and decreased expression of the OA biomarkers MyD88 and MMP-13 ( Vassallo et al, 2021 ). Evidence therefore exists that Chn displays anti-inflammatory properties in mammalian tissues.…”

PLGA Coatings and PLGA Drug-Loading Coatings for Cardiac Stent Samples: Degradation Characteristics and Blood Compatibility

“…A coarser implant surface in direct contact with blood increases coagulation, while high surface smoothness (Ra < 50 nm) helps improve blood compatibility. Studies [27][28][29][30] have shown the vascular walls of organisms are very smooth from a macroscopic viewpoint-an endothelium surface membrane of the vascular endothelium is a bilayer lipid liquid matrix with particles embedded in the membrane. The macroscopic smooth and microscopic multiphase separation structure has excellent anticoagulant properties.…”