Abstract
In this research work, viscosupplements based on linear, derivatized, crosslinked and complexed HA forms were extensively examined, providing data on the hydrodynamic parameters for the water-soluble-HA-fraction, rheology, sensitivity to enzymatic hydrolysis and capacity to modulate specific biomarkers’ expression in human pathological chondrocytes and synoviocytes. Soluble HA ranged from 0 to 32 mg/mL and from 150 to 1330 kDa MW. The rheological behavior spanned from purely elastic to viscoelastic, suggesting the diversity of the categories that are suitable for restoring specific/different features of the healthy synovial fluid. The rheological parameters were reduced in a diverse manner upon dilution and hyaluronidases action, indicating different durations of the viscosupplementation effect. Bioactivity was found for all the samples, increasing the expression of different matrix markers (e.g., hyaluronan-synthase); however, the hybrid cooperative complexes performed better in most of the experiments. Hybrid cooperative complexes improved COLII mRNA expression (~12-fold increase vs. CTR), proved the most effective at preserving cell phenotype. In addition, in these models, the HA samples reduced inflammation. IL-6 was down-regulated vs. CTR by linear and chemically modified HA, and especially by hybrid complexes. The results represent the first comprehensive panel of data directly comparing the diverse HA forms for intra-articular injections and provide valuable information for tailoring products’ clinical use as well as for designing new, highly performing HA-formulations that can address specific needs.
Highlights
Osteoarthritis (OA) is a progressive degenerative disorder characterized by a breakdown of the cartilage in the joints, a deterioration of the synovial fluid and a subchondral osteosclerosis accompanied by osteophyte formation [1]
The potential of the diverse HA forms intended as viscosupplements was evaluated by means of contemporary analysis of their rheological behavior— after dilution and in the presence of hyaluronidase—and their bioactivity
In the absence of chemical modification, they exhibited comparable stability to the cross-linked sample, suggesting prolonged action when delivered into the pathological joints
Summary
Osteoarthritis (OA) is a progressive degenerative disorder characterized by a breakdown of the cartilage in the joints, a deterioration of the synovial fluid and a subchondral osteosclerosis accompanied by osteophyte formation [1]. Availability of in vitro and or in vivo data comparing these injective medical devices in the same experimental set-up is strongly needed to scientifically support clinicians’ awareness in the selection of the product most suitable for each specific clinical case (different stages/patterns of OA) [16]. The third group includes the recently developed physical complexes based on hydrogen cooperative bonds between HA chains of diverse sizes [15,18,29,41,42] We aimed to provide scientific evidence of the diverse biophysical and biochemical properties of these three main categories of products by carrying out an in vitro characterization of preparations belonging to each of the groups indicated above
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