HYBRID effect of HA + Chondroitin Sulfate

The presence of CS increases the tissue adherence properties when compared with an HA alone-based formulation. In this sense, a combining both HA and CS may offer new therapeutic per- spectives, but the exogenous IA CS with its smaller MW—< 50 kDa—may be subject to a faster rate of elimination with respect to HA.
Due to its steric size, high MW HA is supposed to stay in the synovial fluid rather than to easily penetrate the tissue meshwork. For the small CS molecules that stay, surprisingly, in the joint, the probability of penetration into tissue seems high, and cartilage could be the best candidate as tissue receptor,
More recently, a hybrid complex, based on high molecular weight hyaluronan (HHA) and CS (HHA/CS), thus coupling HHA viscosupplementation properties and CS antiinflammatory and degradative abilities, has been obtained, and its biochemical and biological features have been assayed both in vitro and in vivo.
The combination of high molecular weight hyaluronan with BC has been thoroughly characterized in terms of its viscoelastic properties and resistanceto enzymatic degradation. More recently, its beneficial effects on pro-inflammatory biomarkers in human pathological chondrocytes have also been demonstrated , the HHA/CS formulation exhibited rheological properties that support its potential to manage mechanical stress in the synovial joints during walking and running, thereby providing effective viscosupplementation benefits.


Cartılage Protection
Cartilage hydration and elasticity depend on the presence of CS.
The depletion of GAGs is therefore an important factor leading to accelerated cartilage degradation in the OA disease.
GlcNAc was also reported to stimulate hyaluronan synthesis via the upregulation of hyaluronan synthase-2 in human articular chondrocytes , Hyaluronan is reported to inhibit interleukin (IL-) 1β-induced matrix metalloproteinase-13 expression and IL-1α-induced expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 through CD44 signaling in arthritic chondrocytes.