The combination of hyaluronic acids and collagen boosts human Achilles tendon-derived cell escape from inflammation and matrix remodeling in vitro.

Objective: This study explores whether hyaluronic acid (HA) of different molecular weights and collagen, given their role in tendon extracellular matrix maintenance, have a synergistic effect on human tendon-derived cells, with the aim to improve the treatment of tendinopathy.

Material: Human monocytes (CRL-9855™) and primary Achilles tendon-derived cells.

Treatment: The collagen/HA ratio was based on the formulation of the commercial food supplement TendoGenIAL™. The anti-inflammatory activity was evaluated on human lipopolysaccharide (LPS)-stimulated macrophages (24 h) or human Achilles tendon-derived cells under basal and pro-inflammatory conditions (24 and 72 h) and on a co-culture model of tenocytes and inflamed macrophages (24 h).

Results: These data show that the combination of high molecular weight hyaluronic acid and collagen reduces inflammation in macrophages by downregulating CD14, with a mean fluorescence intensity (MFI) of 36,274 (± 1780) (p < 0.0001). Additionally, this combination enhances the modulation of extracellular matrix remodeling proteins, such as CD44 whose MFI is 675,435 (± 28109) (p < 0.00001) and collagen type I at 17.838 µg/mL (± 6,259) (p < 0.00001). The observation of the ultrastructure of tenocytes through electron microscopy reveals increased cell membrane vesiculation and cell size, indicating that tenocytes start to proliferate and create abundant extracellular matrix proteins, important for the matrix remodeling.

Conclusions: Our data confirm the anti-inflammatory activity of both hyaluronic acids and collagen, highlighting a synergistic effect of their combination in a determined ratio.