Articular Joint-Simulating Mechanical Load Activates Endogenous TGF-β in a Highly Cellularized Bioadhesive Hydrogel for Cartilage Repair.

BACKGROUND

The treatment of osteochondral defects (OCDs) constitutes a major problem for orthopaedic surgeons. The altered mechanics and the cell types, with associated soluble factors derived from the exposed subchondral bone, are likely responsible for the mechanically and structurally inferior articular cartilage subsequently obtained as a repair tissue. There is therefore an unmet clinical need for bioresponsive biomaterials that allow cell delivery, reduce cell infiltration from the bone marrow, and support chondrogenesis in the presence of joint mechanical loading.

PURPOSE

To develop a cell-laden injectable biomaterial, with bioadhesive properties, low cell invasion, and good mechanoresilience, in which simulated joint loading could induce tissue maturation through the production and activation of transforming growth factor beta 1 (TGF-β1).

STUDY DESIGN

Controlled laboratory study.

METHODS

Human bone marrow-derived mesenchymal stromal/stem cells were encapsulated in tyramine-modified hyaluronic acid (HA-Tyr) hydrogels, with crosslinking initiated by the addition of horseradish peroxidase (HRP) and various concentrations of hydrogen peroxide (H

RESULTS

The viscoelastic properties of the cell-laden HA-Tyr hydrogels, as crosslinked with different ratios of HRP and H

CONCLUSION

HA-Tyr hydrogels can be mechanically conditioned to induce activation of endogenous TGF-b1 produced by the embedded cells. HA-Tyr hydrogels function as cell carriers supporting biomechanically induced production and activation of TGF-β1 and as bioadhesive materials with low cell invasion, suggesting that they hold promise as a novel biomaterial for OCD repair strategies.

CLINICAL RELEVANCE

Leveraging physiological joint mechanics to support chondrogenic graft maturation in an optimized mechanosensitive hydrogel in the absence of exogenous growth factors is of highest interest for OCD repair.