Purpose

To create an injectable hydrogel that can be used to plaster eroded cartilage surfaces and / or to fill up focal cartilage defects in a minimally invasive arthroscopic procedure. The hydrogel should protect the damaged cartilage surface against further cartilage erosion and possess an optimized environment facilitating cartilage regeneration.

Methods and Materials

We developed an injectable hydrogel by conjugating hydroxyphenyl groups in the backbone of naturally occurring polymers such as dextran and hyaluronic acid, which resemble glycosaminoglycans in the extracellular cartilage matrix. This renders an injectable in situ gelating hydrogel which crosslinks in a peroxidase mediated reaction initiated by non-toxic concentrations of H₂O₂. In vivo studies were performed in an equine focal chondral defect model with 2 weeks, 3 & 7 months follow up. The hydrogel treatment was compared with nanofracture.

Results

The two week study proved that our hydrogel can be easily applied in a minimal invasive, arthroscopically guided procedure. It also revealed that as early as after two weeks cartilage-like cells migrated into the hydrogel and displayed a chondrocyte like growth pattern (figure 1a). In all studies the horses recovered well from surgery and did now show lameness during the entire studies.

In the 7 months study the differences in cartilage repair between the hydrogel and the nanofracture treatment were assessed with the ICRS-II scoring system (blinded n-3). The hydrogel treated joint showed significantly better scores for every ICRS-II criterion except matrix staining with an overall ICRSii score of 72% versus 48%. Defects treated with nanofracture contained mainly fibrous tissue and fibrocartilaginous repair tissue (figure2). Three months after the start one horse died, due to circumstances not related to the experiment, cartilage repair was observed (figure1b).

Conclusion

The clinical and histological outcome of these studies suggest that this hydrogel could provide a clinical effective treatment for the cell-free repair of focal cartilage defects.