Osteochondral Grafts

P241 - Si-HPMC/Si-Chitosan hybrid hydrogel for cartilage regenerative medicine: from in vitro to in vivo assessments

Abstract

Purpose

Articular cartilage may be affected by many injuries including traumatic lesions that predispose to osteoarthritis. Currently there is no efficient cure for cartilage lesions. In this context, we have developed an injectable, self-hardening and mechanically reinforced hydrogel (Si-HPCH) composed of silanised hydroxypropymethyl cellulose (Si-HPMC) mixed with silanised chitosan.

Methods and Materials

The in vitro cytocompatibility of Si-HPCH was tested using human adipose stromal cells (hASC) with a live and dead assay kit. The in vivo biofunctionality of our hydrogel was then determined by implantation in nude mice subcutis. Si-HPMC or Si-HPCH were mixed with hASC. Samples were collected 6 weeks after implantation and characterized by immunohistochemistry.

Si-HPCH was also tested for the repair of calibrated osteochondral defects performed on the medial femoral condyle of dogs. Defects were filled with Si-HPCH alone or mixed with 1 million/ml of autologous ASC. As negative control, 2 defects were left empty. Four months after implantation, samples were analyzed by immunohistochemistry.

Results

Our data demonstrated that Si-HPCH supports hASC viability in 3D culture. Si-HPMC or Si-HPCH also allowed the maintenance of hASC viability in the subcutis of nude mice. Interestingly, explants showed the presence of a low but significant number of cells expressing chondrogenic markers.

In the canine osteochondral defect model, while the empty defects were only partially filled with a fibrous tissue expressing type I collagen and no chondrogenic marker, defects filled with Si-HPCH with or without autologous ASC, revealed a significant osteochondral regeneration. The repair tissue is positively stained for type II collagen.fig 1.jpgfig 2.jpg

Conclusion

Si-HPCH is an injectable, self-setting and cytocompatible hydrogel able to support the viability of hASC in nude mice subcutis. Interestingly, this hydrogel also supports the regeneration of osteochondral defects in dogs when implanted alone or with ASC. Taken together, these data make Si-HPCH a promising candidate for the cell-free regeneration of articular cartilage.

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