Stem-cell based osteochondral interface tissue engineering

Abstract

Formation of an intact, continuous and biological interface with proper zonal organization between mechanically dissimilar tissues is a key challenge in complex tissue engineering.

The presence of a stable interface between soft and hard tissues is important. In particular, the presence of the osteochondral interface can prevent mechanical failure by reducing the shear stress across it. It also prevents vascularization and subsequent mineralization of the uncalcified cartilage, thus maintaining the normal tissue function.

In this study, we demonstrated that with the use of mesenchymal stem cells, the collagen scaffold and the microencapsulation technology, an osteochondral interface with a zone of calcified cartilage could be generated in vitro in 5 weeks.

Specifically, by placing an undifferentiated mesenchymal stem cell-collagen gel between an upper cartilage-like part and a lower bone-like part, cells in the middle layer were able to remodel the collagen gel into an interface similar to that found in vivo. Hypertrophic chondrocytes populated this in vitro generated interface, secreting GAGs, collagen type II and X, and calcium phosphates. Vertically running collagen fibers were found in this interface as well. We also demonstrated the importance of culture medium together with an appropriate configuration for interface formation. In particular, only with the use of both the chondrogenic medium and the three-layer configuration could we generate the osteochondral interface in vitro.

Finally we conducted a pilot animal study on the efficacy of cartilage repair using constructs with a pre-formed osteochondral interface and demonstrated that cartilage re-surfacing was successful in only one month. Hyaline-like cartilage with a continuous tidemark was regenerated. This observed phenomenon could be maintained up to 3 months.

Results of this study contribute to the development of better cartilage repair in future.