Development of a chondron-based matrix-associated ACT

Status:

completed 04/2012

Aims:

Recently, the use of osteoarthritic (OA) chondrocytes for cartilage repair of early-stage OA joint surfaces was investigated.

Activities/Methods:

OA chondrons and OA chondrocytes were enzymatically isolated, cultured in a three-dimensional self-assembling peptide hydrogel or a dextran hydrogel, biomechanically stimulated by intermittent dynamic compression and analyzed.

Results:

OA chondrons and OA chondrocytes were successfully isolated and cultured for a period of 12 weeks. OA chondrons significantly exceeded OA chondrocytes with regard to a) survival of cellular isolation and b) culture in both three-dimensional and monolayer systems, c) a higher collagen type II synthesis rate associated with d) a lower collagen type II degradation rate, and e) adequately maintained gene expression profiles. Another important finding was that f) OA chondrons exhibited a significantly higher glycolytic activity at 2 weeks assessed by the absolute number of mRNA GAPDH molecules per hydrogel and secondly GAPDH enzyme activity. Biomechanical stimulation of OA chondrons significantly enhanced GAG synthesis in peptide hydrogels and collagen type II metabolism in dextran hydrogels. Interestingly, not the biomechanical signal but the choice of hydrogel determined whether GAG or collagen synthesis was significantly enhanced in OA chondrons.

Conclusion

Taken together, the presented data demonstrated that OA chondrons outperform OA chondrocytes quantitatively and qualitatively. Synthesis rates of human OA chondrons can be increased by biomechanical forces. The appropriate choice of scaffold determines whether GAG or collagen type II synthesis is favored. Overall, OA chondrons are a promising cell source for improving current cartilage repair strategies such as ACI and the possible development of a chondron based future biological therapy for OA cartilage.

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