Recapitulating Developmental Condensation and Constructing Self-organised Cartilaginous Tissue for Cartilage Regeneration

Objective: To develop a novel chondrocyte condensation culture strategy recapitulating developmental condensation and construct self-organised cartilaginous tissue for cartilage regeneration.
Methods: Cell-condensation aggregate (CCA) was generated using the condensation culture method by sequential cell seeding. The chondrification capacities and biocompatibilities of CCA were assessed by comparison with the cell–scaffold complex (CSC), which was constructed by cell–scaffold coculture. Preclinical studies including implantation into nude mice subcutaneously and cartilage defect repair in rabbits were performed.
Results: CCA constructed by condensation culture exhibited a morphology of self-organised cartilaginous tissue. Meanwhile, the condensation culture inhibited or abolished expression of HOX genes including HOXC4 and HOXD8, which was partially consistent with developmental HOX gene expression patterns and associated with enhanced regeneration capacities. Compared with CSC, CCA showed a higher capacity for chondrification and regeneration of rabbit cartilage defects.
Conclusion: The therapeutic assessments indicate that CCA is an efficient therapeutic tool for cartilage regeneration, providing a new strategy for tissue engineering by mimicking developmental events.