Z. Yang (Singapore, SG)
National University of Singapore, Life Sciences Institute Tissue Engineering ProgramPresenter Of 1 Presentation
12.1.7 - Bilayered Zonal Chondrocyte Implantation Improved the Zonal Architecture in Regenerated Cartilage and the Subchondral Bone Integrity
Abstract
Purpose
The zonal properties of articular cartilage contribute to the biphasic mechanical properties of the tissue. Current cell-based therapy with autologous chondrocyte implantation (ACI) has not been able to regenerate the zonal architecture with resulting tissue degeneration in the long-term. Stratified implantation of zonal chondrocytes has been hypothesized to improve the recapitulation of zonal architecture and long-term integrity of regenerated tissues. In this study, the efficacy of bilayered implantation of autologous zonal chondrocytes in achieving cartilage regeneration was investigated in a critical size porcine chondral defect model.
Methods and Materials
Autologous zonal chondrocytes were derived by integrating dynamic microcarrier (dMC) expansion followed by high-throughput microchannel size-based cell separation (Figure 1). Expanded zonal chondrocytes were implanted as bilayered fibrin hydrogel of superficial zone (SZ) chondrocytes overlaying middle/deep zone (MZ/DZ) chondrocytes in femoral condyle defects, with a single layer of full-thickness chondrocytes as control. Harvested tissues were subjected to histology, polarised light microscopy, MRI, microCT and mechanical analysis.
Results
The zonal chondrocyte production strategy was able to generate sufficient numbers of high-quality zonal chondrocytes from 0.5 cm2 of clinically relevant non-weight-bearing cartilage plugs for treatment of ≥ 5 cm2 of cartilage lesion, overcoming the challenges of limited autologous chondrocyte availability in the clinical setting and loss of zonal cartilage phenotype during expansion. Six months post-implantation, compared to implant with either tissue culture plate or dMC-expanded full-thickness chondrocytes, the bilayered implantation of dMC-expanded zonal chondrocytes improved cartilage regeneration with a substantial recapitulation of zonal architectures, including chondrocyte arrangement, specific PRG4 distribution and collagen alignment. The recapitulation of stratified architecture in regenerated tissues was accompanied by healthier underlying subchondral bone structure.
Conclusion
With the appropriate zonal chondrocyte isolation and expansion strategy, the approach of stratified zonal chondrocyte implantation represents a significant advancement over the current ACI-based cartilage regeneration, with the potential to improve the long-term integrity of regenerated cartilage tissues.
