Improved Articular Cartilage Repair With Stratified Zonal Chondrocyte Implantation.

Abstract

Background: The zonal organization of articular cartilage is critical for the biphasic mechanical properties of the tissue. Current treatments for articular cartilage have yet to regenerate this zonal architecture, compromising the functional efficacy of the repaired tissue, which could account for tissue failure in the long term. Autologous chondrocyte implantation (ACI) still suffers from inconsistent efficacy and a long recovery period stemming from implantation of a heterogeneous chondrocyte mixture.

Hypothesis: Stratified implantation of zonal chondrocytes would facilitate the recapitulation of articular cartilage zonal properties and improve the repair efficacy of ACI treatment.

Study design: Controlled laboratory study.

Methods: Autologous chondrocytes extracted from porcine articular cartilage were subjected to dynamic microcarrier expansion followed by size-based segregation using a spiral microfluidic device for the enrichment of zonal chondrocytes. Zonal chondrocytes were implanted into a chondral defect as a bilayered hydrogel construct consisting of superficial zone chondrocytes overlaying middle/deep zone chondrocytes (n = 6). Twelve months after implantation, the repair efficacy was compared against implantation of full-thickness cartilage-derived heterogeneous chondrocytes expanded on tissue culture plates (n = 5) or microcarriers (n = 6).

Results: Quantitative assessment of the repair tissues, including gross morphology, histological analysis, micro-computed tomography (micro-CT), compression modulus, and surface lubrication analysis, at 12 months demonstrated statistically significant improvement in cartilage and subchondral bone repair with zonal chondrocyte bilayered implantation. Magnetic resonance imaging (MRI) T2 mapping indicated progressive improvement in graft maturation as early as 3 months, reaching normalcy at 9 months.

Conclusion: This study demonstrates that with appropriate expansion and isolation of zonal chondrocytes, stratified zonal chondrocyte implantation is able to facilitate restoration of articular cartilage zonal architecture and significantly enhance the functional repair as compared with current ACI treatment.

Clinical relevance: With appropriate expansion and enrichment of zonal chondrocytes, stratified zonal chondrocyte implantation could represent a significant advancement over current ACI-based cartilage repair, with the potential to support quicker and better recovery.