Treatment of Focal Cartilage Defects in Minipigs with Zonal Chondrocyte/Mesenchymal Progenitor Cell Constructs

International Journal of Molecular Sciences, 2019 · DOI: 10.3390/ijms20030653 · Published: February 2, 2019

Simple Explanation

This study explores new ways to fix cartilage damage, which is a common problem that can lead to arthritis. The researchers tested a special implant in minipigs to see if it could help the cartilage heal better. The implant had two layers: one with cells that help make cartilage and another with cells that help make bone. The goal was to see if this two-layered approach could create better cartilage repair compared to using just one layer of cells. Unfortunately, the implant didn't work as expected. It caused bone loss and didn't improve cartilage healing compared to leaving the damage untreated. The researchers think the implant might have been too stiff, causing it to press into the bone and disrupt the healing process.

Study Duration

6 Months

Participants

6 minipigs

Evidence Level

Not specified

Key Findings

1
Both zonal and non-zonal constructs showed a signiﬁcantly increased bone loss in the defects when compared to controls, suggesting an osteolytic effect of PCL-enforced implants on the subchondral bone.
2
In 16 out of 18 defects, the constructs were pressed beneath the cartilage level, which may be attributed to its overall thickness.
3
Zonal design of the scaffolds did not differ from the non-zonal design concerning cartilage regeneration, and an important heterogeneity of cartilage regeneration in both treatment groups was observed.

Research Summary

This study investigated the use of zonal chondrocyte/mesenchymal progenitor cell constructs in minipigs for the treatment of focal cartilage defects, comparing them to non-zonal grafts and empty controls. The results showed that both zonal and non-zonal constructs led to significant bone loss compared to controls, with the PCL enforcement often pressed into the subchondral bone. Histological evaluation revealed that the implant-treated groups had significantly lower O’Driscoll scores than empty controls, indicating that the constructs did not improve cartilage regeneration and may have impaired it.

Practical Implications

Re-evaluate construct design

The study suggests a need to re-evaluate the design of PCL-enforced constructs for cartilage repair, particularly regarding their stiffness and potential to cause bone erosion.

Consider acellular constructs

Future studies should consider using acellular constructs to determine whether the construct itself or the cell/hydrogel combination is responsible for the observed negative effects.

Wider use of µCT

The authors recommend a more widespread use of µCT to quantify subchondral bone loss in studies evaluating cartilage repair strategies.

Study Limitations

1
Missing early samples made it difficult to determine the time frame during which zonal structure was retained.
2
The 6-month time point might not have been late enough for full subchondral bone remodeling.
3
The study lacked an additional control group applying only hydrogel- and cell-free constructs.

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