Abstract
BackgroundA gold standard treatment for articular cartilage injuries is yet to be found, and a cost-effective and predictable large animal model is needed to bridge the gap between in vitro studies and clinical studies.Ideally, the animal model should allow for testing of clinically relevant treatments and the biological response should be reproducible and comparable to humans. This allows for a reliable translation of results to clinical studies.This study aimed at verifying the Göttingen minipig as a pre-clinical model for articular cartilage repair by testing existing clinical cartilage repair techniques and evaluating the use of two defects per knee.MethodsSixteen fully mature Göttingen minipigs were used. The minipigs received bilateral trochlear osteochondral drill-hole defects or chondral defects (Ø 6 mm), either one defect per knee or two defects per knee. The defects were treated with one of the following: Matrix-induced autologous chondrocyte implantation (MACI), microfracture (MFx), autologous-dual-tissue transplantation (ADTT), autologous bone graft, autologous cartilage chips. Empty chondral and osteochondral defects were used as controls. MRI and CT were performed 3 and 6 month, histology was performed 6 month postoperative.ResultsThe repair tissue varied in morphology from non-cartilaginous fibrous tissue to fibrocartilaginous tissue as seen on MRI, CT and histology at 6 month. The worst results were seen in the empty controls, while the best results were achieved with the MACI and ADTT treatment. The use of two defects per knee did not have any significant effect on the repair response.ConclusionThe outcomes of the applied treatments were consistent with the outcomes in clinical studies and it was possible to apply two defects per knee. The Göttingen minipig model was easy to handle, cost-effective and provided predictable outcome. Based on this study the use of two defects per knee, one in the medial and one in the lateral trochlear facet, in male Göttingen minipigs is recommended.
Highlights
A gold standard treatment for articular cartilage injuries is yet to be found, and a cost-effective and predictable large animal model is needed to bridge the gap between in vitro studies and clinical studies
The trans-patella-ligament surgical approach provided adequate access to both the medial and lateral trochlear facet. Both the medial and the lateral trochlear facet were well suited for 6 mm defects
The worst results were found in the empty defects (Fig. 3a) where the tissue was predominantly fibrous, whereas the best results were found in the Matrix-induced autologous chondrocyte implantation (MACI) group with a mixture of hyaline tissue and fibrocartilage (Fig. 3d)
Summary
A gold standard treatment for articular cartilage injuries is yet to be found, and a cost-effective and predictable large animal model is needed to bridge the gap between in vitro studies and clinical studies. The animal model should allow for testing of clinically relevant treatments and the biological response should be reproducible and comparable to humans. This allows for a reliable translation of results to clinical studies.This study aimed at verifying the Göttingen minipig as a pre-clinical model for articular cartilage repair by testing existing clinical cartilage repair techniques and evaluating the use of two defects per knee. Healing responses in the animal model as evaluated by histology and imaging should be comparable to those found in humans to allow for reliable translation of results from large animal studies to the clinical setting. The influence of multiple cartilage defects in one joint on cartilage repair response has not been investigated
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