Nasal Chondrocyte–Based Engineered Grafts for the Repair of Articular Cartilage “Kissing” Lesions: A Pilot Large-Animal Study

Author:

Šećerović Amra12,Pušić Maja32,Kostešić Petar2,Vučković Mirta42,Vukojević Rudolf52,Škokić Siniša62,Sasi Biljana12,Vukasović Barišić Andreja72,Hudetz Damir82,Vnuk Dražen2,Matičić Dražen42,Urlić Inga32,Mumme Marcus92,Martin Ivan102,Ivković Alan18112

Affiliation:

1. Department of Histology and Embryology, School of Medicine, University of Zagreb, Zagreb, Croatia

2. Investigation performed at the University of Zagreb, Zagreb, Croatia

3. Department of Biology, Faculty of Science, University of Zagreb, Zagreb, Croatia

4. Clinic for Surgery, Ophthalmology and Orthopaedics, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia

5. Department of Diagnostic and Interventional Radiology, Sisters of Mercy University Hospital Center, Zagreb, Croatia

6. Laboratory for Regenerative Neuroscience, Croatian Institute for Brain Research, Zagreb, Croatia

7. General Hospital Bjelovar, Bjelovar, Croatia

8. Department of Orthopaedic Surgery, University Hospital Sveti Duh, Zagreb, Croatia

9. Clinic for Orthopaedics and Traumatology, University Hospital Basel, University of Basel, Basel, Switzerland; Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland

10. Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland

11. Department of Biotechnology, University of Rijeka, Rijeka, Croatia

Abstract

Background: Bipolar or “kissing” cartilage lesions formed on 2 opposite articular surfaces of the knee joint are commonly listed as exclusion criteria for advanced cartilage therapies. Purpose: To test, in a pilot large-animal study, whether autologous nasal chondrocyte (NC)–based tissue engineering, recently introduced for the treatment of focal cartilage injuries, could provide a solution for challenging kissing lesions. Study Design: Controlled laboratory study. Methods: Osteochondral kissing lesions were freshly introduced into the knee joints of 26 sheep and covered with NC-based grafts with a low or high hyaline-like extracellular matrix; a control group was treated with a cell-free scaffold collagen membrane (SCA). The cartilage repair site was assessed at 6 weeks and 6 months after implantation by histology, immunohistochemistry, and magnetic resonance imaging evaluation. Results: NC-based grafts, independently of their composition, induced partial hyaline cartilage repair with stable integrity in surrounding healthy tissue at 6 months after treatment. The SCA repaired cartilage to a similar degree to that of NC-based grafts. Conclusion: Kissing lesion repair, as evidenced in this sheep study, demonstrated the feasibility of the treatment of complex cartilage injuries with advanced biological methods. However, the potential advantages of an NC-based approach over a cell-free approach warrant further investigations in a more relevant preclinical model. Clinical Relevance: NC-based grafts currently undergoing phase II clinical trials have a high potential to replace existing cartilage therapies that show significant limitations in the quality and reproducibility of the repair method. We have brought this innovative concept to the next level by addressing a new clinical indication.

Funder

horizon 2020

Publisher

SAGE Publications

Subject

Physical Therapy, Sports Therapy and Rehabilitation,Orthopedics and Sports Medicine

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