IOA 2022

Regeneration of Injured Articular Cartilage using a Recombinant Human Amelogenin Protein in a Goat Model

Omer Helwa-Shalom 1 Shany Ivon Elbaz 1 Ariel Arenvaev Cohen 1 Keren Ben David 1 Svetlana Katsman 2 Meir Stern 2 Igal Liapis 2 Hagit Sacks 2 Hani Nevo 3 Anat Blumenfeld 3,4 Amir Haze 3
1Biotechnology, The Hebrew University, Israel
2Dental, Prudentix Ltd, Israel
3Orthopaedics, Hadassah Medical Center, Israel
4Dentistry, The Hebrew University, Israel

Objective:
To analyze the capability of the recombinant human amelogenin protein (rAmelX) to regenerate experimentally induced osteochondral injury (OCI) in the femoral weight-bearing area in a goat model.

Methods:
Six goats were operated. Using a fluoroscopic guidance, mini-arthrotomy was performed at the level of the left medial femoral condyle (MFC). An OCI of 6X10mm was created in the weight-bearing area of the MFC and the defect was filled with a placebo control (carrier and excipients), supplied by Prudentix Ltd. A week later, the right stifle joint was operated and Remelix® (0.5µg/µl rAmelX dissolved in the carrier) was applied (experimental). Six month later, two MRI scans, proton density and T1 weighted sequence, were performed on each knee. Then the goats underwent the same order of operations but 10X10mm cylinders, surrounding the original OCIs, were taken for histology.

Results:
MRI scans performed 6 months after treatment revealed that in 5 out of 6 goats the experimental OCI yielded a hyaline cartilage-like tissue. In contrast, in the control OCI, less cartilage was observed and it looked less differentiated. In these 5 goats the experimental OCIs were smaller and shallower than the control OCIs. Similar results were obtained by Hematoxylin-Eosin and Toluidine blue staining of vertical sections obtained from the center of the OCI. In 3 experimental specimens, continuous and thick cartilage layer, resembling hyaline cartilage, covered the subchondral bone, while in 2 specimens fibrocartilage was detected in the center of the OCI. In control specimens thinner (5 goats) or not continuous (4 goats) layer of cartilage was observed.

Conclusions:
It is well documented that cartilaginous tissue exhibits very limited spontaneous healing, therefore, the regeneration observed may be attributed to the effect of rAmelX and possibly partially to its carrier. Based on these results Remelix® can be developed as a treatment for joint injuries.