Recombinant Human Amelogenin Protein Enhances Healing of Osteochondral Injury in a Goat Model.

Abstract

Osteochondral injuries are common, painful, and lack natural healing abilities. Previous studies demonstrated that recombinant human amelogenin promotes osteochondral repair in rat knee injuries, including improved defect filling and formation of hyaline cartilage. Here, we aimed to evaluate the efficacy and safety of Remelix®, a novel recombinant human amelogenin-based product, in a large animal goat model. Acute osteochondral injuries were created in the weight-bearing region of the medial femoral condyle in thirteen goats. Seven goats received Remelix® at a protein concentration of 0.5 mg/mL, with the contralateral knee applied with PX 407 carrier alone. An additional six goats received Remelix® at 0.25 mg/mL, while contralateral knees were treated with normal saline. Potential adverse effects, along with evaluation of osteochondral healing were assessed. Healing was assessed 24 weeks post-treatment using magnetic resonance imaging (MRI), macroscopic evaluation, and histological and immunohistochemical analyses. No adverse effects were observed. Both Remelix® concentrations resulted in substantial healing of cartilage and subchondral bone. Histological analyses demonstrated improved tidemark formation, predominantly hyaline cartilage filling in the deeper layers of the defect with extension toward the superficial zone, and reduced subchondral bone abnormalities. MRI and macroscopic evaluations revealed a continuous repair surface with good integration at the defect margins. In contrast, PX 407 and saline-treated control knees exhibited inferior repair, characterized by mainly fibrous cartilage, heterogeneous MRI signal intensity, and lower histological scores. Overall, Remelix® substantially improved osteochondral healing in a goat model without observable adverse effects, supporting its potential for further evaluation in human clinical studies.