NEL-like molecule-1-modified bone marrow mesenchymal stem cells/poly lactic-co-glycolic acid composite improves repair of large osteochondral defects in mandibular condyle

Abstract

Articular cartilage of the mandibular condyle has limited ability to regenerate itself after injury. This study was to investigate whether osteochondral defects in mandibular condyle could be repaired by NELL-1(NEL-like molecule-1)-modified autogenous bone marrow mesenchymal stem cells (BMMSCs) and poly lactic-co-glycolic acid (PLGA) composite. Osteochondral defects of 3mm-diameter × 5mm-depth were created unilaterally in the central part of the condyle in 50 adult goats. The injury sites were treated with NELL-1-modified BMMSCs/PLGA, BMMSCs/PLGA, PLGA alone, or left empty. The defect area was monitored using gross examination, histology, immunohistochemistry, and micro-computed tomography (μ-CT). Implanted BMMSCs were tracked using Adeno-LacZ labeling. The NELL-1-modified BMMSCs/PLGA group showed vigorous and rapid repair leading to regeneration of fibrocartilage at 6 weeks and to complete repair of native articular cartilage and subchondral bone at 24 weeks. The BMMSCs/PLGA group also completely repaired the defect with fibrocartilage at 24 weeks, but the cartilage in the BMMSCs/PLGA group was less well-organized than the NELL-1-modified BMMSCs/PLGA. The osteochondral defects in the PLGA and empty defect groups were poorly repaired, and no cartilage in the empty defect group or only small portion of cartilage in the PLGA group was found. In vivo viability of implanted cells was demonstrated by the retention for 6 weeks in the defects. These findings demonstrated that NELL-1-modified BMMSCs/PLGA composite can rapidly repair large osteochondral defect in the mandibular condyle with regeneration of native fibrocartilage and subchondral bone.