NELL-1 Promotes Cartilage Regeneration in an In Vivo Rabbit Model

• Published in: Tissue engineering. Part A 2012-02, Vol.18 (3-4), p.252-261
• Main Authors: Siu, Ronald K., Zara, Janette N., Hou, Yaping, James, Aaron W., Kwak, Jinny, Zhang, Xinli, Ting, Kang, Wu, Benjamin M., Soo, Chia, Lee, Min
• Format: Article
• Language: English
• Subjects: Alginates - chemistry; Alginic acid; Animals; Cartilage; Cartilage - drug effects; Cartilage - pathology; Cartilage - physiology; Cattle; Cbfa-1 protein; Cell growth; chitosan; CHO Cells; Chondrocytes; Collagen (type II); Cricetinae; Cricetulus; Degeneration; Differentiation; Disease Models, Animal; Gene expression; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry; hydrogels; Immunohistochemistry; Implants, Experimental; Kinetics; nanoparticles; Nerve Tissue Proteins - pharmacology; Original; Original Articles; Proteins; Rabbits; Regeneration; safranin-O; Side effects; Skull; Staining and Labeling; Sutures; Tissue engineering; Transcription factors; Trauma
• ISSN: 1937-3341; 1937-335X
• DOI: 10.1089/ten.tea.2011.0142

Repair of cartilage due to joint trauma remains challenging due to the poor healing capacity of cartilage and adverse effects related to current growth factor-based strategies. NELL-1 (Nel-like molecule-1; Nel [a protein strongly expressed in neural tissue encoding epidermal growth factor like domain]), a protein first characterized in the context of premature cranial suture fusion, is believed to accelerate differentiation along the osteochondral lineage. We previously demonstrated the ability of NELL-1 protein to maintain the cartilaginous phenotype of explanted rabbit chondrocytes in vitro . Our objective in the current study is to determine whether NELL-1 can affect endogenous chondrocytes in an in vivo cartilage defect model. To generate the implant, NELL-1 was incorporated into chitosan nanoparticles and embedded into alginate hydrogels. These implants were press fit into 3-mm circular osteochondral defects created in the femoral condylar cartilage of 3-month-old New Zealand White rabbits ( n =10). Controls included unfilled defects ( n =8) and defects filled with phosphate-buffered saline-loaded chitosan nanoparticles embedded in alginate hydrogels ( n =8). Rabbits were sacrificed 3 months postimplantation for histological analysis. Defects filled with alginate containing NELL-1 demonstrated significantly improved cartilage regeneration. Remarkably, histology of NELL-1-treated defects closely resembled that of native cartilage, including stronger Alcian blue and Safranin-O staining and increased deposition of type II collagen and absence of the bone markers type I collagen and Runt-related transcription factor 2 (Runx2) as demonstrated by immunohistochemistry. Our results suggest that NELL-1 may produce functional cartilage with properties similar to native cartilage, and is an exciting candidate for tissue engineering-based approaches for treating diverse pathologies of cartilage defects and degeneration.