ARTHRITIS & RHEUMATISM Vol. 58, No. 1, January 2008, pp 197–208 DOI 10.1002/art.23155 © 2008, American College of Rheumatology Engineered Cartilage Generated by Nasal Chondrocytes Is Responsive to Physical Forces Resembling Joint Loading C. Candrian, 1 D. Vonwil, 1 A. Barbero, 1 E. Bonacina, 2 S. Miot, 1 J. Farhadi, 1 D. Wirz, 3 S. Dickinson, 4 A. Hollander, 4 M. Jakob, 1 Z. Li, 5 M. Alini, 5 M. Heberer, 1 and I. Martin 1 Objective. To determine whether engineered car- tilage generated by nasal chondrocytes (ECN) is respon- sive to different regimens of loading associated with joint kinematics and previously shown to be stimulatory of engineered cartilage generated by articular chondro- cytes (ECA). Methods. Human nasal and articular chondro- cytes, harvested from 5 individuals, were expanded and cultured for 2 weeks into porous polymeric scaffolds. The resulting ECN and ECA were then maintained under static conditions or exposed to the following loading regimens: regimen 1, single application of cyclic deformation for 30 minutes; regimen 2, intermittent application of cyclic deformation for a total of 10 days, followed by static culture for 2 weeks; regimen 3, application of surface motion for a total of 10 days. Results. Prior to loading, ECN constructs con- tained significantly higher amounts of glycosaminogly- can (GAG) and type II collagen compared with ECA constructs. ECN responded to regimen 1 by increasing collagen and proteoglycan synthesis, to regimen 2 by increasing the accumulation of GAG and type II colla- gen as well as the dynamic modulus, and to regimen 3 by increasing the expression of superficial zone protein, at the messenger RNA level and the protein level, as well as the release of hyaluronan. ECA constructs were overall less responsive to all loading regimens, likely due to the lower extracellular matrix content. Conclusion. Human ECN is responsive to physi- cal forces resembling joint loading and can up-regulate molecules typically involved in joint lubrication. These findings should prompt future in vivo studies exploring the possibility of using nasal chondrocytes as a cell source for articular cartilage repair. Cell-based therapies currently in clinical applica- tion for the treatment of articular cartilage lesions typically rely on the use of autologous chondrocytes harvested from a small biopsy specimen of articular cartilage. A cartilage biopsy specimen from a joint, even if harvested from a non–load-bearing site, represents an additional injury to the cartilage surface and has been reported to be detrimental to the surrounding healthy articular cartilage (1). To overcome this problem, sev- eral groups of investigators proposed the use of mesen- chymal progenitor cells from bone marrow (2–4), syno- vial membrane (5–8), or periosteum (9,10) or the use of chondrocytes from nonarticular cartilage, such as the ear (11,12), rib (11), or nasal septum (11,13). Nasal cartilage would be a particularly interesting source of cells, because the tissue is characterized as a hyaline cartilage and contains differentiated chondro- cytes expressing the collagen types typical of articular cartilage (14). Biopsy specimens of nasal cartilage can be harvested under local anesthesia and by a procedure that is less invasive than removing tissue from specific areas of the joint. Morbidity associated with nasal cartilage biopsy is also reduced, because the donor site is not subjected to high levels of physical force (15). Indeed, nasal septal cartilage (sometimes in substantial Supported in part by the European Union (Project FP6 STEPS, contract NMP3-CT-2005-500465), the Swiss National Science Foundation (grant 3200B0-110054), and the “Deutsche Arthrose-Hilfe e.V.” 1 C. Candrian, MD, D. Vonwil, MSc, A. Barbero, PhD, S. Miot, PhD, J. Farhadi, MD, M. Jakob, MD, M. Heberer, MD, I. Martin, PhD: University Hospital Basel, Basel, Switzerland; 2 E. Bona- cina, MSc: University Hospital Basel, Basel, Switzerland and Politec- nico di Milano, Milan, Italy; 3 D. Wirz, MD: University of Basel, Basel, Switzerland; 4 S. Dickinson, PhD, A. Hollander, PhD: University of Bristol, Southmead Hospital, Bristol, UK; 5 Z. Li, PhD, M. Alini, PhD: AO Research Institute, Davos, Switzerland. Address correspondence and reprint requests to Ivan Martin, PhD, Institute for Surgical Research and Hospital Management, University Hospital Basel, Hebelstrasse 20, ZLF, Room 405, 4031 Basel, Switzerland. E-mail: imartin@uhbs.ch. Submitted for publication May 21, 2007; accepted in revised form September 21, 2007. 197