JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE RESEARCH ARTICLE J Tissue Eng Regen Med 2011;5: 578–588. Published online 10 December 2010 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/term.350 Influence of pore size on the redifferentiation potential of human articular chondrocytes in poly(urethane urea) scaffolds H. Stenhamre 1,2∗ , U. Nannmark 3 , A. Lindahl 2 , P. Gatenholm 1 and M. Brittberg 4 1 Biopolymer Technology, Department of Chemical and Biological Engineering, Chalmers University of Technology, S-412 96 Gothenburg, Sweden 2 Molecular Cell Biology and Regenerative Medicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, S-413 45 Gothenburg, Sweden 3 Institute of Anatomy and Cell Biology, Gothenburg University, Gothenburg, Sweden 4 Cartilage Research Unit, University of Gothenburg, Kungsbacka Hospital, S-434 80 Kungsbacka, Sweden Abstract The chemical and physical properties of scaffolds affect cellular behaviour, which ultimately determines the performance and outcome of tissue-engineered cartilage constructs. The objective of this study was to assess whether a degradable porous poly(urethane urea) scaffold could be a suitable material for cartilage tissue engineering. We also investigated whether the post-expansion redifferentiation and cartilage tissue formation of in vitro expanded adult human chondrocytes could be regulated by controlled modifications of the scaffold architecture. Scaffolds with different pore sizes, <150 μm, 150–300 μm and 300 – 500 μm, were seeded with chondrocytes and subjected to chondrogenic and osteogenic induction in vitro. The poly(urethane urea) scaffold with the smaller pore size enhanced the hyaline-like extracellular matrix and thus neocartilage formation. Conversely, the chondrocytes differentiated to a greater extent into the osteogenic pathway in the scaffold with the larger pore size. In conclusion, our results demonstrate that poly(urethane urea) may be useful as a scaffold material in cartilage tissue engineering. Furthermore, the chondrogenic and the osteogenic differentiation capacity of in vitro expanded human articular chondrocytes can be influenced by the scaffold architecture. By tailoring the pore sizes, the performance of the tissue-engineered cartilage constructs might be influenced and thus also the clinical outcome in the long run. Copyright  2010 John Wiley & Sons, Ltd. Received 6 November 2009; Accepted 8 July 2010 Keywords chondrocytes; redifferentiation; scaffold architecture; neocartilage formation 1. Introduction Articular cartilage is a highly organized tissue whose functional biomechanical properties are associated with its unique architecture. This organized tissue endows resistance to compression and tensile strength, providing frictionless movement in the joint. Articular cartilage *Correspondence to: H. Stenhamre, Department of Clinical Chemistry and Transfusion Medicine, Bruna Str˚ aket 16, Sahlgrenska Hospital, G¨oteborg University, S-413 45 Gothen- burg, Sweden. E-mail: hanna.stenhamre@medic.gu.se is one of the tissues that most frequently undergo degradation, which leads to clinical symptoms such as pain and decreased mobility. Over a longer period the structural destruction may lead to osteoarthrosis (Jackson et al., 2001). Damaged articular cartilage represents a major challenge to orthopaedic surgeons, since injured cartilage has very little capacity for spontaneous healing due to the absence of both vascularization and innervation to support repair and remodelling. Cell-based therapies and tissue engineering approaches are being developed and appear to be promising tools for cartilage reconstruction. One cell- based method used today to treat cartilage injuries is Copyright  2010 John Wiley & Sons, Ltd.