The application of POSS nanostructures in cartilage tissue engineering: the chondrocyte response to nanoscale geometry Adelola O. Oseni 1 , Peter E. Butler 2,3 and Alexander M. Seifalian 1,2,3 * 1 Centre for Nanotechnology and Regenerative Medicine, University College London, UK 2 Division of Surgery and Interventional Science, London, UK 3 Department of Plastic and Reconstructive Surgery, Royal Free London NHS Foundation Trust Hospital, London, UK Abstract Despite extensive research into cartilage tissue engineering (CTE), there is still no scaffold ideal for clinical applications. Various synthetic and natural polymers have been investigated in vitro and in vivo, but none have reached widespread clinical use. The authors investigate the potential of POSS–PCU, a synthetic nanocomposite polymer, for use in CTE. POSS–PCU is modified with silsesquioxane nanostructures that improve its biological and physical properties. The ability of POSS–PCU to support the growth of ovine nasoseptal chondrocytes was evaluated against a polymer widely used in CTE, polycaprolactone (PCL). Scaffolds with varied concentrations of the POSS molecule were also synthesized to investigate their effect on chondrocyte growth. Chondrocytes were seeded onto scaffold disks (PCU negative control; POSS–PCU 2%, 4%, 6%, 8%; PCL). Cytocompatibilty was evaluated using cell viability, total DNA, collagen and GAG assays. Chondrocytes cultured on POSS–PCU (2% POSS) scaffolds had significantly higher viability than PCL scaffolds (p < 0.001). Total DNA, collagen and sGAG protein were also greater on POSS–PCU scaffolds compared with PCL (p > 0.05). POSS–PCU (6% and 8% POSS) had improved viability and proliferation over an 18 day culture period compared with 2% and 4% POSS–PCU (p < 0.0001). Increasing the percentage of POSS in the scaffolds increased the size of the pores found in the scaffolds (p < 0.05). POSS–PCU has excellent potential for use in CTE. It supports the growth of chondrocytes in vitro and the POSS modification significantly enhances the growth and proliferation of nasoseptal chondrocytes compared with traditional scaffolds such as PCL. Copyright © 2013 John Wiley & Sons, Ltd. Received 24 January 2012; Revised 6 November 2012; Accepted 20 December 2012 Keywords cartilage tissue engineering; chondrocytes; nanotechnology; nanotopography; polymer; silsesquioxane nanocages; synthetic scaffold 1. Introduction The aim of cartilage tissue engineering is to produce a viable source of ’cartilage-like tissue’ that can be used to reconstruct defects that occur within the human body (Oseni et al., 2011b). Damage to cartilage occurs as a result of degenerative disease, trauma or cancer. It serves as a relevant target for tissue engineering efforts, because it has an impoverished vascular supply resulting in little capacity for regeneration (Raghunath et al., 2005). Cartilage found within the joints, ribcage, nose and ear, is made by specialized cells known as chondrocytes. These chondrocytes secrete the surrounding extracellular matrix (ECM) of collagens, glycoproteins and glycosaminoglycans (Buckwalter and Mankin 1998a, 1998b). Tissue engineering aims to recapitulate processes of human development in vitro, using cells and scaffold matrices. It focuses on the cellular level of development, looking at ways to successfully promote the interactions and biological processes that have been observed during *Correspondence to: A. M. Seifalian, University College London, Pond Street, Belsize Park, London NW3 2PF, UK. E-mail: a. seifalian@ucl.ac.uk Copyright © 2013 John Wiley & Sons, Ltd. JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE RESEARCH ARTICLE J Tissue Eng Regen Med (2013) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/term.1693