“…The different maneuvers which have been tried to increase glycosaminoglycan production all have limitations. An increase in glycosaminoglycan production rate per cell can be induced by addition of growth factors, by providing mechanical or ultrasound stimulation or through alterations to scaffold properties (Blunk et al, 2002, Richmon et al, 2005, van der Kraan et al, 2002, Kuo & Lin, 2006, but the relative increase which can be achieved is limited (usually two-threefold under optimal conditions) and the consequent increase in metabolic demand can lead to a fall in pH in the construct center (Razaq et al, 2004) and thus severely limit growth factor efficacy. Indeed, addition of growth factors to constructs was found to have little effect on the concentration of accumulated glycosaminoglycan although it increased construct size (Walsh et al, 2002, Yoon et al, 2003a, Yoon et al, 2003b, Masuda et al, 2003, Malda et al, 2004.…”