What quantitative mechanical loading stimulates in vitro cultivation best?

Jerry Natenstedt, Aimee C Kok, Jenny Dankelman, Gabrielle JM Tuijthof

Articular cartilage has limited regeneration capacities. One of the factors that appear to affect the in vitro cultivation of articular cartilage is mechanical stimulation. So far, no combination of parameters has been identified that offers the best results. The goal is to review the literature in search of the best available set of quantitative mechanical stimuli that lead to optimal in vitro cultivation.The databases Scopus and PubMed were used to survey the literature, and strict in- and exclusion criteria were applied regarding the presence of quantitative data. The review was performed by studying the type of loading (hydrostatic compression or direct compression), the loading magnitude, the frequency and the loading regime (duration of the loading) in comparison to quantitative evidence of cartilage quality response (cellular, signaling and mechanical).Thirty-three studies met all criteria of which 8 studied human, 20 bovine, 2 equine, 1 ovine, 1 porcine and 1 canine cells using four different types of cultivated constructs. Six studies investigated loading magnitude within the same setup, three studies the frequency, and seven the loading regime. Nine studies presented mechanical tissue response. The studies suggest that a certain threshold exits for enhanced cartilage in vitro cultivation of explants (>20 % strain and 0.5 Hz), and that chondrocyte-seeded cultivated constructs show best results when loaded with physiological mechanical stimuli. That is a loading pressure between 5-10 MPa and a loading frequency of 1 Hz exerted at intermittent intervals for a period of a week or longer. Critical aspects remain to be answered for translation into in vivo therapies.