Abstract
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.
Highlights
Articular cartilage is a nonlinearly permeable, viscoelastic multiphasic material containing chondrocytes and proteoglycan aggregates (3-10 % of volume) that are surrounded by an extracellular matrix (ECM), whose primary constituents are water with mobile ions (60-85 % of volume) and collagen type II (10-30 % of volume) (Fig. 1) (Mow et al 1999; Schulz and Bader 2007; Khan and Scott 2009; Madry et al 2010)
Chondrocytes are responsible for the production of the ECM (Meachim and Stockwell 1973; Buckwalter and Mankin 1998; Cohen et al 1998), since they are likely to synthesize collagen type II and proteoglycans
A careful qualitative interpretation of the results suggests that for chondrocyteseeded cultivated constructs 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 are recommended as appropriate mechanical stimulus
Summary
Articular cartilage is a nonlinearly permeable, viscoelastic multiphasic material containing chondrocytes and proteoglycan aggregates (3-10 % of volume) that are surrounded by an extracellular matrix (ECM), whose primary constituents are water with mobile ions (60-85 % of volume) and collagen type II (10-30 % of volume) (Fig. 1) (Mow et al 1999; Schulz and Bader 2007; Khan and Scott 2009; Madry et al 2010). Damaged articular cartilage presents itself as partial chondral, full thickness chondral or osteochondral defects (Fig. 1). This review will focus on the mechanical loading to promote cartilage cultivation. Due to its unique composition, cartilage can be loaded up to 18 MPa in vivo, which is up to 15 times the body weight (Darling and Athanasiou 2003; Elder and Athanasiou 2009; Spiller et al 2011). A similar mechanism is seen when damaged cartilage (with a disrupted ECM) is loaded during gait with physiological values of around 5 times the body weight (van Dijk et al 2010a, 2010b)
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