Ex vivo culture platform for assessment of cartilage repair treatment strategies

Schwab, Albrecht; Meeuwsen, Abf; Ehlicke, Franziska; Hansmann, Jan; Mulder, Lars; Smits, Anthal I.P.M.; Walles, Heike; Kock, Linda M.

doi:10.14573/altex.1607111

Cited by 34 publications

(64 citation statements)

References 40 publications

(45 reference statements)

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“…Changes in the cartilage during culture observed for the equine plugs were similar to those reported for other species (Chen et al, 1997;de Vries-van Melle et al, 2012;Elson et al, 2015;Schwab et al, 2016). The native cartilage swelled and GAGs leached into the medium, possibly due to the damaged collagen network at the surface of the plugs and the defect edges (Chen et al, 1997;de Vries-van Melle et al, 2012;Elson et al, 2015;Schwab et al, 2016). However, in the current study, both the water and GAG content were stable between days 29 and 57, even though GAGs leached continuously into the medium, indicating that GAGs were produced and that a new stable situation was reached.…”

Section: Discussionsupporting

confidence: 82%

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Ex vivo model unravelling cell distribution effect in hydrogels for cartilage repair

Mouser

2018

ALTEX

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Summary The implantation of chondrocyte-laden hydrogels is a promising cartilage repair strategy. Chondrocytes can be spatially positioned in hydrogels and thus in defects, while current clinical cell therapies introduce chondrocytes in the defect depth. The main aim of this study was to evaluate the effect of spatial chondrocyte distribution on the reparative process. To reduce animal experiments, an ex vivo osteochondral plug model was used and evaluated. The role of the delivered and endogenous cells in the repair process was investigated. Full thickness cartilage defects were created in equine osteochondral plugs. Defects were filled with (A) chondrocytes at the bottom of the defect, covered with a cell-free hydrogel, (B) chondrocytes homogeneously encapsulated in a hydrogel, and (C, D) combinations of A and B with different cell densities. Plugs were cultured for up to 57 days, after which the cartilage and repair tissues were characterized and compared to baseline samples. Additionally, at day 21, the origin of cells in the repair tissue was evaluated. Best outcomes were obtained with conditions C and D, which resulted in well-integrated cartilage-like tissue that completely filled the defect, regardless of the initial cell density. A critical role of the spatial chondrocyte distribution in the repair process was observed. Moreover, the osteochondral plugs stimulated cartilage formation in the hydrogels when cultured in the defects. The resulting repair tissue originated from the delivered cells. These findings confirm the potential of the osteochondral plug model for the optimization of the composition of cartilage implants and for studying repair mechanisms.

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Section: Discussionsupporting

confidence: 82%

“…The following day, the plugs were inserted into a culture platform, which provided separate medium compartments for the cartilage and bone tissue (LifeTec Group B.V., Eindhoven, The Netherlands) (Schwab et al, 2016). The required numbers of chondrocytes defined for conditions A, C, and D ( Fig.…”

Section: Osteochondral Plugsmentioning

confidence: 99%

Ex vivo model unravelling cell distribution effect in hydrogels for cartilage repair

Mouser

2018

ALTEX

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“…The current study focused on equine OC plugs, as the horse is a widely used pre-clinical model for cartilage repair strategies (Malda et al, 2012). Changes in the cartilage during culture observed for the equine plugs were similar to those reported for other species (Chen et al, 1997;de Vries-van Melle et al, 2012;Elson et al, 2015;Schwab et al, 2016). The native cartilage swelled and GAGs leached into the medium, possibly due to the damaged collagen network at the surface of the plugs and the defect edges (Chen et al, 1997;de Vries-van Melle et al, 2012;Elson et al, 2015;Schwab et al, 2016).…”

Section: Discussionsupporting

confidence: 52%

“…However, in view of the reduction and replacement of animal studies, an ex vivo osteochondral (OC) plug model was developed (de Vries-van Melle et al, 2012, 2014a. This model entails OC plugs obtained from cadaveric joints, which can be cultured in a recently developed culture platform (Schwab et al, 2016). A cartilage defect of the desired depth can be generated within the cartilage tissue of the OC plug.…”

Section: Experimental Designmentioning

confidence: 99%

Ex vivo model unravelling cell distribution effect in hydrogels for cartilage repair_suppl

Mouser

2017

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“…). Simultaneously, ex vivo incubation systems are vastly improving, as it has been shown that cartilage‐on‐bone explants can stay intact for up to 8 weeks . These explants can also be compressed and biochemically supplemented as required, and are thus increasingly resembling the in vivo environment .…”

Section: Comparison Between In Vitro and In Vivo Overloading Studiesmentioning

confidence: 99%

Comparison between in vitro and in vivo cartilage overloading studies based on a systematic literature review

Nickien

Heuijerjans

Ito

et al. 2018

Journal Orthopaedic Research

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Methodological differences between in vitro and in vivo studies on cartilage overloading complicate the comparison of outcomes. The rationale of the current review was to (i) identify consistencies and inconsistencies between in vitro and in vivo studies on mechanically‐induced structural damage in articular cartilage, such that variables worth interesting to further explore using either one of these approaches can be identified; and (ii) suggest how the methodologies of both approaches may be adjusted to facilitate easier comparison and therewith stimulate translation of results between in vivo and in vitro studies. This study is anticipated to enhance our understanding of the development of osteoarthritis, and to reduce the number of in vivo studies. Generally, results of in vitro and in vivo studies are not contradicting. Both show subchondral bone damage and intact cartilage above a threshold value of impact energy. At lower loading rates, excessive loads may cause cartilage fissuring, decreased cell viability, collagen network de‐structuring, decreased GAG content, an overall damage increase over time, and low ability to recover. This encourages further improvement of in vitro systems, to replace, reduce, and/or refine in vivo studies. However, differences in experimental set up and analyses complicate comparison of results. Ways to bridge the gap include (i) bringing in vitro set‐ups closer to in vivo, for example, by aligning loading protocols and overlapping experimental timeframes; (ii) synchronizing analytical methods; and (iii) using computational models to translate conclusions from in vitro results to the in vivo environment and vice versa. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 36:2076–2086, 2018.

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Ex vivo culture platform for assessment of cartilage repair treatment strategies

Cited by 34 publications

References 40 publications

Ex vivo model unravelling cell distribution effect in hydrogels for cartilage repair

Ex vivo model unravelling cell distribution effect in hydrogels for cartilage repair

Ex vivo model unravelling cell distribution effect in hydrogels for cartilage repair_suppl

Comparison between in vitro and in vivo cartilage overloading studies based on a systematic literature review

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