Topographic Variations in Biomechanical and Biochemical Properties in the Ankle Joint: An In Vitro Bovine Study Evaluating Native and Engineered Cartilage

Paschos, Nikolaos K.; Makris, Eleftherios; Hu, Jerry C.; Athanasiou, Kyriacos A.

doi:10.1016/j.arthro.2014.05.025

Cited by 9 publications

(19 citation statements)

References 42 publications

(61 reference statements)

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“…Remarkably, the neocartilage constructs presented in this study have tensile modulus approaching that of native, juvenile bovine articular cartilage (4–5 MPa) tested under similar conditions [50, 51]. Collagen/WW (%) and GAG/WW (%) contents of native tissues measured that study were 5–20% and 10–18%, respectively, compared to 2.5% and 10.2% found in the present study.…”

Section: Discussionsupporting

confidence: 64%

“…The GAG/WW:Collagen/WW ratios of the neocartilage were also calculated and were found to be 3.5±0.2, 3.7±0.5, 4.2±0.3, 4.1±0.4, 3.0±0.8, and 5.0±0.8 for the no aggregate group and 3.4±0.4, 4.0±0.7, 3.9±0.6, 3.8±0.4, 1.7±0.3, and 3.2±0.6 for the aggregate group, respectively. The GAG/WW:collagen/WW ratio of native articular cartilage was found to range from 0.8 to 1.2 [39]. …”

Section: Resultsmentioning

confidence: 99%

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Effects of passage number and post-expansion aggregate culture on tissue engineered, self-assembled neocartilage

Huang

Athanasiou

2016

Acta Biomaterialia

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Chondrocyte dedifferentiation presents a major barrier in engineering functional cartilage constructs. To mitigate the effects of dedifferentiation, this study employed a post-expansion aggregate culture step to enhance the chondrogenic phenotype of passaged articular chondrocytes (ACs) before their integration into self-assembled neocartilage constructs. The objective was two-fold: 1) To explore how passage number (P2, P3, P4, P5, P6, and P7), with or without aggregate culture, affect construct properties; and 2) to determine the highest passage number that can form neocartilage with functional properties. Juvenile leporine ACs were passaged to P2–P7, with or without aggregate culture, and self-assembled into 5 mm discs in non-adhesive agarose molds without using any exogenous scaffolds. Construct biochemical and biomechanical properties were assessed. With aggregate culture, neocartilage constructs had significantly higher collagen content, higher tensile properties, and flatter morphologies. These beneficial effects were most obvious at higher passage numbers. Specifically, collagen content, Young’s modulus, and instantaneous compressive modulus in the P7, aggregate group were 53%, 116%, and 178% higher than those in the P7, non-aggregate group. Most interestingly, these extensively passaged P7 ACs (expansion factor of 85,000), which are typically highly dedifferentiated, were able to form constructs with properties similar to or higher than those formed by lower passage number cells. This study not only demonstrated that post-expansion aggregate culture can significantly improve the properties of self-assembled neocartilage, but also that chondrocytes of exceedingly high passage numbers, expanded using the methods in this study, can be used in cartilage engineering applications.

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Section: Discussionsupporting

confidence: 64%

Section: Resultsmentioning

confidence: 99%

Effects of passage number and post-expansion aggregate culture on tissue engineered, self-assembled neocartilage

Huang

Athanasiou

2016

Acta Biomaterialia

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“…Using a scaffoldless approach, self‐assembled cartilage constructs have been formed with compressive aggregate modulus values ranging from 100 to 400 kPa , Ey values as high as 8.4 MPa and UTS values up to 3.3 MPa . Self‐assembled neocartilage has biochemical properties of 2–5% GAG/WW and 15–20% collagen/WW , which are akin to those of the equine facet cartilage. Additionally, the facet joint has a small surface area in comparison to other synovial joints, making it more amenable to engineering a total surface replacement.…”

Section: Discussionmentioning

confidence: 99%

Biochemical and biomechanical characterisation of equine cervical facet joint cartilage

O’Leary

White

et al. 2018

Equine Veterinary Journal

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“…It was also found that in the bovine ankle joint, the tibial plafond exhibited threefold higher tensile properties and twofold higher compressive and shear moduli compared to its articulating talar dome. Neocartilage formed with cells isolated from these locations also exhibited these disparities [10]. Topographical examinations of mechanical properties of different tissues provide benchmark data for future tissue engineering studies of cartilage.…”

Section: Mechanical Properties Vary Topographicallymentioning

confidence: 99%

Harnessing Biomechanics to Develop Cartilage Regeneration Strategies

Athanasiou

Responte²,

Brown

et al. 2015

Journal of Biomechanical Engineering

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laboratory over the past 25 years. The prevalence and severity of degeneration of articular cartilage, a tissue whose main function is largely biomechanical, have motivated the development of cartilage tissue engineering approaches informed by biomechanics. This article provides a review of important steps toward regeneration of articular cartilage with suitable biomechanical properties. As a first step, biomechanical and biochemical characterization studies at the tissue level were used to provide design criteria for engineering neotissues. Extending this work to the single cell and subcellular levels has helped to develop biochemical and mechanical stimuli for tissue engineering studies. This strong mechanobiological foundation guided studies on regenerating hyaline articular cartilage, the knee meniscus, and temporomandibular joint (TMJ) fibrocartilage. Initial tissue engineering efforts centered on developing biodegradable scaffolds for cartilage regeneration. After many years of studying scaffold-based cartilage engineering, scaffoldless approaches were developed to address deficiencies of scaffold-based systems, resulting in the self-assembling process. This process was further improved by employing exogenous stimuli, such as hydrostatic pressure, growth factors, and matrix-modifying and catabolic agents, both singly and in synergistic combination to enhance neocartilage functional properties. Due to the high cell needs for tissue engineering and the limited supply of native articular chondrocytes, costochondral cells are emerging as a suitable cell source. Looking forward, additional cell sources are investigated to render these technologies more translatable. For example, dermis isolated adult stem (DIAS) cells show potential as a source of chondrogenic cells. The challenging problem of enhanced integration of engineered cartilage with native cartilage is approached with both familiar and novel methods, such as lysyl oxidase (LOX). These diverse tissue engineering strategies all aim to build upon thorough biomechanical characterizations to produce functional neotissue that ultimately will help combat the pressing problem of cartilage degeneration. As our prior research is reviewed, we look to establish new pathways to comprehensively and effectively address the complex problems of musculoskeletal cartilage regeneration.

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Topographic Variations in Biomechanical and Biochemical Properties in the Ankle Joint: An In Vitro Bovine Study Evaluating Native and Engineered Cartilage

Cited by 9 publications

References 42 publications

Effects of passage number and post-expansion aggregate culture on tissue engineered, self-assembled neocartilage

Effects of passage number and post-expansion aggregate culture on tissue engineered, self-assembled neocartilage

Biochemical and biomechanical characterisation of equine cervical facet joint cartilage

Harnessing Biomechanics to Develop Cartilage Regeneration Strategies

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