Building an Anisotropic Meniscus with Zonal Variations

Higashioka, Michael M.; Chen, Justin A.; Hu, Jerry C.; Athanasiou, Kyriacos A.

doi:10.1089/ten.tea.2013.0098

Cited by 30 publications

(28 citation statements)

References 56 publications

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“…Ten and 20 mg/ml clamped menisci had similar levels of organization, with 20 mg/ml menisci producing larger diameter fibers and significantly better mechanical properties. Recently, doughnut-shaped boundary constraints were used with a scaffold free construct to develop meniscus-like scaffolds; however without collagen fibrils present, collagen fiber development was limited (Higashioka et al, 2014). In this study, self-assembled collagen fibrils are present within hours of gelling the menisci, providing an infrastructure for cells to align and build on.…”

Section: Discussionmentioning

confidence: 96%

“…Although there has been great effort to generate whole tissue engineered menisci to serve as an alternative to allografts (Balint et al, 2012;Ballyns et al, 2008;Higashioka et al, 2014;Huey and Athanasiou, 2011;Kon et al, 2008;Mandal et al, 2011;Puetzer and Bonassar, 2013;Tienen et al, 2006;Zur et al, 2011), none have achieved clinical use. Such implants often lack the native collagen fiber organization and anisotropic properties essential to distribute the loads of the knee appropriately.…”

Section: Introductionmentioning

confidence: 99%

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Induction of fiber alignment and mechanical anisotropy in tissue engineered menisci with mechanical anchoring

Puetzer

Koo

Bonassar

2015

Journal of Biomechanics

131

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This study investigated the effect of mechanical anchoring on the development of fiber organization and anisotropy in anatomically shaped tissue engineered menisci. Bovine meniscal fibrochondrocytes were mixed with collagen and injected into molds designed to produce meniscus implants with 12 mm extensions at each horn. After a day of static culture, 10 and 20mg/ml collagen menisci were either clamped or unclamped and cultured for up to 8 weeks. Clamped menisci were anchored in culture trays throughout culture to mimic the native meniscus horn attachment sites, restrict contraction circumferentially, and encourage circumferential alignment. Clamped menisci retained their size and shape, and by 8 weeks developed circumferential and radial fiber organization that resembled native meniscus. Clamping also increased collagen accumulation and improved mechanical properties compared to unclamped menisci. Enhanced organization in clamped menisci was further reflected in the development of anisotropic tensile properties, with 2-3 fold higher circumferential moduli compared to radial moduli, a similar ratio to native meniscus. Ten and 20mg/ml clamped menisci had similar levels of organization, with 20mg/ml menisci producing larger diameter fibers and significantly better mechanical properties. Collectively, these data demonstrate the benefit of using bio-inspired mechanical boundary conditions to drive the formation of a highly organized collagen fiber network.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Induction of fiber alignment and mechanical anisotropy in tissue engineered menisci with mechanical anchoring

Puetzer

Koo

Bonassar

2015

Journal of Biomechanics

131

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“…Previously, co-cultures combining meniscus cells with chondrocytes resulted in engineered menisci that exhibited improved biomechanical properties 13,15 . The use of co-cultures was also successful in creating anisotropy in engineered menisci using a sequential cell seeding methodology 18 . This study also indicates the generation of anisotropy among all experimental groups, as values for tensile strength and stiffness are greater when measured in the circumferential direction as compared to the radial direction.…”

Section: Discussionmentioning

confidence: 99%

“…Self-assembling meniscus constructs with mechanical properties approaching native tissue values have been reported 17 . Additionally, two different cell types have been used in co-culture toward creating tissue heterogeneity 18 . Yet, in terms of tensile properties, self-assembling tissues have not yet achieved the values that the native meniscus exhibits, which has been reported as having a Young’s modulus of 50–150 MPa 1 .…”

Section: Introductionmentioning

confidence: 99%

Tendon and ligament as novel cell sources for engineering the knee meniscus

Hadidi

Paschos

Huang

et al. 2016

Osteoarthritis and Cartilage

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Objective The application of cell-based therapies in regenerative medicine is hindered by the difficulty of acquiring adequate numbers of competent cells. For the knee meniscus in particular, this may be solved by harvesting tissue from neighboring tendons and ligaments. In this study, we have investigated the potential of cells from tendon and ligament, as compared to meniscus cells, to engineer scaffold-free self-assembling fibrocartilage. Method Self-assembling meniscus-shaped constructs engineered from a co-culture of articular chondrocytes and either meniscus, tendon, or ligament cells were cultured for 4 weeks with TGF-β1 in serum-free media. After culture, constructs were assessed for their mechanical properties, histological staining, gross appearance, and biochemical composition including cross-link content. Correlations were performed to evaluate relationships between biochemical content and mechanical properties. Results In terms of mechanical properties as well as biochemical content, constructs engineered using tenocytes and ligament fibrocytes were found to be equivalent or superior to constructs engineered using meniscus cells. Furthermore, cross-link content was found to be correlated with engineered tissue tensile properties. Conclusion Tenocytes and ligament fibrocytes represent viable cell sources for engineering meniscus fibrocartilage using the self-assembling process. Due to greater cross-link content, fibrocartilage engineered with tenocytes and ligament fibrocytes may maintain greater tensile properties than fibrocartilage engineered with meniscus cells.

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“…In contrast, the circumferential tensile modulus and collagen/DW of the outer zone was 101% and 129%, respectively, higher than that of the inner zone. There was no difference in the radial tensile modulus between the zonally variant engineered meniscus neocartilage and neocartilage composed completely of a coculture of chondrocytes and fibrochondrocytes, suggesting the inner and outer zones of the zonally variant neocartilage integrated [84].…”

Section: 51mentioning

confidence: 94%

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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Building an Anisotropic Meniscus with Zonal Variations

Cited by 30 publications

References 56 publications

Induction of fiber alignment and mechanical anisotropy in tissue engineered menisci with mechanical anchoring

Induction of fiber alignment and mechanical anisotropy in tissue engineered menisci with mechanical anchoring

Tendon and ligament as novel cell sources for engineering the knee meniscus

Harnessing Biomechanics to Develop Cartilage Regeneration Strategies

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