Inducing articular cartilage phenotype in costochondral cells

Murphy, Meghan K.; DuRaine, Grayson; Reddi, A. Hari; Hu, Jerry C.; Athanasiou, Kyriacos A.

doi:10.1186/ar4409

Cited by 17 publications

(21 citation statements)

References 46 publications

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“…Additionally, treatment of constructs with C-ABC have been reported to enhance construct tensile properties (both Young’s modulus and UTS) (Natoli et al 2009a; Natoli et al 2009b). In addition, the combination of all three stimuli has likewise generated robust neocartilage from non-articular chondrocyte sources (Murphy et al 2013). In this study, we evaluated this stimulated tissue engineered neocartilage for its ability to be sutured into a cartilage defect, giving the constructs clinical relevance.…”

Section: Discussionmentioning

confidence: 99%

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Biomechanical evaluation of suture-holding properties of native and tissue-engineered articular cartilage

DuRaine

Arzi

Lee

et al. 2014

Biomech Model Mechanobiol

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Objective The purpose of this study was to determine suture-holding properties of tissue engineered neocartilage relative to native articular cartilage. To this end, suture pull-out strength was quantified for native articular cartilage and for neocartilages possessing various mechanical properties. Methods Suture holding properties were examined in vitro and in vivo. Neocartilage from bovine chondrocytes was engineered using two sets of exogenous stimuli resulting in neotissue of different biochemical compositions. Compressive and tensile properties and glycosaminoglycan, collagen, and pyridinoline cross-link contents were assayed (study 1). Suture pull-out strength was compared between neocartilage constructs, and bovine and leporine native cartilage. Uniaxial pull-out test until failure was performed after passing 6-0 Vicryl through each tissue (study 2). Subsequently, neocartilage was implanted into a rabbit model to examine short-term suture holding ability in vivo (study 3). Results Neocartilage glycosaminoglycan and collagen content per wet weight reached 4.55% ± 1.62% and 4.21 ± 0.77%, respectively. Tensile properties for neocartilage constructs reached 2.6 ± 0.77 MPa for Young’s modulus and 1.39 ± 0.63 MPa for ultimate tensile strength. Neocartilage reached ~33% of suture pull-out strength of native articular cartilage. Neocartilage cross-link content reached 50% of native values, and suture pull-out strength correlated positively with cross-link content (R2=0.74). Neocartilage sutured into rabbit osteochondral defects was successfully maintained for 3 weeks. Conclusion This study shows that pyridinoline cross-links in neocartilage may be vital in controlling suture pull-out strength. Neocartilage produced in vitro with one-third of native tissue pull-out strength appears sufficient for construct suturing and retention in vivo.

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Section: Discussionmentioning

confidence: 99%

“…Stimulated constructs were further treated with C-ABC at 2 U/ml for 4 hours on days 15 and 29 (Murphy et al 2013; Natoli et al 2009b; Natoli et al 2009a). Control constructs were not treated with any exogenous stimuli.…”

Section: Methodsmentioning

confidence: 99%

Biomechanical evaluation of suture-holding properties of native and tissue-engineered articular cartilage

DuRaine

Arzi

Lee

et al. 2014

Biomech Model Mechanobiol

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“…Catabolic enzyme, C-ABC, and anabolic protein, TGF-b1, were employed to enhance the mechanical properties of engineered cartilage [23]. Neocartilage was treated with 2 unit ml 21 C-ABC in CHG for 4 h on day 14.…”

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confidence: 99%

Neocartilage integration in temporomandibular joint discs: physical and enzymatic methods

Murphy

Arzi

Prouty

et al. 2015

J. R. Soc. Interface.

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Integration of engineered musculoskeletal tissues with adjacent native tissues presents a significant challenge to the field. Specifically, the avascularity and low cellularity of cartilage elicit the need for additional efforts in improving integration of neocartilage within native cartilage. Self-assembled neocartilage holds significant potential in replacing degenerated cartilage, though its stabilization and integration in native cartilage require further efforts. Physical and enzymatic stabilization methods were investigated in an in vitro model for temporomandibular joint (TMJ) disc degeneration. First, in phase 1, suture, glue and press-fit constructs were compared in TMJ disc intermediate zone defects. In phase 1, suturing enhanced interfacial shear stiffness and strength immediately; after four weeks, a 15-fold increase in stiffness and a ninefold increase in strength persisted over press-fit. Neither suture nor glue significantly altered neocartilage properties. In phase 2, the effects of the enzymatic stabilization regimen composed of lysyl oxidase, CuSO 4 and hydroxylysine were investigated. A full factorial design was employed, carrying forward the best physical method from phase 1, suturing. Enzymatic stabilization significantly increased interfacial shear stiffness after eight weeks. Combined enzymatic stabilization and suturing led to a fourfold increase in shear stiffness and threefold increase in strength over press-fit. Histological analysis confirmed the presence of a collagen-rich interface. Enzymatic treatment additionally enhanced neocartilage mechanical properties, yielding a tensile modulus over 6 MPa and compressive instantaneous modulus over 1200 kPa at eight weeks. Suturing enhances stabilization of neocartilage, and enzymatic treatment enhances functional properties and integration of neocartilage in the TMJ disc. Methods developed here are applicable to other orthopaedic soft tissues, including knee meniscus and hyaline articular cartilage.

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“…Expansion of fully differentiated cells in monolayer causes dedifferentiation and therefore requires a redifferentiation step and phenotypic verification before TE culture (previously described in Section 4.2). 33, 54, 59 It was previously thought that passaged cells would irreversibly lose their chondrogenic phenotype and form neocartilage with inferior functional properties. 14 Recently however, with the advent of redifferentiation protocols, it was shown that these conditions result in neocartilage with properties as good or better than neocartilage made with primary cells.…”

Section: Cells Used For Scaffold-free Tissue Engineeringmentioning

confidence: 99%

“…Using a system of expansion and redifferentiation may also allow the proliferation and phenotypic modulation of cartilaginous sources that do not suffer joint pathologies, such as costochondral, auricular, or nasal, to be used for musculoskeletal cartilage TE. 11, 59, 64 The use of expanded cells, especially those of autologous or allogeneic origin, minimizes the limitations associated with the scarcity of healthy cells, while maintaining clinical translatability of engineered cartilage.…”

Section: Cells Used For Scaffold-free Tissue Engineeringmentioning

confidence: 99%

Emergence of Scaffold-Free Approaches for Tissue Engineering Musculoskeletal Cartilages

et al. 2014

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This review explores scaffold-free methods as an additional paradigm for tissue engineering. Musculoskeletal cartilages –for example articular cartilage, meniscus, temporomandibular joint disc, and intervertebral disc – are characterized by low vascularity and cellularity, and are amenable to scaffold-free tissue engineering approaches. Scaffold-free approaches, particularly the self-assembling process, mimic elements of developmental processes underlying these tissues. Discussed are various scaffold-free approaches for musculoskeletal cartilage tissue engineering, such as cell sheet engineering, aggregation, and the self-assembling process, as well as the availability and variety of cells used. Immunological considerations are of particular importance as engineered tissues are frequently of allogeneic, if not xenogeneic, origin. Factors that enhance the matrix production and mechanical properties of these engineered cartilages are also reviewed, as the fabrication of biomimetically suitable tissues is necessary to replicate function and ensure graft survival in vivo. The concept of combining scaffold-free and scaffold-based tissue engineering methods to address clinical needs is also discussed. Inasmuch as scaffold-based musculoskeletal tissue engineering approaches have been employed as a paradigm to generate engineered cartilages with appropriate functional properties, scaffold-free approaches are emerging as promising elements of a translational pathway not only for musculoskeletal cartilages but for other tissues as well.

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Inducing articular cartilage phenotype in costochondral cells

Cited by 17 publications

References 46 publications

Biomechanical evaluation of suture-holding properties of native and tissue-engineered articular cartilage

Biomechanical evaluation of suture-holding properties of native and tissue-engineered articular cartilage

Neocartilage integration in temporomandibular joint discs: physical and enzymatic methods

Emergence of Scaffold-Free Approaches for Tissue Engineering Musculoskeletal Cartilages

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