Growth factor treated tensioned synoviocyte neotissues: Towards meniscal bioscaffold tissue engineering

Warnock, Jennifer J.; Bobe, Gerd; Duesterdieck-Zellmer, Katja F.; Spina, Jason; Ott, Jesse; Baltzer, Wendy I.; Bay, Brian K.

doi:10.1016/j.tvjl.2014.01.010

Cited by 7 publications

(4 citation statements)

References 67 publications

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“…For example, in articular cartilage tissue engineering, a variety of methods, including combinations of hydrostatic pressure and growth factor treatment (3), fluid flow (4), and matrix-modulating enzymes (5), have resulted in improved neotissues with tensile moduli ranging from 1.3 to 2.3 MPa; however, native tissue values range from 5 to 25 MPa (6). Similarly, in neofibrocartilage, tensile properties have been reported to be 2.5-3.5 MPa (7,8), with native fibrocartilage values ranging from 7 to 295 MPa (9,10). These low properties likely result from the immaturity of the ECM of the neotissues, which is mainly due to lack of collagen cross-links (11).…”

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confidence: 99%

Developing functional musculoskeletal tissues through hypoxia and lysyl oxidase-induced collagen cross-linking

Makris¹,

Responte²,

Paschos³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

131

146

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The inability to recapitulate native tissue biomechanics, especially tensile properties, hinders progress in regenerative medicine. To address this problem, strategies have focused on enhancing collagen production. However, manipulating collagen cross-links, ubiquitous throughout all tissues and conferring mechanical integrity, has been underinvestigated. A series of studies examined the effects of lysyl oxidase (LOX), the enzyme responsible for the formation of collagen cross-links. Hypoxia-induced endogenous LOX was applied in multiple musculoskeletal tissues (i.e., cartilage, meniscus, tendons, ligaments). Results of these studies showed that both native and engineered tissues are enhanced by invoking a mechanism of hypoxia-induced pyridinoline (PYR) cross-links via intermediaries like LOX. Hypoxia was shown to enhance PYR cross-linking 1.4- to 6.4-fold and, concomitantly, to increase the tensile properties of collagen-rich tissues 1.3- to 2.2-fold. Direct administration of exogenous LOX was applied in native cartilage and neocartilage generated using a scaffold-free, self-assembling process of primary chondrocytes. Exogenous LOX was found to enhance native tissue tensile properties 1.9-fold. LOX concentration- and time-dependent increases in PYR content (∼ 16-fold compared with controls) and tensile properties (approximately fivefold compared with controls) of neocartilage were also detected, resulting in properties on par with native tissue. Finally, in vivo subcutaneous implantation of LOX-treated neocartilage in nude mice promoted further maturation of the neotissue, enhancing tensile and PYR content approximately threefold and 14-fold, respectively, compared with in vitro controls. Collectively, these results provide the first report, to our knowledge, of endogenous (hypoxia-induced) and exogenous LOX applications for promoting collagen cross-linking and improving the tensile properties of a spectrum of native and engineered tissues both in vitro and in vivo.

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mentioning

confidence: 99%

Developing functional musculoskeletal tissues through hypoxia and lysyl oxidase-induced collagen cross-linking

Makris¹,

Responte²,

Paschos³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

131

146

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“…The main composition of the extracellular matrix of the meniscus is collagen type 1, but in the inner region of the meniscus, which is composed of avascular tissue, extracellular matrix contains collagen type 2 and a greater number of chondrocytic morphology cells than in the outer region of the meniscus [ 45 , 46 ]. Several studies have attempted upregulation of collagen type 2 in meniscus cells using cytokines, mechanical stress and cells [ 10 , 14 , 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

Intra-articular injection of synthetic microRNA-210 accelerates avascular meniscal healing in rat medial meniscal injured model

et al. 2014

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IntroductionThe important functions of the meniscus are shock absorption, passive stabilization and load transmission of the knee. Because of the avascularity of two-thirds of the meniscal center region, the treatment of tears in this area is hard. Recently, microRNAs have been proven to play an important role in the pathogenesis of diseases. We focused on microRNA (miR)-210, which plays a wide spectrum of roles comprising mitochondrial metabolism, angiogenesis, DNA repair and cell survival. This study aimed to investigate the effect of intra-articular injection of synthetic miR-210 on the injured meniscus in the avascular zone.MethodsThe middle segments of the medial meniscus of Spraque Dawley rats were incised longitudinally with a scalpel. An intra-articular injection of double-stranded (ds) miR-210 (for control group using control dsRNA) with atelocollagen was administered immediately after injury. Four weeks and 12 weeks after the injection, we conducted a histologic evaluation, immunohistochemical evaluation and Real-time PCR analysis. In vitro, the inner meniscus and synovial cells were isolated from rat knee joint, and were transfected with ds miR-210 or control dsRNA. Real-time PCR and immunohistochemical evaluations were performed.ResultsTwenty-four hours after the injection, FAM (Fluorescein amidite) labeled miR-210 was observed in the cells around the injured site. Four weeks after the injection, the injured site of the miR-210 group was filled with repaired tissue while that of the control was not repaired. In gene expression analysis of the meniscus, the expression of miR-210, Collagen type 2 alpha 1 (Col2a1), Vascular endothelial growth factor (VEGF), and Fibroblast growth factor-2 (FGF2) in the miR-210 group was significantly higher than that in the control. At 12 weeks, the intra-articular injection of miR-210 had healed the injured site of the meniscus and had prevented articular cartilage degeneration. In vitro, miR-210 upregulated Col2a1 expression in the meniscus cells and VEGF and FGF2 expression in the synovial cells.ConclusionsAn intra-articular injection of ds miR-210 was effective in the healing of the damaged white zone meniscus through promotion of the collagen type 2 production from meniscus cells and through upregulated of VEGF and FGF2 from synovial cells.

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“…14 These synovium-like monolayers have been cultured on various substrates, including filter membranes, 1,30 temperature-responsive dishes, 31 cartilage EXPs, 32 tissueengineered (TE) cartilage, 33 and even in suspension. 34,35 However, simple cell layers lack the dense ECM and threedimensional architecture of the intima and subintima that play an integral role in the function of native tissue. TE synovium may be able to overcome these limitations.…”

Section: Introductionmentioning

confidence: 99%

A Functional Tissue-Engineered Synovium Model to Study Osteoarthritis Progression and Treatment

Stefani

Halder

Estell

et al. 2019

Tissue Engineering Part A

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The synovium envelops the diarthrodial joint and plays a key regulatory role in defining the composition of the synovial fluid through filtration and biosynthesis of critical boundary lubricants. Synovium changes often precede cartilage damage in osteoarthritis. We describe a novel in vitro tissue engineered model, validated against native synovium explants, to investigate the structure-function of synovium through quantitative solute transport measures. Synovium was evaluated in the presence of a proinflammatory cytokine, interleukin-1, or the clinically relevant corticosteroid, dexamethasone. We anticipate that a better understanding of synovium transport would support efforts to develop more effective strategies aimed at restoring joint health.

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Growth factor treated tensioned synoviocyte neotissues: Towards meniscal bioscaffold tissue engineering

Cited by 7 publications

References 67 publications

Developing functional musculoskeletal tissues through hypoxia and lysyl oxidase-induced collagen cross-linking

Developing functional musculoskeletal tissues through hypoxia and lysyl oxidase-induced collagen cross-linking

Intra-articular injection of synthetic microRNA-210 accelerates avascular meniscal healing in rat medial meniscal injured model

A Functional Tissue-Engineered Synovium Model to Study Osteoarthritis Progression and Treatment

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