ERK1/2 Activation Induced by Inflammatory Cytokines Compromises Effective Host Tissue Integration of Engineered Cartilage

Djouad, Farida; Rackwitz, Lars; Song, Yingjie; Janjanin, Sasa; Tuan, Rocky S.

doi:10.1089/ten.tea.2008.0663

Cited by 36 publications

(27 citation statements)

References 34 publications

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“…22 Cartilage tissues (about 2-mm thickness) were harvested from the femoral condyles of adult calves and cultured in the chondrogenesis medium for 1 day. These tissues were then punched into 8-mm-diameter cylinders using biopsy punches (Skylar, West Chester, PA), and a cartilage ring with a central defect was further created by coring out the center using a 4-mm biopsy punch (Fig.…”

Section: Integration Testing Of Cell-laden Constructs Into Cartilagementioning

confidence: 99%

Cartilage Tissue Engineering Application of Injectable Gelatin Hydrogel with In Situ Visible-Light-Activated Gelation Capability in Both Air and Aqueous Solution

Lin

Cheng

Alexander

et al. 2014

Tissue Engineering Part A

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128

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Chondroprogenitor cells encapsulated in a chondrogenically supportive, three-dimensional hydrogel scaffold represents a promising, regenerative approach to articular cartilage repair. In this study, we have developed an injectable, biodegradable methacrylated gelatin (mGL)-based hydrogel capable of rapid gelation via visible light (VL)-activated crosslinking in air or aqueous solution. The mild photocrosslinking conditions permitted the incorporation of cells during the gelation process. Encapsulated human-bone-marrow-derived mesenchymal stem cells (hBMSCs) showed high, long-term viability (up to 90 days) throughout the scaffold. To assess the applicability of the mGL hydrogel for cartilage tissue engineering, we have evaluated the efficacy of chondrogenesis of the encapsulated hBMSCs, using hBMSCs seeded in agarose as control. The ability of hBMSCladen mGL constructs to integrate with host tissues after implantation was further investigated utilizing an in vitro cartilage repair model. The results showed that the mGL hydrogel, which could be photopolymerized in air and aqueous solution, supports hBMSC growth and TGF-b3-induced chondrogenesis. Compared with agarose, mGL constructs laden with hBMSCs are mechanically stronger with time, and integrate well with native cartilage tissue upon implantation based on push-out mechanical testing. VL-photocrosslinked mGL scaffold thus represents a promising scaffold for cell-based repair and resurfacing of articular cartilage defects.

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Section: Integration Testing Of Cell-laden Constructs Into Cartilagementioning

confidence: 99%

Cartilage Tissue Engineering Application of Injectable Gelatin Hydrogel with In Situ Visible-Light-Activated Gelation Capability in Both Air and Aqueous Solution

Lin

Cheng

Alexander

et al. 2014

Tissue Engineering Part A

Self Cite

128

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“…In principle, successful matrix-based cartilage repair in vivo relies on sustained cartilage specific matrix deposition within the cell-laden scaffold, the development of sufficient mechanical properties and, in particular, integration of the developing neocartilage into the surrounding native cartilage (18, 23, 24). Inferior interface stability impairs mechanical integrity of the restored joint surface, and may lead to pathological load distribution in the joint and long-term failure of the cartilage repair procedure.…”

Section: Introductionmentioning

confidence: 99%

“…Compared to in vivo animal cartilage repair models that are time-consuming, expensive, and more difficult to control, in vitro cartilage repair models may be utilized to evaluate certain aspects of joint repair and to optimize specific environmental variables (24, 33, 34). The main aim of this study was to directly compare the in vitro cartilage repair potential of various cell types, as applicable in surgical cartilage repair procedures, in terms of their interaction with native articular cartilage and the development of a functional interface and matrix deposition.…”

Section: Introductionmentioning

confidence: 99%

“…Our experimental approach was based on an established bovine “implant in cartilage ring” model (24) to assess functional integration and biochemical/-mechanical properties of cell-laden agarose constructs in vitro , utilizing differentiated chondrocytes, de-differentiated chondrocytes after 2, 5 or 8 population doublings in monolayer-culture, and MSCs. In the first study, freshly prepared constructs of the stated cell types were applied and cultured inside the native cartilage ring for 28 days in a serum-free, chemically defined medium (CM−).…”

Section: Introductionmentioning

confidence: 99%

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Functional cartilage repair capacity of de-differentiated, chondrocyte- and mesenchymal stem cell-laden hydrogels in vitro

Rackwitz

Djouad

Janjanin

et al. 2014

Osteoarthritis and Cartilage

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Objective The long-term performance of cell seeded matrix based cartilage constructs depends on (1) the development of sufficient biomechanical properties, and (2) lateral integration with host tissues, both of which require cartilage specific matrix deposition within the scaffold. In this study, we have examined the potential of tissue-engineered cartilage analogs developed using different cell types, i.e., MSCs versus chondrocytes and de-differentiated chondrocytes, in an established “construct in cartilage ring” model. Design Cell-laden constructs of differentiated chondrocytes, de-differentiated chondrocytes after 2, 5 or 8 population doublings, and MSCs were either implanted into a native cartilage ring immediately after fabrication (immature group) or pretreated for 21 days in a transforming growth factor-β3 (TGF-β3) containing medium prior to implantation. After additional culture for 28 days in a serum-free, chemically defined medium, the extent of lateral integration, and biochemical and biomechanical characteristics of the implants as hybrid constructs were assessed. Results The quality of integration, the amount of accumulated cartilage-specific matrix components and associated biomechanical properties were found to be highest when using differentiated chondrocytes. De-differentiation of chondrocytes negatively impacted the properties of the implants, as even two population doublings of the chondrocytes in culture significantly lowered cartilage repair capacity. In contrast, MSCs showed chondrogenic differentiation with TGF-β3 pre-treatment and superior integrational behavior. Conclusions Chondrocyte expansion and de-differentiation impaired the cell response, resulting in inferior cartilage repair in vitro. With TGF-β3 pre-treatment, MSCs were able to undergo sustained chondrogenic differentiation and exhibited superior matrix deposition and integration compared to de-differentiated chondrocytes.

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“…IL-1b has been reported to reduce collagen type 2 expression and GAG content of human nasal and articular chondrocytes cultured on a type 1 collagen scaffold, 98 and both IL-1b and TNF-a have been shown to impact the integration of engineered cartilage with native tissue. 99 Additionally, these pro-inflammatory cytokines have been shown to inhibit the migratory potential of chondrogenic progenitor cells in osteoarthritic cartilage, 100 which may limit the success of strategies utilizing cell-free scaffolds for recruitment of endogenous cells and in situ cartilage regeneration. 24 In addition to directly impacting engineered cartilage and endogenous cellular repair, inflammation may also hinder stem cell-based repair strategies.…”

Section: The Effect Of Inflammation On Tissue Engineered Cartilagementioning

confidence: 99%

Immune Modulation to Improve Tissue Engineering Outcomes for Cartilage Repair in the Osteoarthritic Joint

Fahy

Farrell

Ritter

et al. 2015

Tissue Engineering Part B: Reviews

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ERK1/2 Activation Induced by Inflammatory Cytokines Compromises Effective Host Tissue Integration of Engineered Cartilage

Cited by 36 publications

References 34 publications

Cartilage Tissue Engineering Application of Injectable Gelatin Hydrogel with In Situ Visible-Light-Activated Gelation Capability in Both Air and Aqueous Solution

Cartilage Tissue Engineering Application of Injectable Gelatin Hydrogel with In Situ Visible-Light-Activated Gelation Capability in Both Air and Aqueous Solution

Functional cartilage repair capacity of de-differentiated, chondrocyte- and mesenchymal stem cell-laden hydrogels in vitro

Immune Modulation to Improve Tissue Engineering Outcomes for Cartilage Repair in the Osteoarthritic Joint

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