Autologous chondrocyte implantation in a novel alginate-agarose hydrogel

Selmi, Tarik Aït Si; Verdonk, Peter; Chambat, Pierre; Dubrana, F.; Jf, Potel; Barnouin, Laurence; Neyret, Philippe

doi:10.1302/0301-620x.90b5.20360

Cited by 239 publications

(183 citation statements)

References 24 publications

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“…15 Similarly, 10 years after second-generation ACI in 23 patients, the mean subjective IKDC score was 76.4. 16 However, the mean subjective IKDC score improvement in our study was smaller than that reported previously by Selmi et al 7 with the same procedure (31.7 and 40.8, respectively), which was similar to the improvement in our mosaicplasty group (44.3).…”

Section: Discussionsupporting

confidence: 77%

“…This easy-to-handle scaffold provides the cells with a three-dimensional environment, allowing them to develop into an osteochondral-like tissue. 7 In 2008, Selmi et al reported the 2-year outcomes of 17 patients managed using Cartipatch 1 showing significant improvements of the mean International Knee Documentation Committee (IKDC) score, O'Driscoll histological score and MRI analysis. 7 Those improvements were greatest in patients with cartilage defects larger than 3 cm 2 .…”

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confidence: 99%

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Third‐generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2‐year randomized trial

Clavé

Potel

Servien

et al. 2016

Journal Orthopaedic Research

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Numerous surgical techniques have been developed to treat osteochondral defects of the knee. A study reported encouraging outcomes of third-generation autologous chondrocyte implantation achieved using the solid agarose-alginate scaffold Cartipatch 1 . Whether this scaffold is better than conventional techniques remains unclear. This multicenter randomized controlled trial compared 2-year functional outcomes (IKDC score) after Cartipatch 1 versus mosaicplasty in patients with isolated symptomatic femoral chondral defects (ICRS III and IV) measuring 2.5-7.5 cm 2 . In addition, a histological evaluation based on the O'Driscoll score was performed after 2 years. We needed 76 patients to demonstrate an at least 10-point subjective IKDC score difference with a ¼ 5% and 90% power. During the enrolment period, we were able to include 55 patients, 30 of them were allocated at random to Cartipatch 1 and 25 to mosaicplasty. After 2 years, eight patients had been lost to follow-up, six in the Cartipatch 1 group, and two in the mosaicplasty group. The baseline characteristics of the two groups were not significantly different. The mean IKDC score and score improvement after 2 years were respectively 73.7 AE 20.1 and 31.8 AE 20.8 with Cartipatch 1 and 81.5 AE 16.4 and 44.4 AE 15.2 with mosaicplasty. The 12.6-point absolute difference in favor of mosaicplasty is statistically significant. Twelve adverse events were recorded in the Cartipatch 1 group against six in the mosaicplasty group. After 2 years, functional outcomes were significantly worse after Cartipatch 1 treatment compared to mosaicplasty for isolated focal osteochondral defects of the femur. ß

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Section: Discussionsupporting

confidence: 77%

mentioning

confidence: 99%

Third‐generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2‐year randomized trial

Clavé

Potel

Servien

et al. 2016

Journal Orthopaedic Research

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“…Towards this end we theorized that a gel that can limit vascularization may favor hypoxia and hence chondrogenesis. In this study, we demonstrate that hyaline cartilage can be engineered de novo in the IVB by simply injecting agarose, a biocompatible (14,15) polysaccharide biomaterial that has no-inherent angiogenic properties (14,16,17) but promotes hypoxia (18). The engineered cartilage stains positive for collagen type-II and proteoglycans, is hypercellular, and is capable of remodeling within a full-thickness osteochondral defect with complete integration and does not undergo calcification even after 9 mo.…”

mentioning

confidence: 77%

Autologous engineering of cartilage

Emans¹,

Rhijn²,

Welting³

et al. 2010

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

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Treatment of full-thickness damage to hyaline cartilage is hampered by the limited availability of autologous healthy cartilage and the lengthy, cost-prohibitive cell isolation and expansion steps associated with autologous cartilage implantation (ACI). Here we report a strategy for de novo engineering of ectopic autologous cartilage (EAC) within the subperiosteal space (in vivo bioreactor), through the mere introduction of a biocompatible gel that might promote hypoxia-mediated chondrogenesis, thereby effectively overcoming the aforementioned limitations. The EAC is obtained within 3 wk post injection of the gel, and can be press-fit into an osteochondral defect where it undergoes remodeling with good lateral and subchondral integration. The implanted EAC showed no calcification even after 9 mo and attained an average O'Driscoll score of 11 (versus 4 for controls). An "on demand" autologous source of autologous cartilage with remodeling capacity is expected to significantly impact the clinical options in repair of trauma to articular cartilage.A nnually, in the United States alone over 1 million individuals, are treated for lesions in articular cartilage with over 250,000 patients requiring knee arthroscopy (1). Damage to hyaline cartilage often precedes osteoarthritis (2). Among cartilage lesions, osteochondritis dissecans (OCD), which involves full-thickness damage to the hyaline cartilage and underlying bone (3), is being diagnosed with an increasing frequency. While OCD is most often diagnosed in the knee, it may also affect other joints such as ankle, elbow, and shoulder (3). OCD is clinically challenging to treat as it is multifactorial and, furthermore, treatment is hampered by the limited self-repair potential of hyaline cartilage that is due to the absence of resident pluripotent cells and the lack of vasculature and lymphatics (4, 5). Notwithstanding, hyaline cartilage is key to successful repair as its unique cellular organization and extra cellular matrix composition confers load bearing and lubricious properties to the joint surface. Currently, injury to the articular cartilage surface, including OCD lesions, is treated by either physiotherapy, stimulation of regeneration by arthroscopic drilling, autologous osteochondral plugs from non-weight bearing regions, or injection of cells under a periosteal flap (ACI) (5, 6). Whereas the best treatment for cartilage lesions remains to be defined, ACI, in spite of its suboptimal outcomes (i.e., formation of undesirable fibrocartilage, poor, integration, and calcification), along with engineered cartilage and osteochondral tissue constructs, are promising as treatment options (7, 8) However, the clinical implementation of ACI and engineered constructs is hampered by the costs and logistics involved with isolation and expansion of cells and variability in quality of the engineered tissue. We recently proposed a unique paradigm for de novo engineering of tissues, the in vivo bioreactor (IVB), in which a woundhealing response provoked within a confined subperi...

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“…Agarose has been used extensively in the tissueengineering studies of cartilage due to its ability to maintain chondrocytic phenotype in long-term suspension cultures [2,8,9,25]. Additionally, agarose is being used as a copolymer in autologous chondrocyte transplantation (Cartipatch 1 ; Banque de tissues, Mions, France) in Europe [39]. Our previous work demonstrates agarose can support the elaboration of functional cartilage in the chondral layer of bilayered tissue-engineered osteochondral constructs [28,36].…”

Section: Methodsmentioning

confidence: 99%

Bioactive Glass 13-93 as a Subchondral Substrate for Tissue-engineered Osteochondral Constructs: A Pilot Study

Jayabalan

Tan

Rahaman

et al. 2011

Clinical Orthopaedics &Amp; Related Research

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Background Replacement of diseased areas of the joint with tissue-engineered osteochondral grafts has shown potential in the treatment of osteoarthritis. Bioactive glasses are candidates for the osseous analog of these grafts. Questions/purposes (1) Does Bioactive Glass 13-93 (BG 13-93) as a subchondral substrate improve collagen and glycosaminoglycan production in a tissue-engineered cartilage layer? (2) Does BG 13-93 as a culture medium supplement increase the collagen and glycosaminoglycan production and improve the mechanical properties in a tissue-engineered cartilage layer?Methods In Study 1, bioactive glass samples (n = 4) were attached to a chondrocyte-seeded agarose layer to form an osteochondral construct, cultured for 6 weeks, and compared to controls. In Study 2, bioactive glass samples (n = 5) were cocultured with cell-seeded agarose for 6 weeks. The cell-seeded agarose layer was exposed to BG 13-93 either continuously or for the first or last 2 weeks in culture or had no exposure. Results Osteochondral constructs with a BG 13-93 base had improved glycosaminoglycan deposition but less collagen II content. Agarose scaffolds that had a temporal exposure to BG 13-93 within the culture medium had improved mechanical and biochemical properties compared to continuous or no exposure. Conclusions When used as a subchondral substrate, BG 13-93 did not improve biochemical properties compared to controls. However, as a culture medium supplement, BG 13-93 improved the biochemical and mechanical properties of a tissue-engineered cartilage layer. Clinical Relevance BG 13-93 may not be suitable in osteochondral constructs but could have potential as a medium supplement for neocartilage formation.

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Autologous chondrocyte implantation in a novel alginate-agarose hydrogel

Cited by 239 publications

References 24 publications

Third‐generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2‐year randomized trial

Third‐generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2‐year randomized trial

Autologous engineering of cartilage

Bioactive Glass 13-93 as a Subchondral Substrate for Tissue-engineered Osteochondral Constructs: A Pilot Study

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