Graft hypertrophy of matrix-based autologous chondrocyte implantation: a two-year follow-up study of NOVOCART 3D implantation in the knee

Niethammer, Thomas; Pietschmann, Matthias F.; Horng, Annie; Roßbach, Björn P.; Ficklscherer, Andreas; Jansson, Volkmar; Müller, Peter E.

doi:10.1007/s00167-013-2454-7

Cited by 63 publications

(53 citation statements)

References 34 publications

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“…It is worth noting that graft hypertrophy can occur with second-and third-generation ACI. Niethammer et al 30 reported graft hypertrophy on magnetic resonance imaging (MRI) in 11 of 44 patients who had MACI (with Novocart -TETEC AG, B. Braun, Reutlingen, Germany).…”

Section: Lavage and Debridementmentioning

confidence: 99%

Autologous chondrocyte implantation in the knee: systematic review and economic evaluation

Mistry

Connock

Pink

et al. 2017

Health Technol Assess

200

164

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BackgroundThe surfaces of the bones in the knee are covered with articular cartilage, a rubber-like substance that is very smooth, allowing frictionless movement in the joint and acting as a shock absorber. The cells that form the cartilage are called chondrocytes. Natural cartilage is called hyaline cartilage. Articular cartilage has very little capacity for self-repair, so damage may be permanent. Various methods have been used to try to repair cartilage. Autologous chondrocyte implantation (ACI) involves laboratory culture of cartilage-producing cells from the knee and then implanting them into the chondral defect.ObjectiveTo assess the clinical effectiveness and cost-effectiveness of ACI in chondral defects in the knee, compared with microfracture (MF).Data sourcesA broad search was done in MEDLINE, EMBASE, The Cochrane Library, NHS Economic Evaluation Database and Web of Science, for studies published since the last Health Technology Assessment review.Review methodsSystematic review of recent reviews, trials, long-term observational studies and economic evaluations of the use of ACI and MF for repairing symptomatic articular cartilage defects of the knee. A new economic model was constructed. Submissions from two manufacturers and the ACTIVE (Autologous Chondrocyte Transplantation/Implantation Versus Existing Treatment) trial group were reviewed. Survival analysis was based on long-term observational studies.ResultsFour randomised controlled trials (RCTs) published since the last appraisal provided evidence on the efficacy of ACI. The SUMMIT (Superiority of Matrix-induced autologous chondrocyte implant versus Microfracture for Treatment of symptomatic articular cartilage defects) trial compared matrix-applied chondrocyte implantation (MACI®) against MF. The TIG/ACT/01/2000 (TIG/ACT) trial compared ACI with characterised chondrocytes against MF. The ACTIVE trial compared several forms of ACI against standard treatments, mainly MF. In the SUMMIT trial, improvements in knee injury and osteoarthritis outcome scores (KOOSs), and the proportion of responders, were greater in the MACI group than in the MF group. In the TIG/ACT trial there was improvement in the KOOS at 60 months, but no difference between ACI and MF overall. Patients with onset of symptoms < 3 years’ duration did better with ACI. Results from ACTIVE have not yet been published. Survival analysis suggests that long-term results are better with ACI than with MF. Economic modelling suggested that ACI was cost-effective compared with MF across a range of scenarios.LimitationsThe main limitation is the lack of RCT data beyond 5 years of follow-up. A second is that the techniques of ACI are evolving, so long-term data come from trials using forms of ACI that are now superseded. In the modelling, we therefore assumed that durability of cartilage repair as seen in studies of older forms of ACI could be applied in modelling of newer forms. A third is that the high list prices of chondrocytes are reduced by confidential discounting. The main research needs are for longer-term follow-up and for trials of the next generation of ACI.ConclusionsThe evidence base for ACI has improved since the last appraisal by the National Institute for Health and Care Excellence. In most analyses, the incremental cost-effectiveness ratios for ACI compared with MF appear to be within a range usually considered acceptable. Research is needed into long-term results of new forms of ACI.Study registrationThis study is registered as PROSPERO CRD42014013083.FundingThe National Institute for Health Research Health Technology Assessment programme.

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Section: Lavage and Debridementmentioning

confidence: 99%

Autologous chondrocyte implantation in the knee: systematic review and economic evaluation

Mistry

Connock

Pink

et al. 2017

Health Technol Assess

200

164

View full text Add to dashboard Cite

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“…While Niethammer et al 22 observed no correlation between age or BMI with the development of graft hypertrophy, an association between younger patients and a higher incidence of hypertrophy has been observed after periosteal-covered ACI. 16 The origin of the cartilage defect may also play a role, 22 while it has been suggested that graft hypertrophy may have a cellular origin. 13 Henderson et al 13 noted an increased rate of graft hypertrophy in small-sized repairs with periosteal-covered ACI and proposed that the increased cell density in a smaller repair may lead to increased cellularity and matrix deposition within the repair.…”

Section: Discussionmentioning

confidence: 99%

Incidence, Degree, and Development of Graft Hypertrophy 24 Months After Matrix-Induced Autologous Chondrocyte Implantation

Ebert

Smith

Fallon³

et al. 2015

Am J Sports Med

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Hypertrophic grafts after MACI were common and continued to develop through to 24 months after surgery. Hypertrophic growth was associated with being younger and having a lower BMI, was more common on the femoral condyles, and overall was not associated with clinical outcome at 24 months after surgery. However, further research with longer term follow-up is required to evaluate the effect of persistent hypertrophy on graft stability and to assess the use of early surgical intervention to prevent such failure.

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“…In a 2 years prospective MRI study, incomplete graft filling as assessed by MRI was common (55.7%) at 2 years and did not correlate with clinical results; the authors noted that graft thickness appeared to increase throughout the 2 years follow-up period [41]. A 2 years follow-up MRI study showed a 25% graph hypertrophy rate in Novocart 3D patients (11/44 patients), with higher hypertrophy rates in cases of acute traumatic defects or osteochondritis dissecans [42].…”

Section: Novocart 3dmentioning

confidence: 96%

Autologous Chondrocyte Implantation: Scaffold-Based Solutions

Flanigan¹,

Everhart²,

Early³

2018

Cartilage Repair and Regeneration

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Autologous chondrocyte implantation is a surgical technique utilized for repair of articular cartilage defects. The originally described technique for autologous chondrocyte implantation involves applying a liquid suspension of the cultured chondrocytes to a cartilage defect and sealing the defect with a periosteum or collagen patch. Scaffolds for housing chondrocytes were introduced to allow for increased ease of delivery and application, to avoid leakage of chondrocytes out of the defect, and to allow for an implant that more closely mimics the non-uniform tissue architecture of healthy articular cartilage. In this chapter we describe the design, clinical outcomes, and commercial availability of various scaffolds reported in the clinical literature for autologous chondrocyte implantation.

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Graft hypertrophy of matrix-based autologous chondrocyte implantation: a two-year follow-up study of NOVOCART 3D implantation in the knee

Abstract: Case series, Level IV.

Cited by 63 publications

References 34 publications

Autologous chondrocyte implantation in the knee: systematic review and economic evaluation

Autologous chondrocyte implantation in the knee: systematic review and economic evaluation

Incidence, Degree, and Development of Graft Hypertrophy 24 Months After Matrix-Induced Autologous Chondrocyte Implantation

Autologous Chondrocyte Implantation: Scaffold-Based Solutions

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