Revision surgery after third generation autologous chondrocyte implantation in the knee

Niethammer, Thomas; Valentin, Siegfried; Ficklscherer, Andreas; Güleçyüz, Mehmet F.; Pietschmann, Matthias F.; Müller, Peter E.

doi:10.1007/s00264-015-2792-9

Cited by 26 publications

(26 citation statements)

References 29 publications

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“…Niethammer et al 18 investigated the common revision operations after third-generation ACI (NOVOCART 3D; TETEC AG, Reutlingen, Germany) in a population of 143 consecutive patients (171 cartilage defects; mean defect size, 5 cm 2 ) with a mean follow-up of 5 years. The revision rate was 22.4% ( n = 32) with a mean time to revision of 1.15 years (15 MF/drilling, 7 arthrolysis, 3 ACI, 3 arthroscopy, 2 retrograde drilling, 1 arthroplasty, and 1 HTO).…”

Section: Resultsmentioning

confidence: 99%

“…In the study population evaluated by Niethammer et al, 18 of the 143 patients with 171 defects treated with third generation ACI (NOVACART 3D, TETEC AG, Reutlingen, Germany), 34 (19.9%) of these defects had previous failed cartilage repair procedures. At statistical analysis, cartilage defects with second-line therapy after a previously performed cartilage repair before ACI, showed no higher complication or revision rate.…”

Section: Resultsmentioning

confidence: 99%

“… 15 A higher revision rate in patients who underwent periosteum-covered ACI was also reported in other studies. 16 17 In the paper of Niethammer et al, 18 third generation autologous chondrocyte implantation (NOVACART 3D, TETEC AG, Reutlingen, Germany) showed a short time to revision surgeries (1.15 years) even if not all surgeries were related to active manipulation at implant site or to implant removal. 18 …”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

How to Manage a Failed Cartilage Repair: A Systematic Literature Review

Rosa

Donato

Balato

et al. 2017

Joints

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Purpose The aims of this paper are to report the rate and risk factors for the failure of the most common cartilage repair technique, and analyze the most important factors that could influence the choice of a specific surgical treatment to revise a failed cartilage repair. Methods A review of the literature was performed focusing on failed cartilage repair and related treatments. Two of the authors independently screened articles. Conflicts about the inclusion of a paper was resolved by further evaluation by the senior author. Review articles, articles written in languages different from/other than English, case reports, and papers that did not evaluate the outcomes of interest were excluded. Full-text version of each included paper was obtained and relevant data were extracted and collected in a database. Results At the end of the screening process, 31 articles were included. Microfractures and mosaicplasty showed a nonnegligible failure rate at short- and midterm. Better results, especially in terms of time to failure or revision, were reported with the use of autologous chondrocyte implantation (ACI) and osteochondral allograft (OCA) transplantation. Regarding the treatment of failed cartilage repair, the use of OCA transplantation in patients with previous failed cartilage repair may be a safe option. The revision of failed OCA transplantation with further OCA seems to have a greater failure rate. Patients with previous failed ACI or matrix-induced autologous chondrocyte implantation (MACI) who underwent further MACI or ACI reported acceptable results. Otherwise, ACI in patients with history of previous subchondral marrow stimulation (SMS) demonstrated a greater failure rate. Conclusion From the analysis of the literature, OCA transplantation seems to be the most reliable treatment of a failed SMS. ACI or MACI showed acceptable results in patients with previously failed MACI or ACI. Level of Evidence Level IV, systematic review of level I-IV studies.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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How to Manage a Failed Cartilage Repair: A Systematic Literature Review

Rosa

Donato

Balato

et al. 2017

Joints

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“…These findings make AFS cells very attractive for cell‐based articular cartilage repair. However, practical experience with ACI has shown that the differentiation efficiency of the donor cells determines successful clinical outcome [11]. Therefore, AFS‐cell‐based transplantation approaches will rely on efficient ways to differentiate cells before or during the transplantation process.…”

Section: Introductionmentioning

confidence: 99%

Rapamycin-Induced Hypoxia Inducible Factor 2A Is Essential for Chondrogenic Differentiation of Amniotic Fluid Stem Cells

Preitschopf

Schörghofer

Kinslechner

et al. 2016

Stem Cells Translational Medicine

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Amniotic fluid stem (AFS) cells represent a major source of donor cells for cartilage repair. Recently, it became clear that mammalian target of rapamycin (mTOR) inhibition has beneficial effects on cartilage homeostasis, but the effect of mTOR on chondrogenic differentiation is still elusive. Therefore, the objectives of this study were to investigate the effects of mammalian target of rapamycin complex 1 (mTORC1) modulation on the expression of SOX9 and on its downstream targets during chondrogenic differentiation of AFS cells. We performed three-dimensional pellet culturing of AFS cells and of in vitro-expanded, human-derived chondrocytes in the presence of chondrogenic factors. Inhibition of mTORC1 by rapamycin or by small interfering RNA-mediated targeting of raptor (gene name, RPTOR) led to increased AKT activation, upregulation of hypoxia inducible factor (HIF) 2A, and an increase in SOX9, COL2A1, and ACAN abundance. Here we show that HIF2A expression is essential for chondrogenic differentiation and that AKT activity regulates HIF2A amounts. Importantly, engraftment of AFS cells in cell pellets composed of human chondrocytes revealed an advantage of raptor knockdown cells compared with control cells in their ability to express SOX9. Our results demonstrate that mTORC1 inhibition leads to AKT activation and an increase in HIF2A expression. Therefore, we suggest that mTORC1 inhibition is a powerful tool for enhancing chondrogenic differentiation of AFS cells and also of in vitro-expanded adult chondrocytes before transplantation. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:580-590 SIGNIFICANCERepair of cartilage defects is still an unresolved issue in regenerative medicine. Results of this study showed that inhibition of the mammalian target of rapamycin complex 1 (mTORC1) pathway, by rapamycin or by small interfering RNA-mediated targeting of raptor (gene name, RPTOR), enhanced amniotic fluid stem cell differentiation toward a chondrocytic phenotype and increased their engrafting efficiency into cartilaginous structures. Moreover, freshly isolated and in vitro passaged human chondrocytes also showed redifferentiation upon mTORC1 inhibition during culturing. Therefore, this study revealed that rapamycin could enable a more efficient clinical use of cell-based therapy approaches to treat articular cartilage defects.

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“…However, delamination or disturbed fusion to the surrounding native cartilage and subchondral bone are still problems for the third-generation ACI. Niethammer et al 74 reported a revision rate of 23.4% after MACT. The reasons were bone marrow edema, arthrofibrosis, and partial graft deficiency.…”

Section: Developments In Acimentioning

confidence: 99%

Autologous chondrocyte implantation for cartilage repair: current perspectives

Zellner¹,

Krutsch²,

Pfeifer³

et al. 2015

ORR

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Over the last decade, regenerative treatment options have become the more routinely used techniques for treatment of cartilage defects, with predictable outcomes for their specific indications. For large chondral lesions in young patients, in particular, autologous chondrocyte implantation is the treatment of choice for restoration of joint health. This review focuses on indications, results, and outcome predictors of autologous chondrocyte implantation in comparison to other regenerative treatment procedures and discusses improvement options and future perspectives for autologous chondrocyte transplantation. As research activities are increasing in the field of regenerative joint therapy, recent developments may help to overcome remaining limitations step by step.

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Revision surgery after third generation autologous chondrocyte implantation in the knee

Abstract: Revision surgery after third generation autologous chondrocyte implantation is common and is needed primarily in cases with arthrofibrosis, partial graft cartilage deficiency and symptomatic bone marrow oedema resulting in a significantly better clinical outcome.

Cited by 26 publications

References 29 publications

How to Manage a Failed Cartilage Repair: A Systematic Literature Review

How to Manage a Failed Cartilage Repair: A Systematic Literature Review

Rapamycin-Induced Hypoxia Inducible Factor 2A Is Essential for Chondrogenic Differentiation of Amniotic Fluid Stem Cells

Autologous chondrocyte implantation for cartilage repair: current perspectives

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