Autologous Chondrocyte Implantation in the Knee

Nawaz, Syed Zuhair; Bentley, G.; Briggs, Timothy; Carrington, Richard; Skinner, John; Gallagher, Kieran; Dhinsa, Baljinder

doi:10.2106/jbjs.l.01695

Cited by 148 publications

(192 citation statements)

References 21 publications

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“…However, we note that GP18:0 may also have potential clinical use such as in matrix assisted autologous chondrocyte implantation (MACI) and has been developed for repair of osteoarthritic defects 44 .…”

Section: Discussionmentioning

confidence: 99%

Tunable Supramolecular Hydrogels for Selection of Lineage-Guiding Metabolites in Stem Cell Cultures

Alakpa

Jayawarna

Lampel

et al. 2016

Chem

183

195

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Abstract. Stem cells are known to differentiate in response toHowever, identification of these stem cell inducing molecules is non-trivial and rational approaches to discover drugs for achieving reproducible, targeted stem cell control remain elusive. Here, we demonstrate the design of supramolecular hydrogels that allow targeting of a range of stem cell phenotypes, providing a useful platform for discovery of differentiation inducing metabolites. These gels are simple in composition, containing a fibre forming aromatic peptide amphiphile, which is coassembled with a surfactant-like amphiphile that provides hydrophilic surface functionality to the fibres. The stiffness of the gels can be precisely tuned over the entire range that is typically associated with stem cell differentiation (0.1-40 kPa). 3We demonstrate that the gels can be used to direct stem cell differentiation without the need for induction media and they are therefore ideally suited to study stem cell behaviour -including as drug discovery platforms. To achieve this, we study the cell's usage of biological small molecules, metabolites, during differentiation and select bioactive metabolites that can target bone and cartilage formation specifically. This new use of designed supramolecular biomaterials can be envisaged to remove serendipity from discovery of metabolites associated with biological processes as drug candidates. Introduction.

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Section: Discussionmentioning

confidence: 99%

Tunable Supramolecular Hydrogels for Selection of Lineage-Guiding Metabolites in Stem Cell Cultures

Alakpa

Jayawarna

Lampel

et al. 2016

Chem

183

195

View full text Add to dashboard Cite

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“…The most useful study is that from the Stanmore group, by Nawaz et al, 80 because this study is the largest, is of good quality and reports UK practice, albeit from a centre of excellence. The Nawaz paper 80 reports results in 827 patients, which allows for very useful subgroup analysis.…”

Section: Results Of Autologous Chondrocyte Implantationmentioning

confidence: 99%

“…The Nawaz paper 80 reports results in 827 patients, which allows for very useful subgroup analysis. Mean age at baseline was 34 years, range 14-56 years.…”

Section: Results Of Autologous Chondrocyte Implantationmentioning

confidence: 99%

“…Failure was defined as requiring reoperation, somewhat stricter than in the Minas study. 75 One of the largest series of patients having ACI was reported by Nawaz et al from Stanmore: 80 1000 patients had ACI (519 with MACI, the rest ACI-C and some ACI-P) from 1998 to 2008. 80 In 827 patients with full follow-up data (mean follow-up 6.2 years), graft survival was 78% at 5 years and 51% at 10 years.…”

Section: Autologous Chondrocyte Implantation After Previous Microfracmentioning

confidence: 99%

“…75 One of the largest series of patients having ACI was reported by Nawaz et al from Stanmore: 80 1000 patients had ACI (519 with MACI, the rest ACI-C and some ACI-P) from 1998 to 2008. 80 In 827 patients with full follow-up data (mean follow-up 6.2 years), graft survival was 78% at 5 years and 51% at 10 years. Failure of the graft was 4.7 times as likely in the 34% who had had previous procedures (MF, mosaicplasty and drilling -numbers of each not given).…”

Section: Autologous Chondrocyte Implantation After Previous Microfracmentioning

confidence: 99%

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

Mistry

Connock

Pink

et al. 2017

Health Technol Assess

204

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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Probing Multicellular Tissue Fusion of Cocultured Spheroids—A 3D‐Bioassembly Model

et al. 2021

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While decades of research have enriched the knowledge of how to grow cells into mature tissues, little is yet known about the next phase: fusing of these engineered tissues into larger functional structures. The specific effect of multicellular interfaces on tissue fusion remains largely unexplored. Here, a facile 3D-bioassembly platform is introduced to primarily study fusion of cartilage-cartilage interfaces using spheroids formed from human mesenchymal stromal cells (hMSCs) and articular chondrocytes (hACs). 3D-bioassembly of two adjacent hMSCs spheroids displays coordinated migration and noteworthy matrix deposition while the interface between two hAC tissues lacks both cells and type-II collagen. Cocultures contribute to increased phenotypic stability in the fusion region while close initial contact between hMSCs and hACs (mixed) yields superior hyaline differentiation over more distant, indirect cocultures. This reduced ability of potent hMSCs to fuse with mature hAC tissue further underlines the major clinical challenge that is integration. Together, this data offer the first proof of an in vitro 3D-model to reliably study lateral fusion mechanisms between multicellular spheroids and mature cartilage tissues. Ultimately, this high-throughput 3D-bioassembly model provides a bridge between understanding cellular differentiation and tissue fusion and offers the potential to probe fundamental biological mechanisms that underpin organogenesis.

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Autologous Chondrocyte Implantation in the Knee

Abstract: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Cited by 148 publications

References 21 publications

Tunable Supramolecular Hydrogels for Selection of Lineage-Guiding Metabolites in Stem Cell Cultures

Tunable Supramolecular Hydrogels for Selection of Lineage-Guiding Metabolites in Stem Cell Cultures

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

Probing Multicellular Tissue Fusion of Cocultured Spheroids—A 3D‐Bioassembly Model

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