Defect type, localization and marker gene expression determines early adverse events of matrix-associated autologous chondrocyte implantation

Angele, Peter; Fritz, J.; Albrecht, Dirk; Koh, Jason L.; Zellner, Johannes

doi:10.1016/s0020-1383(15)30012-7

Cited by 42 publications

(46 citation statements)

References 40 publications

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“…However, recent studies have revealed that ACI is not only being used for isolated, focal AC defects. In 34% to more than 60% of cases, ACI is also used for treating degenerative AC defects, as graded by the treating physician at the time of AC repair [ 264 , 265 ]. This is relevant for future clinical biomaterials that would utilize material stiffness as a cell-instructive stimulus, as those numbers raise the question whether material stiffness could also be used in a degenerative context.…”

Section: Discussionmentioning

confidence: 99%

Mechanotransduction and Stiffness-Sensing: Mechanisms and Opportunities to Control Multiple Molecular Aspects of Cell Phenotype as a Design Cornerstone of Cell-Instructive Biomaterials for Articular Cartilage Repair

Selig

Lauer

Hart

et al. 2020

IJMS

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Since material stiffness controls many cell functions, we reviewed the currently available knowledge on stiffness sensing and elucidated what is known in the context of clinical and experimental articular cartilage (AC) repair. Remarkably, no stiffness information on the various biomaterials for clinical AC repair was accessible. Using mRNA expression profiles and morphology as surrogate markers of stiffness-related effects, we deduced that the various clinically available biomaterials control chondrocyte (CH) phenotype well, but not to equal extents, and only in non-degenerative settings. Ample evidence demonstrates that multiple molecular aspects of CH and mesenchymal stromal cell (MSC) phenotype are susceptible to material stiffness, because proliferation, migration, lineage determination, shape, cytoskeletal properties, expression profiles, cell surface receptor composition, integrin subunit expression, and nuclear shape and composition of CHs and/or MSCs are stiffness-regulated. Moreover, material stiffness modulates MSC immuno-modulatory and angiogenic properties, transforming growth factor beta 1 (TGF-β1)-induced lineage determination, and CH re-differentiation/de-differentiation, collagen type II fragment production, and TGF-β1- and interleukin 1 beta (IL-1β)-induced changes in cell stiffness and traction force. We then integrated the available molecular signaling data into a stiffness-regulated CH phenotype model. Overall, we recommend using material stiffness for controlling cell phenotype, as this would be a promising design cornerstone for novel future-oriented, cell-instructive biomaterials for clinical high-quality AC repair tissue.

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Section: Discussionmentioning

confidence: 99%

Mechanotransduction and Stiffness-Sensing: Mechanisms and Opportunities to Control Multiple Molecular Aspects of Cell Phenotype as a Design Cornerstone of Cell-Instructive Biomaterials for Articular Cartilage Repair

Selig

Lauer

Hart

et al. 2020

IJMS

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“…A recent publication examining long-term follow-up (15 years) of OA patients treated with MACT, showed that there was a worsening of patient clinical scores (e.g., Tegner, EuroQol visual analog scale) with time and a great majority of patients (60%), either underwent re-operation or experienced clinical failure [7]. A reason for the poor clinical outcome is due to the inflammatory environment created, specifically the presence of the cytokine, interleukin-1β (IL-1β), correlated with poor MACT outcomes post-transplantation [5,8]. Due to the high proportion of degenerative cartilage lesions that require therapeutic intervention, regenerative options are required to overcome this challenging situation.…”

Section: Introductionmentioning

confidence: 99%

Physioxia Expanded Bone Marrow Derived Mesenchymal Stem Cells Have Improved Cartilage Repair in an Early Osteoarthritic Focal Defect Model

Pattappa

Krueckel

Schewior

et al. 2020

Biology

Self Cite

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Focal early osteoarthritis (OA) or degenerative lesions account for 60% of treated cartilage defects each year. The current cell-based regenerative treatments have an increased failure rate for treating degenerative lesions compared to traumatic defects. Mesenchymal stem cells (MSCs) are an alternative cell source for treating early OA defects, due to their greater chondrogenic potential, compared to early OA chondrocytes. Low oxygen tension or physioxia has been shown to enhance MSC chondrogenic matrix content and could improve functional outcomes of regenerative therapies. The present investigation sought to develop a focal early OA animal model to evaluate cartilage regeneration and hypothesized that physioxic MSCs improve in vivo cartilage repair in both, post-trauma and focal early OA defects. Using a rabbit model, a focal defect was created, that developed signs of focal early OA after six weeks. MSCs cultured under physioxia had significantly enhanced in vitro MSC chondrogenic GAG content under hyperoxia with or without the presence of interleukin-1β (IL-1β). In both post-traumatic and focal early OA defect models, physioxic MSC treatment demonstrated a significant improvement in cartilage repair score, compared to hyperoxic MSCs and respective control defects. Future investigations will seek to understand whether these results are replicated in large animal models and the underlying mechanisms involved in in vivo cartilage regeneration.

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“…At final follow-up, hypertrophy was noted via MRI in 16% and incomplete filling (>50%) in 20% of patients [39]. A large case series by Angele et al of 433 patients with mean 6.9 months follow-up (max 2.5 years) found an 8.5% re-operation rate, a 6% graft failure rate in patients with >12 months follow-up [45]. Finally, in a case series with 2 years follow-up, Niethammer noted that clinical outcomes at 2 years were worse for patients who returned to sport/physical activities at earlier than 12 months after surgery [46].…”

Section: Novocart 3dmentioning

confidence: 98%

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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Defect type, localization and marker gene expression determines early adverse events of matrix-associated autologous chondrocyte implantation

Cited by 42 publications

References 40 publications

Mechanotransduction and Stiffness-Sensing: Mechanisms and Opportunities to Control Multiple Molecular Aspects of Cell Phenotype as a Design Cornerstone of Cell-Instructive Biomaterials for Articular Cartilage Repair

Mechanotransduction and Stiffness-Sensing: Mechanisms and Opportunities to Control Multiple Molecular Aspects of Cell Phenotype as a Design Cornerstone of Cell-Instructive Biomaterials for Articular Cartilage Repair

Physioxia Expanded Bone Marrow Derived Mesenchymal Stem Cells Have Improved Cartilage Repair in an Early Osteoarthritic Focal Defect Model

Autologous Chondrocyte Implantation: Scaffold-Based Solutions

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