scholarly journals A tri-component knee plug for the 3rd generation of autologous chondrocyte implantation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lobat Tayebi ◽  
Zhanfeng Cui ◽  
Hua Ye

Abstract Here, we report a newly designed knee plug to be used in the 3rd generation of Autologous Chondrocyte Implantation (ACI) in order to heal the damaged knee cartilage. It is composed of three components: The first component (Bone Portion) is a 3D printed hard scaffold with large pores (~ 850 µm), made by hydroxyapatite and β-tricalcium phosphate to accommodate the bony parts underneath the knee cartilage. It is a cylinder with a diameter of 20 mm and height of 7.5 mm, with a slight dome shape on top. The plug also comprises a Cartilage Portion (component 2) which is a 3D printed gelatin/elastin/sodium-hyaluronate soft thick porous membrane with large pores to accommodate chondrocytes. Cartilage Portion is secured on top of the Bone Portion using mechanical interlocking by designing specific knobs in the 3D printed construct of the Cartilage Portion. The third component of the plug (Film) is a stitchable permeable membrane consisting of polycaprolactone (PCL) on top of the Cartilage Portion to facilitate sliding of the knee joint and to hold the entire plug in place while allowing nutrients delivery to the Cartilage Portion. The PCL Film is prepared using a combination of film casting and sacrificial material leaching with a pore size of 10 µm. It is surface modified to have specific affinity with the Cartilage Portion. The detailed design criteria and production process of this plug is presented in this report. Full in vitro analyses have been performed, which indicate the compatibility of the different components of the plug relative to their expected functions.

2019 ◽  
Vol 20 (7) ◽  
pp. 1545 ◽  
Author(s):  
Martin Sauerschnig ◽  
Markus Berninger ◽  
Theresa Kaltenhauser ◽  
Michael Plecko ◽  
Gabriele Wexel ◽  
...  

Cartilage defects represent an increasing pathology among active individuals that affects the ability to contribute to sports and daily life. Cell therapy, such as autologous chondrocyte implantation (ACI), is a widespread option to treat larger cartilage defects still lacking standardization of in vitro cell culture parameters. We hypothesize that mRNA expression of cytokines and proteases before and after ACI is influenced by in vitro parameters: cell-passage, cell-density and membrane-holding time. Knee joint articular chondrocytes, harvested from rabbits (n = 60), were cultured/processed under varying conditions: after three different cell-passages (P1, P3, and P5), cells were seeded on 3D collagen matrices (approximately 25 mm3) at three different densities (2 × 105/matrix, 1 × 106/matrix, and 3 × 106/matrix) combined with two different membrane-holding times (5 h and two weeks) prior autologous transplantation. Those combinations resulted in 18 different in vivo experimental groups. Two defects/knee/animal were created in the trochlear groove (defect dimension: ∅ 4 mm × 2 mm). Four identical cell-seeded matrices (CSM) were assembled and grouped in two pairs: One pair giving pre-operative in vitro data (CSM-i), the other pair was implanted in vivo and harvested 12 weeks post-implantation (CSM-e). CSMs were analyzed for TNF-α, IL-1β, MMP-1, and MMP-3 via qPCR. CSM-i showed higher expression of IL-1β, MMP-1, and MMP-3 compared to CSM-e. TNF-α expression was higher in CSM-e. Linearity between CSM-i and CSM-e values was found, except for TNF-α. IL-1β expression was higher in CSM-i at higher passage and longer membrane-holding time. IL-1β expression decreased with prolonged membrane-holding time in CSM-e. For TNF-α, the reverse was true. Lower cell-passages and lower membrane-holding time resulted in stronger TNF-α expression. Prolonged membrane-holding time resulted in increased MMP levels among CSM-i and CSM-e. Cellular density was of no significant effect. We demonstrated cytokine and MMP expression levels to be directly influenced by in vitro culture settings in ACI. Linearity of expression-patterns between CSM-i and CSM-e may predict ACI regeneration outcome in vivo. Cytokine/protease interaction within the regenerate tissue could be guided via adjusting in vitro culture parameters, of which membrane-holding time resulted the most relevant one.


2016 ◽  
Vol 34 (4) ◽  
pp. 658-665 ◽  
Author(s):  
Arnaud Clavé ◽  
Jean-François Potel ◽  
Elvire Servien ◽  
Philippe Neyret ◽  
Frédéric Dubrana ◽  
...  

2017 ◽  
Vol 41 (5) ◽  
pp. 991-998 ◽  
Author(s):  
Eva Johanna Kubosch ◽  
Emanuel Heidt ◽  
Philipp Niemeyer ◽  
Anke Bernstein ◽  
Norbert P. Südkamp ◽  
...  

2021 ◽  
Vol 34 (01) ◽  
pp. 039-046
Author(s):  
Nathan W. Skelley ◽  
Chad Kurtenbach ◽  
Kristofer Kimber ◽  
Bruce Piatt ◽  
Benjamin Noonan

AbstractThe return to play outcome is an important measure for orthopaedic sports medicine treatments. This variable is especially important when discussing cartilage treatments because there are many different cartilage options available to athletes with articular injuries and this population is particularly interested in the ability to return to activities. Although many outcome variables are considered in any surgical procedure, the return-to-sport variable is focused on an active population and can be tailored to that patient's sport-specific goals. In this article, we will review some of the most recent and up-to-date articles describing return-to-sport outcomes for various knee cartilage treatments. This article will focus on the most common current knee cartilage treatments including microfracture, autologous chondrocyte implantation, osteochondral autograft transplant, and osteochondral allograft transplantation.


2017 ◽  
Vol 46 (2) ◽  
pp. 431-440 ◽  
Author(s):  
Robert Ossendorff ◽  
Sibylle Grad ◽  
Martin J. Stoddart ◽  
Mauro Alini ◽  
Hagen Schmal ◽  
...  

Background: Autologous chondrocyte implantation (ACI) fails in up to 20% of cases. Advanced intra-articular degeneration paired with an inflammatory environment may be closely related to implantation failure. Certain cytokines have been identified to play a major role during early osteoarthritis. Purpose: To investigate the effects of tumor necrosis factor α (TNFα) and its potential inhibition by adalimumab on cartilage regeneration in an in vitro model of ACI. Study Design: Controlled laboratory study. Methods: Bovine articular chondrocytes were cultivated and transferred at passage 3 to fibrin-polyurethane scaffolds. Constructs were loaded by compression (10%-20% scaffold height) and shear (±25°) in a fully characterized multiaxial load (L) bioreactor to simulate clinical ACI or were subjected to free swelling (FS) conditions for a duration of 2 weeks. TNFα (20 ng/mL), adalimumab (10 µg/mL), or both were added to the medium. To assess the outcome, DNA, GAG (glycosaminoglycan), and total collagen were quantified, and gene expression of anabolic (collagen 2, aggrecan, cartilage oligomeric protein, proteoglycan 4), catabolic (matrix metalloproteinases [MMP] 3 and 13), dedifferentiation (collagen 1), and hypertrophy (collagen 10) markers and proinflammatory cytokines (TNFα, IL-1β) was analyzed. Histological evaluation was performed with safranin O/fast green, toluidine blue, and immunohistochemistry of collagen 1 and 2. Apoptosis was analyzed by immunolabeling of anti-active caspase 3. For statistical evaluation, nonparametric tests were chosen with a significance level of P < .05. Results: A general downregulation of anabolic and upregulation of catabolic markers was detected in the TNFα groups. Collagen 2 was suppressed by TNFα (FS, P = .029; L, P = .006), while MMP 3 was significantly upregulated (FS, P = .035; L, P = .001). Dynamic loading induced a chondrogenic response, which could not fully antagonize the effect of the cytokine. Adalimumab antagonized all effects of TNFα. The histological and immunohistochemical assessments demonstrated less matrix formation in the cytokine-only groups. TNFα induced apoptosis, and this effect was increased by loading. Conclusion: TNFα does negatively affect chondrogenesis under simulated ACI conditions. Both dynamic load and, more potentially, adalimumab showed the capability of antagonizing the negative effects. Clinical Relevance: Catabolic cytokine suppression (ie, TNFα inhibition) combined with compression and shear load may best meet the conditions for chondrogenesis in an osteoarthritic environment.


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