Increased Chondrocytic Gene Expression Is Associated With Improved Repair Tissue Quality and Graft Survival in Patients After Autologous Chondrocyte Implantation

2019 ◽  
Vol 47 (12) ◽  
pp. 2919-2926 ◽  
Author(s):  
Jakob Ackermann ◽  
Gergo Merkely ◽  
Alexandre Barbieri Mestriner ◽  
Nehal Shah ◽  
Andreas H. Gomoll
Keyword(s):  
Gene Expression ◽  
Cell Viability ◽  
Graft Survival ◽  
Tissue Quality ◽  
Expression Ratio ◽  
Cell Identity ◽  
Repair Tissue ◽  
Identity Score ◽  
Autologous Chondrocyte

Background: Assays to quantitate the quality of autologous chondrocyte implants have recently become available. However, the correlation of the assay score with radiological and clinical outcomes has not been established. Purpose/Hypothesis: The purpose was to assess the influence of cell identity (chondrocyte/synoviocyte gene expression ratio) and viability on patient-reported outcome measures, graft survival, and repair tissue quality. It was hypothesized that greater cell product quality as assessed through an identity assay and cell viability is associated with superior outcomes after autologous chondrocyte implantation (ACI) for symptomatic cartilage defects. Study Design: Cohort study; Level of evidence, 3. Methods: Seventy-nine patients with a minimum follow-up of 2 years were included in this study. Of these, 67 patients were available for imaging assessment utilizing the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring system. Patients were assigned to groups either below or above the cohort’s mean based on their individual cell identity score and viability percentage. Results: Patients were predominantly female (57.7%) with a mean age of 30.0 ± 9.3 years. No differences were seen between Knee injury and Osteoarthritis Outcome Score, Lysholm, Tegner, or International Knee Documentation Committee Subjective Knee Evaluation Form within the viability and cell identity groups at a final follow-up of 3.8 ± 1.4 years after ACI ( P > .05). In a subset of patients, the mean MOCART score was 68.3 ± 15.6 at an average magnetic resonance imaging follow-up of 17.7 ± 9.56 months. Low cell identity was significantly associated with the degree of defect filling ( P = .025), integration of border zone ( P = .01), effusion ( P = .024), and ACI graft failure ( P = .002). Patients with above-average cell identity scores had a significantly higher survival rate at 5-year follow-up compared with patients with below-average scores (95.8% vs 64.7%; P = .013). Cell viability did not influence MOCART subscales or graft failure (all P > .05). Cell viability and identity showed no significant correlation with each other ( r = −0.045; P = .694). Conclusion: Cell identity was significantly correlated with structural repair quality and graft survival after second-generation ACI for symptomatic chondral lesions in the knee. While improved imaging outcome and higher graft survivorship were associated with a higher individual cell identity score indicating a higher chondrocyte/synoviocyte gene expression ratio in the final cell product, clinical outcome did not correlate with the identity score.

Arthroscopic Matrix-Encapsulated Autologous Chondrocyte Implantation: A Pilot Multicenter Investigation in Latin America

Cartilage ◽  
2020 ◽  
pp. 194760352091863
Author(s):  
Enrique Villalobos ◽  
Antonio Madrazo-Ibarra ◽  
Valentín Martínez ◽  
Anell Olivos-Meza ◽  
Cristina Velasquillo ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Cell Viability ◽  
Cartilage Repair ◽  
Autologous Chondrocyte Implantation ◽  
T2 Mapping ◽  
Second Look ◽  
Arthroscopic Evaluation ◽  
Chondrocyte Implantation ◽  
Autologous Chondrocyte

Objective. To evaluate minimum biosecurity parameters (MBP) for arthroscopic matrix-encapsulated autologous chondrocyte implantation (AMECI) based on patients’ clinical outcomes, magnetic resonance imaging (MRI) T2-mapping, Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and International Cartilage Repair Society (ICRS) second-look arthroscopic evaluation, laying the basis for a future multicenter study. Design. Pilot clinical study. We analyzed the logistics to perform AMECI to treat focal chondral lesions in different hospitals following strict biosecurity parameters related to tissue and construct transportation, chondrocyte isolation, and cell expansion. Patient progress was analyzed with patient-reported outcome measures, MRI T2-mapping, MOCART, and ICRS arthroscopic second-look evaluation. Results. Thirty-five lesions in 30 patients treated in 7 different hospitals were evaluated. Cell viability before implantation was >90%. Cell viability in construct remnants was 87% ± 11% at 24 hours, 75% ± 17.1% at 48 hours, and 60% ± 8% at 72 hours after implantation. Mean final follow-up was 37 months (12-72 months). Patients showed statistically significant improvement in all clinical scores and MOCART evaluations. MRI T2-mapping evaluation showed significant decrease in relaxation time from 61.2 ± 14.3 to 42.9 ± 7.2 ms ( P < 0.05). Arthroscopic second-look evaluation showed grade II “near normal” tissue in 83% of patients. Two treatment failures were documented. Conclusions. It was feasible to perform AMECI in 7 different institutions in a large metropolitan area following our biosecurity measures without any implant-related complication. Treated patients showed improvement in clinical, MRI T2-mapping, and MOCART scores, as well as a low failure rate and a favorable ICRS arthroscopic evaluation at a mid-term follow-up. Level of Evidence. 2b.

Prior Surgery Negatively Affects Cell Culture Identity in Patients Undergoing Autologous Chondrocyte Implantation

2020 ◽  
Vol 48 (3) ◽  
pp. 635-641
Author(s):  
Jakob Ackermann ◽  
Alexandre Barbieri Mestriner ◽  
Courtney VanArsdale ◽  
Andreas H. Gomoll
Keyword(s):  
Cell Viability ◽  
Surgical Procedures ◽  
Biopsy Specimen ◽  
Autologous Chondrocyte Implantation ◽  
Cell Identity ◽  
Specimen Weight ◽  
Chondrocyte Implantation ◽  
A Cell ◽  
Specific Factors ◽  
Autologous Chondrocyte

Background: Recently, a cell identity assay has been introduced to evaluate the identity of cultured chondrocytes before autologous chondrocyte implantation (ACI), which was shown to be associated with graft survival after ACI. Purpose: To identify the influence of several patient- and lesion-specific factors on cell identity and viability assays. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 187 patients with second-generation ACI were included in this study. Patient and lesion characteristics, cell viability, cell identity, and biopsy specimen weight were recorded for each patient. A binomial logistic regression model was utilized to determine patient-specific predictive factors for cell product quality. Results: The implanted ACI cell products showed a cell viability of 93% ± 2.4% (mean ± SD; range, 84-98) with an identity score of 5.8 ± 2.1 (range, –0.08 to 9.46). Patients with multiple previous surgical procedures on the index knee had significantly lower cell identity scores when compared with patients without previous surgery (odds ratio = 0.31; 95% CI, 0.16-0.59; P < .001). Patients without surgical history had significantly higher cell identity scores than patients with 1 and ≥2 previous surgical procedures on the index knee (6.32 vs 5.32 vs 5.05; P = .006 and P < .001, respectively). Cell viability was not predicted by any preoperative variable ( P > .05). Cell identity and viability were not associated with each other or with biopsy specimen weight ( P > .05). Conclusion: Cartilage biopsy specimens from patients with ≥1 previous surgical procedures resulted in implants with lower cell identity scores when compared with patients without previous operations. None of the other patient- or lesion-specific factors were correlated, specifically biopsy specimen weight.

Sporting Activity Is Reduced 11 Years After First-Generation Autologous Chondrocyte Implantation in the Knee Joint

2017 ◽  
Vol 45 (12) ◽  
pp. 2762-2773 ◽  
Author(s):  
Benjamin Erdle ◽  
Simon Herrmann ◽  
Stella Porichis ◽  
Markus Uhl ◽  
Nadir Ghanem ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Knee Joint ◽  
Autologous Chondrocyte Implantation ◽  
Repair Tissue ◽  
Sporting Activity ◽  
Chondrocyte Implantation ◽  
Sporting Activities ◽  
Autologous Chondrocyte

Background: Little is known about long-term sporting activity after periosteal autologous chondrocyte implantation (ACI-P) and its correlation to clinical, morphological, and ultrastructural cartilage characteristics on magnetic resonance imaging (MRI). Purpose: To evaluate long-term sporting activity after ACI-P and to correlate with clinical and MRI findings. Study Design: Case series; Level of evidence, 4. Methods: Patients who underwent ACI-P for isolated cartilage defects of the knee joint between 1997 and 2001 were analyzed for sporting ability for 3 different time points: lifetime until the onset of pain, the year before ACI-P, and 11 years (range, 9.0-13.4 years) postoperatively. Sporting activity was assessed and patients’ level of activity scaled using standardized questionnaires. MRI scans of the affected knee joint at follow-up were analyzed using the MOCART (magnetic resonance observation of cartilage repair tissue) score and T2 mapping. Results: Seventy of 86 patients (81% follow-up rate) consisting of 25 female and 45 male patients, with a mean age of 33.3 ± 10.2 years at the time of surgery, mean defect size of 6.5 ± 4.0 cm2, and 1.17 treated defects per patient, agreed to participate in the study at a mean 10.9 ± 1.1 years after ACI-P. Fifty-nine patients (69% of total; 84% of follow-up) agreed to MRI, allowing the complete evaluation of 71 transplant sites. Before the onset of symptoms (lifetime), 95.7% of patients played a mean 6.0 sporting activities at a competitive level. In the year before ACI-P, 81.4% of patients played a mean 3.4 sporting activities in 2.4 sessions during 5.4 hours per week at a recreational level. At follow-up, 82.9% of the patients played a mean 3.0 sporting activities in 1.8 sessions during 3.0 hours per week at a recreational level. In contrast to objective factors, 65.6% of the patients felt that their subjective sporting ability had improved or strongly improved after ACI-P, whereas 12.9% felt that their situation had declined or strongly declined, and 21.4% stated that their sporting ability had undergone no change because of surgery. Factors of sporting activity correlated significantly with clinical long-term outcomes. MRI analysis with a mean repair tissue T2 relaxation time of 35.2 milliseconds and mean MOCART score of 44.9 showed no conclusive significant correlation to sporting activity. Level of performance was the only sporting activity factor to show a weak correlation with subgroups of the MOCART score. Conclusion: The premorbid level of sporting and recreational activities cannot be achieved 11 years after ACI-P. The MRI results determined at this time point did not conclusively correlate with long-term sporting activity.

scholarly journals Prospective Long-term Follow-up of Autologous Chondrocyte Implantation With Periosteum Versus Matrix-Associated Autologous Chondrocyte Implantation: A Randomized Clinical Trial

2020 ◽  
Vol 48 (9) ◽  
pp. 2230-2241
Author(s):  
Alexander Barié ◽  
Patrizia Kruck ◽  
Reza Sorbi ◽  
Christoph Rehnitz ◽  
Doris Oberle ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Autologous Chondrocyte Implantation ◽  
Cartilage Defects ◽  
Repair Tissue ◽  
Sf 36 ◽  
Chondrocyte Implantation ◽  
Autologous Chondrocyte ◽  
Time Point

Background: Matrix-associated autologous chondrocyte implantation (MACI) is a further development of the original autologous chondrocyte implantation periosteal flap technique (ACI-P) for the treatment of articular cartilage defects. Purpose: We aimed to establish whether MACI or ACI-P provides superior long-term outcomes in terms of patient satisfaction, clinical assessment, and magnetic resonance imaging (MRI) evaluation. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: A total of 21 patients with cartilage defects at the femoral condyle were randomized to MACI (n = 11) or ACI-P (n = 10) between the years 2004 and 2006. Patients were assessed for subjective International Knee Documentation Committee (IKDC) score, Lysholm and Gillquist score, Tegner Activity Score, and 36-Item Short Form Health Survey (SF-36) preoperatively (T0), at 1 and 2 years postoperatively (T1, T2), and at the final follow-up 8 to 11 years after surgery (T3). Onset of osteoarthritis was determined using the Kellgren-Lawrence score and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and delayed gadolinium-enhanced MRI of cartilage was used to evaluate the cartilage. Adverse events were recorded to assess safety. Results: There were 16 patients (MACI, n = 9; ACI-P, n = 7) who were reassessed on average 9.6 years after surgery (76% follow-up rate). The Lysholm and Gillquist score improved in both groups after surgery and remained elevated but reached statistical significance only in ACI-P at T1 and T2. IKDC scores increased significantly at all postoperative evaluation time points in ACI-P. In MACI, IKDC scores showed a significant increase at T1 and T3 when compared with T0. In the majority of the patients (10/16; MACI, 5/9; ACI-P, 5/7) a complete defect filling was present at the final follow-up as shown by the MOCART score, and 1 patient in the ACI-P group displayed hypertrophy of the repair tissue, which represents 6% of the whole study group and 14.3% of the ACI-P group. Besides higher SF-36 vitality scores in ACI-P at T3, no significant differences were seen in clinical scores and MRI scores between the 2 methods at any time point. Revision rate was 33.3% in MACI and 28.6% in ACI-P at the last follow-up. Conclusion: Our long-term results suggest that first- and third-generation ACI methods are equally effective treatments for isolated full-thickness cartilage defects of the knee. With the number of participants available, no significant difference was noted between MACI and ACI-P at any time point. Interpretation of our data has to be performed with caution due to the small sample size, which was further limited by a loss to follow-up of 24%.

scholarly journals Biomechanical Changes of Repair Tissue after Autologous Chondrocyte Implantation at Long-Term Follow-Up

Cartilage ◽  
2020 ◽  
pp. 194760352092143
Author(s):  
Teemu Paatela ◽  
Anna Vasara ◽  
Heikki Nurmi ◽  
Hannu Kautiainen ◽  
Jukka S. Jurvelin ◽  
...  
Keyword(s):  
Cartilage Repair ◽  
Autologous Chondrocyte Implantation ◽  
Maturation Process ◽  
Tissue Stiffness ◽  
Repair Tissue ◽  
Long Term Follow Up ◽  
Chondrocyte Implantation ◽  
Autologous Chondrocyte

Objective. This study aims to describe biomechanical maturation process of repair tissue after cartilage repair with autologous chondrocyte implantation (ACI) at long-term follow-up. Design. After ACI, 40 patients underwent altogether 60 arthroscopic biomechanical measurements of the repair tissue at various time points during an up to 11-year follow-up period. Of these patients, 30 patients had full-thickness cartilage lesions and 10 had an osteochondritis dissecans (OCD) defect. The mean lesion area was 6.5 cm2 (SD 3.2). A relative indentation stiffness value for each individually measured lesion was calculated as a ratio of repair tissue and surrounding cartilage indentation value to enable interindividual comparison. Results. Repair tissue stiffness improved during approximately 5 years after surgery. Most of the increase in stiffness occurred during the first 2 years. The curvilinear correlation between relative stiffness values and the follow-up time was 0.31 (95% CI 0.07-0.52), P = 0.017. The interindividual variation of the stiffness was high. Lesion properties or demographic factors showed no significant correlation to biomechanical outcome. The overall postoperative average relative stiffness was 0.75 (SD 0.47). Conclusions. Our clinical study describes a biomechanical maturation process of cartilage repair that may continue even longer than expected. A substantial increase in tissue stiffness proceeds for the first two years postoperatively. Minor progression proceeds for even longer. In some repairs, the biomechanical result was equal to native cartilage, suggesting hyaline-type repair. The variation in biomechanical results suggests substantial inconsistency in the structural outcome following ACI.

scholarly journals Minimum 10 Year Clinical and Radiological Outcomes of a Randomized Controlled Trial Evaluating Accelerated Weight Bearing After Matrix-Induced Autologous Chondrocyte Implantation

2019 ◽  
Vol 7 (7_suppl5) ◽  
pp. 2325967119S0026
Author(s):  
Jay R. Ebert ◽  
Michael Fallon ◽  
Greg Janes ◽  
David Wood
Keyword(s):  
Magnetic Resonance ◽  
Clinical Outcomes ◽  
Autologous Chondrocyte Implantation ◽  
Weight Bearing ◽  
Repair Tissue ◽  
Randomized Controlled ◽  
Post Surgery ◽  
Chondrocyte Implantation ◽  
Autologous Chondrocyte

Objectives: Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging clinical outcomes in the treatment of symptomatic knee chondral defects. However, longer term results are still lacking and post-operative management has traditionally been conservative, with little available evidence on how best to progressively increase weight bearing (WB) and rehabilitation post-surgery. This study sought to investigate the longer term clinical and radiological outcomes following an accelerated (versus conservative) WB protocol after MACI. Methods: A randomized controlled study design was used to investigate outcomes in 70 patients who underwent MACI to the medial or lateral femoral condyle between November 2005 and November 2007, in conjunction with either an accelerated (AR, n=34, 8 weeks to full WB) or conservative (CR, n=36, 12 weeks to full WB) approach to post-operative WB rehabilitation. Patients were evaluated pre-surgery and at 3, 6, 12 and 24 months, as well as 5 years post-surgery. At minimum 10 year follow up (range 10.5-11.5 years), 60 patients (86%, AR=31, CR=29) were available for review. Clinical outcomes included the IKDC, KOOS, Lysholm, Cincinnati, Tegner, SF-36, Satisfaction, maximal isokinetic knee extensor and flexor strength and functional hop capacity. Limb Symmetry Indicies (LSIs) comparing the operated and non-operated limbs were calculated for strength and functional measures. High resolution magnetic resonance imaging (MRI) was undertaken to assess the quality and quantity of repair tissue as per the magnetic resonance observation of cartilage repair tissue (MOCART) scoring system. A combined MRI composite score was also evalauted. ANOVA investigated group differecnes over time. Results: While the AR group reported significantly less knee pain in the earlier post-operative timeline, no significant differences (p>0.05) were observed in patient demographics or injury/surgery characteristics between groups, nor clinical and MRI-based scores, at minimum 10 year post-operative follow up. All clinical scores across both groups significantly improved (p<0.001) to 5 years, maintained to 10 years. At minimum 10 years, no differences were observed in mean LSIs for maximal isokinetic knee extension strength (AR=96.8%, CR=97.9%), or the single (AR=95.5%, CR=98.9%) and triple hop (AR=96.7%, CR=99.6%) tests for distance. At a minimum 10 years 82.4% and 83.3% of patients in the AR and CR groups, respectively, demonstrated a good-excellent MRI composite score, while 79.4% and 83.3% demonstrated good-excellent tissue infill, as per the MOCART score. Graft failure was observed on MRI in 5 patients (8.3%, AR=2, CR=3) at 10 years post-surgery. At 10 years, 93.3% of patients were satisfied with MACI for relieving their pain, with 83.4% satisfied with their ability to participate in sport. Conclusion: MACI provided high levels of patient satisfaction and tissue durability beyond 10 years. The outcomes of this randomized trial demonstrate a safe and effective accelerated WB rehabilitation protocol, with improved early patient outcomes albeit comparable longer term results.

scholarly journals AUTOLOGOUS CHONDROCYTE IMPLANTATION IN BRAZIL

2020 ◽  
Vol 28 (3) ◽  
pp. 131-136
Author(s):  
PEDRO NOGUEIRA GIGLIO ◽  
NELSON FORESTO LIZIER ◽  
DÉBORA LEVY ◽  
MARCEL FARACO SOBRADO ◽  
RICCARDO GOMES GOBBI ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Cell Viability ◽  
Repeated Measures ◽  
Autologous Chondrocyte Implantation ◽  
Collagen Membrane ◽  
Resonance Imaging ◽  
Chondrocyte Implantation ◽  
Autologous Chondrocyte

ABSTRACT Objective: To describe the first series of cases of autologous chondrocyte implantation (ACI) in collagen membrane performed in Brazil. Methods: ACI was performed in 12 knees of 11 patients, aged 32.1 ± 10.9 years, with 5.3 ± 2.6 cm2 full-thickness knee cartilage lesions, with a six-month minimum follow-up. Two surgical procedures were performed: arthroscopic cartilage biopsy for isolation and expansion of chondrocytes, which were seeded onto collagen membrane and implanted in the lesion site; the characterization of cultured cells and implant was performed using immunofluorescence for type II collagen (COL2) for cell viability and electron microscopy of the implant. Clinical safety, KOOS and IKDC scores and magnetic resonance imaging were evaluated. We used repeated-measures ANOVA and post-hoc comparisons at α = 5%. Results: COL2 was identified in the cellular cytoplasm, cell viability was higher than 95% and adequate distribution and cell adhesion were found in the membrane. The median follow-up was 10.9 months (7 to 19). We had two cases of arthrofibrosis, one of graft hypertrophy and one of superficial infection as complications, but none compromising clinical improvement. KOOS and IKDC ranged from 71.2 ± 11.44 and 50.72 ± 14.10, in preoperative period, to 85.0 ± 4.4 and 70.5 ± 8.0, at 6 months (p = 0.007 and 0.005). MRI showed regenerated tissue compatible with hyaline cartilage. Conclusion: ACI in collagen membrane was feasible and safe in a short-term follow-up, presenting regenerated formation visualized by magnetic resonance imaging and improved clinical function. Level of evidence IV, Case series.

Gene Expression Assay in the Management of Early Breast Cancer

2020 ◽  
Vol 27 (17) ◽  
pp. 2826-2839 ◽  
Author(s):  
Roberta Caputo ◽  
Daniela Cianniello ◽  
Antonio Giordano ◽  
Michela Piezzo ◽  
Maria Riemma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Decision Making ◽  
Adjuvant Chemotherapy ◽  
Early Breast Cancer ◽  
Treatment Decision ◽  
Endocrine Treatment ◽  
Expression Ratio ◽  
Treatment Decision Making ◽  
Low Sensitivity

The addition of adjuvant chemotherapy to hormonal therapy is often considered questionable in patients with estrogen receptor-positive early breast cancer. Low risk of disease relapse after endocrine treatment alone and/or a low sensitivity to chemotherapy are reasons behind not all patients benefit from chemotherapy. Most of the patients could be exposed to unnecessary treatment- related adverse events and health care costs when treatment decision-making is based only on classical clinical histological features. Gene expression profile has been developed to refine physician’s decision-making process and to tailor personalized treatment to patients. In particular, these tests are designed to spare patients the side effects of unnecessary treatment, and ensure that adjuvant chemotherapy is correctly recommended to patients with early breast cancer. In this review, we will discuss the main diagnostic tests and their potential clinical applications (Oncotype DX, MammaPrint, PAM50/Prosigna, EndoPredict, MapQuant Dx, IHC4, and Theros-Breast Cancer Gene Expression Ratio Assay).

scholarly journals A Novel Method Facilitating the Simple and Low-Cost Preparation of Human Osteochondral Slice Explants for Large-Scale Native Tissue Analysis

2021 ◽  
Vol 22 (12) ◽  
pp. 6394
Author(s):  
Jacob Spinnen ◽  
Lennard K. Shopperly ◽  
Carsten Rendenbach ◽  
Anja A. Kühl ◽  
Ufuk Sentürk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Viability ◽  
Large Scale ◽  
Marker Gene ◽  
Cell Swelling ◽  
Tissue Cell ◽  
Joint Research ◽  
Sample Number ◽  
Tnf Α ◽  
Novel Method

For in vitro modeling of human joints, osteochondral explants represent an acceptable compromise between conventional cell culture and animal models. However, the scarcity of native human joint tissue poses a challenge for experiments requiring high numbers of samples and makes the method rather unsuitable for toxicity analyses and dosing studies. To scale their application, we developed a novel method that allows the preparation of up to 100 explant cultures from a single human sample with a simple setup. Explants were cultured for 21 days, stimulated with TNF-α or TGF-β3, and analyzed for cell viability, gene expression and histological changes. Tissue cell viability remained stable at >90% for three weeks. Proteoglycan levels and gene expression of COL2A1, ACAN and COMP were maintained for 14 days before decreasing. TNF-α and TGF-β3 caused dose-dependent changes in cartilage marker gene expression as early as 7 days. Histologically, cultures under TNF-α stimulation showed a 32% reduction in proteoglycans, detachment of collagen fibers and cell swelling after 7 days. In conclusion, thin osteochondral slice cultures behaved analogously to conventional punch explants despite cell stress exerted during fabrication. In pharmacological testing, both the shorter diffusion distance and the lack of need for serum in the culture suggest a positive effect on sensitivity. The ease of fabrication and the scalability of the sample number make this manufacturing method a promising platform for large-scale preclinical testing in joint research.

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