G. Merkely (Boston, US)
Brigham Women's Hospital, Harvard Medical School Department of Sport MedicinePresenter Of 4 Presentations
10.1.1 - Hypertension Increases Graft Failure Rate After Autologous Chondrocyte Implantation
Abstract
Purpose
Hypertension is the 3rd leading cause of disability worldwide, and a potential link between osteoarthritis and hypertension has been recently revealed. However, its effect on cartilage restoration is yet to be determined. Our aim was to examine whether patients with diagnosed hypertension have an increased risk of graft failure following cartilage repair with either autologous chondrocyte implantation (ACI) or osteochondral allograft transplantation (OCA).
Methods and Materials
Patients that underwent ACI or OCA transplantation between February 2009 and December 2016 by a single surgeon were included in this study. Inclusion criteria comprised: (1) patients with at least 2-years follow-up; (2) availability of information related to the living habits, including smoking; (3) availability of information related to the presence of hypertension, diabetes mellitus or hyperlipidemia. To identify potential independent risk factors of graft failure, univariate analysis was utilized and those factors which showed significance at a level of p<0.1 were entered in multivariant logistic regression models.
Results
Three-hundred and sixty-eight patients (209 ACI, 159 OCA) were included in our study. In the ACI group univariate screening identified older age (p=0.022), female gender (p=0.072), larger defect size (p=0.016), higher prevalence of hypertension (16.4% vs 4.1%; p=0.007) and smoking (21.3% vs 10.1%; p=0.046) as a predictor of graft failure. Following, multivariate logistic regression analysis revealed female gender (OR 1.02, p=0.048), defect size (OR 1.07, p=0.035) and hypertension (OR 3.73, p=0.023) as significant independent risk factors predicting graft failure after ACI. In the OCA group, baseline demographics and clinical characteristics were similar between the failure and successful group, and none of the included factors demonstrated to be a potential risk factor for graft failure.
Conclusion
Hypertension seems to be an independent predictor of graft failure after ACI but not after OCA transplantation. Consequently, OCA transplantation might be preferred for the treatment of symptomatic cartilage defects if patients present with hypertension.
18.4.4 - Cell Identity Assay Result May Correlate with Repair Tissue Quality and Graft Survival in Patients after Carticel
Abstract
Purpose
To assess the associations of cell identity (chondrocyte/synoviocyte gene expression ratio) and cell viability assays with patient-reported outcome measures (PROMs), graft survival and repair tissue quality.
Methods and Materials
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 MOCART scoring system. Patients were assigned to groups either below or above the cohort’s mean based on individual cell identity score or viability percentage. Detailed statistical analyses were performed to assess the correlation of cell product quality and clinical and imaging outcome, as well as graft survival.
Results
No differences were seen between PROMs within the viability and cell identity groups at a final follow-up of 3.8 ±1.4 years after ACI (p > 0.05). In a subset of patients, the mean MOCART score was 68.3 ±15.6 at an average MRI follow-up of 17.7 ±9.6 months. Cell identity score was statistically correlated with the degree of defect filling (p = 0.025), integration of border zone (p = 0.01), effusion (p = 0.024), and ACI graft survival (p = 0.002). Patients with cell identity scores above the mean (n = 41) had a statistically higher graft survival rate at 5-year follow-up compared to patients with scores below the mean (n = 38) (95.8% vs. 64.7%, p = 0.013). Cell viability did not correlate with MOCART subscales or graft survival (all, p > 0.05). Cell viability and identity showed no significant correlation with each other (r = -0.45; p = 0.694).
Conclusion
Improved repair tissue quality and higher graft survival was associated with a higher individual cell identity score indicating higher chondrocyte/synoviocyte gene expression ratio in the final cell product.
23.1.5 - Improved Osteochondral Allograft Preservation Using Cyclic Hydrostatic Pressure
Abstract
Purpose
Osteochondral allografts (OCA) are currently stored at 4˚C for an average of 24 days after procurement. Chondrocyte viability, believed to be a major determinant of graft performance, deteriorates after 2 weeks under such condition, especially in the superficial zone, and falls below acceptable levels ~28 days. Consequently, the improvement of OCA storage condition to extend chondrocyte viability is critical to potentially improve graft availability. We aimed to improve cell viability and matrix integrity of OCAs during storage by promoting mass transfer with cyclic hydrostatic pressure (HP).
Methods and Materials
Osteochondral (OC) explants (6x8 mm) from bovine humeral head were randomly assigned to one of 4 groups: freshly harvested; stored at 4°C on atmospheric pressure (AP), stored at 37°C on AP (95% humidity, 5% CO2); stored at 37°C on cyclic HP at 0-0.5 MPa, 0.5 Hz (95% humidity, 5% CO2) (Figure 1). Explants were stored for 7, 14, 21 days in Dulbecco's Modified Eagle's Medium and antibiotics. Chondrocyte viability and density were assessed using LIVE/DEAD® staining in the entire tissue section and in the superficial, middle, deep zones using Image J program. In addition, OC explants underwent histological (Safranin-O fast green; Hematoxylin and eosin) and immunohistological (Proliferating cell nuclear antigen (PCNA)) evaluation.
Results
Full-thickness chondrocyte viability was significantly higher at 14 and 21 days in the HP group at 37°C compared to 4°C or 37°C storage at AP alone. Specifically, chondrocyte viability in the superficial zone was markedly improved after HP was applied (Figure 2). A greater amount of sulfated glycosaminoglycan matrix and proliferating cells in 37°C HP group were observed in the superficial zone compared to other storage conditions at 21 days.
Conclusion
OCA stored with cyclic HP at 37˚C maintained higher chondrocyte viability and ECM accumulation than OCA stored at AP at 4˚C or 37˚C.
23.1.9 - Severe bone marrow edema following prior marrow stimulation technique is a predictor of autologous chondrocyte implantation failure.
Abstract
Purpose
Autologous chondrocyte implantation (ACI) is a well-established cartilage repair procedure, however, numerous studies have shown higher ACI graft failure rates after prior marrow stimulation techniques (MST). The purpose of this study was to identify which factors may predict decreased graft survival after ACI among patients who underwent prior MST. A secondary aim was to investigate the specificity of these predictors.
Methods and Materials
In this review of prospectively collected data, we analyzed 38 patients who had failed prior MST surgery and subsequently underwent collagen covered ACI (case group). We divided our patient case group to graft failure ACI (n=8, 21%) and successful ACI (n=30, 79%). Fourteen clinical variables were categorized and analyzed to determine predictors for failure of the ACI graft. Preoperative magnetic resonance imaging (MRI) was used to evaluate the severity of subchondral bone marrow edema (BME) graded from I–absent to IV–severe, the presence of subchondral cyst, hypertrophic sclerosis, and intralesional osteophyte. The effects of these MRI findings on the graft survivor were also investigated. Concurrently, a control group, without prior MST was matched to investigate the specificity of the previously determined predictor.
Results
In the case group, the presence of preoperative severe BME was significantly higher in patients with failed ACI as compared to patients with successful ACI (p<0.001). In the control group the presence of severe BME was not significantly different between the failure and successful group (p=0.747). ACI graft failure rate among patients with prior MST and preoperative grade IV BME was 83.7% at 5 years postoperatively resulting a significantly lower survival rate as compared to patients with prior MST and without severe BME (5-year graft failure rate=6.5%) (p < 0.001). Other parameters did not differ significantly.
Conclusion
The presence of grade IV BME after prior MST is a predictive factor for graft failure among patients who then underwent second-generation ACI.