Autologous Oxygen-Releasing Nano-Biomimetic Scaffold with Chondrocytes Promotes Joint Repair After Trauma

Our study assesses the role of a scaffold constructed by co-culture of autologous oxygen-releasing biomimetic scaffold (AONS) and chondrocytes in joint repair after trauma. A composite scaffold structure was used and a scaffold constructed of AONS and chondrocytes was transplanted into SD rats to create models of patellar cartilage fracture and hip osteochondral fracture, respectively followed by analysis of cell proliferation by immunofluorescence method, osteogenesis-related gene expression by RT-PCR, chondrocytes apoptosis by TUNEL staining. The blank control group and AONS composite chondrocytes have significant differences in apoptosis and cell proliferation of two fracture types (P <0.05). The autologous oxygen-releasing nanometers at 4 and 8 weeks showed a significant difference in the number of PCNA and TUNEL cells between biomimetic scaffold and chondrocytes in two groups (P < 0.05). The AONS and chondrocytes were effective for two types of fractures at 1, 4 and 8 weeks. The expression of various markers of intrachondral osteogenesis was decreased and the markers of hip osteochondral fracture were increased significantly (P < 0.05). Joint recovery was better than patellar cartilage fractures. The AONS composite chondrocyte scaffold promotes repair of patellar cartilage fractures and hip osteochondral fractures with a better effect on hip osteochondral fractures.

Quantification of Sodium Relaxation Times and Concentrations as Surrogates of Proteoglycan Content of Patellar CARTILAGE at 3T MRI

Sodium MRI has the potential to depict cartilage health accurately, but synovial fluid can influence the estimation of sodium parameters of cartilage. Therefore, this study aimed to reduce the impact of synovial fluid to render the quantitative compositional analyses of cartilage tissue technically more robust. Two dedicated protocols were applied for determining sodium T1 and T2* relaxation times. For each protocol, data were acquired from 10 healthy volunteers and one patient with patellar cartilage damage. Data recorded with multiple repetition times for T1 measurement and multi-echo data acquired with an additional inversion recovery pulse for T2* measurement were analysed using biexponential models to differentiate longitudinal relaxation components of cartilage (T1,car) and synovial fluid (T1,syn), and short (T2s*) from long (T2l*) transversal relaxation components. Sodium relaxation times and concentration estimates in patellar cartilage were successfully determined: T1,car = 14.5 ± 0.7 ms; T1,syn = 37.9 ± 2.9 ms; c(T1-protocol) = 200 ± 48 mmol/L; T2s* = 0.4 ± 0.1 ms; T2l* = 12.6 ± 0.7 ms; c(T2*-protocol) = 215 ± 44 mmol/L for healthy volunteers. In conclusion, a robust determination of sodium relaxation times is possible at a clinical field strength of 3T to quantify sodium concentrations, which might be a valuable tool to determine cartilage health.

No patella resurfacing total knee arthroplasty leads to reduction in the thickness of patellar cartilage to less than half within 5 years: a quantitative longitudinal evaluation using MRI

Purpose Patellar resurfacing in total knee arthroplasty (TKA) remains controversial as recent meta-analyses have not shown its clear superiority; however, most authors recommend it because it is associated with less frequent anterior knee pain and need for reoperation. We aimed to clarify the changes in patellar cartilage thickness in no patellar resurfacing TKA using a ceramic femoral component on magnetic resonance imaging (MRI). Methods Between 2009 and 2014, 40 consecutive patients (59 knees) were included in this study. All patients underwent TKA using zirconia ceramic femoral implants without patellar resurfacing. Indications for no patellar resurfacing TKA were absence of anterior knee pain, patellar compression pain, and osteoarthritic changes in the patellofemoral joint on plain radiography. The mean postoperative follow-up duration was 81.5 months (range, 25–131 months). Clinical and radiological evaluations were performed preoperatively and 5 years after TKA. Patellar cartilage thickness was evaluated preoperatively and every year for 5 years after TKA using MRI T2-weighted imaging. The patellar cartilage was divided into three regions of interest: medial, central, and lateral. To standardise the variation in patellar thickness among patients, the percent cartilage thickness was calculated. Results The implant’s position was appropriate in all cases. Compared to preoperative scores, 5 years postoperatively, the Japanese Orthopedic Association score and Oxford knee score significantly improved from 52.1 to 84.7; mean tilting angle and congruence angle did not change significantly; mean lateral shift ratio significantly increased from 7.1% to 14.6%; cartilage thickness significantly decreased (P < 0.05); and the percentage cartilage thickness of the central, medial, and lateral cartilage zones gradually thinned to less than half. Four patients underwent conversion to patellar resurfacing due to anterior knee pain, without loosening the femoral and tibial implants. Conclusion The patellar cartilage thickness decreased to less than half its preoperative level within 5 years after no patellar resurfacing TKA; this would led to clinical problems and conversion to patellar resurfacing. Level of evidence Level III.

Patellar cartilage increase following ACL reconstruction with and without meniscal pathology: a two-year prospective MRI morphological study

Background Anterior cruciate ligament reconstruction (ACLR) together with concomitant meniscal injury are risk factors for the development of tibiofemoral (TF) osteoarthritis (OA), but the potential effect on the patellofemoral (PF) joint is unclear. The aim of this study was to: (i) investigate change in patellar cartilage morphology in individuals 2.5 to 4.5 years after ACLR with or without concomitant meniscal pathology and in healthy controls, and (ii) examine the association between baseline patellar cartilage defects and patellar cartilage volume change. Methods Thirty two isolated ACLR participants, 25 ACLR participants with combined meniscal pathology and nine healthy controls underwent knee magnetic resonance imaging (MRI) with 2-year intervals (baseline = 2.5 years post-ACLR). Patellar cartilage volume and cartilage defects were assessed from MRI using validated methods. Results Both ACLR groups showed patellar cartilage volume increased over 2 years (p < 0.05), and isolated ACLR group had greater annual percentage cartilage volume increase compared with controls (mean difference 3.6, 95% confidence interval (CI) 1.0, 6.3%, p = 0.008) and combined ACLR group (mean difference 2.2, 95% CI 0.2, 4.2%, p = 0.028). Patellar cartilage defects regressed in the isolated ACLR group over 2 years (p = 0.02; Z = − 2.33; r = 0.3). Baseline patellar cartilage defect score was positively associated with annual percentage cartilage volume increase (Regression coefficient B = 0.014; 95% CI 0.001, 0.027; p = 0.03) in the pooled ACLR participants. Conclusions Hypertrophic response was evident in the patellar cartilage of ACLR participants with and without meniscal pathology. Surprisingly, the increase in patellar cartilage volume was more pronounced in those with isolated ACLR. Although cartilage defects stabilised in the majority of ACLR participants, the severity of patellar cartilage defects at baseline influenced the magnitude of the cartilage hypertrophic response over the subsequent ~ 2 years.

Cost-Effectiveness of Particulated Juvenile Articular Cartilage Versus Matrix-Induced Autologous Chondrocyte Implantation for Patellar Chondral Lesions (176)

Objectives: Treatment options for articular cartilage lesions of the patella have evolved over the past several years due to the development of novel cell-based cartilage restoration techniques, including particulated juvenile allograft cartilage (PJAC) and matrix-induced autologous chondrocyte implantation (MACI). The objective of this study was to evaluate the cost -effectiveness of these modalities in the management of patellar cartilage defects. Methods: A Markov state-transition model was utilized to evaluate the cost-effectiveness of three strategies for patients with patellar chondral lesions: (1) nonoperative management, (2) PJAC, and (3) MACI. Probabilities, health utilities, and costs of surgical procedures and rehabilitation protocols were derived from institutional data and literature review. Effectiveness was assessed using quality-adjusted life-year (QALY). Cost-effectiveness was evaluated from societal and payer perspectives over a 15-year time horizon. The principal outcome measure was the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed on pertinent model parameters to assess their effect on base case conclusions. Results: From a societal perspective, nonoperative management, PJAC, and MACI cost $4,140, $52,683, and $83,073 respectively. Nonoperative management, PJAC, and MACI were associated with 4.91, 7.07, and 7.79 QALYs gained, respectively. Therefore, PJAC and MACI were cost-effective relative to nonoperative management (ICERs $22,527/QALY and $27,456/QALY, respectively; Figure 1). Although MACI was more cost-effective than PJAC in the base case, this was strongly sensitive to the estimated probabilities of full versus intermediate benefit following PJAC and MACI (Table 1). If the probabilities of full and intermediate benefit following PJAC were assumed to be the same as those following MACI (i.e., PJAC and MACI were equally effective), then PJAC dominated MACI by being cheaper and more effective. At a $100,000/QALY willingness-to-pay threshold, MACI, PJAC, and nonoperative management were the preferred strategies in 63%, 33%, and 4% of the Monte Carlo probabilistic sensitivity analyses, respectively (Figures 2 and 3). Similar results were seen from a payer perspective. Conclusions: In the management of symptomatic patellar cartilage defects, PJAC and MACI were both cost-effective compared to nonoperative treatment in the management of symptomatic patellar cartilage defects; however, MACI was the preferred strategy in our base-case analysis. The cost-effectiveness of PJAC compared to MACI depended heavily on the probability of achieving full versus intermediate benefit after PJAC and MACI.

Good clinical outcomes after patellar cartilage repair with no evidence for inferior results in complex cases with the need for additional patellofemoral realignment procedures: a systematic review

Purpose Focal, patellar cartilage defects are a challenging problem as most cases have an underlying multifactorial pathogenesis. This systematic review of current literature analysed clinical results after regenerative cartilage repair of the patella with a special focus on the assessment and treatment of existing patellofemoral malalignment. Methods A systematic review was conducted to identify articles reporting clinical results after cartilage regenerative surgeries of the patella using the PubMed and Scopus database. The extracted data included patient-reported outcome measures (PROMS) and whether cartilage repair was performed alone or in combination with concomitant surgeries of underlying patellofemoral co-pathologies. In cases of isolated cartilage repair, specific exclusion criteria regarding underlying co-pathologies were screened. In cases of concomitant surgeries, the type of surgeries and their specific indications were extracted. Results A total of 35 original articles were included out of which 27 (77%) were cohort studies with level IV evidence. The most frequently used technique for cartilage restoration of the patella was autologous chondrocyte implantation (ACI). Results after isolated cartilage repair alone were reported by 15 (43%) studies. Of those studies, 9 (60%) excluded patients with underlying patellofemoral malalignment a priori and 6 (40%) did not analyse underlying co-pathologies at all. Among the studies including combined surgeries, the most frequently reported concomitant procedures were release of the lateral retinaculum, reconstruction of the medial patellofemoral ligament (MPFL), and osteotomy of the tibial tubercle. In summary, these studies showed lower preoperative PROMS but similar final PROMS in comparison with the studies reporting on isolated cartilage repair. The most frequently used PROMS were the IKDC-, Lysholm- and the Modified Cincinnati Score. Conclusion This comprehensive literature review demonstrated good clinical outcomes after patellar cartilage repair with no evidence of minor results even in complex cases with the need for additional patellofemoral realignment procedures. However, a meaningful statistical comparison between isolated patellar cartilage repair and combined co-procedures is not possible due to very heterogeneous patient cohorts and a lack of analysis of specific subgroups in recent literature. Level of evidence Level IV.

Elastic, Dynamic Viscoelastic and Model-Derived Fibril-Reinforced Poroelastic Mechanical Properties of Normal and Osteoarthritic Human Femoral Condyle Cartilage

Osteoarthritis (OA) degrades articular cartilage and weakens its function. Modern fibril-reinforced poroelastic (FRPE) computational models can distinguish the mechanical properties of main cartilage constituents, namely collagen, proteoglycans, and fluid, thus, they can precisely characterize the complex mechanical behavior of the tissue. However, these properties are not known for human femoral condyle cartilage. Therefore, we aimed to characterize them from human subjects undergoing knee replacement and from deceased donors without known OA. Multi-step stress-relaxation measurements coupled with sample-specific finite element analyses were conducted to obtain the FRPE material properties. Samples were graded using OARSI scoring to determine the severity of histopathological cartilage degradation. The results suggest that alterations in the FRPE properties are not evident in the moderate stages of cartilage degradation (OARSI 2-3) as compared with normal tissue (OARSI 0-1). Drastic deterioration of the FRPE properties was observed in severely degraded cartilage (OARSI 4). We also found that the FRPE properties of femoral condyle cartilage related to the collagen network (initial fibril-network modulus) and proteoglycan matrix (non-fibrillar matrix modulus) were greater compared to tibial and patellar cartilage in OA. These findings may inform cartilage tissue-engineering efforts and help to improve the accuracy of cartilage representations in computational knee joint models.

Investigation of the relationship between trochlear morphology and medial patellar cartilage defect using magnetic resonance imaging

The aim of this study was to evaluate trochlear morphology in patients with medial patellar cartilage defects via magnetic resonance imaging (MRI). Three hundred patients who were diagnosed with grade 2, 3 and 4 medial patellar cartilage defect using MRI according to the International Cartilage Repair Society Classification System and 100 control subjects were evaluated. Trochlear morphology was evaluated based on lateral trochlear inclination (LTI), medial trochlear inclination (MTI), sulcus angle( SA), femoral lateral and medial condyle symmetry, trochlear facet asymmetry, and trochlear width on the axial MR images. The mean SA was significantly higher in the medial patellar cartilage defect group compared to the control group (p<.05). The LTI and MTI of the cartilage defect group were significantly lower than those of the control group (p<.05). With the decreasing LTI and MTI, there was an increase in medial patellar cartilage loss. LTI (r=-0.46) and MTI (r=-0.53) were moderately correlated with SA. There was no significant differences in femoral lateral and medial condyle symmetry, trochlear facet asymmetry, and trochlear width between groups with and without medial patellar cartilge defect (p > .05). A flattened medial trochlea is a risk factor for cartilage structural damage of the medial patellofemoral joint, and it plays a role in the development of a defect in the medial patellar cartilage. The medial patellar cartilage defect is associated with the flattened lateral trochlea.

POS0186 METABOLOMIC SIGNATURES FOR KNEE CARTILAGE VOLUME LOSS OVER 10 YEARS

Background:Osteoarthritis (OA) is the most common form of arthritis, and its impact is increasing year by year due to an aging population and lack of effective treatments. One of the main structural pathological changes of OA is the loss of articular cartilage. Tools that can predict cartilage loss would help identify people at high risk, thus preventing OA development.Objectives:Using a metabolomics approach, the current study aimed to identify serum metabolomic signatures for predicting the loss of knee cartilage volume over 10 years in a well-established community-based cohort - the Tasmania Older Adult Cohort (TASOAC).Methods:TASOAC is an on-going, prospective, population-based study of older adults who were randomly selected from the roll of electors in Southern Tasmania, Australia. Participants had a right knee magnetic resonance imaging (MRI) scan at baseline and a 10-year follow-up. Cartilage volume was measured in the medial, lateral, and patellar compartments and change in cartilage volume over 10 years was calculated as percentage change per year. Fasting serum samples collected at 2.6-year follow-up were metabolomically profiled using the TMIC Prime Metabolomics Profiling Assay which measures a total of 143 metabolites. 129 metabolite concentrations passed the quality control and the pairwise ratios of them as the proxies of enzymatic reaction were calculated. Linear regression models were used to test the association between each of the metabolite ratios and change in cartilage volume in each of the knee compartments with adjustment for age, sex, and body mass index (BMI). The significance was defined at a=3.0×10-6 to control multiple testing of 16,512 ratios with Bonferroni method.Results:A total of 344 participants (51% females) were included. The mean baseline age was 62.83±6.13 years and the mean BMI was 27.48±4.41 kg/m2. The average follow-up time was 10.84±0.66 years. Cartilage volume reduced by 1.34±0.72%, 1.06±0.58%, and 0.98±0.46% per year in the medial, lateral, and patellar compartments, respectively. Our data showed that an increased ratio of hexadecenoylcarnitine (C16:1) to tetradecanoylcarnitine (C14) was associated with a 0.12±0.02% per year reduction in patellar cartilage volume (p = 8.80×10-7). An increased ratio of hexadecenoylcarnitine (C16:1) to dodecanoylcarnitine (C12) was also associated with a 0.12±0.02% per year reduction in patellar cartilage volume (p = 2.66×10-6). While there were several metabolite ratios associated with cartilage volume loss in the medial and lateral compartments, none of them reached the predefined significance level.Conclusion:Our data suggested that alteration of fatty acid β-oxidation is involved in knee cartilage loss, especially in the patellar compartment, and the serum ratio of C16:1 to C14 and to C12 could be used to predict long-term patellar cartilage loss.Acknowledgements:We thank all the study participants who made the study possible. The original TASOAC study was supported by the National Health and Medical Research Council (NHMRC) and the current study was supported by the Canadian Institutes of Health Research (CIHR).Disclosure of Interests:None declared