Catalpol promotes articular cartilage repair by enhancing the recruitment of endogenous mesenchymal stem cells.

Articular cartilage defect is challenged by insufficient regenerative ability of cartilage. Catalpol (CA), the primary active component of Rehmanniae Radix, could exert protective effects against various diseases. However, the impact of CA on the treatment of articular cartilage injuries is still unclear. In this study, full-thickness articular cartilage defect was induced in a mouse model via surgery. The animals were intraperitoneally injected with CA for 4 or 8 weeks. According to the results of macroscopic observation, micro-computed tomography CT (µCT), histological and immunohistochemistry staining, CA treatment could promote mouse cartilage repair, resulting in cartilage regeneration, bone structure improvement and matrix anabolism. Specifically, an increase in the expression of CD90, the marker of mesenchymal stem cells (MSCs), in the cartilage was observed. In addition, we evaluated the migratory and chondrogenic effects of CA on MSCs. Different concentration of CA was added to C3H10 T1/2 cells. The results showed that CA enhanced cell migration and chondrogenesis without affecting proliferation. Collectively, our findings indicate that CA may be effective for the treatment of cartilage defects via stimulation of endogenous MSCs.

Association between knee magnetic resonance imaging markers and knee symptoms over 6-9 years in young adults.

OBJECTIVES: To describe associations between MRI markers with knee symptoms in young adults. METHODS: Knee symptoms were assessed using the WOMAC scale during the Childhood Determinants of Adult Health Knee Cartilage study (CDAH-knee; 2008-2010) and at the 6- to 9-year follow-up (CDAH-3; 2014-2019). Knee MRI scans obtained at baseline were assessed for morphological markers (cartilage volume, cartilage thickness, subchondral bone area) and structural abnormalities [cartilage defects and bone marrow lesions (BMLs)]. Univariable and multivariable (age, sex, BMI adjusted) zero-inflated Poisson (ZIP) regression models were used for analysis. RESULTS: The participants' mean age in CDAH-knee and CDAH-3 were 34.95 (s.d. 2.72) and 43.27 (s.d. 3.28) years, with 49% and 48% females, respectively. Cross-sectionally, there was a weak but significant negative association between medial femorotibial compartment (MFTC) [ratio of the mean (RoM) 0.99971084 (95% CI 0.9995525, 0.99986921), P < 0.001], lateral femorotibial compartment (LFTC) [RoM 0.99982602 (95% CI 0.99969915, 0.9999529), P = 0.007] and patellar cartilage volume [RoM 0.99981722 (95% CI 0.99965326, 0.9999811), P = 0.029] with knee symptoms. Similarly, there was a negative association between patellar cartilage volume [RoM 0.99975523 (95% CI 0.99961427, 0.99989621), P = 0.014], MFTC cartilage thickness [RoM 0.72090775 (95% CI 0.59481806, 0.87372596), P = 0.001] and knee symptoms assessed after 6-9 years. The total bone area was negatively associated with knee symptoms at baseline [RoM 0.9210485 (95% CI 0.8939677, 0.9489496), P < 0.001] and 6-9 years [RoM 0.9588811 (95% CI 0.9313379, 0.9872388), P = 0.005]. The cartilage defects and BMLs were associated with greater knee symptoms at baseline and 6-9 years. CONCLUSION: BMLs and cartilage defects were positively associated with knee symptoms, whereas cartilage volume and thickness at MFTC and total bone area were weakly and negatively associated with knee symptoms. These results suggest that the quantitative and semiquantitative MRI markers can be explored as a marker of clinical progression of OA in young adults.

A mathematical model of signalling molecule-mediated processes during regeneration of osteochondral defects after chondrocyte implantation.

Treating bone-cartilage defects is a fundamental clinical problem. The ability of damaged cartilage to self-repair is limited due to its avascularity. Left untreated, these defects can lead to osteoarthritis. Details of osteochondral defect repair are elusive, but animal models indicate healing occurs via an endochondral ossification-like process, similar to that in the growth plate. In the growth plate, the signalling molecules parathyroid hormone-related protein (PTHrP) and Indian Hedgehog (Ihh) form a feedback loop regulating chondrocyte hypertrophy, with Ihh inducing and PTHrP suppressing hypertrophy. To better understand this repair process and to explore the regulatory role of signalling molecules on the regeneration process, we formulate a reaction-diffusion mathematical model of osteochondral defect regeneration after chondrocyte implantation. The drivers of healing are assumed to be chondrocytes and osteoblasts, and their interaction via signalling molecules. We model cell proliferation, migration and chondrocyte hypertrophy, and matrix production and conversion, spatially and temporally. We further model nutrient and signalling molecule diffusion and their interaction with the cells. We consider the PTHrP-Ihh feedback loop as the backbone mechanisms but the model is flexible to incorporate extra signalling mechanisms if needed. Our mathematical model is able to represent repair of osteochondral defects, starting with cartilage formation throughout the defect. This is followed by chondrocyte hypertrophy, matrix calcification and bone formation deep inside the defect, while cartilage at the surface is maintained and eventually separated from the deeper bone by a thin layer of calcified cartilage. The complete process requires around 48 months. A key highlight of the model demonstrates that the PTHrP-Ihh loop alone is insufficient and an extra mechanism is required to initiate chondrocyte hypertrophy, represented by a critical cartilage density. A parameter sensitivity study reveals that the timing of the repair process crucially depends on parameters, such as the critical cartilage density, and those describing the actions of PTHrP to suppress hypertrophy, such as its diffusion coefficient, threshold concentration and degradation rate.

Outcomes of Osteochondral Allograft Transplantation for Femoral Head Cartilage Lesions: Minimum 2-Year Follow-Up.

BACKGROUND: The surgical management of large osteochondral lesions of the femoral head in young, active patients remains controversial. Fresh osteochondral allograft (OCA) transplantation can be a highly effective treatment for these lesions in some patients. This study investigated survivorship as well as clinical and radiographic outcomes after fresh OCA transplantation at a minimum 2-year follow-up (mean, 6.6 years; range, 0.6 to 13.7 years). METHODS: A retrospective review of 29 patients who underwent plug OCA transplantation for focal femoral head osteochondral lesions between 2008 and 2021 was performed. Patients were assessed clinically using the modified Harris Hip score (mHHS) preoperatively and at each follow-up visit. Postoperative radiographs were evaluated for graft integrity and osteoarthritis severity. Kaplan-Meier survivorship analyses with 95% confidence intervals (CIs) were performed for the endpoint of conversion to total hip arthroplasty (THA). RESULTS: Overall graft survivorship for included patients was 78.4% (95% CI: 62.9 to 93.9) and 62.7% (95% CI: 39.6 to 85.8) at 5 and 10 years, respectively. There were ten patients (34.5%) who underwent conversion to THA. There was a significant difference using the log-rank test between survival for patients who had a preoperative diagnosis of osteonecrosis (ON) versus those who had other diagnoses (P = .002). The ten-year survival for those who had ON was 41.8% (95% CI: 4.8 to 78.8), and the ten-year survival for diagnoses other than ON was 85.7% (95% CI: 59.8 to 100). The mean mHHS score improved significantly (P < .001) from 48.9 (19 to 84) preoperatively to 77.4 (35 to 100) at the final follow-up. There were twenty patients (69.0%) who had mHHS ≥ 70 at the latest follow-up. Arthritic progression, indicated by an increase in the Kellgren and Lawrence grade, occurred in 7 hips (26.9%). CONCLUSIONS: An OCA transplantation is a viable treatment option for osteochondral defects of the femoral head in young, active patients who have minimal preexisting joint deformity. It may delay the progression of arthritis and the need for THA. Patients who had a preoperative diagnosis of ON had worse clinical outcomes than those who had other diagnoses.

Atelocollagen-associated autologous chondrocyte implantation for the repair of large cartilage defects of the knee: Results at three to seven years.

BACKGROUND: Recently, various types of engineered autologous chondrocyte implantation (ACI) have been developed. Atelocollagen-associated ACI (A-ACI) is the only ACI procedure covered by Japanese Health Insurance since 2013. The indications of the A-ACI are traumatic cartilage defects and osteochondral dissecans (OCD) for knee joints. PURPOSE: To evaluate midterm clinical results after A-ACI for the treatment for full-thickness cartilage defects of the knee. METHODS: Thirteen consecutive patients who underwent A-ACI between 2014 and 2018 had been prospectively enrolled in this study. There were 11 men and 2 women with a mean age of 34 years at the time of surgery. The causes of the cartilage defect were trauma in 10 knees and OCD in 3 knees. The total number of lesions was 15, which were comprised of the medial femoral condyle in 5 knees, the lateral femoral condyle in 5 knees, and the femoral trochlea in 5 knees. The mean size of the lesion was 5.3 cm2. Each knee was clinically and radiologically evaluated preoperatively and postoperatively. RESULTS: The mean Lysholm score improved significantly from 74.0 points to 94.0 points (p = 0.008) and each subscale in Knee injury and Osteoarthritis Outcome Score improved significantly (p < 0.001) at the mean final follow-up period of 51 months (range, 36-84 months). The magnetic resonance observation of cartilage repair tissue 2.0 score at the mean follow-up of 38 months was significantly higher than that at 2 months postoperatively (p = 0.014). According to the International Cartilage Repair Society (ICRS) grading scale, 3 knees were graded as normal, 3 knees as nearly normal, and 1 knee as severely abnormal in second-look arthroscopic evaluation at a mean of 22 months (range, 8-41 months) after A-ACI. CONCLUSION: The present study showed a significant subjective and objective clinical improvement in the A-ACI for large cartilage defects of the knee at a mean follow-up of 51 months (range, 36-84 months).

Potency Assay Considerations for Cartilage Repair, Osteoarthritis and Use of Extracellular Vesicles.

Articular cartilage covers the ends of bones in synovial joints acting as a shock absorber that helps movement of bones. Damage of the articular cartilage needs treatment as it does not repair itself and the damage can progress to osteoarthritis. In osteoarthritis all the joint tissues are involved with characteristic progressive cartilage degradation and inflammation. Autologous chondrocyte implantation is a well-proven cell-based treatment for cartilage defects, but a main downside it that it requires two surgeries. Multipotent, aka mesenchymal stromal cell (MSC)-based cartilage repair has gained attention as it can be used as a one-step treatment. It is proposed that a combination of immunomodulatory and regenerative capacities make MSC attractive for the treatment of osteoarthritis. Furthermore, since part of the paracrine effects of MSCs are attributed to extracellular vesicles (EVs), small membrane enclosed particles secreted by cells, EVs are currently being widely investigated for their potential therapeutic effects. Although MSCs have entered clinical cartilage treatments and EVs are used in in vivo efficacy studies, not much attention has been given to determine their potency and to the development of potency assays. This chapter provides considerations and suggestions for the development of potency assays for the use of MSCs and MSC-EVs for the treatment of cartilage defects and osteoarthritis.

The role of mechano growth factor in chondrocytes and cartilage defects: a concise review.

Mechano growth factor (MGF), an isoform of insulin-like growth factor 1 (IGF-1), is recognized as a typical mechanically sensitive growth factor and has been shown to play an indispensable role in the skeletal system. In the joint cavity, MGF is highly expressed in chondrocytes, especially in the damaged cartilage tissue caused by trauma or degenerative diseases such as osteoarthritis (OA). Cartilage is an extremely important component of joints because it functions as a shock absorber and load distributer at the weight-bearing interfaces in the joint cavity, but it can hardly be repaired once injured due to its lack of blood vessels, lymphatic vessels, and nerves. MGF has been proven to play an important role in chondrocyte behaviors, including cell proliferation, migration, differentiation, inflammatory reactions and apoptosis, in and around the injury site. Moreover, under the normalized mechanical microenvironment in the joint cavity, MGF can sense and respond to mechanical stimuli, regulate chondrocyte activity, and maintain the homeostasis of cartilage tissue. Recent reports continue to explain its effects on various cell types and sport-related tissues, but its role in cartilage development, homeostasis and disease occurrence is still controversial, and its internal biological mechanism is still elusive. In this review, we summarize recent discoveries on the role of MGF in chondrocytes and cartilage defects, including tissue repair at the macroscopic level and chondrocyte activities at the microcosmic level, and discuss the current state of research and potential gaps in knowledge.

Chitosan based scaffold applied in patellar cartilage lesions showed positive clinical and MRI results at minimum 2 years of follow up.

PURPOSE: New scaffold-based cartilage regeneration techniques have been developed to improve the results of microfractures also in complex locations like the patello-femoral joint. The aim of this study was to analyse the results obtained in patellar lesions treated with a bioscaffold,  a mixture composed by a chitosan solution, a buffer, and the patient's whole blood  which forms a stable clot into the lesion. METHODS: Fifteen patients with ICRS grade 3-4 cartilage lesions of the patellar surface were treated with a chitosan bioscaffold. Fourteen patients were clinically and radiologically evaluated prospectively for a minimum follow-up of 2 years with IKDC, KOOS, Tegner score, and MRI. The mean age of patients at the time of surgery was 31.8 ± 11.9 and nine patients presented degenerative aetiology, four patients with previous trauma, and 1 patient with osteochondritis dissecans.  RESULTS: The IKDC subjective score improved from 46.2 ± 19.3 preoperatively to 69.5 ± 20.3 (p < 0.05) and 74.1 ± 23.2 (p < 0.05) at 12 and 24 months, respectively. Also KOOS Pain, KOOS Sport/Rec and KOOS QOL showed a significant improvement from baseline to 12 months and to the final follow-up. MRI evaluation showed a complete filling of the cartilage defect at the final follow-up in 70% of the lesions, obtaining a total MOCART 2.0 score of 71.5 ± 13.6 at 24 months after surgery. CONCLUSION: Chondral patellar lesions represent a complex pathology, with lower results compared to other sites. This bioscaffold represents a safe surgical treatment providing a significant clinical improvement at 24 months in the treatment of patellar cartilage lesions. LEVEL OF EVIDENCE: IV.

Preoperative patellar bone marrow lesions with full thickness cartilage defects correlate with residual anterior knee pain in total knee arthroplasty without patellar resurfacing.

PURPOSE: Residual anterior knee pain is one of the most common problems after total knee arthroplasty (TKA). However, the contributing factors affecting postoperative anterior knee pain (AKP) remain poorly understood. This study aimed to evaluate the effect of preoperative patellar bone marrow lesions (BMLs) and patellar cartilage defects on postoperative AKP after patellar non-resurfacing TKA. METHODS: This retrospective study included 336 patients who underwent unilateral TKA without patella resurfacing. All patients underwent preoperative magnetic resonance imaging (MRI) to assess the presence of BMLs and the degree of cartilage defects in the patella. Patients were categorized into four groups according to the presence of BMLs (with or without BMLs) and the degree of cartilage defects (with or without full thickness cartilage defects). The Kujala Anterior Knee Pain Scale (AKPS) and the Hospital for Special Surgery Knee Rating Scale (HSS) scores at 2 years after TKA were compared among the groups. RESULTS: Preoperative BMLs in the patella were found in 132 (39.3%) of 336 cases. Among the four groups, the group with both BMLs and full-thickness cartilage defects demonstrated significantly lower AKPS compared to the other groups at 2 years after TKA (p < 0.01), but no significant difference was shown in the HSS scores, between these groups. There were no significant differences in either AKPS or HSS scores among the other three patient groups. CONCLUSIONS: The presence of preoperative BMLs with full-thickness cartilage defects in the patella was associated with worse postoperative AKP after TKA without patella resurfacing. Patella resurfacing should be considered in this patient group to minimize the risk of developing residual AKP after TKA. LEVEL OF EVIDENCE: III.

Sustained superiority in KOOS subscores after matrix-associated chondrocyte implantation using spheroids compared to microfracture.

PURPOSE: To evaluate the safety and efficacy of matrix-associated autologous chondrocyte implantation (ACI) using spheroids in comparison to arthroscopic microfracture for the treatment of symptomatic cartilage defects of the knee. METHODS: In a prospective multicenter-controlled trial, patients aged between 18 and 50 years, with single symptomatic focal cartilage defects between 1 and 4 cm2 (mean 2.6 ± 0.8, median 2.75, range 1.44-5.00) in the knee were randomized to treatment with ACI with spheroids (n = 52) or microfracture (n = 50). Primary clinical outcome was assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Analyses were performed in a defined hierarchical manner where outcomes of ACI were first compared to baseline values followed by a comparison to the microfracture group with repeated-measures ANCOVA with a non-inferiority approach. Subgroup analyses were performed to investigate the influence of age and defect size on the overall KOOS. Secondary clinical outcomes were the magnetic resonance observation of cartilage repair tissue (MOCART), modified Lysholm score and International Knee Documentation Committee (IKDC) examination form. Safety data focused on adverse events. Here the 5 years results are presented at which there were 33 observed cases in the ACI group and 30 in the microfracture group. RESULTS: The overall KOOS and its five subscores were significantly improved compared to baseline for both the ACI and microfracture group. Non-inferiority of ACI to microfracture was confirmed for the overall KOOS and the subscores, while for the subscores activities of daily living, quality of life and sports and recreation of the threshold for superiority was passed. In the ACI group, a notably more rapid initial improvement of the KOOS was found at three months for the older age group compared to the younger age group and the microfracture group. No other differences were found based on age or defect size. In addition, clinical improvement was found for the MOCART, modified Lysholm and IKDC examination form both the ACI and microfracture group. No safety concern related to either treatment was observed. CONCLUSION: This study confirms the safety and efficacy of matrix-associated ACI with spheroids at a mid to long-term follow-up. Non-inferiority of ACI to microfracture was confirmed for the overall KOOS and all subscores, while superiority was reached for the subscores activities of daily living, quality of life and sports and recreation in the ACI group. This underlines the importance of ACI for the young and active patients. LEVEL OF EVIDENCE: I.

Rhinoplasty with Mortise-Tenon Cartilaginous Framework for Caudal Septal Cartilage Defects.

INTRODUCTION: Rhinoplasty for caudal septal cartilage defects is a challenge due to the difficulty of fixation of the grafts. OBJECTIVES: This study presents an approach for correcting defects in caudal septal cartilage with the costal cartilaginous framework using a mortise-tenon technique. METHODS: From May 2019 through May 2022, a retrospective analysis of patients with caudal septal cartilage defects underwent rhinoplasty using a mortise-tenon cartilaginous framework by a senior surgeon was performed. The surgical outcomes were evaluated both preoperatively and postoperatively. RESULTS: This study involved 17 patients, ranging in age from 27 to 58 years. There were 22.4 months of follow-up on average. There was no long-term or short-term complication observed. The aesthetic outcome of all cases was satisfactory. The mean score for the patients of the perceptions of improvement in their noses was 8.11. CONCLUSION: Correction of caudal septal cartilage defects with this costal cartilaginous framework using the mortise-tenon technique is feasible and effective. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Treatment of knee cartilage by cultured stem cells and three dimensional scaffold: a phase I/IIa clinical trial.

PURPOSE: Damage of the knee cartilage is a common condition manifesting itself mainly by pain and/or swelling that may substantially reduce the quality of life while ultimately leading to osteoarthritis in affected patients. Here, we aimed to evaluate the safety and efficacy of cultured autologous bone marrow mesenchymal stem cells (BM-MSCs) attached to the 3D Chondrotissue® scaffold by autologous blood plasma coagulation (BiCure® ortho MSCp) in the treatment of knee cartilage defects. METHODS: The primary endpoint of this phase I/IIa clinical trial was to evaluate the safety of the treatment. The secondary objective was to determine the short-to-medium-term therapeutic outcomes by standardized scoring questionnaires including Lysholm Knee Scoring Scale (Lysholm score), Knee Injury and Osteoarthritis Outcome Score (KOOS), and pain Visual Analogue Scale (VAS) systems and imaging (X-ray and magnetic resonance imaging, MRI). A total of six patients were included and followed for 12 months after the surgery. RESULTS: BiCure® ortho MSCp was well tolerated with no adverse events associated with the investigational medicinal product. Significant improvements were observed in Lysholm scores and KOOS while X-ray showed no deterioration of the arthritis and MRI revealed a persistent filling of the chondral defects by the implant. CONCLUSION: Overall, our data demonstrate the safety of the tested investigational medicinal product. The function of the treated knee improved within one year after surgery in all enrolled patients. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: EudraCT No.: 2018-004,067-31; October 18 2018.

Hypoxia Preconditioned Serum (HPS) Promotes Proliferation and Chondrogenic Phenotype of Chondrocytes In Vitro.

Autologous chondrocyte implantation (ACI) for the treatment of articular cartilage defects remains challenging in terms of maintaining chondrogenic phenotype during in vitro chondrocyte expansion. Growth factor supplementation has been found supportive in improving ACI outcomes by promoting chondrocyte redifferentiation. Here, we analysed the chondrogenic growth factor concentrations in the human blood-derived secretome of Hypoxia Preconditioned Serum (HPS) and assessed the effect of HPS-10% and HPS-40% on human articular chondrocytes from osteoarthritic cartilage at different time points compared to normal fresh serum (NS-10% and NS-40%) and FCS-10% culture conditions. In HPS, the concentrations of TGF-beta1, IGF-1, bFGF, PDGF-BB and G-CSF were found to be higher than in NS. Chondrocyte proliferation was promoted with higher doses of HPS (HPS-40% vs. HPS-10%) and longer stimulation (4 vs. 2 days) compared to FCS-10%. On day 4, immunostaining of the HPS-10%-treated chondrocytes showed increased levels of collagen type II compared to the other conditions. The promotion of the chondrogenic phenotype was validated with quantitative real-time PCR for the expression of collagen type II (COL2A1), collagen type I (COL1A1), SOX9 and matrix metalloproteinase 13 (MMP13). We demonstrated the highest differentiation index (COL2A1/COL1A1) in HPS-10%-treated chondrocytes on day 4. In parallel, the expression of differentiation marker SOX9 was elevated on day 4, with HPS-10% higher than NS-10/40% and FCS-10%. The expression of the cartilage remodelling marker MMP13 was comparable across all culture conditions. These findings implicate the potential of HPS-10% to improve conventional FCS-based ACI culture protocols by promoting the proliferation and chondrogenic phenotype of chondrocytes during in vitro expansion.

Hydrogel-based autologous chondrocyte implantation leads to subjective improvement levels comparable to scaffold based autologous chondrocyte implantation.

PURPOSE: Scaffold-based autologous chondrocyte implantation is a well-established treatment for cartilage defects in the knee joint. Hydrogel-based autologous chondrocyte implantation using an in situ polymerizable biomaterial is a relatively new treatment option for arthroscopic cartilage defects. It is therefore important to determine if there are significant differences in the outcomes. The aim of this study is to compare the outcomes (using subjective parameters) of hydrogel-based autologous chondrocyte implantation (NOVOCART® Inject) with the outcomes of scaffold based autologous chondrocyte Implantation (NOVOCART® 3D) using biphasic collagen scaffold. METHODS: The data of 50 patients, which were paired with 25 patients in each treatment group, was analyzed. The main parameters used for matching were gender, number of defects and localization. Both groups were compared based on Visual Analogue Scale (VAS) and subjective IKDC scores, both of which were examined pre-operatively and after 6, 12 and 24 months. RESULTS: Significant benefits in both VAS and IKDC scores after 2 years of follow-up in both groups were found. Comparing the groups, the results showed that in the hydrogel-based autologous chondrocyte implantation group, significant changes in IKDC scores are measurable after 6 months, while it takes 12 months until they are seen in the scaffold based autologous chondrocyte group. CONCLUSION: Hydrogel-based autologous chondrocyte and scaffold based autologous chondrocyte show comparable improvements and significant benefits to the patients' subjective well-being after a 2-year-follow-up. LEVEL OF EVIDENCE: III.

Good healing potential of patellar chondral defects after all-arthroscopic autologous chondrocyte implantation with spheroids: a second-look arthroscopic assessment.

PURPOSE: To report second-look arthroscopic assessment after all-arthroscopic autologous chondrocyte implantation (ACI) for articular cartilage defects at the patella. METHODS: A second-look arthroscopy after all-arthroscopic ACI using chondrospheres® (ACT3D) was performed in 30 patients with 30 full-thickness retropatellar cartilage defects. The mean time from ACI to second-look arthroscopy was 14.9 ± 16.3 (6-71) months. The quality of cartilage regeneration was evaluated by the International Cartilage-Repair Score (ICRS)-Cartilage Repair Assessment (CRA). RESULTS: Eleven lesions (36.7%) were classified as CRA grade I (normal) and 19 lesions (63.3%) as grade II (nearly normal). Concerning the degree of defect repair, 25 lesions (83.3%) were repaired up to the height of the surrounding articular retropatellar cartilage. Five lesions (16.7%) showed 75% repair of defect depth. The border zone was completely integrated into the surrounding articular cartilage shoulder in 28 lesions (93.3%) and demarcated within 1 mm in 2 lesions (6.7%). Macroscopically and by probing, 12 lesions (40%) had intact smooth surface, 17 lesions (56.7%) had fibrillated surface and 1 lesion (3.3%) had small, scattered fissures. A negative correlation was found between the overall repair assessment score and the defect size (r2 = - 0.430, p = 0.046) and between integration into border zone and defect size (r2 = - 0.340, p = 0.045). A positive correlation was found between macroscopic appearance and age (r2 = + 0.384, p = 0.036). CONCLUSIONS: All-arthroscopic ACI using chondrospheres® (ACT3D) for full-thickness retropatellar articular cartilage defects proved to be reproducible and reliable. The advantage of the procedure is that it is minimal invasive. Arthroscopic second-look demonstrated a high grade of normal or nearly normal cartilage regeneration. Although statistically significant differences were not observed, larger defect size and younger age may compromise the result of overall repair. LEVEL OF EVIDENCE: III.

Third generation autologous chondrocyte implantation is a good treatment option for athletic persons.

PURPOSE: Autologous chondrocyte implantation is an established method for the treatment of joint cartilage damage. However, to date it has not been established that autologous chondrocyte implantation is an appropriate procedure for cartilage defects therapy in athletic persons. The aim of this study is to analyze if third-generation autologous chondrocyte implantation is an appropriate treatment for athletic persons with full cartilage defect of the knee joints. METHODS: A total of 84 patients were treated with third-generation autologous chondrocyte implantation (NOVOCART® 3D). The mean follow-up time was 8 years (5-14). Sports activity was measured via UCLA Activity Score and Tegner Activity Scale before the onset of knee pain and postoperatively in an annual clinical evaluation. 41 athletic persons and 43 non-athletic persons (UCLA-Cut-off: 7; Tegner Activity Scale-Cut-off: 4) were analyzed. Patient reported outcomes were captured using IKDC subjective, KOOS, Lysholm score and VAS score on movement. RESULTS: Patient reported outcomes (IKDC, VAS at rest, VAS on movement) showed significant improvement (p < 0.001) postoperatively. Athletic persons demonstrated significantly better results than non-athletic persons in the analyzed outcome scores (IKDC: p < 0.01, KOOS: p < 0.01, Lysholm score: p < 0.01). 96.4% of the patients were able to return to sport and over 50% returned or surpassed their preinjury sports level. The remaining patients were downgraded by a median of two points on the UCLA- and 2.5 on the Tegner Activity Scale. A shift from high-impact sports to active events and moderate or mild activities was found. Furthermore, it was shown that preoperative UCLA score and Tegner Activity Scale correlated significantly with the patient reported outcome postoperatively. CONCLUSION: Autologous chondrocyte implantation is a suitable treatment option for athletic persons with full-thickness cartilage defects in the knee. The return to sports activity is possible, but includes a shift from high-impact sports to less strenuous activities.

Effect of the defect localization and size on the success of third-generation autologous chondrocyte implantation in the knee joint.

INTRODUCTION: Femoral and patellar cartilage defects with a defect size > 2.5 cm2 are a potential indication for an autologous chondrocyte implantation (ACI). However, the influence of the localization and the absolute and relative defect size on the clinical outcome has not yet been determined. The purpose of this study is to analyze the influence of the localization and the absolute and relative defect size on the clinical outcome after third-generation autologous chondrocyte implantation. METHODS: A total of 50 patients with cartilage defects of the knee were treated with third-generation autologous chondrocyte implantation (Novocart® 3D). A match paired analysis was performed of 25 treated femoral and 25 treated patella defects with a follow-up of three years. MRI data was used to do the manual segmentation of the cartilage layer throughout the knee joint. The defect size was determined by taking the defect size measured in the MRI in relation to the whole cartilage area. The clinical outcome was measured by the IKDC score and VAS pre-operatively and after six, 12, 24, and 36 months post-operatively. RESULTS: IKDC and VAS scores showed a significant improvement from the baseline in both groups. Femoral cartilage defects showed significantly superior clinical results in the analyzed scores compared to patellar defects. The femoral group improved IKDC from 33.9 (SD 18.1) pre-operatively to 71.5 (SD 17.4) after three years and the VAS from 6.9 (SD 2.9) pre-operatively to 2.4 (SD 2.5) after three years. In the patellar group, IKDC improved from 36.1 (SD 12.6) pre-operatively to 54.7 (SD 20.3) after three years and the VAS improved from 6.7 (SD 2.8) pre-operatively to 3.4 (SD 2.) after three years. Regarding the defect size, results showed that the same absolute defect size at med FC (4.8, range 2-15) and patella (4.6, range 2-12) has a significantly different share of the total cartilaginous size of the joint compartment (med FC: 6.7, range 1.2-13.9; pat: 18.9, range 4.0-47.0). However, there was no significant influence of the relative defect size on the clinical outcome in either patellar or femoral localization. CONCLUSION: Third-generation autologous chondrocyte implantation in ACI-treated femoral cartilage defects leads to a superior clinical outcome in a follow-up of three years compared with patellar defects. No significant influence of the defect size was found in either femoral or patellar cartilage defects.

Arthroscopic and open partial arthroplasty for the treatment of focal grade IV cartilage defects of the humeral head.

INTRODUCTION: Focal Outerbridge grade IV cartilage defects of the proximal humerus may lead to pain and an impaired shoulder function. In cases of failed operative or conservative treatment options such as intraarticular injections or arthroscopic microfracturing of the subchondral bone, partial arthroplasty of the humeral may restore the articular surface of the humeral head without altering the anatomy. This study evaluates mid-term results of open and arthroscopic partial resurfacing of the humeral head in the context of focal grade IV cartilage defects. METHODS: Eighteen patients (f = 3, m = 15, mean age = 57.7 years) out of 22 patients were available for follow-up after 65 (24-116) months. Thirteen patients were treated with a partial humeral head prosthesis in an open technique and five patients received a partial humeral head prosthesis in an arthroscopic technique. The patients were followed-up clinically using the Constant-Score, the ASES Score as well as the range of motion. Plain radiographs (anterior-posterior and axial view) were carried out for radiologic assessment. RESULTS: At follow-up the mean CS rated 79.5. The mean ASES Score was 85.8 points. Mean active forward flexion measured 163.8°, while mean active abduction was 160.0°. The average pain level on a visual analogue scale (VAS) made out 0.7 out of 10. Patients treated with an arthroscopically implanted prosthesis achieved a mean CS of 88.8 points and a mean ASES Score of 92.6 points. The patients with openly implanted prosthesis had a CS of 75.3 points and an ASES Score of 83 points. There were no intraoperative or immediate postoperative complications. Until the final follow-up one patient needed to be converted to total shoulder arthroplasty due to progressive glenohumeral osteoarthritis. Nine patients (50%) showed progressive glenohumeral osteoarthritis. Aseptic loosening of the implants was not observed. CONCLUSION: Partial arthroscopic or open arthroplasty of the humeral head is related to good functional results after mid-term follow-up. Resurfacing of the humeral head is a safe procedure without any implant-related complications. There is a risk for progression of glenohumeral osteoarthritis, which may require surgical revision with conversion to anatomic shoulder arthroplasty. LEVEL OF EVIDENCE: Level IV (retrospective study).

[Guidelines for the treatment of unicompartmental cartilage defects of the knee-Cartilage repair, osteotomy, mini-implant or arthroplasty?] / Leitfaden unikompartimenteller Gelenkknorpelschaden am Knie ­ Knorpelersatz, Osteotomie, Mini-Implantat oder Prothese?

The treatment of unicompartmental cartilage defects offers a large variety of therapeutic options. With help of an algorithm, decision-making for the most suitable treatment approach is supported. Correction of malalignment is key for successful treatment. Defect size, influencing factors such as "age" and prior treatments play an important role in choosing the most appropriate operative treatment option.

[Osteochondral lesions of the talus : Individualized approach based on established and innovative reconstruction techniques]. / Osteochondrale Läsionen des Talus : Individualisiertes Vorgehen mithilfe etablierter und innovativer Rekonstruktionsverfahren.

Osteochondral lesions (OCL) of the talus are defined as chondral damage with subchondral involvement. The traumatic etiology is important; in particular, sprains and fractures can lead to lesions of the articular surface and the subchondral plate. As a result, unstable lesions and subchondral cysts can trigger substantial persistent pain and functional impairments. A primary conservative treatment can be considered and is especially recommended in children and adolescents; however, return to previous sports activity and level is often not achieved. The principles of reconstructive surgical management include internal fixation of osteochondral fragments, bone marrow stimulation, autologous membrane-augmented chondrogenesis ± bone grafting, osteochondral transfer, retrograde techniques ± bone grafting, (matrix-associated) autologous chondrocyte implantation and autologous osteoperiosteal graft from the iliac crest. Additional surgical procedures for ankle stabilization and deformity correction should be considered if necessary.