Cartilage lesions do not heal spontaneously and predispose to osteoarthritis. Functional cartilage tissues, engineered using autologous chondrocytes, have a therapeutic advantage over conventional cellular therapies in preclinical studies. Here, we tested whether ex vivo maturation of engineered grafts for cartilage repair leads to improved patient benefit. Using autologous nasal chondrocytes (NCs), we tested whether implantation of in vitro–matured NC-tissue-engineered cartilage (N-TEC) versus undifferentiated NC-cell-activated matrices (N-CAM) in focal cartilage lesions would result in a superior clinical outcome. The prospective, randomized, parallel, open-label phase-2 trial ( ClinicalTrials.gov , NCT02673905) enrolled 108 patients in five hospitals from four countries. Patients ranging in age from 30 to 46 years with full-thickness knee cartilage defects (size, 2.7 to 6.0 square centimeters) were equally randomized and treated with N-TEC or N-CAM. The primary preregistered outcome was the overall Knee Injury Osteoarthritis Outcome Score (KOOS) at 24 months. N-TEC, which underwent a longer NC culture time, was phenotypically, structurally, and functionally more like hyaline cartilage than N-CAM. The overall KOOS increased with clinical relevance in both groups compared with preoperative values. KOOS was higher at 24 months for N-TEC [85; interquartile range (IQR), 74 to 91] than for N-CAM (79; IQR, 65 to 85). N-TEC, but not N-CAM, was similarly effective in patients with larger defects or revision surgery. Radiologically, N-TEC resulted in a superior composition of both repair tissue and surrounding cartilage, whereas structural scores were similar. This trial validates the clinical efficacy of NC-based grafts for articular cartilage repair and supports the clinical relevance of engineering mature tissues, even for patients with more challenging cartilage defects.

Nasal chondrocytes (NCs) have a higher and more reproducible chondrogenic capacity than articular chondrocytes, and the engineered cartilage tissue they generate in vitro has been demonstrated to be safe in clinical applications. Here, we aimed at determining the feasibility for a single-stage application of NCs for cartilage regeneration under minimally invasive settings. In particular, we assessed whether NCs isolated using a short collagenase digestion protocol retain their potential to proliferate and chondro-differentiate within an injectable, swiftly cross-linked and matrix-metalloproteinase (MMP)-degradable polyethylene glycol (PEG) gel enriched with human platelet lysate (hPL). NC-hPL-PEG gels were additionally tested for their capacity to generate cartilage tissue in vivo and to integrate into cartilage/bone compartments of human osteochondral plugs upon ectopic subcutaneous implantation into nude mice. NCs isolated with a rapid protocol and embedded in PEG gels with hPL at low cell density were capable of efficiently proliferating and of generating tissue rich in glycosaminoglycans and collagen II. NC-hPL-PEG gels developed into hyaline-like cartilage tissues upon ectopic in vivo implantation and integrated with surrounding native cartilage and bone tissues. The delivery of NCs in PEG gels containing hPL is a feasible strategy for cartilage repair and now requires further validation in orthotopic in vivo models.

Background: Pediatric anterior cruciate ligament reconstruction (ACLR) in skeletally immature patients is still controversially debated, with several gaps in its literature. More information is needed about the role of concomitant meniscal injuries in postoperative outcomes and return to pre-injury sports level (RTS). Methods: Fifty skeletally immature patients who underwent ACLR were enrolled prospectively: 21 had meniscal injury additionally, and 29 did not. Patients were assessed with Tegner, Lysholm, Pedi-IKDC, and subjective knee value (SKV) scores presurgery and 6, 12, and 24 months postoperatively. The primary outcome was RTS at 24 months. Secondary outcomes were the 24-month clinical results and the mapping of prognostic factors to RTS in the meniscal injury group. Logistic regression model to estimate OR [95% CI], t test for parametric and Wilcoxon test for nonparametric variables (comparisons of 2 independent groups) were used, as well as t test or Wilcoxon test for paired data, according to the distribution of differences (postoperative-preoperative, paired groups) were used. Results: Out of 50 patients with a mean age of 13.2 years (range 9 to 16), the meniscal injury group had 67% RTS (12/18), and the isolated ACLR group had 75% RTS (18/24) after 24 months, which was not statistically significant, OR=0.67 [0.17 to 2.60], P=0.6. 24-month Lysholm scores were significantly higher in the isolated ACLR group (medians, 95.5 vs. 100.0, P=0.01). There was no significant difference between the groups of Tegner scores, Pedi-IKDC and SKV. No prognostic factors were found for worse RTS after meniscal injury. Conclusions: There is no difference in RTS 24 months after ACLR with or without meniscal injury in the skeletally immature patient. Level of Evidence: Level of evidence I—prospective, comparative cohort study.

Purpose: Trochlear dysplasia (TD) is a common malformation in adolescents, leading to anterior knee pain and instability. Surgical interventions such as trochleoplasty require precise planning to correct the trochlear groove. However, no standardized preoperative plan exists to guide surgeons in reshaping the femur. This study aims to generate patient-specific, pseudo-healthy MR images of the trochlear region that should theoretically align with the respective patient’s patella, potentially supporting the preoperative planning of trochleoplasty. Methods: We employ a wavelet diffusion model (WDM) to generate personalized pseudo-healthy, anatomically plausible MR scans of the trochlear region. We train our model using knee MR scans of healthy subjects. During inference, we mask out pathological regions around the patella in scans of patients affected by TD and replace them with their pseudo-healthy counterpart. An orthopedic surgeon measured the sulcus angle (SA), trochlear groove depth (TGD) and Déjour classification in MR scans before and after inpainting. The code is available at https://github.com/wehrlimi/Generate-Pseudo-Healthy-Knee-MRI. Results: The inpainting by our model significantly improves the SA, TGD and Déjour classification in a study with 49 knee MR scans. Conclusion: This study demonstrates the potential of WDMs in providing surgeons with patient-specific guidance. By offering anatomically plausible MR scans, the method could potentially enhance the precision and preoperative planning of trochleoplasty and pave the way to more minimally invasive surgeries.

Introduction Knee osteoarthritis often starts in the patellofemoral compartment of the knee and is diagnosed in about 39% of people with knee pain aged above 30 years. Patellofemoral osteoarthritis plays a crucial role in the reduction of quality of life and in the rise of healthcare costs. There is still no consensus for treatment recommendation for isolated patella-femoral osteoarthritis in clinical guidelines. Current therapeutic approaches are limited to pain management, alleviation of symptoms or total knee replacement. Nasal chondrocyte tissue-engineered cartilage (N-TEC) has already been successfully introduced in clinical studies phase I and II for the treatment of focal cartilage lesions and in pilot studies in osteoarthritis patients. Methods and analysis A randomised controlled trial involving 75 patients with patellofemoral osteoarthritis from nine different clinical centres in Switzerland, Germany and Croatia is being conducted to evaluate the effectiveness of N-TEC implantation compared with standard treatment with platelet-rich plasma (PRP). In the intervention group, an autologous nasal cartilage cell-derived graft is implanted into the cartilage defects of the patella and/or trochlea during an open surgical procedure. The control group receives three PRP injections at weekly intervals. The primary outcome is the mean Knee Injury and Osteoarthritis Outcome Score Pain Change from baseline to 24 months between groups. Secondary outcomes, including patients’ self-assessed questionnaires, X-ray and MRI scans, physiotherapeutic assessments and safety, will be assessed and compared between the intervention and control group. In addition, the study is complemented with a health-economic evaluation to establish the intervention’s value for money and impact on productivity in working-age individuals. The planned duration of the study is 4 years including baseline and follow-up measurements at 6, 12 and 24 months. Ethics and dissemination All centres involved in the implementation of the intervention have obtained approval from their respective competent ethics committees. This includes approval from the following ethics committees: Ethics Committees of North-Western and Central Switzerland (EKNZ): 2024–00075 (associated ethical committees: Cantonal Ethics Committee Bern, Cantonal Research Ethics Commission Geneva (CCER), Cantonal Ethics Committee Ticino, Cantonal Ethics Committee Zurich). The EKNZ covers several cantons in Switzerland, including Basel. The site in Lugano falls under the Cantonal Ethics Committee Ticino. Ethics Germany according to CTIS: 2023-508640-21-00 (Medicinal Ethical Commission of the Julius-Maximilians-University Wuerzburg, Ethical Commission of the Albert-Ludwigs-University Freiburg) and Central Ethical Committee Croatia, Republic of Croatia Ministry of Health: 2023-508640-21-00. The Swissmedic reference number is 701788. Prior to participation, all participants must have signed informed consent. Study information will be disseminated via hospital websites, newsletters and an open-access publication of the protocol. Results will be published in peer-reviewed journals, presented at national and international conferences and shared with the public. Trial registration number ClinicalTrials.gov Registration No.: NCT06163573; Registration number CTIS: 2023-508640-21-00.

Articular cartilage (AC) damage heals poorly and can progress to osteoarthritis. Implantation of AC fragments (Minced Cartilage Implantation, MCI) is a promising one-step repair technique but is constrained by the limited availability of healthy AC. In this study, we evaluated the feasibility of MCI using nasal septal cartilage (NSC) as an alternative source of hyaline tissue with strong regenerative capacity. NSC obtained from rhinoplasties was decontaminated using a novel protocol, minced with or without Poloxamer 188 (P188), embedded in collagen I gel (0.5 mL per sample), and cultured for 42 days in platelet-rich plasma (PRP)-supplemented medium. The decontamination procedure with a combination of antibiotics was effective and did not impair cell viability. Histology of the resulting constructs confirmed robust cellular outgrowth and matrix deposition. Tissues produced from NSC and fragmented with P188 contained more cartilaginous matrix than those from NSC fragmented without P188 and those from AC fragmented with P188. NSC fragments embedded in a 1 mL hydrogel, sufficient for clinically relevant defect volumes, also demonstrated strong outgrowth and satisfactory matrix formation. Overall, the developed protocol supports the use of NSC as a viable tissue source in gel-based, injectable MCI grafts for focal cartilage repair.