Effect of Autologous Ear Cartilage Micrografting in Knee Osteoarthritis

Overview

The goal of this clinical trial is to learn if a single injection of autologous cartilage micrografts suspension, obtained through processing with a specialized technology patient's own small piece of ear cartilage, can improve knee osteoarthritis in adult men and women aged 18-75 with confirmed moderate knee osteoarthritis. The main questions it aims to answer are: * Does a single intra-articular injection of autologous ear-cartilage micrografts improve patients' clinical symptoms and knee function over 12 months? * What percentage of patients experience improvement in their complaints following treatment? * Do MRI scans show measurable improvement in knee cartilage condition 6 months after treatment? * Do inflammatory cytokine levels (IL-1β, IL-1α, IL-6, TNF-α) in joint fluid and cartilage tissue correlate with treatment response?

Background and Rationale Knee osteoarthritis is among the most common orthopedic conditions, affecting an estimated 10-12% of the population. Left untreated, it tends to progress, leading to worsening degenerative joint changes and functional loss. Treatment remains difficult because articular cartilage has very limited natural regenerative capacity. Currently used approaches - arthroscopic debridement, radiofrequency chondroplasty, and hyaluronic acid injection - have inconsistent or unsatisfactory efficacy. This study reproduces a previously published treatment procedure using autologous cartilage micrografts sourced from the patient's own auricular (ear) cartilage, rather than from the knee joint itself or from cultured chondrocytes. Ear cartilage was selected as the donor tissue for three reasons: (1) elastic auricular cartilage has physical and biological properties closer to the hyaline cartilage found in the knee joint than other readily accessible cartilage sources; (2) the sampling procedure is simple and minimally invasive compared to harvesting from a weight-bearing joint; and (3) the perichondrial tissue surrounding ear cartilage contains a high density of chondroprogenitor cells responsible for regenerative processes. Study Design The research has two components conducted on the same patient cohort: a clinical component evaluating the treatment's effect on patients' symptoms and joint imaging, and a laboratory component measuring inflammatory cytokine concentrations in tissue and joint fluid samples collected during the same procedure. This is a single-arm interventional study; there is no placebo or active comparator, and no randomization or blinding, since every enrolled participant receives the identical intervention on one knee affected by osteoarthritis. Procedure Each participant is treated on a single, affected knee. The procedure begins with drainage and storage of synovial fluid from the affected knee, for two reasons: synovial fluid in patients with knee osteoarthritis is expected to carry a high concentration of inflammatory cytokines that may impede improvement or contribute to discomfort, and removing it prevents dilution of the cartilage micrograft suspension subsequently injected. Cartilage tissue is then harvested from the patient's own ear using a 2,5 mm dermatological punch - 3 biopsies maintaining a sterile field, under local anesthesia with lidocaine to ensure the harvesting is painless. The biopsies are placed inside a sterile medical disposable device class IIa (Rigeneracons RS) and 4 milliliters of sterile physiological saline are added to the harvested tissue. The device mechanically mills the cartilage into 80 microns micrografts thanks to Rigenera Technology - Mytocel MSK. This suspension is drawn into a syringe and delivered via a single anterolateral-approach injection directly into the synovial space of the osteoarthritic knee. The full procedure takes approximately 30 minutes and is considered as minimally invasive. Cytokine Sub-Study For the laboratory component, a small aliquot (100 microliters) of the harvested ear cartilage suspension is frozen and stored (initially at -20°C, then at -80°C) at the time of tissue collection, before the remainder is injected. The synovial fluid drained from the knee prior to injection is handled and stored the same way. Concentrations of four cytokines associated with inflammation - IL-1β, IL-1α, IL-6, and TNF-α - are measured in both sample types. These measurements generate an individual inflammatory profile for each participant at baseline, which is then considered when interpreting each patient's clinical outcomes, on the hypothesis that a patient's baseline inflammatory state may influence how well they respond to treatment. Basis for Expected Results A prior study using the same procedure and the same medical device reported successful interventions in all cases, with no wound-healing disorder or infection, no aesthetic deficit at the ear donor site, universal patient-reported pain relief and return to daily activity, significant improvement on clinical questionnaires, and an increase in lateral femoral condyle thickness on MRI performed at three years post-intervention. This study is designed to evaluate whether comparable outcomes are observed in the current knee osteoarthritis patient cohort. Data Handling Data collection and processing are conducted solely for research purposes. Samples are processed anonymously using a code number system. A single technical record is maintained per participant, documenting all data, facts, and events relevant to or potentially influencing the study outcome. Code sheets linking code numbers to personal identifying data are kept in a locked file and separated from experimental data. Data are handled confidentially and are not shared with third parties. After processing, participant data are aggregated so that individuals cannot be identified from published results. Statistical Analysis Outcome measures (KOOS subscales, including Pain and Symptoms/Stiffness; and Visual Analog Scale pain scores for current, worst, and best pain) were analyzed using repeated-measures ANOVA across five assessment timepoints (Baseline, Week 1, Month 3, Month 6, and Year 1) to test for an overall effect of visit/time. Mauchly's test of sphericity was applied to each outcome; where sphericity was violated, the Greenhouse-Geisser correction was used to adjust the degrees of freedom and significance values. Where the overall visit effect was significant, simple contrasts compared each follow-up timepoint (Week 1, Month 3, Month 6, Year 1) against Baseline, with effect sizes reported as Cohen's d for each pairwise comparison. Descriptive statistics (mean, standard deviation, standard error, coefficient of variation) were reported for each timepoint.