Recorded Adverse Events and Patient-Reported Outcomes After Intra-articular Extracellular-Vesicle Product Administration for Knee Osteoarthritis: A Retrospective Single-Practice Case Series.

Background Exosome-based products are being used for symptomatic knee osteoarthritis (OA), although human efficacy data remain limited and no extracellular vesicle product is approved by the United States Food and Drug Administration for intra-articular use. This study evaluated patient-reported outcomes, subsequent interventions, conversion to total knee arthroplasty (TKA), and recorded adverse events following intra-articular treatment. Objective The aim of the study was to compare pre-injection Knee injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) scores with scores obtained at six weeks and at the latest follow-up, and to document subsequent conversion to TKA. Study design This retrospective case series provides Level IV evidence. Methods Consecutive intra-articular knee treatments administered between December 2024 and August 2026 were retrospectively reviewed. Patients received either Patient Pure X (PPX™), an autologous platelet-derived extracellular-vesicle preparation, or DayZero™, an allogeneic perinatal tissue-derived extracellular-vesicle preparation manufactured by ZEO ScientifiX. For the primary patient-level analysis, one eligible index knee per patient was included to preserve independence of observations; laterality-ambiguous bilateral KOOS-JR observations were excluded from knee-specific patient-reported outcome analyses. Primary outcomes were paired changes in KOOS-JR from baseline to six weeks and latest follow-up. Secondary outcomes included subsequent nonsurgical interventions, subsequent TKA, and documented administration-related adverse events. Paired t-tests and Wilcoxon signed-rank tests were used. Results Fifty-one treated knees in 47 patients were included. Mean age was 75 years (range, 44-94 years); 28 patients were women, and 19 were men. In the primary patient-level analysis, 33 patients had complete, laterality-attributable paired baseline and six-week KOOS-JR data. Mean KOOS-JR increased from 60.0 to 78.5, a mean increase of 18.5 points (95% CI, 13.2-23.8; p<0.001); 30 of 33 patients (90.9%) had higher scores. At the latest follow-up, 36 patients had complete paired data; mean KOOS-JR increased from 60.6 to 77.4, a mean increase of 16.8 points (95% CI, 11.4-22.3; p<0.001), with 30 of 36 patients (83.3%) having higher scores. Three of 47 patients subsequently underwent TKA. No administration-related adverse events were documented in the available practice records; however, adverse-event ascertainment was retrospective. Conclusions In this retrospective single-practice case series, mean KOOS-JR was 18.5 points higher at six weeks than at baseline among 33 patients with complete, laterality-attributable paired data following intra-articular administration of extracellular-vesicle products. Later outcome assessments were limited by nonuniform follow-up and subsequent treatments. Three of 47 patients subsequently underwent TKA. No administration-related adverse events were documented in the available practice records; however, retrospective ascertainment and the limited sample size preclude conclusions regarding safety or tolerability. These descriptive findings do not establish efficacy, clinical importance, comparative effectiveness, structural disease modification, or long-term benefit. Prospective controlled studies using well-characterized products, standardized follow-up, prespecified management of subsequent interventions, and active adverse-event surveillance are warranted.