## 4 Discussion
This was manifested in improvements in knee flexion and extension angles, perceived pain, stiffness, functional capacity, and health-related quality of life. These clinical benefits observed after the cycles of mud therapy with artificially controlled maturation of peloids are at least as effective as those observed in previous studies with naturally matured peloids and the same application techniques at the same medicinal spa [42], as well as in other balneological interventions using local medicinal mud packs to evaluate similar parameters [44]. It is important to note that, given its comparable clinical effects, the controlled maturation of peloids may offer the balneotherapy industry not only greater control over production and composition, which would be less dependent on annual climatic variations, but also the opportunity to integrate the biological phase with additional components possessing potential therapeutic properties. In this context, Rosa, due to its natural anti-inflammatory properties in pain reduction [22], has been proposed as a therapeutic adjunct in chronic conditions, such as osteoarthritis (OA). However, although these properties have been explored using Rosa emulsions [23] or, more broadly, in food sciences [22; 26], to the best of our knowledge, this is the first study to evaluate the role of Rosa in balneotherapy with peloids or mud therapy. The addition of Rosa to the artificially matured peloid also resulted in improvements across all clinical variables assessed in this study, further confirming the effectiveness of this balneological intervention. Notably, only the OA patients receiving the peloid with the biological phase enriched with Rosa showed improvements in anxiety/stress as a dimension of health, suggesting a potential enhancement of the therapy for future studies and interventions in OA patients, which may also have a beneficial impact on their mental health. Once the safety of applying peloids containing Rosa has been established, with no allergic reactions or other visible side effects observed and considering that some of the effects attributed to Rosa are related to the immune system, we focused on evaluating its impact on the innate immune response. This is particularly relevant in OA patients, who exhibit a reduced phagocytic capacity of neutrophils [33]. Additionally, given that the hyperthermia-induced stress from the intervention could potentially lead to transient immunosuppression in elderly individuals, understanding these immune responses is crucial. Surprisingly, the results clearly indicate that while controlled mud therapy without Rosa intervention did not affect the percentage of neutrophils with phagocytic capacity and reduced those with oxygen-dependent microbicidal capacity, the controlled mud therapy with the Rosa-fortified peloid significantly stimulated both phagocytic and microbicidal capacities, enhancing the ability of elderly OA patients to combat pathogen challenges. This supports an additional benefit induced by the incorporation of Rosa into the biological phase, further demonstrating a novel beneficial effect of Rosa on the immune system when applied in pelotherapy. In conclusion, this pilot study demonstrates that mud therapy interventions using peloids artificially matured in a controlled environment and composition offer both industrial and clinical benefits in the context of balneological treatments for OA patients. In addition to the similar functional and symptomatic benefits, the main clinical relevance of incorporating Rosa into the biological phase of the peloid is that, in contrast to the peloid without Rosa, it enhances the innate immune response to pathogen challenges. This could potentially compensate, at least in part, for the deficiencies in immune response reported in elderly OA patients.