Non-clinical assessment of lubrication and free radical scavenging of an innovative non-animal carboxymethyl chitosan biomaterial for viscosupplementation: An in-vitro and ex-vivo study.

OBJECTIVE: Lubrication and free radical scavenging are key features of biomaterials used for viscosupplementation (VS) of joints affected by osteoarthritis (OA). The objective of this study was to describe the non-clinical performance characterization of KiOmedine® CM-Chitosan, a non-animal carboxymethyl chitosan, in order to assess its intended action in VS and to compare it to existing viscosupplements based on crosslinked hyaluronan (HA) formulations. METHOD: The lubrication capacity of the tested viscosupplements (VS) was evaluated in-vitro and ex-vivo. In-vitro, the coefficient of friction (COF) was measured using a novel tribological system. Meanwhile, an ex-vivo biomechanical model in ovine hindlimbs was developed to assess the recovery of join mobility after an intra-articular (IA) injection. Free radical scavenging capacity of HA and KiOmedine® CM-Chitosan formulations was evaluated using the Trolox Equivalent Antioxidant Capacity (TEAC) assay. RESULTS: In the in-vitro tribological model, KiOmedine® CM-Chitosan showed high lubrication capacity with a significant COF reduction than crosslinked HA formulations. In the ex-vivo model, the lubrication effect of KiOmedine® CM-Chitosan following an IA injection in the injured knee was proven again by a COF reduction. The recovery of joint motion was optimal with an IA injection of 3 ml of KiOmedine® CM-Chitosan, which was significantly better than the crosslinked HA formulation at the same volume. In the in-vitro TEAC assay, KiOmedine® CM-Chitosan showed a significantly higher free radical scavenging capacity than HA formulations. CONCLUSION: Overall, the results provide a first insight into the mechanism of action in terms of lubrication and free radical scavenging for the use of KiOmedine® CM-Chitosan as a VS treatment of OA. KiOmedine® CM-Chitosan demonstrated a higher capacity to scavenge free radicals, and it showed a higher recovery of mobility after a knee lesion than crosslinked HA formulations. This difference could be explained by the difference in chemical structure between KiOmedine® CM-Chitosan and HA and their formulations.

Safety and efficacy of a carboxymethyl chitosan dermal injection device for the treatment of skin defects: a first-in-man, pilot, comparative, split-body study.

Injectable soft-tissue devices are increasingly used for improving skin defects and deficiencies related to ageing. To assess the safety and efficacy of KIO015, a new injectable soft-tissue device formulated with carboxymethyl chitosan for the intradermal treatment of skin defects associated with ageing. Twenty-two subjects (40-65 years) were randomized to receive injections in the neckline of KIO015 and a non-cross-linked HA-based device, and were followed for up to 10 months. Injection site reactions (ISRs) and adverse events (AEs) were documented. Skin improvement was assessed instrumentally and clinically. Skin biopsies at injection zones in the lower back were taken at Day 28 for histopathology and immunohistochemistry analyses, to further assess product performance. Histomorphometric analyses on rabbits and in vitro assessment of KIO015 antioxidant capacity were also conducted. KIO015 was very well tolerated. Only expected and transient ISRs were observed; mainly erythema and hematoma. No adverse local effects or foreign body granuloma were observed histologically. Both clinical and instrumental evaluations confirmed the performance of KIO015. The skin was firmer and more elastic. Skin hydration showed significant improvement three days after injection. KIO015 exhibited superior overall maintenance of skin hydration after 10 months as compared to HA. These clinical results were supported by in vitro trials and implantation tests in the rabbit. The results from this pilot study support the use of KIO015 as an innovative alternative to HA-based devices for intradermal treatment of skin disorders.