Biological Safety Evaluation of KiOmedine® CM-chitosan, an Innovative Non-animal Carboxymethyl-Chitosan Biomaterial Intended for Injectable Biomedical Applications

Abstract

When designing innovative biomaterials, biocompatibility is regarded as a prerequisite for safe clinical use in humans. In this study, the biological safety of KiOmedine® CM-chitosan, which is a non-animal carboxymethyl chitosan biomaterial, was evaluated using a large panel of both in vitro and in vivo biocompatibility tests in accordance with the ISO 10993 series. KiOmedine® CM-chitosan was non-cytotoxic and non-genotoxic in vitro. The biomaterial was neither found to be haemolytic nor was it able to potentiate the activation of the central complement component C5a or the inflammatory mediators IL-1β and IL-8 in the presence of human whole blood. Furthermore, no evidence of any significant irritation, sensitization, pyrogenicity, and organ toxicity was detected in specific animal studies conducted with KiOmedine® CM-chitosan, and only minimal local tissue effects were observed after the intra-articular or intra-dermal injection of KiOmedine® CM-chitosan in the rabbit model. KiOmedine® CM-chitosan had minimal potential to induce immunotoxic reactions in the mouse air pouch model. Its biodegradation process was appropriately characterized at the histological level. In summary, our study represents an unprecedented body of work supporting the biological safety evaluation of KiOmedine® CM-chitosan, allowing its use in injectable medical devices.

First-in-human Study to Evaluate a Single Injection of KiOmedine®CM-Chitosan for Treating Symptomatic Knee Osteoarthritis

“…No long-term onset of adverse events was reported at the end of the study. These treatment-related adverse events seem to be induced by a physiological macrophage reaction that is needed to degrade the CM-chitosan implant [9]. This reaction could be exacerbated in pre-reactivated synovial membrane (even in low-grade inflammation osteoarthritis patients) but responded well to conservative concomitant pain medication and had no impact on the clinical benefit.…”

“…It is a singleinjection treatment. A 3-mL volume of KiOmedine ® CM-Chitosan is suitable for intra-articular injection into the knee in order to provide synovial joint lubrication [9]. Compared to the cross-linked hyaluronan, KiOmedine ® CM-Chitosan has a higher lubrication capacity and a higher ability to fight against oxidative stress [10].…”