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

PLoS One. 2021 Oct 11;16(10):e0256770. doi: 10.1371/journal.pone.0256770. eCollection 2021.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / administration & dosage
  • Biocompatible Materials / pharmacology
  • Chitosan / administration & dosage
  • Chitosan / analogs & derivatives*
  • Chitosan / pharmacology
  • Free Radical Scavengers / administration & dosage
  • Free Radical Scavengers / pharmacology*
  • Injections, Intra-Articular
  • Knee Joint / drug effects
  • Sheep
  • Viscosupplementation
  • Viscosupplements / administration & dosage
  • Viscosupplements / pharmacology*

Substances

  • Biocompatible Materials
  • Free Radical Scavengers
  • Viscosupplements
  • carboxymethyl-chitosan
  • Chitosan

Grants and funding

This study was supported by the Research and Technological Innovation programs of Biowin and the Walloon Region in the framework of project n°7842 and project n°7360 supporting the innovative program of Kiomed, which provided financial support (service: realization of ex-vivo study) to Université Libre de Bruxelles (Bernado Innocenti) and OASIS (Jean-Michel Vandewerd & Fanny Hontoir). KiOmed Pharma provided support in the form of salaries for authors GR,SEG,PD,LH,MC. Jean-Michel Vandeweerd, Bernado Innocenti and Fanny Hontoir are paid consultants for KiOmed Pharma to perform ex-vivo study. The above funding organizations did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support to KiOmed Pharma (Research subsidies).