Foreign body response to alginate beads injected in the equine intercarpal joint

Abstract

Introduction - Osteoarthritis (OA) is the most important chronic musculoskeletal disorder in both humans and horses. OA is a major cause of early retirement in horses. During the whole process from initiation to the end stage of OA pain is experienced. Horses with OA can be treated systemically with anti- inflammatory and/or pain reducing pharmaceuticals. Intra-articular (IA) administration of corticosteroids, opioids and/or hyaluronic is used in modern-day equine veterinary practice. Treating horses IA repeatedly bears disadvantages and risks. The use of alginate beads as a slow-release carrier for pharmaceuticals or mesenchymal stem cells appears a promising new approach. This pilot study was designed to determine if alginate beads can be safely injected in an equine joint. The reaction along the study raised more questions on what happened in the joint as a reaction to the alginate beads. Materials and Methods - Three separate horses were selected for a pilot study. The protocols were adjusted after each horse, according to the clinical reaction of the horses to the IA administration of solely alginate beads. Sampling of synovial fluid and synovium took place for further investigation on presence of biomarkers and histology. IL-1β) and Tumor Necrosis Factor alfa (TNFα) were performed on sampled synovial fluid. Haematoxylin Eosin staining was done on synovium samples. An attempt was made to design an in vitro predictor for the in vivo reaction to biomaterials like alginate beads using whole blood of 6 healthy blood donors. ELISA’s against IL-8 en CCL2 were performed on the supernatant of the whole blood assay (WBA). Enzyme-linked immunosorbent assays (ELISAs) against Interleukin-8 (IL-8), Chemokine Ligand 2 (CCL2), Interleukin-1 beta ( Results - After IA administration of alginate beads horses showed severe lameness. There were clear increasing values of all tested biomarkers in the synovial fluid sampled from the pilot study. Histology showed clear reaction to something present in the synovial fluid, without clear differentiation on what type of reaction was present. The WBA showed clear increasing values of IL-8 and CCL2 in reaction to the alginate beads that were used during the pilot study. Discussion – Adjustments to the experimental design of this pilot study might have contributed to more valuable results. Knowing alginate itself is immunogenic could have predicted a reaction to alginate beads in horses, especially since it is known that horses seem particularly sensitive to a foreign body reaction in the joint. Horses often present with (transient) lameness and elevated white blood cell counts after injection of a biomaterial. Even materials that do not normally elicit an adaptive immune response and have been tested in other animals, can lead to swollen and painful joints in horses. Conclusion - More research needs to be performed before extensive in vivo testing with alginate beads in horses can be done. The increase of biomarkers against Interleukin-8 (IL-8), Chemokine Ligand 2 (CCL2), Interleukin-1 beta (IL-1β) and Tumor Necrosis Factor alfa (TNFα) suggest a foreign body response is active in the treated joints. An equine whole blood assay appears a promising in vitro test to predict an in vivo reaction to biomaterials.