Gelatin hydrogels with eicosapentaenoic acid can prevent osteoarthritis progression in vivo in a mouse model

Eicosapentanoic acid (EPA) is an antioxidant and omega‐3 polyunsaturated fatty acid that reduces inflammatory cytokine production. Gelatin hydrogel can be used as a carrier of a physiologically active substance that release it gradually for an average of ~3 weeks. Therefore, this study aimed to clarify the effect of EPA‐incorporating gelatin hydrogels on osteoarthritis (OA) progression in vivo. Ten‐week‐old male C57BL/6J mice were randomly divided into six groups (n = 6): Sham, destabilization of the medial meniscus (DMM), Corn: DMM + 2 µL corn oil, EPA injection alone (EPA‐I): DMM + 2 µL corn oil + 125 μg/μL EPA, Gel: DMM + gelatin hydrogels, and EPA‐G: DMM + 125 μg/μL EPA‐incorporating gelatin hydrogels. The mice were euthanized at 8 weeks after DMM or Sham surgery, and subjected to histological evaluation. Matrix‐metalloproteinases‐3 (MMP‐3), MMP‐13, interleukin‐1β (IL‐1β), p‐IKK α/β, CD86, and CD163 protein expression in the synovial cartilage was detected by immunohistochemical staining. F4/80 expression was also assessed using the F4/80 score of macrophage. Histological score was significantly lower in EPA‐G than in EPA‐I. MMP‐3‐, MMP‐13‐, IL‐1β‐, and p‐IKK α/β‐positive cell ratio was significantly lower in EPA‐G than in EPA‐I. However, CD86‐ and CD163‐positive cell ratio was not significantly different between EPA‐I and EPA‐G. The average‐sum F4/80 score of macrophage in EPA‐G was significantly lower than that in EPA‐I. EPA‐incorporating gelatin hydrogels were shown to prevent OA progression in vivo more effectively than EPA injection alone. Our results suggested that intra‐articular administration of controlled‐release EPA can be a new therapeutic approach for treating OA.