Fabrication of novel biomimetic nano-hydroxyapatite/chitosan injectable hydrogel with chikusetusaponin IVa on chondral injury in osteoarthritis

The management of pain and the chondral injury resulting from osteoarthritis (OA) present serious challenges in clinical treatment. The conventional method of injecting hyaluronic acid (HA) directly into the joint can alleviate the condition, but it is constrained by the challenge of preserving its effectiveness over an extended time. Recent studies indicate that the total Chikusetusaponin IVa (ChS IVa) found in the Panax japonicas have the ability to reduce oxidative stress and inflammation. This study involved the development of a new hydrogel formulation by combining nano-hydroxyapatite-modified chitosan hydrogel with encapsulated Chikusetusaponin IVa (ChS IVa-nHA/CS) to treat osteoarthritis (OA). The supramolecular ChS IVa-nHA/CS hydrogel exhibited favorable biocompatibility to chondrocytes and demonstrated potent antioxidant activity <i>in vitro</i>. During the 24-hour degradation studies, it was observed that the sample exhibited greater resistance to chemical degradation compared to the HA samples. An <i>in vitro</i> study demonstrated that the administration of this novel hydrogel through intra-articular injection can effectively reduce the local inflammation in knee joints. This results in suppressing the production of inflammatory cytokines (COX-2, iNOS, TNF-α, IL-1β, IL-6, IL-17) in the chondrocytes (cartilage cells) at 12 weeks after the injection. Histological and behavioral evaluations proved that the administration of hydrogel injection provided protection against cartilage degradation and alleviated pain in rats with osteoarthritis, as compared to the treatment of HA injection. This novel hydrogel, overcoming the traditional HA injection, indicates significant potential for treating OA.