Icariin-loaded hydrogel with concurrent chondrogenesis and anti-inflammatory properties for promoting cartilage regeneration in a large animal model

Abstract

Currently, an effective repair method that can promote satisfactory cartilage regeneration is unavailable for cartilage damages owing to inevitable inflammatory erosion. Cartilage tissue engineering has revealed considerable treatment options for cartilage damages. Icariin (ICA) is a flavonoid component of Epimedii folium with both chondrogenic and anti-inflammatory properties. In this study, we prepared an ICA/CTS hydrogel by loading ICA into chitosan (CTS) hydrogel to impart chondrogenesis and anti-inflammatory properties to the ICA/CTS hydrogel. In vitro results revealed that ICA showed sustained release kinetics from the ICA/CTS hydrogel. In addition, compared to the CTS hydrogel, the ICA/CTS hydrogel exhibited a favorable in vitro anti-inflammatory effect upon incubation with lipopolysaccharide pre-induced RAW264.7 macrophages, as indicated by the suppression of inflammatory-related cytokines (IL-6 and TNF-α). Additionally, when co-cultured with chondrocytes in vitro, the ICA/CTS hydrogel showed good cytocompatibility, accelerated chondrocyte proliferation, and enhanced chondrogenesis compared to the CTS hydrogel. Moreover, the in vitro engineered cartilage from the chondrocyte-loaded ICA/CTS hydrogel achieved stable cartilage regeneration when subcutaneously implanted in a goat model. Finally, the addition of ICA endowed the ICA/CTS hydrogel with a potent anti-inflammatory effect compared to what was observed in the CTS hydrogel, as confirmed by the attenuated IL-1β, IL-6, TNF-α, and TUNEL expression. The prepared ICA/CTS hydrogel offered an effective method of delivery for chondrogenic and anti-inflammatory agents and served as a useful platform for cartilage regeneration in an immunocompetent large animal model.

Enhanced Surface Immunomodification of Engineered Hydrogel Materials through Chondrocyte Modulation for the Treatment of Osteoarthritis

“…The nuclear factor-κB (NF-κB) signaling pathway is crucial in inflammation, leading to the production of factors like IL-1β, IL-6, IL-17, and IL-8, stimulating inflammation and worsening OA. Inhibiting the NF-κB pathway may alleviate OA [125]. Zhang et al attenuated OA progression by inhibiting the NF-κB pathway and suppressing chondrocyte senescence [126].…”

The Immunosuppressive Niche Established with a Curcumin-Loaded Electrospun Nanofibrous Membrane Promotes Cartilage Regeneration in Immunocompetent Animals

“…The other 40% of the engineered cartilages were adversely affected by inflammatory cell infiltration, resulting in the erosion and absorption of the cartilage’s extracellular matrix (ECM). Other studies have also reported immune-cell-mediated cartilage destruction [ 6 , 7 , 8 ]. Hence, there is a need to develop strategies to protect the tissue-engineered cartilage against inflammatory cell infiltration.…”

Synergistic Effects of Icariin and Extracellular Vesicles Derived from Rabbit Synovial Membrane‐Derived Mesenchymal Stem Cells on Osteochondral Repair via the Wnt/β‐Catenin Pathway

“…Icariin (ICA) is a flavonoid glycoside compound extracted from Epimedium and promotes against inflammation, oxidative stress, and osteoporosis [ 31 ]. Intriguingly, ICA has been identified as a potential compound for use in repairing cartilage defects [ 32 , 33 , 34 , 35 ]. For example, ICA was found to regulate the proliferation and differentiation of chondrocytes to promote articular cartilage repair [ 36 ].…”