Nanoengineered hydrogels as 3D biomimetic extracellular matrix with injectable and sustained delivery capability for cartilage regeneration

The regeneration of articular cartilage remains a great challenge due to the difficulty in effectively enhancing spontaneous healing. Recently, the combination of implanted stem cells, suitable biomaterials and bioactive molecules has attracted attention for tissue regeneration. In this study, a novel injectable nanocomposite was rationally designed as a sustained release platform for enhanced cartilage regeneration through integration of a chitosan-based hydrogel, articular cartilage stem cells (ACSCs) and mesoporous SiO₂ nanoparticles loaded with anhydroicaritin (AHI). The biocompatible engineered nanocomposite acting as a novel 3D biomimetic extracellular matrix exhibited a remarkable sustained release effect due to the synergistic regulation of the organic hydrogel framework and mesopore channels of inorganic mSiO₂ nanoparticles (mSiO₂ NPs). Histological assessment and biomechanical tests showed that the nanocomposites exhibited superior performance in inducing ACSCs proliferation and differentiation in vitro and promoting extracellular matrix (ECM) production and cartilage regeneration in vivo. Such a novel multifunctional biocompatible platform was demonstrated to significantly enhance cartilage regeneration based on the sustained release of AHI, an efficient bioactive natural small molecule for ACSCs chondrogenesis, within the hybrid matrix of hydrogel and mSiO₂ NPs. Hence, the injectable nanocomposite holds great promise for use as a 3D biomimetic extracellular matrix for tissue regeneration in clinical diagnostics.