Articular osteochondral defect is commonly seen after trauma or in patients with degenerative osteoarthritis. Currently, the treatment of osteochondral lesions is still challenging due to the limited healing ability of cartilage as well as the poorly effective traditional method. In this study, we fabricated a bilayer peptide-loaded scaffold consisting of CK2.1 coated β-glycerophosphate/chitosan ( [email protected] ) for cartilage regeneration and LL37 modified layered double hydroxide/chitosan ( [email protected] ) for subchondral bone regeneration, designed in an integrated strategy involving mesenchymal stem cells (MSCs) recruitment and multifunctional therapeutic biomaterials of bone regeneration and vascularization. The lower LC scaffold is highlighted with a biomimetic lamellar structural design, providing a novel platform for the integration of newborn bone tissue and blood vessels. In vitro results showed our peptide-loaded bilayer scaffold could induce the MSCs to differentiate into chondrocytes and osteoblasts in different layers respectively. [email protected] could also attract MSCs and promote vasculogenesis in vitro. Meanwhile, osteochondral defect could be efficiently repaired by this peptide-modified bilayered scaffold in the rabbit model. This study demonstrated that our composite scaffold could smartly enhance the repair of hyaline cartilage and subchondral bone defect, which shed light on a novel therapeutic strategy for the intervention of patients with articular osteochondral defect.
In osteoarthritic chondrocytes, dysregulation of mitochondrial dynamics due to excessive intracellular reactive oxygen species (ROS) under inflammatory conditions is a significant contributory factor to poor treatment outcomes, because it leads to a reduced cell response to chondrogenic drugs during this state. The aim of this study was to develop a multifunctional Au@CeO 2 yolk-shell nanozyme (YSN) as a novel therapeutic nanomaterial and drug delivery system. Under photothermal conditions, Au@CeO 2 nanozymes neutralized excessive ROS, enhanced antioxidant capacity, and maintained mitochondrial homeostasis of osteoarthritic chondrocytes, thereby restoring cellular responsiveness to external stimuli. Furthermore, bioactive peptide CK2.1 loaded in YSNs (Au@CeO 2 -CK2.1) achieved ordered release under photothermal conditions, effectively promoting chondrocyte anabolic activity. In a mice osteoarthritis (OA) model, local Au@CeO 2 -CK2.1 photothermal therapy effectively enhanced cartilage repair and regeneration in vivo . Mechanically, our research uncovers that decreased chondrogenic drug response is associated with activation of extracellular regulated kinase-1 and -2 (ERK1/2) pathway, and Au@CeO 2 -CK2.1 YSNs regulates mitochondrial dynamics through inhibiting ERK1/2 and dynamin-1-like protein (DRP1) phosphorylation. The results of this study demonstrated an effective therapeutic strategy that rescued chondrogenic drug response in osteoarthritic chondrocytes, achieving anti-inflammation and cartilage regeneration.
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