Bone tissue engineering provides a promising strategy for the treatment of bone defects. Nonetheless, the clinical utilization of biomaterial-based scaffolds is constrained by their inadequate mechanical strength and absence of osteo-inductive properties. Here, we proposed to endow nano-scaffold (NS) constructed by coaxial electrospinning technique with enhanced osteogenic bioactivities and mechanical properties by incorporating biocompatible magnetic iron oxide nanoparticles (IONPs) and icaritin (ICA). Four types of nano-scaffolds (NS, ICA@NS, NS-IONPs and ICA@NS-IONPs) were prepared. The incorporation of ICA and IONPs minimally impact their surface morphological and chemical properties. IONPs enhanced the mechanical properties of NS scaffolds, including hardness, tensile strength, and elastic modulus. In vitro assessments demonstrated that ICA@NS-IONPs exhibited enhanced osteogenic bioactivities towards mouse calvarial pre-osteoblast cell line MC3T3-E1 as evidenced by detecting the alkaline phosphatase (ALP) activity level, expressions of osteogenesis-related genes and proteins as well as mineralized nodule formation. Mechanistic investigations revealed that MEK/ERK (MAP kinase-ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK)) signaling pathway could offer a plausible explanation for the osteogenic differentiation of MC3T3-E1 cells induced by ICA@NS-IONPs. Furthermore, the implantation of nano-scaffolds in rat skull defects exhibited a substantial improvement in in vivo bone regeneration. Therefore, IONPs and ICA incorporated coaxial electrospinning nano-scaffolds present a novel strategy for the optimization of scaffolds for bone tissue engineering.

Osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women, and the hyperfunction of osteoclasts is the primary contributor to postmenopausal osteoporosis. However, the development of effective therapeutic drugs and precise delivery systems remains a challenge in the field of anti-absorption therapy. Here, we reported the α-cyperone (α-CYP) for anti-osteoporosis and developed a liposome-based nano-drug delivery system of α-CYP, that specifically targets the bone resorption interface. Firstly, we found that the α-CYP, one of the major sesquiterpenes of Cyperus rotundus L., attenuated the progression of osteoporosis in ovariectomized (OVX) mice and down-regulated the expression of phosphorylated proteins of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), causing down-regulation of osteoclast-related genes/proteins and curbing osteoclast differentiation. Furthermore, α-CYP reversed the activation of osteoclastic differentiation and enhanced osteoporosis-related proteins expression caused by PI3K/Akt agonist (YS-49). More importantly, we adopted the osteoclastic resorption surface targeting peptide Asp8 and constructed the liposome (lipαC@Asp8) to deliver α-CYP to osteoclasts and confirmed its anti-osteoporosis effect and enhanced osteoclast inhibition by blocking PI3K/Akt axis. In conclusion, this study demonstrated that α-CYP inhibits osteoclast differentiation and osteoporosis development by silencing PI3K/Akt pathway, and the liposome targeting delivery systems loaded with α-CYP might provide a novel and effective strategy to treat osteoporosis.

Tissue engineering scaffolds have presented effective value in bone repair. However, the integration of the diverse components, complex structures, and multifunction to impart the scaffolds with improved applicability is still a challenge. Here, we propose a novel fish-derived scaffold combined with photothermal therapy and mesenchymal stem cells (MSCs) to promote bone regeneration. The fish-derived scaffold is composed of the decellularized fish scale and gelatin methacrylate synthesized from fish gelatin (fGelMA), which can promote the proliferation and osteogenesis of MSCs with no obvious immunological rejection. Furthermore, the black phosphorus (BP) nanosheets are incorporated into the fGelMA hydrogel network, which can endow the hydrogel with the capacity of photothermal conversion stimulated by near-infrared (NIR) light. The fish-derived scaffold can promote the osteogenesis process of MSCs with higher expression of osteogenic markers and higher mineralization assisted by the NIR light in vitro. The regeneration of mice calvarial defect has also been accelerated by the scaffold with photothermal therapy and MSCs. These results suggest that the fish-derived scaffold, photothermal therapy, and MSCs-based regenerative therapy is a promising clinical strategy in bone regeneration.