Functionalization of Ti substrate with pH-responsive naringin-ZnO nanoparticles for the reconstruction of large bony after osteosarcoma resection.
Yulu YangBailong TaoYi GongRui ChenWeihu YangChuanchuan LinMaowen ChenLu QinYile JiaKaiyong CaiPublished in: Journal of biomedical materials research. Part A (2020)
After bone tumor resection, the large bony deficits are commonly reconstructed with Ti-based metallic endoprosthesis, which provide immediate stable fixation and allow early ambulation and weight bearing. However, when used in osteosarcoma resection, Ti implant-relative infection and tumor recurrence were recognized as the two critical factors for implantation failure. Hence, in this work, a novel zinc oxide nanoparticle decorating with naringin was prepared and immobilized onto Ti substrate. The drugs delivery profiles proved that in the bacterial infection and Warburg effect of osteosarcoma-induced acidic condition, naringin and Zn2+ can be released easily from the functional Ti substrate. The anti-osteosarcoma and antibacterial assay showed the delivered naringin and Zn2+ can induce a remarkable increase of oxidative stress in bacteria (Escherichia coli and Staphylococcus aureus) and osteosarcoma (Saos-2 cells) by producing reactive oxygen species (ROS). Accumulation of ROS results in damage of bacterial biofilm and bacterial membrane, leading to the leakage of bacterial RNA and DNA. Meanwhile, the increase of ROS induces osteosarcoma cell apoptosis by activating ROS/extracellular signal-regulated kinase signaling pathway. Furthermore, in vitro cellular experiments, including cell viability, alkaline phosphatase activity, collagen secretion, extracellular matrix mineralization level, indicated that the functional Ti substrate exhibited great potential for osteoblasts proliferation and differentiation. Hence, this study provides a simple and promising strategy of developing multifunctional Ti-based implants for the reconstruction of large bony after osteosarcoma resection.
Keyphrases
- reactive oxygen species
- signaling pathway
- staphylococcus aureus
- oxidative stress
- dna damage
- extracellular matrix
- cell death
- escherichia coli
- induced apoptosis
- traumatic brain injury
- pseudomonas aeruginosa
- soft tissue
- heavy metals
- cell proliferation
- pi k akt
- physical activity
- minimally invasive
- quantum dots
- circulating tumor
- bone mineral density
- gold nanoparticles
- cancer therapy
- epithelial mesenchymal transition
- high throughput
- body composition
- silver nanoparticles
- tyrosine kinase
- reduced graphene oxide
- heat stress
- magnetic nanoparticles