Chemical functionalization of bone implants with nanoparticle-stabilized chitosan and methotrexate for inhibiting both osteoclastoma formation and bacterial infection

Abstract

A great challenge in orthopedic tumor operation faced by orthopedic implants is the high recurrence and metastasis of bone tumor as well as the bacterial infection associated with the implants. Thus ideal titanium (Ti)-based bone implants should be able to not only inhibit cancer cell adhesion and proliferation, promote cancer cell apoptosis, but also resist bacterial infections. Towards this end, we developed a new approach to modify the surface of Ti-based bone implants so that they can restrain functions of osteoclastoma (Giant cell tumor of bone) cancer cells (GCTs) and inhibit the adhesion of bacteria. First, the surface of pristine Ti substrates was functionalized with dopamine (DA) to form DA-Ti substrates. Then nanoparticles electrostatically assembled from poly-lysine (PLL) and heparin (Hep) were chemically immobilized onto the DA-Ti substrates to form PLL/Hep-Ti substrates. Chitosan (CH) and methotrexate (MTX) were then electrostatically immobilized onto the PLL/Hep-Ti substrates to generate CH-MTX-Ti substrates. The successful functionalization of the Ti substrates was confirmed by X-ray photoelectron spectroscopy. GCTs cultured on differently functionalized Ti substrates were investigated in terms of cell adhesion, cytoskeleton, proliferation, cytotoxicity and apoptosis. The growth of Staphylococcus aureus bacteria in the presence of different substrates was also assayed. Our results showed that CH-MTX-Ti substrates not only significantly inhibited the adhesion, proliferation and viability of GCTs, promoted the apoptosis of GCTs, but also prevented the adhesion of the bacteria and the subsequent formation of bacterial biofilms, when compared to other Ti substrates. Thus CH-MTX-Ti substrates are expected to be used as orthopedic prostheses in bone tumor surgery that can inhibit both osteoclastoma formation and bacterial infections.

An antibacterial and absorbable silk-based fixation material with impressive mechanical properties and biocompatibility

“…Moreover, GSS and PSS have Young’s modulus values of approximately 8 GPa compared with approximately 18 GPa for cortical bone4849. However, the Young’s modulus of Ti-6Al-4V is 113.8 GPa, which can result in stress shielding during fracture healing50. It has been reported that more flexible and absorbable fixation devices make bone healing faster and more complete51.…”

Characterization of TiO2 nanoparticle suspensions in aqueous solutions and TiO2 nanoparticle retention in water-saturated columns packed with glass beads

“…Besides the above-mentioned environmental applications, NPs are used in Enhanced Oil Recovery for altering the interfacial tension values or contact angles in two-phase (wateroil) or three-phase flow systems (gas-water-oil) [31] or applications concerning hydraulic fracturing [32]. Also, NPs are used in medicine for functionalized bone implants [33], in photovoltaic devices [34] or memory devices [35].…”

Effects of Programmed Local Delivery from a Micro/Nano‐Hierarchical Surface on Titanium Implant on Infection Clearance and Osteogenic Induction in an Infected Bone Defect

“…Grade 4 commercially available 1 mm thick Cp‐Ti plates were cut to disks with the diameter of 14 ± 0.35, 33 ± 0.56, and 59 ± 0.42 mm, which were appropriate for 24‐well, 6‐well, and 6 cm tissue culture plates (TCPs). The substrates were polished using 320, 400, 600, 800, 1000, and 1200 grid sandpapers and sonicated in acetone, ethanol, and ultrapure water for 30 min . The substrates were then air dried.…”