Development of high-efficiency superparamagnetic drug delivery system with MPI imaging capability.

In this study, a high-efficiency superparamagnetic drug delivery system was developed for preclinical treatment of bladder cancer in small animals. Two types of nanoparticles with magnetic particle imaging (MPI) capability, i.e., single- and multi-core superparamagnetic iron oxide nanoparticles (SPIONs), were selected and coupled with bladder anti-tumor drugs by a covalent coupling scheme. Owing to the minimal particle size, magnetic field strengths of 270 mT with a gradient of 3.2 T/m and 260 mT with a gradient of 3.7 T/m were found to be necessary to reach an average velocity of 2 mm/s for single- and multi-core SPIONs, respectively. To achieve this, a method of constructing an in vitro magnetic field for drug delivery was developed based on hollow multi-coils arranged coaxially in close rows, and magnetic field simulation was used to study the laws of the influence of the coil structure and parameters on the magnetic field. Using this method, a magnetic drug delivery system of single-core SPIONs was developed for rabbit bladder therapy. The delivery system consisted of three coaxially and equidistantly arranged coils with an inner diameter of Φ50 mm, radial height of 85 mm, and width of 15 mm that were positioned in close proximity to each other. CCK8 experimental results showed that the three types of drug-coupled SPION killed tumor cells effectively. By adjusting the axial and radial positions of the rabbit bladder within the inner hole of the delivery coil structure, the magnetic drugs injected could undergo two-dimensional delivery motions and were delivered and aggregated to the specified target location within 12 s, with an aggregation range of about 5 mm × 5 mm. In addition, the SPION distribution before and after delivery was imaged using a home-made open-bore MPI system that could realistically reflect the physical state. This study contributes to the development of local, rapid, and precise drug delivery and the visualization of this process during cancer therapy, and further research on MPI/delivery synchronization technology is planned for the future.

Enhancement of surface bioactivity on carbon fiber-reinforced polyether ether ketone via graphene modification.

BACKGROUND AND OBJECTIVE: The modulus of carbon fiber-reinforced polyether ether ketone (CFR-PEEK), a composite containing layers of carbon fiber sheets, can be precisely controlled to match bone. However, CFR-PEEK is biologically inert and cannot promote bone apposition. The objective of this study was to investigate whether graphene modification could enhance the bioactivity of CFR-PEEK. METHODS AND RESULTS: In vitro, the proliferation and differentiation of rat bone marrow stromal cells on scaffolds were quantified via cell-counting kit-8 assay and Western blotting analysis of osteoblast-specific proteins. Graphene modification significantly promoted bone marrow stromal cell proliferation and accelerated induced differentiation into osteogenic lineages compared to cells seeded onto nongraphene-coated CFR-PEEK. An in vivo rabbit extraarticular graft-to-bone healing model was established. At 4, 8, and 12 weeks after surgery, microcomputed tomography analyses and histological observations revealed significantly better microstructural parameters and higher average mineral apposition rates for graphene-modified CFR-PEEK implants than CFR-PEEK implants (P<0.05). van Gieson staining indicated more new bone was formed around graphene-modified CFR-PEEK implants than CFR-PEEK implants. CONCLUSION: Graphene may have considerable potential to enhance the bioactivity and osseointegration of CFR-PEEK implants for clinical applications.

Effects of graphene modification on the bioactivation of polyethylene-terephthalate-based artificial ligaments.

The objective of this study was to investigate whether surface coating with graphene could enhance the surface bioactivation of PET-based artificial ligaments to accelerate graft-to-bone healing after anterior cruciate ligament reconstruction. In an in vitro study, the proliferation of MC3T3-E1 cells and their differentiation on the scaffolds were quantified via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and real-time polymerase chain reaction assays. The significantly higher optical-density values and transcription levels of osteoblast-specific genes indicated that graphene modification could promote the proliferation of MC3T3-E1 cells and accelerate their specific differentiation into osteogenic lineages on scaffolds. In an in vivo test, rabbits were used to establish an extra-articular graft-to-bone healing model. At 4, 8, and 12 weeks after surgery, biomechanical tests, microcomputed tomography analysis, and histological observations were performed. The final results demonstrated that the microstructural parameters, the average mineral apposition rate of the bone, and the biomechanical properties of the graphene-coated polyethylene terephthalate (PET)-based artificial ligament (G-PET-AL) group were significantly higher than those of the PET-AL graft group (P < 0.05). The results of Van Gieson staining indicated that in the G-PET-AL group, there was more newly formed bone than there was in the group in which nongraphene-coated PET-ALs were used. In conclusion, graphene exhibits considerable potential for enhancing the surface bioactivation of materials.