Effects of cyclic fluid stress at different frequencies on behaviors of cells incubated on titanium alloy.

The orthopedic external fixation is always in dynamic mechanical environment with the somatic movement. We used a self-designed mini oscillator to simulate this condition by providing the reciprocating cyclic fluid stress, and observed the behavioral responses of fibroblasts implanted on titanium alloy plane to the stress at different frequencies, including 0.2 Hz, 0.6 Hz, and 1.0 Hz. We found that the cell angle, shape index and expression of vinculin were mostly biphasic-dependent with the increase of frequency, with peaks at 0.6 Hz. Whereas the cell area, expression of Col-I and α-SMA were mainly affected by the 1.0 Hz stress. Interestingly, 1.0 Hz stress also promoted Col-I expression of bone marrow mesenchymal stem cells (BMSCs), although it did not increase α-SMA. These results reveal that 0.6 Hz stress improves the alignment, polarity and adherence of fibroblasts on titanium alloy substrates, thus improving the sealing of implants; the 1.0 Hz force activates the differentiation of fibroblasts into myofibroblasts and increases collagen produced by stem cells, which probably cause the formation of fibrous capsules around implants.

Co-Delivery of Curcumin and Paclitaxel by "Core-Shell" Targeting Amphiphilic Copolymer to Reverse Resistance in the Treatment of Ovarian Cancer.

BACKGROUND: Ovarian cancer is a common malignancy in the female reproductive system with a high mortality rate. The most important reason is multidrug resistance (MDR) of cancer chemotherapy. To reduce side effects, reverse resistance and improve efficacy for the treatment of ovarian cancer, a "core-shell" polymeric nanoparticle-mediated curcumin and paclitaxel co-delivery platform was designed. METHODS: Nuclear magnetic resonance confirmed the successful grafting of polyethylenimine (PEI) and stearic acid (SA) (PEI-SA), which is designed as a mother core for transport carrier. Then, PEI-SA was modified with hyaluronic acid (HA) and physicochemical properties were examined. To understand the regulatory mechanism of resistance and measure the anti-tumor efficacy of the treatments, cytotoxicity assay, cellular uptake, P-glycoprotein (P-gp) expression and migration experiment of ovarian cancer cells were performed. In addition, adverse reactions of nanoformulation to the reproductive system were examined. RESULTS: HA-modified drug-loaded PEI-SA had a narrow size of about 189 nm in diameters, and the particle size was suitable for endocytosis. The nanocarrier could target specifically to CD44 receptor on the ovarian cancer cell membrane. Co-delivery of curcumin and paclitaxel by the nanocarriers exerts synergistic anti-ovarian cancer effects on chemosensitive human ovarian cancer cells (SKOV3) and multi-drug resistant variant (SKOV3-TR30) in vitro, and it also shows a good anti-tumor effect in ovarian tumor-bearing nude mice. The mechanism of reversing drug resistance may be that the nanoparticles inhibit the efflux of P-gp, inhibit the migration of tumor cells, and curcumin synergistically reverses the resistance of PTX to increase antitumor activity. It is worth noting that the treatment did not cause significant toxicity to the uterus and ovaries with the observation of macroscopic and microscopic. CONCLUSION: This special structure of targeting nanoparticles co-delivery with the curcumin and paclitaxel can increase the anti-tumor efficacy without increasing the adverse reactions as a promising strategy for therapy ovarian cancer.

Low-Temperature Additive Manufacturing of Biomimic Three-Dimensional Hydroxyapatite/Collagen Scaffolds for Bone Regeneration.

Low-temperature additive manufacturing (AM) holds promise for fabrication of three-dimensional (3D) scaffolds containing bioactive molecules and/or drugs. Due to the strict technical limitations of current approaches, few materials are suitable for printing at low temperature. Here, a low-temperature robocasting method was employed to print biomimic 3D scaffolds for bone regeneration using a routine collagen-hydroxyapatite (CHA) composite material, which is too viscous to be printed via normal 3D printing methods at low temperature. The CHA scaffolds had excellent 3D structure and maintained most raw material properties after printing. Compared to nonprinted scaffolds, printed scaffolds promoted bone marrow stromal cell proliferation and improved osteogenic outcome in vitro. In a rabbit femoral condyle defect model, the interconnecting pores within the printed scaffolds facilitated cell penetration and mineralization before the scaffolds degraded and enhanced repair, compared to nonprinted CHA scaffolds. Additionally, the optimal printing parameters for 3D CHA scaffolds were investigated; 600-µm-diameter rods were optimal in terms of moderate mechanical strength and better repair outcome in vivo. This low-temperature robocasting method could enable a variety of bioactive molecules to be incorporated into printed CHA materials and provides a method of bioprinting biomaterials without compromising their natural properties.