CyMAD bioreactor: A cyclic magnetic actuation device for magnetically mediated mechanical stimulation of 3D bioprinted hydrogel scaffolds.

Mechanical stimulation of bioprinted constructs can enhance the differentiation of cells within these scaffolds, such as driving chondrocytes towards cartilage tissue substitutes. In this study, a holistic approach is presented for designing and engineering a material-specific device based on a magnetic field setup using the Maxwell configuration for a touchless cyclic magnetic stimulation of (bioprinted) hydrogel scaffolds containing magnetic microparticles. We describe the entire development process, from the design of the magnetic field to the construction of the bioreactor and provide an evaluation of the calculation. Finally, an analysis of the distribution and orientation of the particles within the hydrogels and a cytocompatibility test after applying the intended stimulation regime were conducted. As a proof-of-principle, a model system in the shape of a cylindrical bending beam consisting of the established magnetisable bioink based on alginate, methylcellulose and magnetite microparticles (algMC + mag), was used instead of 3D printed, macroporous scaffolds of this material. Requirements for the dimensioning of the force, such as the Young's modulus, were determined experimentally. The magnetic field was calculated using the software Finite Element Method Magnetics (FEMM). The cyclic stimulation of the samples was performed over 14 days with a duration of 3 h per day. The aim was to achieve an elongation of up to 10%. The homogeneous particle distribution in stimulated and non-stimulated samples was proven via µCT and digital image processing (DIP). Even after applying a static magnetic field over 30 min, no structure formation such as chains or agglomeration of the magnetic particles were observed. The deformation behaviour defined as a shifted position of the neutral fibre (centre line of an object) during stimulation was measured via µCT and analysed using DIP. From these data, an elongation of approx. 9% was calculated for day 14. This elongation was achieved for both the stimulated samples and the control group without stimulation, which corresponds to the theoretically calculated value. The cytocompatibility of the bioink, scaffold environment and stimulation approach was demonstrated for bioprinted scaffolds with embedded human mesenchymal stem cells and chondrocytes. These findings proved the suitability and versatility of the bioreactor and the presented approach for stimulation experiments.

Effect of cellulose compositions and fabrication methods on mechanical properties of polyurethane-cellulose composites.

A variety of cellulose-based polymer composite materials has been developed and show different impacts on the morphologies and properties of composites. Herein, we report the morphologies and properties of composites by blending polyurethane (PU) with either ethyl cellulose (EC) or cellulose nanofiber (CNF) through either drop-casting or electrospinning process. EC is homogenously mixed with PU without microphase separation and enhanced Young's modulus of composites from 0.04 to 6.94 MPa. The CNF is heterogeneously distributed in PU/CNF composites without interference on the PU microstructure and slightly increased modulus to 0.24 MPa. While the shearing force of the electrospinning process slightly affects the PU/EC composites, it drastically enhances PU crystallinity and Young's modulus to 54.95 MPa in PU/CNF composites. A model is established to summarize the effect of cellulose additives, compositions, and processes on PU/cellulose composites, providing a comprehensive understanding for designing future cellulose composites.

Spatially Uniform Tumor Treatment and Drug Penetration by Regulating Ultrasound with Microbubbles.

Tumor microenvironment has different morphologies of vessels in the core and rim regions, which influences the efficacy of tumor therapy. Our study proposed to improve the spatial uniformity of the antivascular effect and drug penetration within the tumor core and rim in combination therapies by regulating ultrasound-stimulated microbubble destruction (USMD). Focused ultrasound at 2 MHz and lipid-shell microbubbles (1.12 ± 0.08 µm, mean ± standard deviation) were used to perform USMD. The efficiency of the antivascular effect was evaluated by intravital imaging to determine the optimal USMD parameters. Tumor perfusion and histological alterations in the tumor core and rim were used to analyze the spatial uniformity of the antivascular effect and liposomal-doxorubicin (5 mg/kg) penetration in the combination therapy. Tumor vessels of specific sizes were disrupted by regulating USMD: vessels with sizes of 11 ± 3, 14 ± 5, 19 ± 7, and 23 ± 10 µm were disrupted by stimulation at acoustic pressures of 3, 5, 7, and 9 MPa, respectively (each p < 0.05). The effective treatment time of USMD (at 2 × 107 microbubbles/mouse, 7 MPa, and three cycles) was 60-120 min, which resulted in the disruption of 21-44% of vessels smaller than 50 µm. The reductions in perfusion and vascular density after combination therapy did not differ significantly between the tumor core and rim. This study found that regulating USMD can result in homogeneous antivascular effects and drug penetration within tumors and thereby improve the efficacy of combination therapies.

Current progress in antivascular tumor therapy.

The tumor vasculature transports oxygen, nutrients and drugs for crucial roles in tumor therapy. Antivascular therapy directly targets existing tumor vessels to reduce blood perfusion and then inhibit tumor growth. Vascular disrupting agents and ultrasound-stimulated microbubble destruction use chemical toxicity and physical effect, respectively, to damage vascular endothelial cells for antivascular therapy. Moreover, antivascular therapy can break vessel wall barriers and change the tumor microenvironment to compensate for the limitations of conventional chemotherapy or radiotherapy. This review presents current progress and an overview of antivascular therapy, which can inform the development and application in cancer research.

Protective Effects of Pyridoxamine Against UVC-induced Programmed Cell Death in HaCaT Cells.

BACKGROUND: Exposure to ultraviolet (UV) light is closely related to human diseases, such as skin cancer, due to irreversible injuries to the skin cells. The UV-induced DNA damage and programmed cell death are important determinants for skin carcinogenesis. The aim of the present study was to investigate the anti-ultraviolet-C (UVC) effects of pyridoxamine in human keratinocyte HaCaT cells and its mechanisms of action. RESULTS: UVC-induced programmed cell death in HaCaT cells was abrogated by treated the cells immediately after UVC irradiation with 40, 80 and 160 µM of pyridoxamine. Monitoring the UVC-induced-specific reactive oxygen species, we found that 20, 40, 80 and 160 µM of pyridoxamine was also effective in suppressing the induction of reactive oxygen species by UVC. CONCLUSION: Overall, our results provided evidence showing that pyridoxamine was effective in protecting HaCaT cells from UVC-induced programmed cell death and may be a potential anti-UVC agent in life and clinical practice.

Significant Association of Cyclo-oxygenase 2 Genotypes with Upper Tract Urothelial Cancer.

AIM: Reliable biomarkers are in urgent need for diagnosis, outcome prediction and treatment-effect monitoring for upper tract urothelial carcinomas (UTUC). Although up-regulation of cyclo-oxygenase 2 (COX2) is found in stroma and tumor cells in more than half of the patients with UTUC investigated, the genomic contribution of COX2 to UTUC has not been studied. The study aimed to evaluate the association of six polymorphic genotypes of COX2 with UTUC within a Taiwanese population. MATERIALS AND METHODS: A total of 218 patients with UTUC and 580 healthy controls were genotyped for six COX2 polymorphisms, namely A-1195G, G-765C, T+8473C, intron 1, intron 5 and intron 6, and examined for their association with UTUC risk. RESULTS: The distribution of genotypes of COX2 G-765C and intron 5 were significantly different between patient and control groups (p=0.0001 and 0.0016, respectively), while others were not (p>0.05). The haplotype analysis showed that compared to the GG/TT haplotype of COX2 G-765C/intron 5, those carrying GG/AT variants have a significantly increased risk of UTUC (odds ratio=4.83, 95% confidence interval=1.79-13.06), while those carrying CG/TT variants have a decreased risk (odds ratio=0.26, 95% confidence interval=0.14-0.49). CONCLUSION: Our results suggest that individual and combined COX2 G-765C/intron 5 genotypes play a role in controlling COX2 expression and UTUC development.