A novel core–shell microcapsule system is developed in this study to mimic the miniaturized 3D architecture of pre-hatching embryos with an aqueous liquid-like core of embryonic cells and a hydrogel-shell of zona pellucida. This is done by microfabricating a non-planar microfluidic flow-focusing device that enables one-step generation of microcapsules with an alginate hydrogel shell and an aqueous liquid core of cells from two aqueous fluids. Mouse embryonic stem (ES) cells encapsulated in the liquid core are found to survive well (>92%). Moreover, ~20 ES cells in the core can proliferate to form a single ES cell aggregate in each microcapsule within 7 days while at least a few hundred cells are usually needed by the commonly used hanging-drop method to form an embryoid body (EB) in each hanging drop. Quantitative RT-PCR analyses show significantly higher expression of pluripotency marker genes in the 3D aggregated ES cells compared to the cells under 2D culture. The aggregated ES cells can be efficiently differentiated into beating cardiomyocytes using a small molecule (cardiogenol C) without complex combination of multiple growth factors. Taken together, the novel 3D microfluidic and pre-hatching embryo-like microcapsule systems are of importance to facilitate in vitro culture of pluripotent stem cells for their ever-increasing use in modern cell-based medicine.

Therapeutic hyperthermia is a procedure that involves heating tissues to a higher temperature level, typically ranging from 41°C to 45°C. Its combination with radiotherapy and/or chemotherapy has been performed for many years, with remarkable success in treating advanced and recurrent cancers. The current hyperthermia strategies generally include local, regional, and whole-body hyperthermia, which can be implemented by many heating methods, such as microwave, radiofrequency, laser, and ultrasound. There are several hyperthermic treatment modalities in conjunction with radiotherapy/chemotherapy. Numerous studies have attempted to explain the mechanisms of thermosensitization from radiation and chemotherapy; however, a generalized standard for determining an optimal hyperthermia modality combined with radiotherapy/chemotherapy has not been established, so more research is needed. Fortunately, phase II/III clinical trials have demonstrated that hyperthermia combination therapy is beneficial for local tumor control and survival in patients with high-risk tumors of different types. The aim of this article is to present a comprehensive review of the latest advances in tumor hyperthermia combined with radiotherapy and/or chemotherapy. We specifically focus on synergistic cellular and molecular mechanisms, thermal dose, treatment sequence, monitoring and imaging, and clinical outcomes of the combination therapy. The role of nanoparticles in sensitization during radio-/chemotherapy is also evaluated. Finally, research challenges and future trends in the related areas are presented.