As the main precursor of cardiovascular diseases, atherosclerosis is a complex inflammatory disorder that preferentially occurs in stenotic, curved, and branched arterial regions. Although various in vitro models are established to understand its pathology, reconstructing the native atherosclerotic environment that involves both co‐cultured cells and local turbulent flow singling remains challenging. This study develops an arterial construct via in‐bath coaxial cell printing that not only facilitates the direct fabrication of three‐layered conduits with tunable geometry and dimensions but also maintains structural stability. Functional vascular tissues, which respond to various stimulations that induce endothelial dysfunction, are rapidly generated in the constructed models. The presence of multiple vascular tissues under stenotic and tortuous turbulent flows allows the recapitulation of hallmark events in early atherosclerosis under physiological conditions. Furthermore, the fabricated models are utilized to investigate the individual and synergistic functions of cell co‐culture and local turbulent flows in regulating atherosclerotic initiation, as well as the dose‐dependent therapeutic effect of atorvastatin. These outcomes suggest that the constructed atherosclerotic model via a novel fabrication strategy is a promising platform to elucidate the pathophysiology of atherosclerosis and seek effective drugs and therapies.

The musculoskeletal system is a vital body system that protects internal organs, supports locomotion, and maintains homeostatic function. Unfortunately, musculoskeletal disorders are the leading cause of disability worldwide. Although implant surgeries using autografts, allografts, and xenografts have been conducted, several adverse effects, including donor site morbidity and immunoreaction, exist. To overcome these limitations, various biomedical engineering approaches have been proposed based on an understanding of the complexity of human musculoskeletal tissue. In this review, the leading edge of musculoskeletal tissue engineering using 3D bioprinting technology and musculoskeletal tissue-derived decellularized extracellular matrix bioink is described. In particular, studies on in vivo regeneration and in vitro modeling of musculoskeletal tissue have been focused on. Lastly, the current breakthroughs, limitations, and future perspectives are described.

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Traumatic brain injury is one of the leading causes of accidental death and disability. The loss of parts in a severely injured brain induces edema, neuronal apoptosis, and neuroinflammation. Recently, stem cell transplantation demonstrated regenerative efficacy in an injured brain. However, the efficacy of current stem cell therapy needs improvement to resolve issues such as low survival of implanted stem cells and low efficacy of differentiation into respective cells. We developed brain-derived decellularized extracellular matrix (BdECM) bioink that is printable and has native brain-like stiffness. This study aimed to fabricate injured cavity-fit scaffold with BdECM bioink and assessed the utility of BdECM bioink for stem cell delivery to a traumatically injured brain. Our BdECM bioink had shear thinning property for three-dimensional (3D)-cell-printing and physical properties and fiber structures comparable to those of the native brain, which is important for tissue integration after implantation. The human neural stem cells (NSCs) (F3 cells) laden with BdECM bioink were found to be fully differentiated to neurons; the levels of markers for mature differentiated neurons were higher than those observed with collagen bioink in vitro. Moreover, the BdECM bioink demonstrated potential in defect-fit carrier fabrication with 3D cell-printing, based on the rheological properties and shape fidelity of the material. As F3 cell-laden BdECM bioink was transplanted into the motor cortex of a rat brain, high efficacy of differentiation into mature neurons was observed in the transplanted NSCs; notably increased level of MAP2, a marker of neuronal differentiation, was observed. Furthermore, the transplanted-cell bioink suppressed reactive astrogliosis and microglial activation that may impede regeneration of the injured brain. The brain-specific material reported here is favorable for NSC differentiation and suppression of neuroinflammation and is expected to successfully support regeneration of a traumatically injured brain.

Given its ability to modulate neuronal excitability, low-intensity magnetic stimulation (LIMS) has therapeutic potential in the treatment of neurological disorders. However, the underlying of LIMS effects remain poorly understood because LIMS does not directly generate action potentials. We aimed to elucidate these mechanisms by studying and systematically comparing the neurochemical changes induced in vitro by LIMS. To this end, we developed a simple in vitro magnetic stimulation device that allowed delivery of a range of stimulation parameters in order to generate sufficient field intensity for the subthreshold. In characterizing our custom-built system, we conducted computational simulations to determine the electromagnetic field exposure to a cell culture dish. Subsequently, using the custom-built LIMS system, we applied three different stimulation protocols to differentiated neuroblastoma cells for 30 min and then assessed the resultant neurochemical changes. We found that high-frequency (HF: 10 Hz) stimulation increased levels of the excitatory neurotransmitter, glutamate, while low-frequency (LF: 1 Hz) stimulation increased levels of the inhibitory neurotransmitter, GABA. These results suggest that LIMS effects are frequency-dependent: suppression of neuroexcitability occurs at LF and facilitation occurs at HF. Furthermore, we observed pattern-dependent changes when comparing repetitive high-frequency (rHF) and intermittent high-frequency (iHF) stimulations: iHF took more time to induce neurochemical change than rHF. In addition, we found that calcium changes were closely associated with glutamate changes in response to different stimulation parameters. Our experimental findings indicate that LIMS induces the release of neurotransmitters and affects neuronal excitability at magnetic field intensities far lower than suprathreshold, and that this in turn induces action potentials. Therefore, this study provides a cellular framework for understanding how low-intensity magnetic stimulation could affect clinical outcomes.

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