3D Printing and Electrospinning for Neural Tissue Engineering and Cancer Modeling Applications Open Access

Nervous system injuries occur commonly among people of many different ages and backgrounds. The gold standard to address injured nerves involves the utilization of an autograft where a nerve is harvest from a less important position in the body. However, this strategy associates with major drawbacks including limited availability of donor tissues, donor site infection and even morbidity. Therefore, a novel transplantable neural construct which could mitigate the negative effects and potentially replace an autologous nerve graft while additionally offering a great alternative approach to patient care is highly desirable. Tissue engineering offers a promising avenue for regeneration of many tissue types, including the neural context. In the present study, we apply a series of tissue engineering approaches, such as electrospinning, 3D printing as well as many other nanotechnology, to develop functional nerve scaffolds and investigate their potential in neural regeneration. In order to improve regeneration efficacy, we also introduced electrical and laser simulations regarding their positive effects on enhancing neural cell function. We found both electrospinning and 3D printing techniques are showing great promise in neural tissue regeneration. The introduction of electrical and laser stimulations is able to improve neural differentiation. Electrospinning and 3D printing have their own advantages and disadvantage for neural scaffolds fabrication. It is suggested to use electrospinning in neural scaffold fabrication when the defective site has small size and uncomplex shape, while 3D printing can be used to address nerve injury with large size and showing complex geometries.In addition to tissue regeneration applications, 3D scaffolds can also be used as in vitro tumor models to study the progression of various cancers. Traditionally, 2D and animal models are popularly used to investigate cancer progression. However, 2D cancer models oversimplify the native 3D microenvironment due to the lack of spatial cues, while in vivo animal models contain limitations including uncontrolled complex microenvironment, costly, lack of an immune system. 3D in vitro model is considered as an alternative to bridge the gap between simple 2D and complex animal models. It can be used to study the mechanism of cancer development as well as offers a platform for drug discovery and screening. Therefore, we develop 3D cancer models using 3D printing method to study breast cancer bone metastasis process. The native bone mineral (hydroxyapatite nanoparticles (nHA)), native bone cells (bone marrow mesenchymal stem cells (MSCs), and osteoblast cells) effects on breast cancer development were investigated. It was found the nHA can promote cancer cell growth and tumor spheroid formation on the 3D printed scaffolds. The co-culture of cancer cells with native bone cells increased the formation of spheroid clusters in comparison to 3D mono-cultured cells and 2D culture. These results demonstrate that 3D printed cancer model can mimic tumor microenvironment for cell growth, migration, and tumor mass formation and might serve as a tool for studying cancer progression and assessing drug sensitivity.

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