The use of non-chemical methods to differentiate stem cells has attracted researchers from multiple disciplines, including the engineering and the biomedical fields. No doubt, growth factor based methods are still the most dominant of achieving some level of proliferation and differentiation control - however, chemical based methods are still limited by the quality, source, and amount of the utilized reagents. Well-defined non-chemical methods to differentiate stem cells allow stem cell scientists to control stem cell biology by precisely administering the pre-defined parameters, whether they are structural cues, substrate stiffness, or in the form of current flow. We have developed a culture system that allows normal stem cell growth and the option of applying continuous and defined levels of electric current to alter the cell biology of growing cells. This biphasic current stimulator chip employing ITO electrodes generates both positive and negative currents in the same culture chamber without affecting surface chemistry. We found that biphasic electrical currents (BECs) significantly increased the proliferation of fetal neural stem cells (NSCs). Furthermore, BECs also promoted the differentiation of fetal NSCs into neuronal cells, as assessed using immunocytochemistry. Our results clearly show that BECs promote both the proliferation and neuronal differentiation of fetal NSCs. It may apply to the development of strategies that employ NSCs in the treatment of various neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases.

The development of reliable long-term encapsulation technologies for implantable biomedical devices is of paramount importance for the safe and stable operation of implants in the body over a period of several decades. Conventional technologies based on titanium or ceramic packaging, however, are not suitable for encapsulating microfabricated devices due to their limited scalability, incompatibility with microfabrication processes, and difficulties with miniaturization. A variety of emerging materials have been proposed for encapsulation of microfabricated implants, including thin-film inorganic coatings of Al₂O₃, HfO₂, SiO₂, SiC, and diamond, as well as organic polymers of polyimide, parylene, liquid crystal polymer, silicone elastomer, SU-8, and cyclic olefin copolymer. While none of these materials have yet been proven to be as hermetic as conventional metal packages nor widely used in regulatory approved devices for chronic implantation, a number of studies have demonstrated promising outcomes on their long-term encapsulation performance through a multitude of fabrication and testing methodologies. The present review article aims to provide a comprehensive, up-to-date overview of the long-term encapsulation performance of these emerging materials with a specific focus on publications that have quantitatively estimated the lifetime of encapsulation technologies in aqueous environments.

Purpose.: To develop a liquid crystal polymer (LCP)-based, long-term implantable, retinal stimulation microelectrode array using a novel fabrication method. Methods.: The fabrication process used laser micromachining and customized thermal-press bonding to produce LCP-based microelectrode arrays. To evaluate the fabrication process and the resultant electrode arrays, in vitro reliability tests and in vivo animal experiments were performed. The in vitro tests consisted of electrode site impedance recording and electrode interlayer adhesion monitoring during accelerated soak tests. For in vivo testing, the fabricated electrode arrays were implanted in the suprachoroidal space of rabbit eyes. Optical coherence tomography (OCT) and electrically evoked cortical potentials (EECPs) were used to determine long-term biocompatibility and functionality of the implant. Results.: The fabricated structure had a smooth, rounded edge profile and exhibited moderate flexibility, which are advantageous features for safe implantation without guide tools. After accelerated soak tests at 75°C in phosphate-buffered saline, the electrode sites showed no degradation, and the interlayer adhesion of the structure showed acceptable stability for more than 2 months. The electrode arrays were safely implanted in the suprachoroidal space of rabbit eyes, and EECP waveforms were recorded. Over a 3-month postoperative period, no chorioretinal inflammation or structural deformities were observed by OCT and histologic examination. Conclusions.: LCP-based flexible microelectrode arrays can be successfully applied as retinal prostheses. The results demonstrate that such electrode arrays are safe, biocompatible, and mechanically stable and that they can be effective as part of a chronic retinal implant system.

Objective . The aim of this study is to evaluate the long-term reliability of a recently presented liquid crystal polymer (LCP) -based retinal prosthesis in vitro as well as in vivo . Because an all-polymer implant introduces another intrinsic leak type due to gas permeation, for which the traditional helium leak test for metallic packages was not designed to quantify, a new method to investigate its durability is required. Approach . We designed and carried out a series of reliability tests specifically for all-polymer implants by quantitatively investigating moisture ingress through various pathways of the polymer surface, and the polymer–polymer and polymer–metal adhesions. Moisture permeation through the bulk material was estimated by analytic calculation, while water ingress through the adhesively sealed LCP–LCP and LCP–metal interfaces was investigated using the separate parts of an electrode array and a package in an accelerated aging condition. In vivo tests were done in rabbits to examine the long-term biocompatibility and implantation stability by fundus observation and optical coherence tomography (OCT) imaging. Main results . The analytic calculation estimated good barrier properties of the LCP. Samples of the LCP-based electrode array failed after 114 days in 87 °C saline as a result of water penetration through the LCP–metal interface. An eye-conformable LCP package survived for 87 days in an accelerated condition at 87 °C. The in vivo results confirmed that no adverse effects were observed around the retina 2.5 years after the implantation of the device. Significance . These long-term evaluation results show the potential for the chronic use of LCP-based biomedical implants to provide an alternative to traditional metallic packages.