23 Mandel and his team perform many of the fabrication processes required in their research in BINA’s extensive nano center. “We’ve been using nanotech for quite a few years including photolithography coatings, imaging, electron microscopy imaging, imaging with light microscopy, confocal microscopy, and other tech in the center,” describes Mandel. “It’s a crucial infrastructure for our research.” In a recent article published in the Journal of Biological Engineering, entitled, “Optimizing the fabrication of a 3D high-resolution implant for neural stimulation,” published in August 2023, Mandel and his team describe working on the first step of the hybrid retinal implant - creating small electronic devices that can be implanted into the eye to stimulate the remaining neural cells. In this case, the devices can help restore vision. The work was completed as part of the PhD thesis of Gal Shpun and with the collaboration of two other BINA members, namely Prof. Zeev Zalevsky, dean of the Engineering faculty, and Prof. Doron Gerber, a group leader in the Faculty of Life Science. Making these devices is a tricky process, and Mandel has faced many challenges. The small implant for the eye is about 1 millimeter in size and has tiny gold electrodes, each located in the bottom of a tiny 15-micrometer microwell. These microwells are designed to host a neural cell, engineered from human embryonic cells. First tests have been conducted in the lab and on animals to make sure the implant is working correctly and won’t harm the eye. They also made the implant more compatible with the body’s cells by adding special molecules to it. In addition, Mandel is focused on the in-vivo and histological studies of implant integration in rat retinas. The implant was designed for neural stimulation and was tested in rats. Various challenges in the fabrication process were overcome, including optimizing UV exposure, improving gold electrode attachment to the SU-8 surface, avoiding thermal stress, addressing multilayer lithography issues, and ensuring successful implant release. Moreover, the implant was given bio-functional properties by introducing an RGD peptide to improve the connection between cells and electrodes. (The most extensively examined adhesive peptide in the realm of biomaterials is the tri-amino acid sequence known as arginine-glycine-aspartate or RGD). Experimental tests showed that the implant effectively stimulated the sub-retinal region in isolated retinas and displayed promising anatomical compatibility when integrated into the host retina of rats. These outcomes indicate the potential utility of these implants in the field of neural prosthetics. Mandel and his group detailed the fabrication process of a complex 3D implant and discussed the challenges faced, along with the solutions applied to address them. The paper also described the successful integration of the implant in both in-vitro and invivo settings, with no significant signs of immune reactions. The findings provide valuable insights for the development of neural prosthetic implants and other bio micro-devices. “Our hope is that we will have a new technology to enable people to see at high resolution and with high quality, but this will take quite a few years to produce,” Mandel explains. “We are using a mixture of biological technologies, stem cell technologies, CRISPR-Cas9, imaging, and neuro technologies to attract cells and to manipulate them from cells or from retinas. We are still not in human patient studies.” Mandel points to several clinical trials in the field of retinal prosthesis. “What I’m trying to do is the next generation of devices,” he asserts. “The capabilities of the equipment in the nano center are very profound and have a lot of proficiencies for fabrication.” Born in Eilat, Mandel pursued a 20-year career in the IDF Medical Corps and Ministry of Defense (MAFAT) before entering academia. He performed his postdoc at Stanford University under the guidance of Prof. Daniel Palanker, a world leader in the field of retinal prosthetics, before returning to Israel. This year marks his 10th anniversary at Bar-Ilan. “BINA has been instrumental in many of our research projects, and the use of the nano equipment has enabled our explorations to be cutting edge,” he declares. “It adds an amazing dimension to our work.” “Our main project is fabricating retinal prosthesis, a specific type that we called hybrid retinal prosthesis because it’s composed of both electrodes and living cells,”
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