Tissue engineering applied to the retinal prosthesis: Neurotrophin-eluting polymeric hydrogel coatings

Fig. 1. Multi-electrode polyimide array for retinal prosthesis studies. The array has 15 electrodes each 400 mm in diameter arranged in a 3 × 5 matrix.

Summary:

This article discusses the possibility of improving visual prosthetics for those who have lost or severely damaged their visual ability. The current prospective replacement for a damaged retina (where the photoreceptors are located) is using a multi-electrode polyimide array as seen in the photograph above. One of the problems faced by bioengineers is that this array transmits low resolution due to the relatively large electrodes that require a high stimulation threshold. Scientists cannot reduce the size of the electrodes because a larger size is needed to decrease charge density that would otherwise cause damage to the electrodes and the tissue surrounding it. Additionally, implantation of devices often involves scar tissue that increases the physical separation between the electrodes and neurons, thereby creating an even greater threshold. In this study they use a popular neural tissue engineering material, biodegradable drug-releasing hydrogels, to try to improve these electron-tissue concerns. An advantage of using these hydrogels is that they can be engineered to release neurotrophins (i.e. BDNF, or brain derived neurotrophic factor), which can promote neuron survival and neurite extensions, and can effectively bring the neurons closer to the electrodes in the retina.

This experimental study cultured explants of rabbit retinas in neurotrophin-eluting PEGPLA poly(ethyleneglycol)-poly(lactic acid) hydrogel boluses to study the effect of BDNF-releasing polymer boluses on neurite length. These cultures were then exposed to six different medium conditions: 1540LA2, 1540LA4 BDNF-releasing boluses, BDNF+ control, 1540LA2 and 1540LA4 BSA-releasing shams, and negative control receiving no BDNF for 7 days in vitro. The results of this study indicate that there is a significant increase in neurite length after 7 days in samples exposed to BDNF in comparison to the control study. Additionally, it was found that the polymer itself does not increase neurite length. BDNF was not found to make a significant difference in neurite density. After 14 days, neurite length only increased for BDNF+ samples. Possible explanations of these findings include the possibility that: BDNF affects cell adhesion of the explants to the cell culture layer, or a BDNF concentration gradient caused a slow/stop in neurite growth. These significances led the researchers to conclude that PEGPLA hydrogel boluses can promote short-term neurite extension and that PEGPLA + BDNF boluses can promote extension equal to or better than BDNF being directly injected into the culture medium. On the other hand, a decline in BDNF release induces a retraction of growth in neurites.

Why I chose this article:

Most people consider vision as the most valued of their senses (at least I do). Also, there is much medical and technological advancement that has not been touched upon in the study of vision (e.g. a permanent treatment for glaucoma or corrective vision). This study shows one significant method for increasing neurite growth in the retina, which brings us a step closer to developing a better resolution multi-electrode array for use as a retinal prosthetic. It also provides a vision (no pun intended) for other bioengineers to look for other factors besides BDNF to sustainably extend neurite length. In the very distant future, this could eventually even lead to bioengineering a fully-functional prosthetic eye (not just the retina!)… and wouldn’t that be pretty awesome?