ABSTRACT
BACKGROUND: Tissue-integrated micro-electronic devices for neural stimulation hold great potential in restoring the functionality of degenerated organs, specifically, retinal prostheses, which are aimed at vision restoration. The fabrication process of 3D polymer-metal devices with high resolution and a high aspect-ratio (AR) is very complex and faces many challenges that impair its functionality. APPROACH: Here we describe the optimization of the fabrication process of a bio-functionalized 3D high-resolution 1mm circular subretinal implant composed of SU-8 polymer integrated with dense gold microelectrodes (23µm pitch) passivated with 3D micro-well-like structures (20µm diameter, 3µm resolution). The main challenges were overcome by step-by-step planning and optimization while utilizing a two-step bi-layer lift-off process; bio-functionalization was carried out by N2 plasma treatment and the addition of a bio-adhesion molecule. MAIN RESULTS: In-vitro and in-vivo investigations, including SEM and FIB cross section examinations, revealed a good structural design, as well as a good long-term integration of the device in the rat sub-retinal space and cell migration into the wells. Moreover, the feasibility of subretinal neural stimulation using the fabricated device was demonstrated in-vitro by electrical activation of rat's retina. CONCLUSIONS: The reported process and optimization steps described here in detail can aid in designing and fabricating retinal prosthetic devices or similar neural implants.
ABSTRACT
To evaluate the effect of bevacizumab and sildenafil on stroke parameters in a mouse model, middle cerebral artery occlusion was induced in male C57Bl/6 mice using an intra-arterial filament method. The filament was removed after 60 minutes, and the mice were immediately given a single intraperitoneal injection of saline, bevacizumab, or sildenafil. An additional group of mice (n = 7) received bevacizumab 6 h after MCAO induction. The mice were euthanized 24 hours later and evaluated for infarct area and brain edema using triphenyltetrazolium chloride staining and ImageJ. In the saline-treated mice (n = 16), total stroke volume was 19.20 ± 6.38 mm(3), mean penumbra area was 4.5 ± 2.03 mm(3), and hemispheric asymmetry was 106.5%. Corresponding values in the bevacizumab group (n = 19) were 17.79 ± 5.80 mm(3), 7.3 ± 3.5 mm(3), and 108.6%; in the delayed (6 h) bevacizumab injected mice (n = 7) they were 9.80 ± 8.00 mm(3), 2.4 ± 2.0 mm(3), and 98.2%; and in the sildenafil group (n = 16) they were 18.42 ± 5.41 mm(3), 5.7 ± 2.02 mm(3), and 109.9%. The bevacizumab group had a significantly larger mean penumbra area when given immediately and smaller total stroke area in both groups than the saline- (p = 0.03) and sildenafil-treated (p = 0.003) groups. Only delayed bevacizumab group had reduced edema. Bevacizumab, injected immediately or delayed after injury, exerts a neuroprotective/salvage effect, whereas immediate treatment with sildenafil does not. Inflammation may play a role in the neuroprotective effect.
