Mechanically Matched Silicone Brain Implants Reduce Brain Foreign Body Response

Abstract

Brain implants are increasingly used to treat neurological disorders and diseases. However, the brain foreign body response (FBR) elicited by implants affects neuro-electrical transduction and long-term reliability limiting their clinical adoption. The mismatch in Young’s modulus between silicon implants (∼180 GPa) and brain tissue (∼1-30 kPa) exacerbates the FBR resulting in the development of flexible implants from polymers such as polyimide (∼1.5-2.5 GPa). However, a stiffness mismatch of at least two orders of magnitude remains. Here, we introduce (i) the first mechanically matched brain implant (MMBI) made from silicone (∼20 kPa), (ii) new microfabrication methods, and (iii) a novel dissolvable sugar shuttle to reliably implant MMBIs. MMBIs were fabricated via vacuum-assisted molding using sacrificial sugar molds and were then encased in sugar shuttles that dissolved within 2 min after insertion into rat brains. Sections of rat neocortex implanted with MMBIs, PDMS implants, and silicon implants were analyzed by immunohistochemistry 3 and 9-weeks post-implantation. MMBIs resulted in significantly higher neuronal density and lower FBR within 50 µm of the tissue-implant interface compared to PDMS and silicon implants suggesting that materials mechanically matched to brain further minimize the FBR and could contribute to better implant functionality and long-term reliability.

Advanced strategies to thwart foreign body response to implantable devices

“…Ecoflex, a silicone‐based material with a low stiffness (20 kPa) was assessed as a mechanically matched brain implant (MMBI) in rats 156 . MMBIs consistently elicited a reduced level of activated microglia, reactive astrocytes, and neuronal loss than the stiffer PDMS (~1.6 MPa) and silicon (~180 GPa) implants at both 3‐ and 9‐week postimplantation.…”

Recent advances in materials and applications for bioelectronic and biorobotic systems

“…PDMS is a promising material for soft medical robotics. However, other softer silicone formulations, such as Ecoflex, can be considered due to their even higher compliance with soft biological tissues 12 …”

Significantly reduced inflammatory foreign-body-response to neuroimplants and improved recording performance in young compared to adult rats

“…Despite the overwhelming progress in neuronal engineering of implanted multielectrode arrays (MEA) [1][2][3][4][5][6][7][8], their use is impeded by the deterioration of their recording performance over time, which is manifested in a low signal-to-noise ratio (SNR), poor source resolution, as well as a drop in the number of functional implanted platforms and live electrodes [9][10][11]. Aside from mechanical breakdown issues that will not be discussed here [12,13], brain implants initiate and perpetuate cascades of local noninfectious inflammatory responses culminating in the formation of encapsulating scar tissue around the implant (classically known as the 'foreign body response', or FBR).…”