Design, Fabrication, and In Vitro Testing of an Anti-biofouling Glaucoma Micro-shunt

Abstract

Glaucoma, one of the leading causes of irreversible blindness, is a progressive neurodegenerative disease. Chronic elevated intraocular pressure (IOP), a prime risk factor for glaucoma, can be treated by aqueous shunts, implantable devices, which reduce IOP in glaucoma patients by providing alternative aqueous outflow pathways. Although initially effective at delaying glaucoma progression, contemporary aqueous shunts often lead to numerous complications and only 50% of implanted devices remain functional after 5 years. In this work, we introduce a novel micro-device which provides an innovative platform for IOP reduction in glaucoma patients. The device design features an array of parallel micro-channels to provide precision aqueous outflow resistance control. Additionally, the device's microfluidic channels are composed of a unique combination of polyethylene glycol materials in order to provide enhanced biocompatibility and resistance to problematic channel clogging from biofouling of aqueous proteins. The microfabrication process employed to produce the devices results in additional advantages such as enhanced device uniformity and increased manufacturing throughput. Surface characterization experimental results show the device's surfaces exhibit significantly less non-specific protein adsorption compared to traditional implant materials. Results of in vitro flow experiments verify the device's ability to provide aqueous resistance control, continuous long-term stability through 10-day protein flow testing, and safety from risk of infection due to bacterial ingression.

Nano-structured glaucoma drainage implant safely and significantly reduces intraocular pressure in rabbits via post-operative outflow modulation

“…Kam and coworkers demonstrated that nanoscale features with high aspect ratios decrease expression of several growth factors associated with fibrosis 26 . Their experiments revealed that these features can also reduce protein adsorption, which has been implicated in glaucoma device fouling and can lead to infection, increase in IOP, or device failure 27 . The methods used to manufacture marketed drainage devices are limited in their capacity to achieve these effects through manufacturing alone 39 .…”

“…Electrospinning is a promising platform for the development of GDIs for glaucoma surgery, as it allows for incorporation of almost any absorbable or non-absorbable polymer into nano-or micro-fibers which can be configured into devices of myriad dimensions and conformations 24,25 . Importantly, nanoscale features have been shown to mimic a more native environment for cells, down-regulate fibrosis, and limit protein adsorption, which has been previously implicated in glaucoma device fouling and failure 26,27 . To date, electrospinning has been used widely in tissue engineering, and more recently, in the manufacture of medical devices 28 .…”

<p>Potential Therapeutic Usage of Nanomedicine for Glaucoma Treatment</p>

“…However, additional studies with most common microbes and in vivo animal studies are yet to be completed to validate the efficiency of the device. 158 …”

Nanotechnology for Medical and Surgical Glaucoma Therapy—A Review

“…Harake et al [179] designed an anti-biofouling micro-device which provides an innovative platform, also using MEMS, for IOP reduction in patients with glaucoma. This novel device has an array of parallel micro-channels built inside to yield controlled aqueous outflow resistance.…”