Nanofiber-based glaucoma drainage implant improves surgical outcomes by modulating fibroblast behavior.

Biomaterials are implanted in millions of individuals worldwide each year. Both naturally derived and synthetic biomaterials induce a foreign body reaction that often culminates in fibrotic encapsulation and reduced functional lifespan. In ophthalmology, glaucoma drainage implants (GDIs) are implanted in the eye to reduce intraocular pressure (IOP) in order to prevent glaucoma progression and vision loss. Despite recent efforts towards miniaturization and surface chemistry modification, clinically available GDIs are susceptible to high rates of fibrosis and surgical failure. Here, we describe the development of synthetic, nanofiber-based GDIs with partially degradable inner cores. We evaluated GDIs with nanofiber or smooth surfaces to investigate the effect of surface topography on implant performance. We observed in vitro that nanofiber surfaces supported fibroblast integration and quiescence, even in the presence of pro-fibrotic signals, compared to smooth surfaces. In rabbit eyes, GDIs with a nanofiber architecture were biocompatible, prevented hypotony, and provided a volumetric aqueous outflow comparable to commercially available GDIs, though with significantly reduced fibrotic encapsulation and expression of key fibrotic markers in the surrounding tissue. We propose that the physical cues provided by the surface of the nanofiber-based GDIs mimic healthy extracellular matrix structure, mitigating fibroblast activation and potentially extending functional GDI lifespan.

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

Glaucoma is a leading cause of irreversible vision loss predicted to affect more than 100 million people by 2040. Intraocular pressure (IOP) reduction prevents development of glaucoma and vision loss from glaucoma. Glaucoma surgeries reduce IOP by facilitating aqueous humor outflow through a vent fashioned from the wall of the eye (trabeculectomy) or a glaucoma drainage implant (GDI), but surgeries lose efficacy overtime, and the five-year failure rates for trabeculectomy and tube shunts are 25-45%. The majority of surgical failures occur due to fibrosis around the vent. Alternatively, surgical procedures can shunt aqueous humor too well, leading to hypotony. Electrospinning is an appealing manufacturing platform for GDIs, as it allows for incorporation of biocompatible polymers into nano- or micro-fibers that can be configured into devices of myriad combinations of dimensions and conformations. Here, small-lumen, nano-structured glaucoma shunts were manufactured with or without a degradable inner core designed to modulate aqueous humor outflow to provide immediate IOP reduction, prevent post-operative hypotony, and potentially offer significant, long-term IOP reduction. Nano-structured shunts were durable, leak-proof, and demonstrated biocompatibility and patency in rabbit eyes. Importantly, both designs prevented hypotony and significantly reduced IOP for 27 days in normotensive rabbits, demonstrating potential for clinical utility.

A New Strategy for Intestinal Drug Delivery via pH-Responsive and Membrane-Active Nanogels.

Oral administration of hydrophobic and poorly intestinal epithelium-permeable drugs is a significant challenge. Herein, we report a new strategy to overcome this problem by using novel, pH-responsive, and membrane-active nanogels as drug carriers. Prepared by simple physical cross-linking of amphiphilic pseudopeptidic polymers with pH-controlled membrane-activity, the size and hydrophobicity-hydrophilicity balance of the nanogels could be well-tuned. Furthermore, the amphiphilic nanogels could release hydrophobic payloads and destabilize cell membranes at duodenum and jejunum pH 5.0-6.0, which suggests their great potential for intestinal drug delivery.