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

Aditya Josyula, Ann Mozzer, Julia Szeto, Youlim Ha, Nicole Richmond, Seung Woo Chung, Sri Vishnu Kiran Rompicharla, Janani Narayan, Samiksha Ramesh, Justin Hanes, Laura Ensign, Kunal Parikh, Ian Pitha

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbere10487
JournalBioengineering and Translational Medicine
Volume8
Issue number3
DOIs
StatePublished - May 2023

Keywords

  • fibrosis
  • glaucoma shunts
  • nanofibers
  • ocular biomaterials

ASJC Scopus subject areas

  • Biotechnology
  • Biomedical Engineering
  • Pharmaceutical Science

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