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

Author:

Josyula Aditya12ORCID,Mozzer Ann13,Szeto Julia13,Ha Youlim12,Richmond Nicole14,Chung Seung Woo13,Rompicharla Sri Vishnu Kiran13ORCID,Narayan Janani12,Ramesh Samiksha15,Hanes Justin12356,Ensign Laura12357ORCID,Parikh Kunal1358ORCID,Pitha Ian139

Affiliation:

1. Center for Nanomedicine Johns Hopkins University School of Medicine Baltimore Maryland USA

2. Department of Chemical and Biomolecular Engineering Johns Hopkins University Baltimore Maryland USA

3. Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine Baltimore Maryland USA

4. Department of Biology Johns Hopkins University Baltimore Maryland USA

5. Department of Biomedical Engineering Johns Hopkins University School of Medicine Baltimore Maryland USA

6. Departments of Pharmacology and Molecular Sciences, Environmental Health Sciences, Oncology, and Neurosurgery Johns Hopkins University School of Medicine Baltimore Maryland USA

7. Departments of Pharmacology and Molecular Sciences, Infectious Diseases, Oncology, and Gynecology and Obstetrics Johns Hopkins University School of Medicine Baltimore Maryland USA

8. Center for Bioengineering Innovation & Design Johns Hopkins University Baltimore Maryland USA

9. Glaucoma Center of Excellence, Wilmer Eye Institute Johns Hopkins University School of Medicine Baltimore Maryland USA

Abstract

AbstractBiomaterials 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.

Funder

National Institutes of Health

Publisher

Wiley

Subject

Pharmaceutical Science,Biomedical Engineering,Biotechnology

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