A 3D Printed Self-Sustainable Cell-Encapsulation Drug Delivery Device for Periocular Transplant-Based Treatment of Retinal Degenerative Diseases

Abstract

Self-sustainable release of brain-derived neurotrophic factor (BDNF) to the retina using minimally invasive cell-encapsulation devices is a promising approach to treat retinal degenerative diseases (RDD). Herein, we describe such a self-sustainable drug delivery device with human retinal pigment epithelial (ARPE-19) cells (cultured on collagen coated polystyrene (PS) sheets) enclosed inside a 3D printed semi-porous capsule. The capsule was 3D printed with two photo curable polymers: triethylene glycol dimethacrylate (TEGDM) and polyethylene glycol dimethylacrylate (PEGDM). The capsule’s semi-porous membrane (PEGDM) could serve three functions: protecting the cells from body’s immune system by limiting diffusion (5.97 ± 0.11%) of large molecules like immunoglobin G (IgG)(150 kDa); helping the cells to survive inside the capsule by allowing diffusion (43.20 ± 2.16%) of small molecules (40 kDa) like oxygen and necessary nutrients; and helping in the treatment of RDD by allowing diffusion of cell-secreted BDNF to the outside environment. In vitro results showed a continuous BDNF secretion from the device for at least 16 days, demonstrating future potential of the cell-encapsulation device for the treatment of RDD in a minimally invasive and self-sustainable way through a periocular transplant.

3D Printing in Eye Care

“…Kojima et al described their development of a periocular, transscleral, 3D-printed delivery device containing human RPE cells and providing sustained release of brain-derived neurotrophic factor to the retina. In vitro data showed continuous secretion for at least 16 days [ 162 ]. Lee et al designed an intravitreal, transscleral-sutured delivery device consisting of micro- and nanochannels and a reservoir system whose components were produced using 3D-printed molds [ 163 ].…”

Injectable Hydrogels: A Paradigm Tailored with Design, Characterization, and Multifaceted Approaches

“…[468][469][470] Other methods that make use of injectable SHHs include the injection of stem/progenitor cells, antioxidative hydrogels to prevent macular degeneration, and cell encapsulation therapy, which involves the intake of hydrogels bearing gene-adapted cells that unceasingly secrete antivascular endothelial growth factors. [471][472][473][474][475]…”

Multidisciplinary Approaches in the Treatment of Retinal Degenerative Diseases: A Review

“…For example, Kojima et al encapsulated modified ARPE-19 cells in periocular transplant-based devices to release brain-derived neurotrophic factor, which is capable of reviving damaged photoreceptors. [30,31] The self-sustainable device offers the benefit of limiting immunoglobulin diffusion while allowing oxygen and nutrients to be transmitted and secreting brain-derived neurotrophic factor for at least 16 days in vitro. Similarly, Neurotech developed an encapsulated cell therapy to transmit ciliary neurotrophic factor.…”