Digital Light Processing 3D Printing Method for Magnetically Controllable Intraocular Dexamethasone Implants

Abstract

Purpose : Intravitreal dexamethasone (DEX) implants are increasingly used for retinal medical therapies, including age-related macular degeneration, diabetic retinopathy, and macular edema. Despite good results in halting the disease and improving vision, therapy with the DEX implant may cause unexpected complications that could have serious consequences for the patient, requiring further surgery due to the displacement of the implant or uncontrolled release of the drug. This project aims to overcome these challenges through milli-scale magnetically actuated hydrogel-based retinal drug implants.

Methods : We designed and built a magnetically controllable and biodegradable intraocular implant from scratch. The mechanical properties of various natural hydrogels were modified to enable them to create helical swimmers. These hydrogels were loaded with magnetic iron platinum (FePt) particles and DEX. After characterization, they were 3D printed with a digital light processing (DLP)-based bioprinter. Lastly, the optimized hydrogel-based magnetic intraocular implants were actuated with rotating magnetic fields, and their biocompatibility and efficiency were investigated in ARPE-19 cells and ex vivo porcine eyes under optical coherence tomography (OCT).

Results : Comparable to the current size of commercial DEX implants,6 mm length and 1 mm width were selected as the optimal scale for long-term drug release in the eye. The methacrylated forms of the natural hydrogels for magnetically controllable double helical intraocular implants showed high 3D printing fidelity in the DLP-based bioprinting method. While high concentrations of FePt (~10 mg/ml) and DEX (~700 mg/ml) were achieved, their mechanical properties, actuation speeds, and biocompatibility with ARPE-19 varied due to different constituents and crosslinks. We achieved the production of magnetically controllable and biodegradable retinal drug implants and tracked them inside an ex-vivo eye model in real-time.

Conclusions : This simple photocrosslinking-based 3D bioprinting method can be used to produce magnetically controllable intraocular implants. These active natural hydrogel-based implants showed higher drug loading and longer drug release periods compared to commercial intravitreal implants. They could be used for actuation of the implants for better targeting of the diseased areas or non-invasive relocation of the implants after displacement.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.