The technical and scientific achievements of the project can be classified into five sections: Materials for intraocular implants, 3D-printing methods, magnetic actuation constraints, medical imaging possibilities, pharmacokinetics of hydrogel-based carriers, and aspects of biocompatibility. While each section is important per se, they are interconnected to each other for successful intraocular robotic implants. A detailed discussion on these topics was included in these two publications during the PHOTODOCTOR project (Bozuyuk U., et al., Adv. Mat., 2024; Wang T., et al., Nat. Rev. Bioeng., 2024).
Durability, strength, and controllable degradation were three important parameters for the hydrogels in this project. Several hydrogels are tested during the project and their stiffnesses, degradation products, and degradation time are investigated (Table 1). While the focus in these experiments was on the organic hydrogels, the durability and degradation mechanisms of the synthetic hydrogels exceed their organic counterparts. Because of that, PEGDA is selected as the main constituent for the hydrogel-based degradable body of the small-scale robots. During these investigations, we also published articles on other hydrogel-based structures, such as hydrogel muscles (Zhang M. et al., Nat. Mat., 2023).
There are several fabrication methods to build hydrogel-based small-scale robots, but only 3-D printing methods have both high throughput and high fidelity. Thus, we focused on various 3D printing methods, from two-photon polymerization to digital light processing. We found out that digital light processing (DLP) based 3D printing is significantly more reproducible, accessible, and affordable compared to other methods. Thus the small-scale intraocular robots produced with DLP 3D printing can easily integrate into the clinical practice and enhance personalized medicine options. We presented these results at the most prestigious conference in ophthalmology (Yildiz E., et al., IOVS, 2024).
During the investigation of the magnetic actuation systems for the small-scale robots, electromagnetic coils, and rotating permanent magnets are investigated. While electromagnetic coils can create more complex magnetic fields, rotating permanent magnets can enable the clinical usage of magnetic actuators without high-voltage electrical supplies. Because of their low energy profile and transportability, the rotating permanent magnets are selected as magnetic actuation controllers. Also, magnetic nanoparticles with high ferromagnetic profiles are required for the precise control and cargo-carrying capacity of the small-scale robots. For this reason, several magnetic nanoparticles were investigated, such as nickel-gold, iron-oxide, and iron platinum. At the end of the production of several nanoparticles in-house, iron platinum nanoparticles were selected for the magnetic actuation of small-scale robots. During this part of the project, we also build other magnetic microscale robots with other magnetic nanoparticles (Han M., et al., Nat. Comm., 2024).
In the last steps of the project, we focused on the pharmacokinetics and biocompatibility of these robotic implants. We investigated both dexamethasone levels and the negative effects of high-concentration dexamethasone on both retinal epithelium and immune cells. These results indicate that the slow-release profile of the passively degrading hydrogels can be better for clinical scenarios. Due to that, we avoided the actively induced degradation of hydrogels with light. The detailed results of both pharmacokinetics and biocompatibility will be shared with the public in the latest article of the project (Yildiz E., et al., In prep., 2024).
