The new lens-type biodegradable DDS was designed with the following initial settings of the 3D printer: printer head temperature, 26°C; printer bed temperature, 9°C; diameter, 15 mm; height, 4 mm; and thickness, 0.3 mm. The DDS was created with the same values as the initial modeling values, and the shape was maintained when using a nozzle pressure of 80 kPa and speed of 4 mm/sec for 0.1% hyaluronic acid, a nozzle pressure of 50 kPA and speed of 3 mm/sec for 0.15% hyaluronic acid, a nozzle pressure of 60 kPA and the speed of 8 mm/sec for 0.3% hyaluronic acid (Fig. 1A, 1B). In conditions other than the optimal ones, either the diameter of the lens increased to 17-20 mm or the height decreased to 2.5-3.0 mm, and the shape was not maintained after production.

Cell viability according to the concentration of tobramycin was confirmed through MTT assay. When 1% tobramycin and live cells were mixed, more than 90% of the normal cells survived (p > 0.05). At 2%, 4%, and 5% tobramycin, the survival rate was 84% (p < 0.05), 52% (p < 0.005), and 31% (p < 0.005) respectively. In other words, cytotoxicity was shown at a concentration of 2% tobramycin (p < 0.05). Since no cytotoxicity was observed at 1% tobramycin (p > 0.05), and pharmacological effects were as clinically expected at this concentration, it was determined to be appropriate (Fig. 2).

When the new lens-type biodegradable DDS manufactured under the most appropriate conditions above was stored in PBS at 4°C, it was confirmed that biodegradation did not occur regardless of the UV crosslink post-processing and the concentration of hyaluronic acid (Fig. 3). In other words, it was found that it could be stored continuously at 4°C.

Biodegradation was shown when the new lens-type biodegradable DDS made of different concentrations of hyaluronic acid was stored in PBS at 37°C after 60 seconds of UV crosslink post-processing. Degradation of up to 42%-54% occurred within the first 24 hours, and the DDS remained at a similar concentration until 14 days thereafter. As a result, when the DDS was stored at 37°C and UV crosslink post-processing was performed for 60 seconds, it was stored at a constant level for more than 14 days regardless of the concentration of hyaluronic acid (Fig. 4).

Bio-ink is a biomaterial that transports living cells during bioprinting. It refers to materials that can be applied to bioprinting technology to produce necessary structures, including living cells and biomolecules. Bio-ink material requires excellent biocompatibility to be used in bioprinting and physical properties that can be printed in the desired pattern by smoothly passing through a micro-diameter nozzle, and it should be able to maintain its role as a mechanical support while providing a cell-specific signal after printing [13-15]. Currently, bio-inks are being actively studied to produce substitute materials for organs and tissues. It is possible to manufacture bio-inks as a structure, but there is still a limitation with regard to their functional role. For example, heart replacement material can be manufactured so that it can function almost identically similar to the real one in terms of structure. However, there is a limit to its role in making and transmitting the electric current of cardiomyocytes in terms of its functional aspect [16,17]. Bio-inks currently widely use include gelatin, hyaluronic acid, collagen, fibrinogen, and glycerol. These materials are hydrophilic polymers cross-linked by cohesive force and have a 3D polymer network structure that can absorb a large amount of water and swell in an aqueous solution. In addition, these may be biodegradable and biocompatible materials, and degradation and transparency can be controlled according to concentration. In the field of ophthalmology, there is a report on the replacement of the cornea using bioprinting [18]. In this study, the new lens-type biodegradable DDS was manufactured using gelatin-based gelatin methacryloly and hyaluronic acid. Hyaluronic acid is a hydrophilic substance that is abundantly present in the eyes and joints. In addition, it is possible to control its degree of degradation by changing the structure according to temperature [19]. Using these features, it can be stored at 4°C normally, and it can be manufactured to an appropriate level even at 37°C, which is the body temperature. Moreover, in this study, 1% tobramycin was mixed to prevent infection, thereby showing the possibility that other eye drops, as well as antibiotics, can be mixed when manufacturing such lenses. Since a constant concentration was maintained during biodegradation, it is expected that it can be manufactured successfully to treat various types of eye diseases. It is a patient-customized DDS using 3D bioprinting technology. It is formed according to the curves to make it easier on the cornea when worn, and the surface of the structure is slightly irregular but soft. In particular, when worn on the human body and exposed to tears, it is reached to the decomposition temperature since drug secretion progresses. Also, transparency and surface smoothness are increased by tears due to the nature of bio-ink. Still, more research is needed to secure the visibility of the lens and maintain the drug at a specific concentration after degradation. However, a new lens-type biodegradable DDS can be mass-produced quickly and easily using a 3D printer. The material produced in this way has excellent adhesion to the eye, biocompatibility, and bio absorption and increased adhesion time, thereby confirming the possibility of treating various diseases as well as dry eye disease, which is a meaningful result of this study.