3D-Printed Therapeutic Vitamin E Bandage Contact Lenses

Abstract

The ocular surface is extremely effective at protecting the eye through such physiological barriers as the cornea and tear film. The exposed nature of the cornea can still lead to a significant number of injuries and harm from the external environment. Management and treatment of ocular injuries involves a combination of a bandage contact lens (BCL) along with therapeutic eye drops that require frequent and strict dosing regimens that can be difficult to maintain and are inefficient due to the high clearance rate of the eye. Therapeutic contact lenses (TCL) with vitamin E (VE) incorporated have been shown to steadily release a desired therapeutic agent and potentially simplify a patient’s treatment process. Vat polymerization (VP), a form of 3D printing, was utilized in this work to explore a platform design for developing customizable VE-containing TCLs, using dexamethasone phosphate (DXP) as a model drug. VP was also used to explore the creation of a multi-material TCL, using a VE embedded ring that could be directly printed within the lens in a streamlined and automated manner. Three lens formulations consisting primarily of hydroxy ethyl methacrylate (HEMA) and polyethylene glycol diacrylate (PEGDA) with modified formulations containing methacrylated VE (VEMA) and Methacryloxypropyltris (Trimethylsiloxy) silane (TRIS) as a model silicone material were prepared. These lenses were synthesized and characterized to examine 3D printing for lens creation in comparison to commercial standards. The base and VEMA formulations were used to examine the feasibility of a multi-material (MM) lens with an embedded ring directly incorporated during the printing process. All three formulations showed shear thinning properties suitable for VP bioprinting applications. The base formulation produced a very homogenous print while VEMA prints showed defects and clear phase separation. The VEMA+TRIS formulation showed significant improvement as the prints were more homogenous with fewer defects. The MM lenses showed a mixture of properties between the base and VEMA formulations, with the center appearing more homogenous and the edge that included the embedded ring showing defects similar to VEMA prints. Surface wettability and water content decreased from the base formulation with an increasing presence of hydrophobic moieties in the modified formulations. The increased hydrophobicity can be correlated with an increase in stiffness seen from the base formulation. While all materials had high moduli due to the high crosslinking density and presence of PEGDA, the VEMA prints had a higher modulus than the base material but were quite brittle due to the increased hydrophobicity and poor print quality. The VEMA+TRIS prints showed a significant (p < 0.05) increase in stiffness without the brittleness of the VEMA prints due to the better print quality. The MM prints had the lowest moduli, most similar to the base material, indicating that this lens design could mitigate the brittleness seen with the VEMA prints. A comparison of 3DP and casting showed the cast material having a significantly (p < 0.05) higher modulus than the 3DP material presumably due to the bulk vs. layer-by-layer polymerization processes that the respective manufacturing methods utilize. The base material produced significantly more transparent prints, with transmissions (wavelength) that ranged between 80-88%, compared to the VEMA and VEMA+TRIS prints which ranged from 18-47%. The MM lenses showed promise for minimizing the effect of the poor transparency of the VEMA ring with transparency of 62-85%. Besides the formulations, the lens thickness, print quality and print plate surface were found to be major contributors to the printed lenses not meeting commercial standards. The VEMA+TRIS loaded lenses showed the greatest changes in the release kinetics with a larger burst release, attributed to the weaker affinity DXP has to the hydrophobic components, while the base and VEMA lens’ profiles were very similar. The weaker drug-polymer interaction and more mobile silicone-oxygen bonds of TRIS are likely the reason for the VEMA+TRIS formulation releasing significantly more DXP than the base or VEMA lenses, with 69.21 ± 3.62%, 44.09 ± 4.63% and 37.09 ± 4.81% released respectively. It is believed that the high degree of crosslinking within the lens polymer matrix causes high levels of physical entrapment, resulting in an incomplete release of DXP from the lenses. Another possibility is that some DXP reacted with the acrylate components of the lens formulations as the photopolymerization process creates free radicals which could lead to the formation of covalent bonds of DXP with one of the monomers in the formulation. The use of 3DP to develop customizable TCLs on-demand has a lot of potential as the biomedical and healthcare industries shift to more of a personalized rather than a one-size-fits all approach. The MM lens design allows for the incorporation of materials with poor lens properties without significantly impacting the lens’ functions such as its tensile stiffness and transparency. The freedom of design that 3DP provides will allow for tailor-made lenses that can meet a patient’s specific needs, including lens fitting, which would maximize the patient’s comfort.