Natalia Rekowska

Hydrogels are 3D polymeric networks, which exhibit properties such as softness, viscoelasticity and their ability to absorb large amounts of water. These characteristics make them exceptionally suitable in biomedicine as e.g. tissue scaffolds, drug delivery systems, wound dressings or contact lenses. One of these hydrogels is the biocompatible, hydrophilic and photopolymerizable poly(ethylene glycol) diacrylate (PEGDA). It is used in different biomedical applications due to its tunable mechanical characteristics. In our study, the mechanical properties of different PEGDA hydrogel compositions with variyng molecular masses and contents of water/methanol, were investigated. Different compositions containing 20 m%, 30 m% or 40 m% of PEGDA_4K(4,000 g/mol), PEGDA_10K(10,000 g/mol) or PEGDA_20K(20,000 g/mol) in ultrapure water/methanol (1:2) were produced. Dumbbell-shaped samples were prepared in molds via photopolymerization in a UV chamber. Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) was used as photoinitiator (0.5% w/w). The mechanical testing was performed using a uniaxial testing system. The obtained results showed averagely 78% higher tensile strength (σmax) values for 30 m% and 40 m% samples in comparison with 20 m% samples for all of the tested polymers. PEGDA_20K30 m% samples showed the highest σmax among all of the samples with 12.8 MPa. All of the PEGDA20K samples exhibited the highest elongation at break (εB) values (up to 958%), whereas the lowest values were found for PEGDA_4K(up to 105%). The obtained stress-strain curves for most of the samples were typical for deformable, amorphous polymers with a deformation upon reaching a critical stress point. The PEGDA materials showed variable mechanical characteristics according to changing molecular mass or polymer concentration. These promising results showed that it should be possible to compose scaffolds with desired mechanical stability according to the needed application.

Novel fabrication techniques based on photopolymerization enable the preparation of complex multi-material constructs for biomedical applications. This requires an understanding of the influence of the used reaction components on the properties of the generated copolymers. The identification of fundamental characteristics of these copolymers is necessary to evaluate their potential for biomaterial applications. Additionally, knowledge of the properties of the starting materials enables subsequent tailoring of the biomaterials to meet individual implantation needs. In our study, we have analyzed the biological, chemical, mechanical and thermal properties of photopolymerized poly(ethyleneglycol) diacrylate (PEGDA) and specific copolymers with different photoinitiator (PI) concentrations before and after applying a post treatment washing process. As comonomers, 1,3-butanediol diacrylate, pentaerythritol triacrylate and pentaerythritol tetraacrylate were used. The in vitro studies confirm the biocompatibility of all investigated copolymers. Uniaxial tensile tests show significantly lower tensile strength (82% decrease) and elongation at break (76% decrease) values for washed samples. Altered tensile strength is also observed for different PI concentrations: on average, 6.2 MPa for 1.25% PI and 3.1 MPa for 0.5% PI. The addition of comonomers lowers elongation at break on average by 45%. Moreover, our observations show glass transition temperatures (T_g) ranging from 27 °C to 56 °C, which significantly increase with higher comonomer content. These results confirm the ability to generate biocompatible PEGDA copolymers with specific thermal and mechanical properties. These can be considered as resins for various additive manufacturing-based applications to obtain personalized medical devices, such as drug delivery systems (DDS). Therefore, our study has advanced the understanding of PEGDA multi-materials and will contribute to the future development of tools ensuring safe and effective individual therapy for patients.

Here, we present a new hybrid additive manufacturing (AM) process to create drug delivery systems (DDSs) with selectively incorporated drug depots. The matrix of a DDS was generated by stereolithography (SLA), whereas the drug depots were loaded using inkjet printing. The novel AM process combining SLA with inkjet printing was successfully implemented in an existing SLA test setup. In the first studies, poly(ethylene glycol) diacrylate-based specimens with integrated depots were generated. As test liquids, blue and pink ink solutions were used. Furthermore, bovine serum albumin labeled with Coomassie blue dye as a model drug was successfully placed in a depot inside a DDS. The new hybrid AM process makes it possible to place several drugs independently of each other within the matrix. This allows adjustment of the release profiles of the drugs depending on the size as well as the position of the depots in the DDS.

The technology of pharmaceutical drug delivery systems (DDS) as an individual and adjustable tool for drug administration has been intensively developed in the last years. Additive manufacturing (AM) techniques, such as stereolithography, are a promising approach towards DDS scaffold manufacturing. Stereolithography, by using layerby- photo-polymerisation, creates DDS scaffolds with highly controlled 3D geometry. Combined with inkjet printing it allows a very precise positioning of the drug depot in the basic scaffold and therefore also a better control of the drug release. Furthermore, this hybrid AM technique also allows for the creation of a multi-drug DDS with a several drug depots localized in desired positions within the scaffold. Determination of the scaffold and drug depot material properties is one of the initial steps for such novel DDS development. Basic characteristics, such as stiffness, elasticity or glass transition temperature (T_g), are important for designing and adapting the material for biomedical application. The photosensitive poly(ethylene glycol) diacrylate (PEGDA) can be easily formed into a desired biocompatible scaffold geometry via stereolithography. In this study we have focused on the evaluation of PEGDA (Mn=700 g/mol) as a pure and copolymer system in combination with other acrylates (butanediol diacrylate, pentaerythritol triacrylate) as possible materials for DDS using this novel hybrid AM technique. Irgacure 2959, a biocompatible photoinitiator (PI), was used as a radical starter for photopolymerisation. Samples varying in PI and coacrylate concentration were prepared by conventional photopolymerisation. Physico-chemical analyses of the samples were performed and several parameters, such as stiffness, elongation at break and glass transition temperatures, were determined.

Current research activities focus on personalized, comfortable and safe products for systemic or local drug application in patients. Poly(ethylene glycol) diacrylate is in particular interest as a drug delivery material, as it shows appropriate biological properties such as hydrophilicity and low toxicity. Additionally, as an easily photopolymerizable compound it can be also utilized for the production of scaffolds with the use of different techniques such as stereolithography. Even though it is often used as a biomaterial or as a copolymer in many photopolymer systems for drug delivery, thermomechanical analysis and basic understanding are rare.Therefore, we investigated the tensile stress and the glass transition temperature of pure PEGDA and of its copolymers with 1,3-butanediol diacrylate or pentaerythritol triacrylate, as a function of the photoinitiator (PI) or acrylate concentration. Additionally, we demonstrated that the washing procedure decreases the tensile stress values. We showed, that by the means of composing PEGDA with these, it is possible to influence thermomechanical properties of the sample. Our outcomes have revealed, that there is no clear influence of the PI concentration on the thermomechanical properties. However there is an influence of the monomer concentration. Therefore, it should be possible to modify drug release profiles in future experiments.

Three-dimensional (3D) printing has become a popular technique in many areas. One emerging field is the use of 3D printing for the development of 3D drug delivery systems (DDS) and drug-loaded medical devices. This article describes a novel concept for the fabrication of timecontrolled drug delivery systems based on stereolithography combined with inkjet printing. An inkjet printhead and an UV-LED light source have been integrated into an existing stereolithography system. Inkjet printing is used to selectively incorporate active pharmaceutical ingredients (API) during a stereolithographic 3D printing process. In an initial experimental study, poly (ethylene glycol) diacrylate (PEGDA) was used as polymer whereas 2-Hydroxy-4´-(2- hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959) and Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) were used as photoinitiators. Basic structures could be manufactured successfully by the new hybrid 3D printing system.