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Inkjet printing is a versatile tool for the precise positioning of droplets that is used in many application areas such as 3D printing, biotechnology or pharmacy. This work focused on comparing the inkjet printability of different drug solutions of celecoxib (CLX), a non-steroidal anti-inflammatory drug, to produce drug depots in medical implants. CLX was dissolved in dimethyl sulfoxide (DMSO), poly(ethylene glycol) diacrylate (PEGDA) and a mixture of DMSO and PEGDA in a ratio of 1:1. The pure solvents and the drug solutions were inkjet printed using a Nanoplotter 2.1 with the NanoTip J printhead (GeSiM mbH, Radeberg, Germany). The voltage was varied from 60 V to 150 V using a step size of 5 V. Droplet volume and the trajectory of the droplets were investigated. For DMSO, DMSO-CLX, DMSO-PEGDA and DMSOPEGDA- CLX, reproducible droplet formation occurred with a droplet volume of approximately 300 pl - 500 pl and not more than one satellite droplet in a voltage range between 60 V to 80 V. Inkjet printing of PEGDA and PEGDA-CLX was not reproducible in the range of 60 V to 150 V. DMSO, DMSOPEGDA, DMSO-CLX and DMSO-PEGDA-CLX showed a high inkjet printability. In contrast, inkjet printability of PEGDA and PEGDA-CLX was very limited.

Physical vapor deposition (PVD) sputtering is a promising technique for the generation of electrically conductive coatings on complex structured biomaterials, such as nonwovens, that can be used in implants. The ultra-thin coatings can fulfil a variety of purposes, such as drug depot or biosensor. The aim of our studies was to determine the feasibility of generating thin silver (Ag) coatings on complex structured poly-L-lactide (PLLA) nonwovens by sputtering and their morphological characterization. PVD sputter process was performed using a customized plasma chamber and a complex rotation of the tender electrospun PLLA nonwovens. Morphological analysis revealed a promising homogenous Ag coating, representing the structure of the nonwovens.

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 PEGDA4K(4,000 g/mol), PEGDA10K(10,000 g/mol) or PEGDA20K(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. PEGDA20K30 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 PEGDA4K(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.

Poly(N-isopropylacrylamide) (PNIPAM) hydrogels are one of the most commonly studied thermoresponsive biomaterials. In this work, we investigate ball milling as a method of producing PNIPAM nanogels and confirm that the temperature responsiveness is maintained in the nanogel form based on hydrodynamic diameter and zeta potential measurements.

Heart valve tissue engineering aims at creating living valves through colonization of scaffolds with patient’s own cells. Various cell sources have been explored focusing mainly on endothelialization of the scaffold surface. Endothelial like cells, such as endothelial progenitor cells (EPCs), which can be isolated from peripheral blood or bone marrow could be a suitable option. In this study we investigated cell colonization potential of ovine EPCs (OEPCs) on thermoplastic silicone-based polyurethane (TSPU) polymer scaffolds. TSPU nonwovens with and without vascular endothelial growth factor (VEGF) functionalization were used. SEM images showed that by day 3 the cells were growing as patches on the surface of both polymer groups. The cell patches continued growing and started covering more of the nonwoven surface. On day 7 the cells had almost covered the scaffold surface. The cells were more uniformly distributed as monolayer on the functionalized TSPU compared to the non-functionalized nonwovens. Live/Dead staining provided bright green fluorescence on the samples, indicating metabolically active alive cells. These static cell seeding experiments demonstrated that functionalized TPSU nonwovens support endothelialization. The feasibility of TPSU nonwovens as heart valve prosthesis scaffold could be further explored with animal studies in an ovine model.

Drug delivery systems (DDS) are suitable for controlled local drug release in order to ensure safety and effectiveness of medical treatment. The choice and characterization of biomaterials that can be used as a DDS is a challenging step in the administration of drugs. Novel 3D printing photopolymerization-based techniques create the possibility for designing individual, patient-tailored DDS. Poly(ethylene glycol) diacrylate`s (PEGDA`s) chemical and biological properties make it a suitable photopolymerisable resin for the creation of DDS. This study describes the in vitro release of the antiseptic drug chlorhexidine (CHX) from UV-cured PEGDA and its copolymers (butanediol diacrylate, pentaerythritol triacrylate and pentaerythritol tetraacrylate) samples. A substantial decrease in CHX release with increasing concentration of the copolymers in comparison to pure PEGDA was obtained only for butanediol diacrylate. For pentaerythritol triacrylate and pentaerythritol tetraacrylate only a tendency of decreased CHX release with increasing concentration was detected. Therefore, release profiles of the low molecular drug CHX from PEGDA samples could be modified by the addition of copolymers with a different number of acrylate groups and PEGDA can be considered as a promising candidate for the preparation of novel DDS.

Poly(N-isopropylacrylamide) hydrogels are a popular temperature sensitive biomaterial. Bulk hydrogels can be quickly and easily processed into microgels using a ball mill. However, there is no information on whether the mechanical milling process affects critical PNIPAM characteristics. In this work, we compare swelling and thermo-responsive properties for a series of PNIPAM gels in bulk and microgel forms.

For the investigation of in vitro drug release, methods have been used in which samples of drug delivery systems are immersed in release medium. The medium is used to measure drug concentration via chromatography or photometry. These systems are suitable to investigate the drug release of different systems or to simulate tissue environments. When considering predominantly humid regions, e.g. for drug release into the cochlea through the round window membrane by a drug delivery system placed at that membrane, reproducible in vitro determination of drug release becomes particularly challenging. In this study the development of a system is reported that allows the investigation of the in vitro drug release simulating such conditions.

For the generation of tailor-made polymer coatings on nanofibrous nonwovens plasma enhanced chemical vapor (PECVD) is a promising process, even for complex geometries. The plasma coatings can greatly improve their suitability for biomedical applications by optimising biocompatibility to the local needs, especially for cardiovascular disease treatments. Therein, wound healing and endothelialisation are important steps which are connected by a complex interaction. The monomers allylamine and hexamethyldisiloxane, as well as different process conditions were studied for the coating of nanofibrous thermoplastic silicone polycarbonate polyurethane (TSPCU) nonwovens. Aim of this study was to investigate the feasibility of plasma polymer coating under preservation of the nanofibrous morphological structure. Beside characterization of the nonwoven, biological evaluation with endothelial and fibroblast cells was performed. The prepared nonwoven samples support the feasibility of plasma coating under preservation of the nanofibrous structure. Also, different effects of the surfaces in contact with fibroblasts and endothelial cells could be observed.

Electrospinning is a popular method for creating nonwoven fiber materials for a wide variety of applications. In the field of biomaterials, electrospun materials are favoured because of a high surface-to-volume ratio which can be useful for drug loading and release, and because nanoscale fibers mimic native tissue structures, improving cell interactions. However limitations exist with regards to traditional solvent evaporation-based electrospinning techniques. A new area of research into reactive electrospinning is investigating methods of electrospinning that rely on in situ crosslinking rather than solvent evaporation to stabilize fibers. These techniques can potentially reduce the waste of excess solvents and make it easier to electrospin water soluble polymers. In this work, UV photocrosslinked PEGDA is evaluated as a material for reactive electrospinning. To facilitate the electrospinning process poly(ethylene glycol) diacrylate (PEGDA) is combined with polyvinyl alcohol (PVA). PEGDA/PVA solutions can be successfully electrospun under constant UV light exposure to initiate the crosslinking of the PEGDA. Reactive electrospun fibers appear more stable immediately after spinning and after washing with water, indicating successful photo crosslinking.

The use of biomaterials in medicine is becoming increasingly important. One of the main concerns is the foreign body associated infection caused by direct microbial contamination or clinical infections. The bacterial biofilm formation on biomaterials depends on their surface properties. Therefore, several anti-adhesive surface modifications were developed. Nevertheless, the demand for antimicrobial agents that prevent bacterial colonisation is still largely unmet. The immobilization of active antimicrobial agents, such as antibacterial peptides or enzymes, offers a potential approach to achieve long-lasting effectiveness. In this investigation, the hydrolytic enzyme papain with its published antibacterial activity was covalently immobilized on the well-established biodegradable biomaterial poly-L-lactic acid (PLLA). For the characterization of the enzymes on the PLLA surfaces, the protein content and enzyme activity were determined. A biofilm assay was performed to test the effect of the papain-modified PLLA samples on the biofilm-forming bacterial strain Clostridioides difficile, one of the most frequently occurring human nosocomial pathogens. The investigated hydrolytic enzyme papain could be immobilized by coupling via the crosslinker EDC to the PLLA surface. Detection was performed by determination of the amount of protein and the reduced biofilm growth after 24 h and 72 h compared to the reference.

Sustained local drug release and high local drug concentrations can be achieved by specially designed DDSs, which can be created for different applications. This results in therapeutic drug amounts at the site of action, simultaneously providing a very low drug amount in total. Bodily compartments that contain liquids may be used to transport the drugs from DDS into the tissue, such as the cochlea with the perilymph in the case of cochlea implants. However, predominantly dry environments, such as the middle ear, are lacking such a medium but may deliver enough moisture for the use of swellable DDS through the surrounding mucus membranes. Therefore, DDS with new functionalities are needed to ensure a sustained drug release. In this study, the release of dexamethasone out of a photopolymer system is presented. The system is built from UV-polymerized PEGDA followed by the incorporation of dexamethasone via swelling. The drug release is tested in vitro with isotonic NaCl solution for specified time periods, showing two phases: a swelling phase and a release phase. After the swelling phase the concentration of dexamethasone in the release medium was not controlled by diffusion, although sink conditions were ensured. In contrast, this system can be used to release the drug until equilibrium with a final medium concentration that is far below the solubility of dexamethasone. Hence, such DDS may be useful for dexamethasone delivery into the cochlea through the round window membrane by ensuring a constant concentration in the perilymph.

Individually tailored drug delivery systems (DDSs) are considered one of the most promising therapeutic tools for the creation of safe and effective treatments. DDSs as a novel approach should be beneficial in curing systemic as well as local ailments, where a high topical concentration of the drug and a reduction of side effects are desirable. It could also be favorable for patients requiring customized treatments, showing atypical profiles of drug metabolism. Development of particular drug delivery devices require the selection of a suitable scaffold material, which should exhibit proper mechanical and biological properties, but also enable adjustment of the drug release according to a specific need. Thus, it is extremely important to expand the knowledge concerning potential DDS components. Poly(ethylene glycol) diacrylate (PEGDA) according to its properties can be easily used as a DDS resin and shaped into a desired structure with the employment of techniques based on photopolymerization, including some novel 3D printing techniques. As a continuation of our previous works, in this paper drug release studies from conventionally prepared PEGDA scaffolds are presented. We have shown that in PEGDA materials, the release profile of the low molecular weight model drug acetylsalicylic acid can be altered by water content. PEGDA as a delivery material should be further investigated to specify its potential as a comonomer and a matrix for pharmaceutical agents.

Mimicking the structural properties of natural tissue was aimed to be achieved by combining complementary mechanical properties of materials showing high tensile strength with those of high elasticity. By using two polymers with different properties, the advantages of both can be combined to access innovative materials for biomedical applications. Dual co-electrospinning was established to generate biocompatible nonwoven fibre composites with fused properties from polyamide (PA6) and polyurethane based silicone elastomers (PU-co-Si), respectively. By electrospinning both compounds simultaneously, significant advantages, such as combining different fibre thicknesses and mechanical properties, are accessible. Furthermore, the effect on the fibres via an optional post-processing step in the shape of different thermal treatments was investigated. Initial results concerning surface morphology, biocompatibility and tensile properties of the obtained electrospun nonwovens are very auspicious. Thus, the suitability of two complementary polymer classes for tissue biomimicry through a synthetic approach was shown, offering the opportunity of novel implant materials for permanent replacement of biological tissue.

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.

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.

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 (Tg), 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.

Insertion of a cochlear implant (CI) into the scala tympani evokes electrode insertion trauma that can result in mechanical damage of the lateral and medial wall and causes ingrowth of fibrous tissue on the implant surface. In consequence, it is of great clinical interest to modify the silicone surface of CI electrodes in order to inhibit and minimize the overgrowth by connective tissue. In this case, the covalent coupling of bifunctional polymers on common CI silicone surfaces is a versatile method to influence the implant cell interaction, but is still a challenge due to the chemically unreactive properties of silicone. We present a sophisticated method to apply a biodegradable polymer coating, such as polylactide or polyhydroxybutyrate, on silicone surfaces to generate a drug delivery system using a covalently bound intermediate layer. The adhesive coatings were applied via spincoating processes with different adherence to the intermediate layer. Changes in surface morphology were investigated by comparison of pure silicone and coated silicone. Specific polymer bands of the infrared spectra were detected by IR spectroscopy. Results indicate a complete coating with polylactide or polyhydroxybutyrate. The presented method is a versatile tool for the coating of silicone CI electrodes with degradable polymer layers.

Plasma enhanced chemical vapor deposition is a promising process for the generation of tailor-made polymer coatings on medical devices in order to improve their implant/ host interaction. The ultra-thin coatings can fulfil a variety of purposes, depending on the monomers used, the process conditions and the location of the coated implants in the human body. In addition, even complex geometries can be coated easily and without the application of solvents. Particularly hydrophilic and hydrophobic plasma polymer coatings can improve biocompatibility, especially in blood contact. Furthermore, the selection of the monomers used enables the generation of specific functional groups for further surface immobilization of drugs, such as proteins, by chemical crosslinking. The release of toxic residues from polymeric implants, such as monomers, additives or degraded components, can also be avoided. The aim of our investigation was the generation of plasma polymer films, their characterization and application as coatings for biodegradable metallic biomaterials in order to retard the degradation process. Metallic biomaterials, in various forms are frequently used in orthopaedics, dentistry, cardiovascular and neurosurgical equipment, because of their tensile strength, fracture toughness, fatigue strength and electrical conductivity. Plasma polymerization was performed using the monomers hexamethyldisiloxane and allylamine. The resulting plasma polymers were analysed in an accelerated degradation test. Both plasma polymers appear to be promising, while polyHMDSO appears to degrade over time and polyallylamine indicates to be stable.

Drug Delivery Systems (DDS) are frequently operating in a surrounding liquid environment, such as blood in the case of drug-eluting stents or perilymph in the case of cochlear implants. However, there is also a demand for systems with sustained drug release in predominantly dry environments, mostly consisting of ambient air. Examples are the treatment of diseases located in the middle ear or the paranasal sinuses. On the one hand, due to the lack of transportation media, the functionality of a polymer/drug combination for delayed release would be limited in such environments. On the other hand, these environments are generally equipped with mucus membranes. Hence, a somewhat humid surrounding is ensured. In this study, a concept of a hydrogel equipped DDS for drug delivery through the round window membrane is presented, addressing two objectives. First objective is to ensure the drug transport by serving as a diffusion channel. For instance the route to the drug target destination, the round window membrane, can be provided by a hydrogel. The second objective is to ensure the adhesion to the membrane. Two promising approaches are presented in this study: The photo induced immobilisation of PEGDA700, as well as the immobilisation of chitosan on poly(l-lactid) (PLLA). For both approaches PLLA specimen had to be modified with oxygen plasma followed by activation for crosslinking with subsequent immobilisation of the hydrogel. With these methods a layer thickness of at least 5 μm was achieved. All steps were characterized with contact angle measurements. After the immobilization of the hydrogel, the swelling factor, as well as the layer thickness was examined.

For a long-term efficient drug-eluting stent for vascular applications, the development of drug-loaded coating, combining the effective inhibition of smooth muscle cell proliferation while promoting the re-endothelialization, is a promising concept. However the mostly required simultaneous incorporation of drugs can influence decisively the stability, efficacy and release of the respective drug. Therefore, the mutual influence of a dual local drug delivery coatings based on poly(L-lactide-co-ε-caprolactone) (PLLA-co-CL) containing vascular endothelial growth factor (VEGF165) coupled to the surface and an embedded drug, such as fluorescein diacetate (FDAc) instead of Paclitaxel (PTX) on the in vitro drug release was investigated. Surprisingly, for the investigated coating the immobilized VEGF loading was enhanced and the release profile was accelerated by FDAc incorporation. Even a manifold increase for the in vitro released amounts of VEGF was detected. In contrast, the immobilization of VEGF seems to have a negligible influence on the in vitro FDAc release profiles.

In the last decades PLLA-based copolymers have been among the most attractive polymeric candidates used to fabricate devices for drug delivery and stent applications in the cardiovascular system. PLLA is biocompatible and biodegradable, exhibits a wide range of erosion times and has tunable mechanical properties. Therefore, the influence of drug incorporation on the physicochemical properties of biodegradable PLLA copolymers were examined in this study using Fluorescein diacetate (FDAc) and Paclitaxel (PTX). A percental amount of these drugs (17.5 %) were incorporated into poly(L-lactide-co-glycolide) (P(LLA-co-GA)) and poly(L-lactide-co-ε-caprolactone) (P(LLA-co-CL)) made via spray coating. The polymer surface properties, such as surface morphology and hydrophilicity were also examined and remained rather unchanged for both polymers after drug loadings. Furthermore, also the contact angle changed rather marginally. However, both polymers have already different thermal properties without the drug embedded, especially the glass transition temperature (TG) is for P(LLA-co-CL) under 37°C and for P(LLA-co-GA) considerable above with around 66°C. An rather high increase in TG achieved by addition of FDAc or PTX, crucial influences the drug release profiles for P(LLA-co-CL) in contrast to P(LLA-co-GA). Besides these results preliminarily experiments of additional coupling of other drugs on the polymer surface were performed and we obtained an influence of FDAc or PTX. The drug incorporation and physicochemical characterization data obtained in this study is relevant in optimizing the incorporation or coupling of further drugs on the polymer surface and delivery properties of these potential multi drug delivery coatings.

The particle generation of medical implants and drug coated balloons (DCB) is evaluated by simulating the implantation process and collecting the released particle material. In addition to size and particle counts their material composition is of interest. Raman spectroscopy and micros-copy are established methods for chemical identification. For the manual analysis of the particles different filter or rather background materials are suitable because different require-ments in height and intensity of the spectra can be compen-sated by the user. The aim of this study was to find suitable background materials for automatic particle identification.

For fabrication of polymeric implants and drug carriers volatile organic solvents, such as chloroform, are widely used. In order to remove solvents for patient safety several processes have to be carried out to avoid changes in the thermal characteristics of the polymers, as well as in the drug release profile and mechanical properties. We analyzed films of the polymer poly(ε−caprolactone) (PCL), a common commercial medical grade polymer which is widely used in implants and drug carriers. Considering the influence on the morphology and thermal properties we screened different post treatment processes. Acceptable chloroform contents according to recommendations of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) without changes in morphology and crystallinity were achieved via a simple annealing process for 24 h at 40°C and 40 mbar.

Chemical identification of particles increasingly gains importance concerning regulatory affairs of medical devices. Particle numbers of samples very easily add up to orders larger than 1.000. Therefore an automated particle measurement is absolutely worthwhile. As a method of chemical identification Raman spectroscopy combined with microscopy is commonly used. The challenge is to distinguish small particles in a range of a few microns on a surface from the background. Different specimen holder made of glass, polymer (e.g. polycarbonate) or metal are commonly used. After the choice of suitable background parameters such as magnification, optical resolution, focal plane and brightness have to be optimized. The used software for Raman microscopy offers the possibility to select particles for the subsequent measurement. Therefore the xand y-coordinates of particles have to be added to a list manually and separately. This so called point list can be processed automatically. However, this procedure is very laborious and requires a high degree of user interaction especially in case of large particle numbers. Furthermore the software offers the possibility to perform a so called area scan, where a defined surface of the the specimen will be spectroscopically analyzed. The measurements are performed in defined distances on a grid, e.g. every 10 micrometer in xand y-direction. The choice of this tool leads to a large number of measuring points associated with an unwanted long measuring time. By means of the freely accessible software ImageJ an alternative path was found to relate xand y-coordinates to every particle. These coordinates can be imported into the point list of the software for Raman microscopy. Afterwards a Raman spectrum for every particle can be measured without further high effort in time.

Toxic volatile organic chemicals (VOCs), such as chloroform, are widely used in polymer manufacture in the field of implants and polymeric drug carriers. Several processes have to be carried out in order to remove toxic VOCs for patient safety without changing the thermal characteristics of the polymers. Therefore, we analyze the common commercial implant polymer poly(L-lactide) (PLLA) and screen different annealing- and rinsing processes considering influence on their morphology and thermal properties. For PLLA a rinsing step followed by annealing results in acceptable chloroform contents according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) recommendations. Annealing processes reveal the lowest chloroform content after one day, which did not further decrease significantly with extended annealing time.

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 (Tg) 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. [ABSTRACT FROM AUTHOR]