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Filter membranes (pore size 0.2 μm) are frequently used to perform a sterile filtration. To characterize the pore size of filter membranes, a method to determine the particle retention of nanoparticles was defined. The Dynamic Light Scattering method was first analysed and calibrated to correlate the particle concentration with absolute intensity of scattered light. Afterwards, standard particle suspensions with particle sizes of 0.150 μm and 0.239 μm were lead through an infusion filter and the particle retention of the filter was evaluated by the determination of the original and the filtrated particle concentration. The test filter retained 91% of the smaller and 98% of the larger particles. Evaluating the particle retention with Dynamic Light Scattering could be a time saving method with lesser effort compared to existing methods.

Polycarbonate-urethane-co-silicone (PCU-Sil) are gaining increasing interest in biomedical application, such as drug delivery systems, coatings and combination products, due to their adjustable mechanical properties. They can be easily processed using a wide range of methods. Biocompatibility can be improved by surface modifications, such as coupling drugs, proteins, antibodies or polymer layers, which extends the range of biomedical applications. To generate additional coupling, the first step would be the generation of functional groups on the polymer surface using surface activations, such as plasma activation. In this context, the assignment of the functional groups is important, which can be done by XPS measurements. Within this study the analysis of the generated functional groups after oxygen (O2) plasma activation of two PCU-Sils was performed. In addition, the stability of the generated surface modification was evaluated after 24 hours. It was surprising that the generated groups were differently stable and also different groups were generated or rearranged over time, which would not have been recognizable if only contact angle measurements were used.

For the use of polymers as biomaterials in the production of implants, several processing methods are needed. Besides injection molding or Fused Deposition Modeling as temperature based processes, also solvent based processes were performed such as solvent-casting and electrospinning. As fabrication of medical devices makes use of potentially hazardous or toxic solvents, they have to be extracted from the final medical device. For analyses of residual solvents different methods can be used e.g. gas chromatography (GC), coulometric elemental analysis or thermogravimetrical analyses (TGA). Here we present first results for the use of X-ray photoelectron spectroscopy (XPS) to yield elemental as well as spatial information on residual solvents in polymeric materials. Therefore we analysed PLLA as biodegradable electrospun polymer, TPC-ET as biostable polymer and a PLLA-iron composite as example of a polymer metal composite via XPS and etching processes. It was possible to determine residual halogen containing solvents in all tested polymers processed from polymeric solution. As discrimination between polymer and solvent was made possible by specific elements, XPS measurements may be a suitable tool to identify even small amounts of solvent. Thus XPS analyses will help to optimize polymer processing in order to remove residual solvents.

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.

Photopolymerizing, high-resolution 3D printing methods such as Stereolithography (SLA) or Digital Light Processing (DLP) are very promising for the manufacturing of drug-incorporated, patient specific implants. However, a drug-load may be limited by adequately solubility of the active pharmaceutical ingredient (API) in the photopolymer. Furthermore, a drug-load may affect the mechanical properties of the material negatively. Here, we investigate the DLP 3D printing of drugincorporated photopolymers. Polyethylene glycol diacrylate (PEGDA, Mn = 700 g/mol) is used as matrix polymer and Dexamethasone (DEX) is used for drug-loading (10 g/L and 20 g/L). Compressive properties, drug release and drug stability of 3D printed test samples were analyzed. DEX was found to be sparingly soluble in the PEGDA-based photopolymer. Not all drug particles can be dissolved at a concentration of 20 g/L and a slurry-like suspension is formed. Drug-incorporated photopolymers of 10 g/L (solution) and 20 g/L (suspension) were processed successfully via DLP. The higher the drug-load, the lower the compressive strength. Mechanical properties can be improved via a post-curing in a UV light curing box. Drug-incorporated 3D printed test samples show burst-release of DEX. The post-curing process does not affect drug release. DEX degrades in 3D-printed test samples significantly (~ 30 %) over a several days time period.

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.

In this study, initial experiments are presented regarding the suitability of polyester based nonwoven composite materials for guided tissue regeneration based on degradation. The in vitro degradation of poly(lactic-coglycolic acid)/polydioxanone and polycaprolactone/ polydioxanone mats has been performed under accelerated condition in alkaline glycine buffer at 50 °C for 21 days. The degradation of the materials has been characterized regarding total mass loss and macroscopic morphological changes, as well as determination of the molecular weight degradation via GPC experiments.

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.

Electrospun poly(L-lactide) (PLLA) nonwoven represent potential options for biodegradable medical implants. They can be manufactured with high reproducibility and do offer the potential for chemical modification to alter matrix properties. In our study, we investigate the mechanical, thermal and morphological properties of PLLA fiber matrices. Fibrous nonwovens were fabricated from polymer solution by needle electrospinning. The polymer solutions were loaded with Triton X-100 (TX- 100), formic acid and tetraethyl ammonium chloride (TEAC) with respect to polymer weight. Morphology of the PLLA nonwoven scaffolds was examined with SEM. We performed uniaxial tensile tests and differential scanning calorimetry (DSC). Different concentrations of the additives TEAC, formic acid and Triton X-100 lead to strong changes regarding mechanical and thermal properties of the electrospun PLLA fiber matrices. In comparison with mechanical properties of established biological tissue materials, the results indicate the suitability for medical applications.

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.

Sirolimus incorporated nonwoven polymer matrices were fabricated via electrospinning. Release kinetics considering different fiber diameters and layer thicknesses were investigated. In vitro drug release profiles were evaluated by measuring the drug concentration in an established drug release medium (0.9% saline solution with additives, not buffered) at predetermined time points. Furthermore, an NH3-plasma pretreatment was examined to ensure complete wetting from the beginning of the study. In comparison to thin drug-loaded PLLA spray coatings it was shown that the release of sirolimus is diffusion- and degradation-controlled regardless of the surface-to-volume ratio, though fiber diameters or a hydrophilization can affect its release kinetics.

Resveratrol is a member of stilbenoids with promising anti-atherosclerotic properties. This hallmark makes it an extremely interesting candidate for local drug delivery to damaged tissue adjacent to the implant in order to reduce implant-related complications. For the regulatory approval drug-eluting medical devices have to be thoroughly tested for safety, efficacy and interactions with the surrounding tissue, including tests for sensitization among others. Studies for sensitization help to estimate the risk for an allergic reaction upon prolonged exposure to a chemical compound. Due to increased social and regulatory demand for replacement of animal experiments by in vitro approaches a number of reliable predictive non-animal tests have been developed. Here, we assessed the skin sensitization potential of resveratrol by the direct peptide reactivity assay (DPRA), one of the first non-animal tests adopted by the OECD.

The generation of electrospun nonwovens from polyimide (PI) is challenging as the fibers are prone to distinct delamination. In consequence, the resulting nonwoven material has particularly low structural integrity and loose fibre interlocking, demanding for a follow-up treatment, such as high temperature thermal treatment. In this work, a facile method for a post-processed treatment of PI nonwoven is presented in order to obtain a mechanically stable material while maintaining the characteristics of the electrospun nonwoven. The procedure was performed using a solution of EDA in methanol at 37 °C and ambient pressure to achieve a modified fiber interaction. Overall, the developed protocol opens new possibilities in the processing of PI into delamination-free nonwovens. Potential adverse effects of a high temperature thermal treatment are being avoided, and new applications in the field of medical devices may become accessible.

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.

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.

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.

The use of the electrospinning technique is a promising and versatile method for producing fibrous nonwovens from various polymers. Here we present fibre formation via direct electrospinning of a soluble polyimide, a class of polymers that is typically insoluble. In this study solution parameters as the solvent and the polymer concentration are investigated. Furthermore relevant process parameters are varied for optimization of the performance. The presented data indicate polyimide as a promising material for the fabrication of nanofibrous nonwovens via direct electrospinning.

Glaucoma is the second most common cause of blindness. An increased intraocular pressure is the only treatable symptom of glaucoma. Because patients often exhibit a poor therapy adherence, a drug depot consisting of ELA-NCO and hyaluronic acid with timolol was developed to ensure sustained drug release. This drug depot is formed by in situ polymerisation after injection into the subconjunctival space. To test the in vivo drug release of timolol in serum and aqueous humour, a liquid chromatography mass spectrometry (LCMS) method was developed and tested using spike- and recovery experiments, and on in vivo samples after topical application. Samples of serum and aqueous humour were taken from New Zealand White rabbits. For topical application, a commercially available formulation of timolol was used. This study presents results concerning the recovery of timolol from spiked samples. Serum and aqueous humour samples were spiked with timolol maleate to a final concentration of 50 ng/mL. Subsequently, the samples were extracted and analysed by LCMS. External calibration of the developed method showed high linearity. Recovery experiments showed no loss of timolol. Hence, the extraction method is robust and able to recover the whole amount of timolol from aqueous humour and serum.

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.