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The effect of molecular weight Mwon the polymorphous crystallization and melting behavior of poly(Llactide) PLLA (L206, L210 and L214) were systemically studied by differential scanning calorimetry (DSC). Melting and reorganization of conformationally disordered crystals (α′-phase) of PLLA are analyzed with respect to the cooling rate qcin a range between about 4 and 50 K/min and the heating rate qhin a range between about 5 and 200 K/min. It was shown that the α′- to α-crystalline phase transition prior to the dominant melting depends on cooling rate qcand Mw. Unlike very high-MwPLLA L214, for low-MwPLLA L206 crystallized at high qc, the α′-form crystals only partially transformed into the α-modification, and certain amounts of α′-form crystals melted directly without α′- to α-transition during the heating process. With increasing qc, the melting of PLLA L210 changed from phase-transition- and -melting mechanism to the common melt-recrystallization mechanism. It was also found that the polymorphism of PLLA significantly affected the crystallization kinetics. Consequently, the reorganization of α′-crystals into stable α- crystals could be inhibited by fast heating (qh> 150 K/min).

In this study, DSC experiments were used to elaborate an annealing protocol for injection molded very high molecular weight (VHMW) PLLA with two molecular masses, 320,000 g/mol and 700,000 g/mol. The initial material obtained from the injection molding process was found to be highly amorphous and not in thermodynamic equilibrium state, as distinct cold crystallization and enthalpy relaxation were observed in DSC data. Thermal annealing to 85 °C for 60 - 90 min under controlled conditions using a DSC device showed to be sufficient to stabilize the polymer and increase the crystallinity to up to 50 %. Annealing did not result in any signs of thermal decomposition. The elaborated thermal treatment has been transferred to manual annealing of large specimen geometries for subsequent DMA analysis.

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.

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.

The novel concept of stenting the Eustachian tube was established to provide an effective and safe therapy of Eustachian tube dysfunction. Biodegradable polymer stents are being developed to restore impaired tube function. As the supporting effect may be required for different time periods, PLA-co-PEG copolymers, PLLGA, PDLLA and PDS, having shorter degradation times compared to PLLA, were evaluated as potential stent materials. Since tensile tests and thermal analyses of solvent cast films from PLA-co-PEG copolymers showed comparable properties to PLLA, stent samples were manufactured from these materials. Mechanical stent testing revealed an increase of elastic recoil and slight decrease of collapse pressure compared to PLLA. In a short term accelerated degradation study a considerable percentage molar mass reduction and an increasing degree of crystallinity depending on PEG content was found. Based on the results obtained, the tested polymers offer a promising, faster degradable alternative to the established stent material PLLA.

Polymer materials can be manufactured with high reproducibility and do offer the potential for chemical modification. This enables matrix property modification and fine-tuning of several material characteristics, such as tissue-implant interaction, inflammatory potential or susceptibility to biofilm formation. Whereas manufacturing protocols are crucial for the resulting material properties, also the evaluation in terms of performance and safety has to be considered. Regarding this, both, temperature and composition of test medium may affect the physicochemical properties of implant materials. The present study addresses the influence of test medium compared to dry test conditions, each at two different temperatures, on the mechanical properties of elastomeric film and nonwoven materials.

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.

Electrospun fiber nonwoven materials of different polymer classes provide promising perspectives in almost all fields of application, including medical science. In this paper we present the fiber generation of selected biostable polymers (PBT, TPC-ET, PA 6.12 and PVDF) by direct electrospinning, as an extremely powerful tool for manufacturing of new superfiber implant materials. This initial study includes the variation of some relevant process parameters, such as polymer concentrations or electrode spacing. The influence on fiber morphology, tensile strength and biocompatibility is shown. The results presented indicate that the choice and combination of materials is crucial for the application on load-bearing implants, independent of the processing technology and thus of the fiber bonding, delamination or fiber strength.

Fast scanning calorimetry (FSC) is an effective analytical tool to characterize the thermal properties of polymers. Heating rates up to 100 000 K/s allow studies at time scales inaccessible with conventional calorimeters, whose rates are typically less than about 0.5 K/s. Recent studies have successfully demonstrated methods for obtaining quantitative analysis of thermal properties of polymer samples using chip-based FSC. Therefore very small sample sizes, such as particles or nonwovens, can be characterized. In this study, we investigated the thermal properties of poly(L-lactide) PLLA with FSC compared to the results from standard DSC methods. PLLA specimens were fabricated via solution casting and needle electrospinning. The results suggest a significant influence of heating rates on the melting temperature of PLLA. The results show that different fabrication methods lead to changes in crystallinity and that FSC results are not completely comparable with standard DSC measurements.

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.

In this work ion functionalized hydrogels as potent drug delivery systems are presented. The ion functionalization of the hydrogel enables the retention of ionic drug molecules and thus a reduction of burst release effects. Timolol maleate in combination with polymerized anionic 3-sulfopropylmethacrylate potassium and ibuprofen combined with cationic poly-[2-(methacryloyloxy)ethyl] trimethylammonium chloride are investigated in respect to their drug release profile. The results are showing an ion exchange depending release behavior instead of a diffusion-controlled drug release as it is known from common drug delivery systems. Furthermore, the suitability of such hydrogels for standard methods for sterilization is investigated.

Polycarbonate urethane and polyether urethane nonwovens as promising representatives of novel polymer heart valve materials were analysed regarding the susceptibility to calcification in comparison to porcine pericardium and polyamide 6. The applied method represents an accelerated calcification out of a metastable solution in short time with significant precipitates on the reference material. As our results show, urethane based nonwoven structures exhibit considerably lower susceptibility to calcification compared to pericardium as widely established material for leaflet design.

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.

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.

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.

Blends of PLLA and PCL yielded by solvent casting usually exhibit phase separation and crystallization behavior which have a strong impact on their suitability for certain biomedical applications such as degradable coatings or drug carriers. Therefore, it is important to understand the underlying mechanisms. In this study, high-molecular biodegradable semi-crystalline poly(L-lactide) (PLLA) (Mw = 320 kDa) was blended with low-molecular biodegradable semi-crystalline poly(ε-caprolactone) (PCL) (Mw = 40 kDa) in various combinations (10, 50 and 90 wt.% PCL) by solvent casting. The yielded blends were subjected to annealing at 40 °C, 80 °C and 200 °C and cooled down slowly to maintain thermodynamic equilibrium. Scanning electron microscopy, atomic force microscopy, Raman images and differential scanning calorimetry were used to investigate the structure, morphology and thermal properties of the solvent cast PLLA/PCL blends. It was shown that the physico-chemical properties of PLLA/PCL blends prepared by solvent casting differ substantially compared to those accessed by melt manufacturing processes. In summary, the blends showed a complex phase separation behavior, which is completely dependent on the method of preparation and the adjusted temperature during production process.

A mild and carbon monoxide gas-free palladium-catalyzed aminocarbonylation of indole has been developed for the synthesis of N-benzoylindoles. This method uses Mo(CO)6 as a convenient CO-precursor and BuPAd2 as the ligand. A number of substituents on the aryl bromide species is tolerated under the presented conditions and gave the desired products in up to excellent yields.

2-Dihydroquinazolin-4(1H)-thiones were prepared in up to excellent yields from 2-aminobenzothioamides and aldehydes. The reaction is carried out in water without the use of any catalyst or promoter. The sulfur-containing substrate can be obtained easily by thiation of the corresponding nitrile by solid sodium hydrosulfide.

A convenient procedure for the synthesis of N-(2-cyanoaryl)benzamides has been developed. Using aryl bromides and 2-aminobenzonitriles as the substrates, Mo(CO)6 as the CO source, the desired amides were produced in good yields. Quinazolinones were produced in good yields in a sequential manner as well.

We describe here a convenient and mild, carbon monoxide gas-free palladium-catalyzed procedure to obtain N-substituted phthalimides with molybdenum hexacarbonyl as carbon monoxide precursor. These conditions tolerate a number of functional groups on the benzene ring as well as a number of amines and give the corresponding phthalimides in good to excellent yields.

A mild and carbon monoxide gas-free palladium-catalyzed aminocarbonylation of indole has been developed for the synthesis of N-benzoylindoles. This method uses Mo(CO)6 as a convenient CO-precursor and BuPAd2 as the ligand. A number of substituents on the aryl bromide species is tolerated under the presented conditions and gave the desired products in up to excellent yields.

2-Dihydroquinazolin-4(1H)-thiones were prepared in up to excellent yields from 2-aminobenzothioamides and aldehydes. The reaction is carried out in water without the use of any catalyst or promoter. The sulfur-containing substrate can be obtained easily by thiation of the corresponding nitrile by solid sodium hydrosulfide.

An environmentally friendly and mild procedure to obtain 2,3-dihydroquinazolin-4(1H)-ones from 2-aminobenzonitriles and aromatic aldehydes has been developed. The reactions took place in water with inorganic base (K3PO4) as the only promoter. Various desired products have been prepared in moderate to good yields under identical conditions. Further transformation of dihydroquinazolinones to quinazolinones was carried out as well with TBHP as the oxidant.

A convenient procedure for the synthesis of N-(2-cyanoaryl)benzamides has been developed. Using aryl bromides and 2-aminobenzonitriles as the substrates, Mo(CO)6 as the CO source, the desired amides were produced in good yields. Quinazolinones were produced in good yields in a sequential manner as well.

Application of tert-butylamine or unsubstituted aniline as well as heterocyclic dibromoaryl derivatives leads to formation of the corresponding amides and only trace amounts of the phthalimides.

An environmentally friendly and mild procedure to obtain 2,3-dihydroquinazolin-4(1H)-ones from 2-aminobenzonitriles and aromatic aldehydes has been developed. The reactions took place in water with inorganic base (K3PO4) as the only promoter. Various desired products have been prepared in moderate to good yields under identical conditions. Further transformation of dihydroquinazolinones to quinazolinones was carried out as well with TBHP as the oxidant.