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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).

Extrusion is a common manufacturing process for semi-finished polymer products in various biomedical applications. Extrusion enables processing of a wide range of biomaterials, as well as different cross-sectional geometries. Furthermore, feasibility of drug elution, as it is used for a variety of medical devices, for example microstents for minimally invasive glaucoma therapy, was assessed. The current study deals with manufacturing of polymeric microtubes by extrusion processing. Semi-finished products were made of biodegradable poly-L-lactide (PLLA) and a non-biodegradable polycarbonate-based silicone elastomer (SIL) and covered with a polymer/drug combination, with resveratrol as active ingredient. Three different concentrations of polymer/resveratrol were applied by means of spray-coating. The release behavior of active ingredient was analyzed in vitro at 37°C and showed a correlation between the amount of drug and release time. With higher drug content, a faster release was observed. In addition, the release from SIL was faster compared with PLLA.

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.

Bacterial biofilm formation on surfaces is still a critical challenge regarding the application of implants. Generally, in order to avoid this, an additional systemic administration of antibiotics is given, which can lead to side effects, such as the reduction of the intestinal flora. Continuous treatment may lead to antibiotics resistance. Within this study we investigated the local drug delivery of N-acetyl-L-cysteine (NAC) from a Poly-L-lactide (PLLA) coating, an ished biodegradable polymer and a polyetherurethane (PEU) coating, a promising representative non-degradable polymer for cardiovascular applications as alternative to the administration of antibiotics. The incorporation of NAC influenced the surface properties of PEU in contrast to that of PLLA. The in vitro NAC release is almost completed after 24 h for PEU. For PLLA only small amounts of incorporated NAC, depending on the NAC loading, is released after a short time. Both systems are rather useful as local NAC delivery system directly after implantation.

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.

In various biomedical applications extrusion represents a common manufacturing process for polymeric semi-finished products. Extrusion allows the processing of a wide range of biomaterials, as well as different cross-sectional geometries. The present work focuses on the development of an extrusion process for polymer micro-tubes used for medical devices manufacturing, e.g. microstents for minimally invasive glaucoma therapy. Semi-finished products were manufactured by means of extrusion and dip-coating. Morphology was investigated using biaxial laser measurement and scanning electron microscopy (SEM). For the analysis of mechanical and thermal properties of the specimens uniaxial tensile testing and differential scanning calorimetry (DSC) were performed. While dip-coated micro-tubes reveal a smooth and homogeneous surface, SEM micrographs of extruded micro-tubes exhibit some longitudinal grooves. Mechanical properties of extruded and dip-coated micro-tubes are comparable, so that the presented extrusion process can be regarded suitable for the manufacturing of polymer microtubes in a sub-millimeter scale. A future improvement of nozzle design will allow for a smooth surface of extruded semi-finished products.

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.

Although current drug eluting stents show low risks of in-stent restenosis and stent thrombosis, the presence of a permanent foreign body inside the vessel represents a major limitation. In order to overcome this limitation, stents made of biodegradable polymeric materials are currently being developed. The present work describes an optimized fabrication process for tubular semi-finished products for manufacturing of stents made of poly-L-lactide (PLLA). The impact of the haul-off speed as a major parameter during extrusion processing on the cross-sectional area of tubular specimens was analyzed. It could be shown that the crosssection of the extrudate, in particular the tubing diameter and wall thickness, can be adjusted by varying haul-off speed. In a subsequent blow molding process the influence of the holding time on polymer cold crystallization was analyzed. Thermal properties of the polymeric material after processing were examined by differential scanning calorimetry (DSC). The results showed that there is almost no cold crystallization using a holding time of at least 20 minutes. The investigations showed that semi-finished products with variable geometry and improved mechanical properties can be produced with the described extrusion and blow molding process.

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.

Conventional permanent stent systems for vascular applications are associated with long-term risks, such as restenosis and thrombosis. To overcome these limitations, novel approaches using various biodegradable materials for stent construction have been investigated. In this context, thermal treatment of polymer materials is investigated to adjust the mechanical properties of biodegradable stents. In this work polymeric tubular specimens of biodegradable poly(L-lactide) (PLLA) were extruded and subjected to a molding process using different temperatures above glass transition temperature TG. Physicochemical properties of the molded samples were analyzed using DSC measurements and uniaxial tensile tests. The molding process resulted in a weakening of the PLLA tubular specimens with a simultaneous increase in the degree of crystallinity (χ).