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.

Patients with cardiac arrhythmias are currently treated with conventional transvenous rhythm implants. Complications are frequently associated with intracardiac implanted leads primary insulated by silicone and polyurethane. However, experiences show that polyurethanes in particular are susceptible to various degradation mechanisms including hydrolysis, environmental stress cracking (ESC) and metal ion induced oxidation (MIO). In vivo, pacemaker leads are exposed to a complex thermal, chemical, mechanical and biological loading. The current study focusses on in vitro analyses to assess the biostability of Pellethane 2363 55D and the silicone MED 4765 as cardiac pacemaker lead insulations. Degradation processes were simulated in vitro in a load-free state and under static mechanical loading by subjecting a coaxial lead design to bending radii from 3 mm to 19 mm. Physiological environmental conditions were mimicked using a physiological saline solution and a tempered oxidative solution. Surface morphological and thermal analyses were performed before and after in vitro testing by means of scanning electron microscopy (SEM) and differential scanning calorimetry. Melting temperatures of silicones around 40°C were measured, before and after in vitro testing, respectively. Pellethane insulation layers had two endothermal melting regions at 100°C and 170°C before and a third melting region at 45°C after in vitro testing. The additional melting peak may indicate a change of thermal material properties due to degradation. SEM images showed degradation phenomena similar to in vivo studies, varying in severity and depending on the bending radius. Thus, the relevance of mechanical loading for in vitro replication of clinically relevant lead insulation degradation was demonstrated.

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.

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).

Designing laboratory-scale degradation experiments for polymer-based biomaterials is crucial for the development of safe and functional implants, in particular regarding high molecular weight polyesters. Within this work, we compared accelerated degradation of solvent cast HMW-PLLA and HMW-P3HB films at 55 °C (16 weeks) with enzyme-associated (proteinase K and lipases) real-time degradation at 37 °C (108 weeks). During real-time degradation, PLLA showed mass loss up to 83%, in contrast to accelerated conditions, where no changes occurred. Moreover, we observed wave-shape development of crystallinity for PLLA and PHB for both degradation conditions applied, whereby PLLA χ value nearly doubled to up to 75%. These results were used to develop a correlation model based on molecular weight decrease and were furthermore discussed in light of a detailed literature review. In summary, real-time in vitro studies could be adapted to accelerated protocols providing the same limiting conditions such as molecular weight and initial crystallinity are given.

To simulate the specific material properties of thermoplastic polymers a suitable constitutive model is essential. The parallel rheological framework (PRF) model was calibrated and evaluated in this study as potential constitutive model for polymer stent application. Tensile as well as recovery tests with different loading rates were performed using PLLA specimens. In order to calibrate the constitutive model, the conducted material tests were simulated accordingly. The parameters of the model were iteratively varied to obtain good accordance of the simulation with the material tests. In contrast to elastic plastic material models, viscoelastic material behavior can be represented with the nonlinear viscoelastic-plastic PRF model. The generated and possibly further refined model can be used for the simulation of polymer stents.

Abstract 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.

Abstract The characterization of mechanical properties of materials used in biomedical applications is essential for performance evaluation. In addition to quasi-static tests, dynamic tests extend the range of methods and allow predictions of failure, as well as information on durability. Appropriate specimen grips according to the test sample geometry are crucial for a reliable examination of mechanical testing and therefore valid experimental data. In particular, the investigation of polymers is challenging, as properties show major differences depending on temperature and applied loading rate. This could result in slipping or tearing of samples in the specimen grip area. Numerical simulations of reference grips, as well as alternative custom designs, were performed evaluating damage due to the clamping process and to provide appropriate specimen grips for future dynamic-mechanical investigations of materials with variable properties. Both the results of the numerical simulation and preliminary tests with 3D-printed prototypes show a distinct improvement in specimen clamping. Plastic deformation and local stress peaks were reduced while maintaining the same tightening torque.

Local drug delivery has become indispensable in biomedical engineering with stents being ideal carrier platforms. While local drug release is superior to systemic administration in many fields, the incorporation of drugs into polymers may influence the physico-chemical properties of said matrix. This is of particular relevance as minimally invasive implantation is frequently accompanied by mechanical stresses on the implant and coating. Thus, drug incorporation into polymers may result in a susceptibility to potentially life-threatening implant failure. We investigated spray-coated poly-l-lactide (PLLA)/drug blends using thermal measurements (DSC) and tensile tests to determine the influence of selected drugs, namely sirolimus, paclitaxel, dexamethasone, and cyclosporine A, on the physico-chemical properties of the polymer. For all drugs and PLLA/drug ratios, an increase in tensile strength was observed. As for sirolimus and dexamethasone, PLLA/drug mixed phase systems were identified by shifted drug melting peaks at 200 °C and 240 °C, respectively, whereas paclitaxel and dexamethasone led to cold crystallization. Cyclosporine A did not affect matrix thermal properties. Altogether, our data provide a contribution towards an understanding of the complex interaction between PLLA and different drugs. Our results hold implications regarding the necessity of target-oriented thermal treatment to ensure the shelf life and performance of stent coatings.

Electrospinning (ES) is a suitable and cost effective method to mimic the chemical composition, morphology, and functional surface of natural tissues, for example of the nervous, dermal, vascular, and musculoskeletal systems. This technique is a versatile tool to obtain tailored fibrous scaffolds from various polymer materials. By varying the diameter, porosity, orientation, layering, surface structuring, mechanical properties and biodegradability of the fibers the properties can be adapted for specific applications ranging from implantable medical devices to wound repair and protective clothing. Especially the combination of different polymer types offers a high potential. In this study electrospun two-component nonwoven structures of thermoplastic copolyester elastomer (TPC-ET) and bioresorbable polylactide (PLLA) were fabricated, using different ES setups. A comparative evaluation in terms of porosity, thermal and mechanical properties as well as required fabrication effort, was performed. Nonwovens made from polymer blends and coaxial spun core-sheath fibers showed similar tensile strength, which was higher than dual electrospun fabrics. Porosity was found to be in the range of 80 - 90%. By modifying the polymer solution and process parameters multicomponent nonwoven structures with tailored properties and drug release profiles can be manufactured.

Abstract Electrospinning is used for producing nonwovens for medical polymer-based implants, such as prosthetic valves or covered scaffolds. In this study, nonwovens for prosthetic venous valves are investigated regarding their morphology and mechanics in physiological medium. Spinning molds were developed based on previous venous valve leaflet designs, 3D printed in different sizes and covered with electrospun nonwovens. Samples were stored in a physiological 0.9% saline at 37°C to investigate the influence of fiber rearrangement and swelling in medium for several weeks. Two different nonwovens of thermoplastic silicone-based polycarbonaturethane (TSPCU) were compared. Tensile test results show that storage in medium has a relevant influence on the mechanical properties. SEM images of TSPCU show substantially increased fiber diameters after 8 days stored in medium. After detaching the valve leaflet nonwovens from the molds, shrinkage of the material of approximately 12% was detected. A suitable valve size could be identified for joining with the stent structure into an interventional prosthetic venous valve. The results demonstrate the influence of storage conditions on the morphological and mechanical properties of electrospun TSPCU nonwovens. For development and dimensioning of venous valve leaflets, this change in mechanical behavior and possible shrinkage of the material has to be considered.

Abstract 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.

Abstract 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.

Abstract We present a thermal processing device, equipped for local heating and welding of biomaterials, e.g. electrospun nonwovens or polymer films. Depending on the application and choice of materials, we aim to determine appropriate processing parameters for permanent and non-permanent welds. Due to the modular device structure, applicationspecific heating tools can be used. Process temperature up to 250 °C is feasible. In this concept study, a welding tool with interchangeable small-size heating tips of different geometric shapes were investigated regarding their suitability for welding of polycarbonate urethane based silicone elastomer nonwovens. Generated welds were examined by imaging techniques and tensile testing. Regardless of the tip shape, welds were generated withstanding forces up to 3.0 N and 4.3 N for tensile and shear loading, respectively.

Abstract The selection of appropriate test conditions is of critical importance in mechanical testing of biomaterials. In particular the definition of dynamic test conditions is requiring high efforts. In this work, a thermoplastic semicrystalline polymer was characterized regarding mechanical properties by dynamic mechanical analysis (DMA). Timetemperature- superposition (TTS) of dynamic mechanical data provides an efficient method for the experimental design of follow-up studies. Our focus was to provide test conditions for cyclic tests, which correspond to viscoelastic materials. The results show, that the test temperature for dynamic mechanical fatigue tests, as an indicator of mechanical modification for viscoelastic materials, should necessarily remain below the onset temperatures of storage modulus and loss modulus. Moreover, changes in material characteristics due to varying frequencies should be considered when constructing a master curve for the evaluation of test frequencies. Therefore, TTS is particularly beneficial for the rapid determination of test parameters for accelerated material examination.

Abstract 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.

Abstract The development and advancement of polymeric implant materials is a frequent focus in current research. The combination of polymeric materials with diverging properties provides a wide range of new materials with innovative characteristics. One technology for combining materials is to apply a coated layer onto a base material. In this work, a hyperelastic, synthetic base material was combined with a rigid biopolymer coating layer. A multilayered material with combined characteristics of both was built. In the field of processed polymers, the analysis of coating adhesion is not feasible using established methods. Therefore, a dynamic-mechanical method was investigated, which supplements the uniaxial tensile test and provides knowledge regarding mechanical resistance of the multilayered polymer structure. Furthermore, the method gets validated by SEM-imaging and evaluation of coating composition before and after testing under dynamic conditions.

An ongoing challenge in drug delivery systems for a variety of medical applications, including cardiovascular diseases, is the delivery of multiple drugs to address numerous phases of a treatment or healing process. Therefore, an extended dual drug delivery system (DDDS) based on our previously reported cardiac DDDS was generated. Here we use the polymer poly(L-lactide) (PLLA) as drug carrier with the cytostatic drug Paclitaxel (PTX) and the endothelial cell proliferation enhancing growth factor, human vascular endothelial growth factor (VEGF), to overcome typical in-stent restenosis complications. We succeeded in using one solution to generate two separate DDDS via spray coating (film) and electrospinning (nonwoven) with the same content of PTX and the same post processing for VEGF immobilisation. Both processes are suitable as coating techniques for implants. The contact angle analysis revealed differences between films and nonwovens. Whereas, the morphological analysis demonstrated nearly no changes occurred after immobilisation of both drugs. Glass transition temperatures (Tg ) and degree of crystallinity (χ) show only minor changes. The amount of immobilised VEGF on nonwovens was over 300% higher compared to the films. Also, the nonwovens revealed a much faster and over three times higher PTX release over 70 d compared to the films. The almost equal physical properties of nonwovens and films allow the comparison of both DDDS independently of their fabrication process. Both films and nonwovens have significantly increased in vitro cell viability for human umbilical vein endothelial cells (EA.hy926) with dual loaded PTX and VEGF compared to PTX-only loaded samples.

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.