TY - JOUR A1 - Zaupa, Alessandro A1 - Neffe, Axel T. A1 - Pierce, Benjamin F. A1 - Lendlein, Andreas A1 - Hofmann, Dieter T1 - A molecular dynamic analysis of gelatin as an amorphous material Prediction of mechanical properties of gelatin systems JF - The international journal of artificial organs N2 - Biomaterials are used in regenerative medicine for induced autoregeneration and tissue engineering. This is often challenging, however, due to difficulties in tailoring and controlling the respective material properties. Since functionalization is expected to offer better control, in this study gelatin chains were modified with physically interacting groups based on tyrosine with the aim of causing the formation of physical crosslinks. This method permits application-specific properties like swelling and better tailoring of mechanical properties. The design of the crosslink strategy was supported by molecular dynamic (MD) simulations of amorphous bulk models for gelatin and functionalized gelatins at different water contents (0.8 and 25 wt.-%). The results permitted predictions to be formulated about the expected crosslink density and its influence on equilibrium swelling behavior and on elastic material properties. The models of pure gelatin were used to validate the strategy by comparison between simulated and experimental data such as density, backbone conformation angle distribution, and X-ray scattering spectra. A key result of the simulations was the prediction that increasing the number of aromatic functions attached to the gelatin chain leads to an increase in the number of physical netpoints observed in the simulated bulk packing models. By comparison with the Flory-Rehner model, this suggested reduced equilibrium swelling of the functionalized materials in water, a prediction that was subsequently confirmed by our experimental work. The reduction and control of the equilibrium degree of swelling in water is a key criterion for the applicability of functionalized gelatins when used, for example, as matrices for induced autoregeneration of tissues. KW - Physical Network KW - Biopolymer material KW - Molecular modeling KW - Gelatin Y1 - 2011 U6 - https://doi.org/10.5301/IJAO.2010.6083 SN - 0391-3988 VL - 34 IS - 2 SP - 139 EP - 151 PB - Wichtig CY - Milano ER - TY - JOUR A1 - Wessig, Pablo A1 - Pick, Charlotte T1 - Photochemical synthesis and properties of axially chiral naphthylpyridines JF - Journal of photochemistry and photobiology : A, Chemistry N2 - Five alkynyl pyridines were prepared and cyclized to naphthylpyridines as the main products in the course of a Photo-Dehydro-Diels-Alder reaction. Four of the final products are axially chiral and the determination of the rotational barrier by DFT calculations, dynamic NMR and H PLC experiments is demonstrated. (C) 2011 Elsevier B.V. All rights reserved. KW - Photochemistry KW - Axial chirality KW - Photo-Dehydro-Diels-Alder reaction KW - Dynamic NMR KW - Dynamic HPLC KW - Molecular modeling Y1 - 2011 U6 - https://doi.org/10.1016/j.jphotochem.2011.06.006 SN - 1010-6030 VL - 222 IS - 1 SP - 263 EP - 265 PB - Elsevier CY - Lausanne ER - TY - JOUR A1 - Ghobadi, Ehsan A1 - Heuchel, Matthias A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Influence of different heating regimes on the shape-recovery behavior of poly(L-lactide) in simulated thermomechanical tests JF - Journal of applied biomaterials & functional materials N2 - Aim: Multifunctional polymer-based biomaterials, which combine degradability with a shape-memory capability and in this way enable the design of actively moving implants such as self-anchoring implants or controlled release systems, have been recently introduced. Of particular interest are approved degradable polymers such as poly(L-lactide) (PLLA), which can be easily functionalized with a shape-memory effect. In the case of semicrystalline PLLA, the glass transition can be utilized as shape-memory switching domain. Methods: In this work we applied a fully atomistic molecular dynamics simulation to study the shape-memory behavior of PLLA. A heating-deformation-cooling programming procedure was applied to atomistic PLLA packing models followed by a recovery module under stress-free conditions allowing the shape recovery. The recovery was simulated by heating the samples from T-low = 250 K to T-high = 500 K with different heating rates beta of 125, 40 and 4 K.ns(-1). Results: We could demonstrate that the obtained strain recovery rate (R-r) was strongly influenced by the applied simulation time and heating rate, whereby R-r values in the range from 46% to 63% were achieved. On its own the application of a heating rate of 4 K.ns(-1) enabled us to determine a characteristic switching temperature of T-sw = 473 K for the modeled samples. Conclusions: We anticipate that the atomistic modeling approach presented should be capable of enabling further study of T-sw with respect to the molecular structure of the investigated SMP and therefore could be applied in the context of design and development of new shape-memory (bio) materials. KW - Molecular modeling KW - Polymers KW - Shape-memory effect Y1 - 2012 U6 - https://doi.org/10.5301/JABFM.2012.10440 SN - 2280-8000 VL - 10 IS - 3 SP - 259 EP - 264 PB - Wichtig CY - Milano ER - TY - THES A1 - Zaupa, Alessandro T1 - Physical crosslinking of gelatin : a supramolecular approach to biomaterials T1 - Physikalische Quervernetzung von Gelatine : ein supramolekularer Zugang zu Biomaterialien N2 - This work describes the realization of physically crosslinked networks based on gelatin by the introduction of functional groups enabling specific supramolecular interactions. Molecular models were developed in order to predict the material properties and permit to establish a knowledge-based approach to material design. The effect of additional supramolecular interactions with hydroxyapaptite was then studied in composite materials. The calculated properties are compared to experimental results to validate the models. The models are then further used for the study of physically crosslinked networks. Gelatin was functionalized with desaminotyrosine (DAT) and desaminotyrosyl-tyrosine (DATT) side groups, derived from the natural amino acid tyrosine. These group can potentially undergo to π-π and hydrogen bonding interactions also under physiological conditions. Molecular dynamics (MD) simulations were performed on models with 0.8 wt.-% or 25 wt.-% water content, using the second generation forcefield CFF91. The validation of the models was obtained by the comparison with specific experimental data such as, density, peptide conformational angles and X-ray scattering spectra. The models were then used to predict the supramolecular organization of the polymer chain, analyze the formation of physical netpoints and calculate the mechanical properties. An important finding of simulation was that with the increase of aromatic groups also the number of observed physical netpoints increased. The number of relatively stable physical netpoints, on average zero 0 for natural gelatin, increased to 1 and 6 for DAT and DATT functionalized gelatins respectively. A comparison with the Flory-Rehner model suggested reduced equilibrium swelling by factor 6 of the DATT-functionalized materials in water. The functionalized gelatins could be synthesized by chemoselective coupling of the free carboxylic acid groups of DAT and DATT to the free amino groups of gelatin. At 25 wt.-% water content, the simulated and experimentally determined elastic mechanical properties (e.g. Young Modulus) were both in the order of GPa and were not influenced by the degree of aromatic modification. The experimental equilibrium degree of swelling in water decreased with increasing the number of inserted aromatic functions (from 2800 vol.-% for pure gelatin to 300 vol.-% for the DATT modified gelatin), at the same time, Young’s modulus, elongation at break, and maximum tensile strength increased. It could be show that the functionalization with DAT and DATT influences the chain organization of gelatin based materials together with a controlled drying condition. Functionalization with DAT and DATT lead to a drastic reduction of helical renaturation, that could be more finely controlled by the applied drying conditions. The properties of the materials could then be influenced by application of two independent methods. Composite materials of DAT and DATT functionalized gelatins with hydroxyapatite (HAp) show a drastic reduction of swelling degree. In tensile tests and rheological measurements, the composites equilibrated in water had increased Young’s moduli (from 200 kPa up to 2 MPa) and tensile strength (from 57 kPa up to 1.1 MPa) compared to the natural polymer matrix without affecting the elongation at break. Furthermore, an increased thermal stability from 40 °C to 85 °C of the networks could be demonstrated. The differences of the behaviour of the functionalized gelatins to pure gelatin as matrix suggested an additional stabilizing bond between the incorporated aromatic groups to the hydroxyapatite. N2 - Diese Arbeit beschreibt die Entwicklung von durch spezifische physikalische Wechselwirkungen quervernetzten Gelatine-basierten Materialien. Dazu wurden zunächst Computermodelle entwickelt, mit denen Eigenschaften der Materialien vorhergesagt werden sollten, um so eine wissensbasierte Entwicklung zu ermöglichen, um dann die Ergebnisse mit experimentellen Daten zu vergleichen und die Materialien und Modelle als Grundlage für weitere Entwicklungen zu nutzen. Gelatine wurde mit Desaminotyrosin (DAT) und Desaminotyrosyltyrosin (DATT) funktionalisiert, die sich von der natürlichen Aminosäure Tyrosin ableiten. Diese Gruppen können potentiell π-π Wechselwirkungen und Wasserstoffbrückenbindungen auch unter physiologischen Bedingungen eingehen. Es wurden Computersimulationen der Materialien mittels Moleküldynamik durchgeführt, wobei Modelle mit 0.8 Gew.-% und 25 Gew.-% Wassergehalt betrachtet wurden. Die Validierung der Modelle erfolgte durch Vergleich der errechneten mit experimentellen Daten wie z.B. der Dichte, Bindungswinkeln sowie Röntgenstreuungsspektren. Die Modelle wurden dann zur Vorhersage der molekularen Organisation der Polymerketten, Formierung physikalischer Netzpunkte und Berechnung der mechanischen Eigenschaften eingesetzt. Die Funktionalisierung der Gelatine mit DAT bzw. DATT führten wie gewünscht zur Ausbildung physikalischer Netzpunkte durch π-π Wechselwirkungen und Wasserstoffbrücken¬bindungen. Ein Schlüsselergebnis der Simulationen war, dass mit zunehmender Zahl an aromatischen Gruppen auch eine Zunahme der physikalischen Netzpunkte beobachtet werden konnte. Die funktionalisierten Gelatinen konnten durch chemoselektive Reaktion der Aminogruppen der Gelatine mit den freien Carboxylgruppen von DAT und DATT hergestellt werden. Materialien mit 25 Gew.-% Wassergehalt hatten in der Simulation und im Experiment mechanische Eigenschaften derselben Größenordnung (z.B. E-Moduln im unteren GPa-Bereich). Der Quellungsgrad der Materialien im Experiment nahm mit zunehmender Zahl an aromatische Gruppen ab (von 2800 Vol.-% auf 300 Vol.-%), wobei der Elastizitätsmodul, die Bruchdehnung sowie die Zugfestigkeit zunahmen. Die Funktionalisierung der Gelatine ist eine chemische Methode, um die Kettenanordnung auf molekularer Ebene zu beeinflussen, während die genaue Kontrolle der Trocknungs¬bedinguungen von Gelatine-basierten Materialien eine physikalische Methode mit demselben Ziel ist. Es konnte gezeigt werden, dass die Funktionalisierung von Gelatine mit DAT oder DATT zu einer stark verminderten Helixausbildungstendenz, die jedoch durch Variation der Trocknunsgbedingungen noch fein abgestimmt werden konnte. Somit konnten die mechanischen Eigenschaften von Filmen aus funktionlisierter Gelatine mit zwei unabhängigen Methoden eingestellt werden. Komposite der mit DAT oder DATT funktionalisierten Gelatine und Hydroxyapatit (HAp) zeigten deutlich verringerter Quellung. In Zugdehnungsexperimenten und rheologischen Untersuchungen zeigten die Komposite im Gleichgewichtsquellungszustand erhöhte Elastizitätsmoduln (von 200 kPa auf bis zu 2 MPa) und Zugfestigkeit (von 57 kPa auf bis zu 1.1 MPa). Darüber hinaus konnte die Übergangstemperatur Tc deutlich gesteigert werden (von ca. 40 °C auf > 85 °C). Dieses Verhalten ließ sich auf stabilisierende Bindungen zwischen den aromatische Gruppen und dem HAp zurückführen. KW - Physikalische Quervernetzung KW - Supramolekularen Wechselwirkung KW - Molekulare Modellierung KW - Biomaterialien KW - Gelatine KW - Komposite KW - Hydroxyapatit KW - Physical Network KW - Supramolecular Interaction KW - Molecular modeling KW - Biomaterial KW - Gelatin KW - Composite KW - Hydroxyapatite Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-52888 ER -