Multivalent Polyaspartamide-based Hydrogels with Controllable Physical and Biological Properties

Department of ChemistryHydrogels provide suitable microenvironment for various fields of bioengineering, as they can be engineered to mimic the structure and properties of natural extracellular matrix (ECM); a network of hydrophilic and biocompatible polymers possessing elasticity and high water content ideal for supporting biological molecules and species. Due to these attractive properties, hydrogels are widely used in such biomedical applications as tissue engineering and drug delivery. Their structure can be designed and altered at a molecular level with various functional groups of constituting polymers, which results in the changes in various physically properties (e.g. rigidity, toughness, and permeability). However, controlling those physical properties via chemical modifications are usually difficult, requiring several time-consuming steps. Herein, highly versatile polyaspartamide, which allows for the efficient control of the type and number of functional groups, was developed in order to engineer hydrogels with tunable properties for biomedical applications. In Chapter 1, a brief introduction to hydrogels as biomaterials and the importance of controlling their mechanical properties are described. Also, a history of polysuccinimide and its derivatization to various forms of polyaspartamide is introduced to highlight the importance of this subject in the field of biomedical engineering. Chapter 2 presents the development of various polyaspartamides, presenting thiol, hydrazide, and amine functional groups, and their applications into fabricating hydrogels with controllable physical properties. In addition, the biomedical application of polyaspartamide-based hydrogels is demonstrated through controlled drug release and in vitro cell culture. Finally in Chapter 3, the multifunctional nature of polyaspartamide is further introduced with the polyaspartamide presenting isopropyl groups for thermoresponsiveness.ope

Die Berechnung der induzierten Ladung

One of the main aspects of statistical mechanics is that the properties of a thermodynamics state point do not depend on the choice of the statistical ensemble. It breaks down for small systems e.g. single molecules. Hence, the choice of the statistical ensemble is crucial for the interpretation of single molecule experiments, where the outcome of measurements depends on which variables or control parameters, are held fixed and which ones are allowed to fluctuate. Following this principle, this thesis investigates the thermodynamics of a single polymer pulling experiments within two different statistical ensembles. The scaling of the conjugate chain ensembles, the fixed end-to-end vector (Helmholtz) and the fixed applied force (Gibbs), are studied in depth. This thesis further investigates the ensemble equivalence for different force regimes and polymer-chain contour lengths. Using coarse-grained molecular dynamic simulations, i.e. Langevin dynamics, the simulations were found to complement the theoretical predictions for the scaling of ensemble difference of Gaussian chains in different force-regimes, giving special attention to the zero force regime. After constructing Helmholtz and Gibbs conjugate ensembles for a Gaussian chain, two different data sets of thermodynamic states on the force-extension plane, i.e. force-extension curves, were generated. The ensemble difference is computed for different polymer-chain lengths by using force-extension curves. The scaling of the ensemble difference versus relative polymer-chain length under different force regimes has been derived from the simulation data and compared to theoretical predictions. The results demonstrate that the Gaussian chain in the zero force limit generates nonequivalent ensembles, regardless of its equilibrium bond length and polymer-chain contour length. Moreover, if polymers are charged in confinement, coarse-graining is problematic, owing to dielectric interfaces. Hence, the effect of dielectric interfaces must be taken into account when describing physical systems such as ionic channels or biopolymers inside nanopores. It is shown that the effect of dielectrics is crucial for the dynamics of a biopolymer or an ion inside a nanopore. In the simulations, the feasibility of an efficient and accurate computation of electrostatic interactions in the presence of an arbitrarily shaped dielectric domain is challenging. Several solutions for this problem have been previously proposed in the literature such as a density functional approach, or transforming problem at hand into an algebraic problem ( Induced Charge Computation (ICC) ) and boundary element methods. Even though the essential concept is the same, which is to replace the dielectric interface with a polarization charge density, these approaches have been analyzed and the ICC algorithm has been implemented. A new superior boundary element method has been devised utilizing the force computation via the Particle-Particle Particle-Mesh (P3M) method for periodic geometries (ICCP3M). This method has been compared to the ICC algorithm, the algebraic solutions, and to density functional approaches. Extensive numerical tests against analytically tractable geometries have confirmed the correctness and applicability of developed and implemented algorithms, demonstrating that the ICCP3M is the fastest and the most versatile algorithm. Further optimization issues are also discussed in obtaining accurate induced charge densities. The potential of mean force (PMF) of DNA modelled on a coarsed-grain level inside a nanopore is investigated with and without the inclusion of dielectric effects. Despite the simplicity of the model, the dramatic effect of dielectric inclusions is clearly seen in the observed force profile.Eines der wichtigsten Ergebnisse der statistischen Mechanik ist, dass unterschiedliche statistische Ensembles dieselben thermodynamischen Zustände erzeugen. Dieses Prinzip gilt nicht notwendigerweise für kleine Systeme, wie zum Beispiel einzelne Moleküle oder ein einzelnes Polymer. Deshalb ist die Wahl des statistischen Ensembles von entscheidender Bedeutung für die Interpretation von Einzelmolekülexperimenten ( im Englischen "Single Molecule Experiment" (SME) ), denn das Ergebnis der Messung hängt davon ab, welche Variablen oder Kontrollparameter festgehalten werden und welche fluktuieren können. Ausgehend von diesem Problem haben wir Zugexperimente an einem einzigen Polymer in zwei verschiedenen Ensembles durchgeführt und den thermodynamischen Limes (Anzahl der Polymersegmente wächst gegen unendlich) untersucht. Wir haben zwei konjugierte Ensembles, nämlich das, in dem der End-zu-End Abstand (Helmholtz) festgehalten wurde, mit dem, wo wir die Kraft (Gibbs) festgehalten haben, gründlich und auf verschiedene Arten verglichen. Wir haben den Ensemble-Unterschied als Funktion der Anzahl der Polymersegmente in unterschiedlichen Zugkraftbereichen mittels Molekulardynamik Simulationen untersucht, wobei wir eine Langevin Dynamik benutzt haben. Die untersuchten Messgrössen waren die Bestimmung von sogenannten Kraft-Dehnungskurven, wie sie auch in AFM Experimenten gemessen werden. Diese Kurven wurden für zwei verschieden Gauss Ketten verschiedenster Polymerlänge durchgeführt, einmal mit verschwindender Bondlänge und einmal mit Bondlänge eins. Aufgrund unserer Simulationen konnten wir zeigen, das sowohl Gauss-Ketten mit endlicher, wie auch verschwindender Bondlänge für den Bereich verschwindender Zugkraft einen endlichen Ensembleunterschied besitzen, der nicht von der Kettenlänge abhängt. Dieses Phänomen wurde bereits vor 20 Jahren von R. Neumann beschrieben. Trotz der relativ einfachen Argumente von Neumann gibt es bis heute noch Arbeiten, die diesen Sachverhalt entweder anzweifeln oder verkehrt darstellen. Wir hoffen, durch diesen Teil der Arbeit den Sachverhalt zufriedenstellend aufgeklärt zu haben. Im zweiten Teil der Arbeit behandeln wir geladen Polymere unter einem räumlichen Einschluss. Dies können zum Beispiel Ionen in schmalen Kanälen sein (Ionenkanäle), oder DNA in Nanoporen. In vergröberten Simulationen werden geladene Polymere immer in einem dielektrischen Kontinuum dargestellt. Wasser hat eine relative dielektrische Konstante von 80 bei Raumtemperatur, die dann in dieses Model als Parameter gesteckt wird. Wenn feste Grenzflächen vorhanden sind, haben diese meist niedrige dielektrische Konstanten ($\approx 2$). Diese Grenzflächen haben grosse Auswirkungen auf die elektrostatischen Wechselwirkungen. In den Simulationen ist es wichtig, diese Effekte korrekt *und schnell* zu berechnen. Deshalb haben wir einen effizienten und präzisen Algorithmus entwickelt, der genau dies bewerkstelligt. In der Literatur wurden mehrere Möglichkeiten vorgeschlagen, wie dieses Problem für Simulationen lösbar sein sollte, wie zum Beispiel Dichtefunktionalmethoden, Umwandlung des Problems in ein algebraisches Problem (Induced Charge Computation, ICC) oder die Randelement Methode. Das wesentliche Konzept besteht darin, die Polarisationsladung auf dem dielektrischen Rand so zu bestimmen, dass die dielektrischen Randbedingungen erfüllt werden. Wir haben den ICCP3M Algorithmus entwickelt, dessen Kernstück darin besteht, den P3M Algorithmus zur Bestimmung der induzierten Ladung auf den Randelementen zu benutzen. Durch diesen Trick lässt sich die Ladungsberechnung in CPU Zeit $\mathscr{O}(Nlog N)$, wobei $\mathscr{O}(N)$ die Anzahl der Ladungen im System ist, durchführen. Wir haben den Algorithmus innerhalb des Espresso Programmpakets implementiert und optimiert. Im letzten Teil der Arbeit wurde das Potential der mittleren Kraft einer vergröberten DNA innerhalb einer Nanopore untersucht, wobei wir die Unterschiede zwischen korrekter Behandung der dielektrischen Ränder und der Ignorierung derselben quantifiziert haben. Trotz seiner Einfachheit zeigt unser Modell den dramatischen Einfluss, den die dielektrischen Ränder auf die gemessene efffektive Kraft und das Potential der mittleren Kraft ausüben

Multivalent Polyaspartamide Cross-Linker for Engineering Cell-Responsive Hydrogels with Degradation Behavior and Tunable Physical Properties

Hydrogels possess favorable physical properties ideally suited for various biotechnology applications. To tailor to specific needs, a number of modification strategies have been employed to tune their properties. Herein, a multifunctional polymeric cross-linker based on polyaspartamide is developed, which allows for the facile adjustment of the type and number of reactive functional groups to fit different reaction schemes and control the physical properties of the hydrogels. The amine-based nucleophiles containing desired functional groups are reacted with polysuccinimide to synthesize polyaspartamide cross-linkers. The cross-linking density and the concurrent change in mechanical properties of the resulting hydrogels are controlled in a wide range only with the degree of substitution. This multivalency of the polyaspartamide linkers also induced the degradation of hydrogels by the unreacted functional groups on polyaspartamide involved in the hydrolysis. Furthermore, the polyaspartamide cross-linker conjugated with cell-recognition molecules via the same conjugation mechanism (i.e., nucleophilic substitution) render the hydrogels cell-responsive without the need of additional processing steps. This versatility of polyaspartamide-based cross-linker is expected to provide an efficient and versatile route to engineer hydrogels with controllable properties for biomedical applications

Extremely Stable Luminescent Crosslinked Perovskite Nanoparticles under Harsh Environments over 1.5 Years

© 2020 Wiley-VCH GmbHOrganic–inorganic hybrid perovskite nanoparticles (NPs) are a very strong candidate emitter that can meet the high luminescence efficiency and high color standard of Rec.2020. However, the instability of perovskite NPs is the most critical unsolved problem that limits their practical application. Here, an extremely stable crosslinked perovskite NP (CPN) is reported that maintains high photoluminescence quantum yield for 1.5 years (>600 d) in air and in harsher liquid environments (e.g., in water, acid, or base solutions, and in various polar solvents), and for more than 100 d under 85 °C and 85% relative humidity without additional encapsulation. Unsaturated hydrocarbons in both the acid and base ligands of NPs are chemically crosslinked with a methacrylate-functionalized matrix, which prevents decomposition of the perovskite crystals. Counterintuitively, water vapor permeating through the crosslinked matrix chemically passivates surface defects in the NPs and reduces nonradiative recombination. Green-emitting and white-emitting flexible large-area displays are demonstrated, which are stable for >400 d in air and in water. The high stability of the CPN in water enables biocompatible cell proliferation which is usually impossible when toxic Pb elements are present. The stable materials design strategies provide a breakthrough toward commercialization of perovskite NPs in displays and bio-related applications.