Hematopoietic stem cells (HSCs) are blood forming cells which possess the ability to differentiate into all types of blood cells. T cells are one important cell type HSCs can differentiate into, via ...corresponding progenitor cells. T cells are part of the adaptive immune system as they mediate cellular immune responses. Due to this crucial function, in vitro differentiated T cells are the subject of current studies in the biomedical field in terms of cell transplantation. Studies show that the density of the immobilized Notch ligand Delta-like 1 (DLL1) presented in HSCs' environment can stimulate their differentiation toward T cells. The development of reliable synthetic cell culture systems presenting variable densities of DLL1 is promising for the future expansion of T cells' clinical applications. Here we introduce bifunctional polyethylene glycol-based (PEG-based) hydrogels as a potential instructing platform for the differentiation of human hematopoietic stem and progenitor cells (HSPCs) to T cells. PEG hydrogels bearing the cell adhesion supporting motif RGD (arginyl-glycyl-aspartic acid) were synthesized by UV-light induced radical copolymerization of PEG diacrylate and RGD modified PEG acrylate. The hydrogels were furthermore nanostructured by incorporation of gold nanoparticle arrays that were produced by block copolymer micelle nanolithography (BCML). BCML allows for the decoration of surfaces with gold nanoparticles in a hexagonal manner with well-defined interparticle distances. To determine the impact of DLL1 density on the cell differentiation, hydrogels with particle distances of ~40 and 90 nm were synthesized and the gold nanoparticles were functionalized with DLL1. After 27 days in culture, HSPCs showed an unphysiological differentiation status and, therefore, the differentiation was evaluated as atypical T lymphoid differentiation. Cluster of differentiation (CD) 4 was the only tested T cell marker which was expressed clearly in all samples. Thus, although the applied nanopatterned hydrogels affected two important signaling pathways (integrins and Notch) for T cell differentiation, it appears that more functionalities that control T cell differentiation in nature need to be considered for achieving fully synthetic in vitro T cell differentiation strategies.
Chemical heterogeneity on biomaterial surfaces can transform its interfacial properties, rendering nanoscale heterogeneity profoundly consequential during bioadhesion. To examine the role played by ...chemical heterogeneity in the adsorption of viruses on synthetic surfaces, a range of novel coatings is developed wherein a tunable mixture of electrostatic tethers for viral binding, and carbohydrate brushes, bearing pendant α‐mannose, β‐galactose, or β‐glucose groups, is incorporated. The effects of binding site density, brush composition, and brush architecture on viral adsorption, with the goal of formulating design specifications for virus‐resistant coatings are experimentally evaluated. It is concluded that virus‐coating interactions are shaped by the interplay between brush architecture and binding site density, after quantifying the adsorption of adenoviruses, influenza, and fibrinogen on a library of carbohydrate brushes co‐immobilized with different ratios of binding sites. These insights will be of utility in guiding the design of polymer coatings in realistic settings where they will be populated with defects.
A tunable coating comprising nonfouling carbohydrate brushes and electrostatic binding sites for viruses is employed to study the relationship between surface design parameters and viral adsorption. Ultimately, brush architecture determines whether the binding sites are exposed to, or shielded from viruses. These insights will guide the design of polymer coatings that can resist viral binding despite being populated with defects.
Large or complex bone fractures often need clinical treatments for sufficient bone repair. New treatment strategies have pursued the idea of using mesenchymal stromal cells (MSCs) in combination with ...osteoinductive materials to guide differentiation of MSCs into bone cells ensuring complete bone regeneration. To overcome the challenge of developing such materials, fundamental studies are needed to analyze and understand the MSC behavior on modified surfaces of applicable materials for bone healing. For this purpose, we developed a fibrous scaffold resembling the bone/bone marrow extracellular matrix (ECM) based on protein without addition of synthetic polymers. With this biomimetic in vitro model we identified the fibrous structure as well as the charge of the material to be responsible for its effects on MSC differentiation. Positive charge was introduced via cationization that additionally supported the stability of the scaffold in cell culture, and acted as nucleation point for mineralization during osteogenesis. Furthermore, we revealed enhanced focal adhesion formation and osteogenic differentiation of MSCs cultured on positively charged protein fibers. This pure protein-based and chemically modifiable, fibrous ECM model allows the investigation of MSC behavior on biomimetic materials to unfold new vistas how to direct cells' differentiation for the development of new bone regenerating strategies.
Surface-initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization was used to synthesize poly(methyl methacrylate) (PMMA) and ...poly2-(methacryloyloxy)ethyldimethyl-(3-sulfopropyl)ammoniumhydroxide (PMEDSAH) brushes grafted from reactive polyp-xylylene surfaces. The synthetic approach involved functionalization of substrates via chemical vapor deposition polymerization of an electron-deficient alkynyl-functionalized 2.2paracyclophane derivative. An azide-functionalized RAFT agent was anchored to the resulting poly(p-xylylene-4-methyl propiolate)-co-p-xylylene films via copper-free click-chemistry. Subsequent SI-RAFT polymerization yielded PMMA and PMEDSAH films with narrow dispersity which was further tuned by varying the concentration of a sacrificial RAFT agent in solution. Polymer dispersity was determined by size exclusion chromatography to be in the range of 1.2–1.4 for both polymers. This work provides a novel surface modification strategy to decorate a wide range of different substrates with polymer brushes, thereby eliminating the need for cumbersome modification protocols, which so far had to be established for each substrate material independently.
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•Novel approach for SI-RAFT polymerization strategy applicable to a range of organic and inorganic surfaces.•Vapor-based reactive coatings based on functionalized poly-p-xylylene for SI-RAFT polymerization.•The surface modification strategy can be extended to the synthesis of a variety of polymers.
Polymers prepared by chemical vapor deposition (CVD) polymerization have found broad acceptance in research and industrial applications. However, their intrinsic lack of degradability has limited ...wider applicability in many areas, such as biomedical devices or regenerative medicine. Herein, we demonstrate, for the first time, a backbone‐degradable polymer directly synthesized via CVD. The CVD co‐polymerization of 2.2para‐cyclophanes with cyclic ketene acetals, specifically 5,6‐benzo‐2‐methylene‐1,3‐dioxepane (BMDO), results in well‐defined, hydrolytically degradable polymers, as confirmed by FTIR spectroscopy and ellipsometry. The degradation kinetics are dependent on the ratio of ketene acetals to 2.2para‐cyclophanes as well as the hydrophobicity of the films. These coatings address an unmet need in the biomedical polymer field, as they provide access to a wide range of reactive polymer coatings that combine interfacial multifunctionality with degradability.
Breaking back: A new class of backbone‐degradable polymer coatings was developed via chemical vapor deposition co‐polymerization. These polymer coatings address a significant unmet need in the biomedical polymer field, as they provide access to a wide range of reactive polymer coatings that combine interfacial multifunctionality with degradability.
We report the chemical vapor deposition (CVD) of dual-functional polymer films for the specific and orthogonal immobilization of two biomolecules (notch ligand delta-like 1 (DLL1) and an RGD-peptide) ...that govern the fate of hematopoietic stem and progenitor cells. The composition of the CVD polymer and thus the biomolecule ratio can be tailored to investigate and optimize the influence of the relative surface concentrations of biomolecules on stem cell behavior. Prior to cell experiments, all surfaces were characterized by infrared reflection adsorption spectroscopy, time-of-flight secondary ion mass spectrometry, and X-ray photoelectron spectroscopy to confirm the presence of both biomolecules. In a proof-of-principle stem cell culture study, we show that all polymer surfaces are cytocompatible and that the proliferation of the hematopoietic stem and progenitor cells is predominantly influenced by the surface concentration of immobilized DLL1.
This paper focuses on readily accessible thiourea hydrogen bond catalysts derived from amino acids, whose steric and electronic features are modulated by their degree of substitution at the carbinol ...carbon center. These catalysts were applied in the asymmetric transfer hydrogenation of nitroolefins furnishing the chiral products in up to 99% yield and 86% enantiomeric excess. The proposed catalyst's mode of action is supported by mechanistic investigations.
A general synthetic strategy is described that enables access to a library of new sulfobetaine methacrylates starting from commercially available precursors. The three‐step procedure allows the ...distance between the quaternary amine and the sulfonate group (inner charge distance) to be varied by selecting the corresponding dibromoalkane in the first step. A key step is the final esterification, in which methacrylic acid acts as solvent as well as reagent for the zwitterionic hydroxy intermediates. Thus, it is possible to synthesize monomeric precursors with up to twelve methylene groups between the positive and the negative charge. A selection of these monomers has been successfully tested for their ability to polymerize using free‐radical polymerization.
A simple and highly universal three‐step procedure has been developed for the synthesis of sulfobetaine methacrylates with variation of the charge separation distance. The protocol provides access to a library of new zwitterionic precursors that have potential for a range of applications in polymer chemistry and materials science.
Abstract
Polymers prepared by chemical vapor deposition (CVD) polymerization have found broad acceptance in research and industrial applications. However, their intrinsic lack of degradability has ...limited wider applicability in many areas, such as biomedical devices or regenerative medicine. Herein, we demonstrate, for the first time, a backbone‐degradable polymer directly synthesized via CVD. The CVD co‐polymerization of 2.2
para
‐cyclophanes with cyclic ketene acetals, specifically 5,6‐benzo‐2‐methylene‐1,3‐dioxepane (BMDO), results in well‐defined, hydrolytically degradable polymers, as confirmed by FTIR spectroscopy and ellipsometry. The degradation kinetics are dependent on the ratio of ketene acetals to 2.2
para
‐cyclophanes as well as the hydrophobicity of the films. These coatings address an unmet need in the biomedical polymer field, as they provide access to a wide range of reactive polymer coatings that combine interfacial multifunctionality with degradability.
Provider: - Institution: - Data provided by Europeana Collections- Karlsruhe, Karlsruher Institut für Technologie (KIT), Diss., 2015- All metadata published by Europeana are available free of ...restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
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