Mesoscale Characterization of Supramolecular Transient Networks Using SAXS and Rheology

Hydrogels and, in particular, supramolecular hydrogels show promising properties for application in regenerative medicine because of their ability to adapt to the natural environment these materials are brought into. However, only few studies focus on the structure-property relationships in supramolecular hydrogels. Here, we study in detail both the structure and the mechanical properties of such a network, composed of poly(ethylene glycol), end-functionalized with ureido-pyrimidinone fourfold hydrogen bonding units. This network is responsive to triggers such as concentration, temperature and pH. To obtain more insight into the sol-gel transition of the system, both rheology and small-angle X-ray scattering (SAXS) are used. We show that the sol-gel transitions based on these three triggers, as measured by rheology, coincide with the appearance of a structural feature in SAXS. We attribute this feature to the presence of hydrophobic domains where cross-links are formed. These results provide more insight into the mechanism of network formation in these materials, which can be exploited for tailoring their behavior for biomedical applications, where one of the triggers discussed might be used

Macrocyclization of enzyme-based supramolecular polymers

AB type monomers for supramolecular polymers have been developed based on the strong and reversible noncovalent interaction between ribonuclease S-peptide (A) and S-protein (B), resulting in an active enzyme complex as the linking unit. Two AB-type protein constructs are synthesized differing in the length of the flexible oligo(ethylene glycol) spacer separating the two end groups. Using an experimental setup where size exclusion chromatography is directly coupled to Q-TOF mass spectrometry, we have analyzed the self-assembled architectures as a function of concentration. The theory of macrocyclization under thermodynamic control is used to quantitatively analyze the experimental data. Using this theory, we show that AB-type monomers linked by flexible linkers grow reversibly via ring-chain competition. Inherently the formation of linear polymeric assemblies is beyond the capability of these types of building blocks due to concentration limits of proteins. The results therefore contribute to the general understanding of supramolecular polymerization with biological building blocks and demonstrate design requirements for monomers if linear polymerization is desired

A Fast pH-Switchable and Self-Healing Supramolecular Hydrogel Carrier for Guided, Local Catheter Injection in the Infarcted Myocardium

Minimally invasive intervention strategies after myocardial infarction use state-of-the-art catheter systems that are able to combine mapping of the infarcted area with precise, local injection of drugs. To this end, catheter delivery of drugs that are not immediately pumped out of the heart is still challenging, and requires a carrier matrix that in the solution state can be injected through a long catheter, and instantaneously gelates at the site of injection. To address this unmet need, a pH-switchable supramolecular hydrogel is developed. The supramolecular hydrogel is switched into a liquid at pH > 8.5, with a viscosity low enough to enable passage through a 1-m long catheter while rapidly forming a hydrogel in contact with tissue. The hydrogel has self-healing properties taking care of adjustment to the injection site. Growth factors are delivered from the hydrogel thereby clearly showing a reduction of infarct scar in a pig myocardial infarction model

From supramolecular polymers to multi-component biomaterials

The most striking and general property of the biological fibrous architectures in the extracellular matrix (ECM) is the strong and directional interaction between biologically active protein subunits. These fibers display rich dynamic behavior without losing their architectural integrity. The complexity of the ECM taking care of many essential properties has inspired synthetic chemists to mimic these properties in artificial one-dimensional fibrous structures with the aim to arrive at multi-component biomaterials. Due to the dynamic character required for interaction with natural tissue, supramolecular biomaterials are promising candidates for regenerative medicine. Depending on the application area, and thereby the design criteria of these multi-component fibrous biomaterials, they are used as elastomeric materials or hydrogel systems. Elastomeric materials are designed to have load bearing properties whereas hydrogels are proposed to support in vitro cell culture. Although the chemical structures and systems designed and studied today are rather simple compared to the complexity of the ECM, the first examples of these functional supramolecular biomaterials reaching the clinic have been reported. The basic concept of many of these supramolecular biomaterials is based on their ability to adapt to cell behavior as a result of dynamic non-covalent interactions. In this review, we show the translation of one-dimensional supramolecular polymers into multi-component functional biomaterials for regenerative medicine applications

Immunocytochemical evidence for production of luteinizing hormone and follicle-stimulating hormone in separate cells in the bovine.

In all mammalian females, follicular growth and maturation are essentially dependent on the pituitary gonadotropins, FSH and LH. These glycoprotein hormones have many similarities, but their action, based on high affinity binding to specific membrane receptors, are quite different. The purpose of this study was to perform a sensitive localization of FSH and LH in secretory granules of gonadotrophs using highly specific antisera. This morphological study included light microscopy (PAP) and electron microscopy (immunogold single and double labeling) procedures. Histologically, approximatively 11.5% of cells were positive for LH, whereas only 5.4% of cells were positive for FSH. With the electron microscope, single labeling allowed identification of morphologically distinct LH-containing cells and FSH-containing cells. Double immunostaining confirmed that no cells contained both hormones. The finding that FSH and LH are produced in separate pituitary cells is in agreement with recent studies that have suggested a specific role and regulatory process for gonadotropins in the bovine species

The other face of Eurolegalism: The multifaceted convergence of national enforcement styles

Contains fulltext : 179935.pdf (publisher's version ) (Closed access)This article analyzes the implications of European integration for national regulatory enforcement. More specifically, it tests the Eurolegalism thesis, which holds that the tendency of using more detailed, prescriptive European Union (EU) regulation combined with more public and private enforcement leads to a convergence in national enforcement styles. It does so by developing and applying a fine-grained conceptualization of enforcement style. This conceptualization forms the basis of a focused comparison of enforcement of the highly detailed and strict EU Packaging Waste Directive in the Netherlands and Germany – two countries known for their opposed enforcement styles. Our analysis shows that although convergence toward a more insistent enforcement style seems to have taken place, the two countries have arrived at this position in markedly different ways. By identifying differences in style underneath the surface of convergence, the article qualifies the Eurolegalism argument, thus, advancing the literature on EU enforcement styles and deepening our understanding of the subtle and divergent ways in which common international regulatory inputs may affect domestic enforcement.1 augustus 201

Long-latency motor evoked potentials in congenital hemiplegia

OBJECTIVE: To investigate long-latency motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation in congenital hemiplegia (CH) and to seek for correlation with paretic hand movement deficits. METHODS: MEPs were recorded from the first dorsal interosseous of both hands in 12 CH patients and 12 age-matched controls; dexterity and upper limb function were quantitatively assessed in both groups. RESULTS: In CH patients, long-latency MEPs, occurring much later than the commonly reported MEPs, were frequently observed in the paretic and non-paretic hands. Four distinct groups of long-latency MEPs were found, each cluster being identified by its mean latency, namely 35, 85, 160 and 225 ms. The residual dexterity of the paretic hand was correlated with the presence of contralateral MEPs with a 20 and 225 ms latency and was negatively correlated with ipsilateral MEPs, irrespective of their latency. In controls, only few MEPs with a latency of 225 ms were found in 4 out of 12 subjects. CONCLUSIONS: The pattern of MEPs found in CH patients differs dramatically from that reported in adult stroke patients, suggesting that long-latency MEPs are a rather distinctive consequence of early corticospinal lesions. The hypothesis that a given cluster of long-latency MEPs is mediated by a particular pathway appears very unlikely. Rather, we suggest that an exacerbation of cortical and/or spinal excitability is at the origin of these long-latency MEPs