Enhancement of Intracellular Calcium Ion Mobilization by Moderately but Not Highly Positive Material Surface Charges

Electrostatic forces at the cell interface affect the nature of cell adhesion and function; but there is still limited knowledge about the impact of positive or negative surface charges on cell-material interactions in regenerative medicine. Titanium surfaces with a variety of zeta potentials between −90 mV and +50 mV were generated by functionalizing them with amino polymers, extracellular matrix proteins/peptide motifs and polyelectrolyte multilayers. A significant enhancement of intracellular calcium mobilization was achieved on surfaces with a moderately positive (+1 to +10 mV) compared with a negative zeta potential (−90 to −3 mV). Dramatic losses of cell activity (membrane integrity, viability, proliferation, calcium mobilization) were observed on surfaces with a highly positive zeta potential (+50 mV). This systematic study indicates that cells do not prefer positive charges in general, merely moderately positive ones. The cell behavior of MG-63s could be correlated with the materials’ zeta potential; but not with water contact angle or surface free energy. Our findings present new insights and provide an essential knowledge for future applications in dental and orthopedic surgery. © Copyright © 2020 Gruening, Neuber, Nestler, Lehnfeld, Dubs, Fricke, Schnabelrauch, Helm, Müller, Staehlke and Nebe

Terminal chemical functions of polyamidoamine dendrimer surfaces and its impact on bone cell growth

Besides their use for drug and gene delivery, dendrimer molecules are also favorable for the design of new surface coatings for orthopedic and dental implants due to the wide variety of functional terminal groups and their multivalent character. The purpose of this work was to observe how covalently immobilized polyamidoamine (PAMAM) dendrimer molecules with different terminal chemical groups influenced serum protein adsorption and osteoblast behavior. To this end, fifth-generation PAMAM dendrimers were immobilized on silicon surfaces with an anhydride-containing silane coupling agent which results in positively charged terminal NH2-groups. Coatings with a net negative charge were generated by introduction of terminal CO2H- or CH3- groups. Surface characterization was performed by static and dynamic contact angle and zeta potential. The in vitro studies with human MG-63 osteoblastic cells focused on cell adhesion, morphology, cell cycle, apoptosis and actin formation within 24 h. This work demonstrated that cell growth was dependent on surface chemistry and correlated strongly with the surface free energy and charge of the material. The positively charged NH 2 surface induced tight cell attachment with well-organized actin stress fibers and a well spread morphology. In contrast, CO2H- and CH3-functional groups provoked a decrease in cell adhesion and spreading and indicated higher apoptotic potential, although both were hydrophilic. The knowledge about the cell-material dialogue is of relevance for the development of bioactive implants in regenerative medicine

Saliva and Serum Protein Adsorption on Chemically Modified Silica Surfaces

Biomaterials, once inserted in the oral cavity, become immediately covered by a layer of adsorbed proteins that consists mostly of salivary proteins but also of plasma proteins if the biomaterial is placed close to the gingival margin or if it becomes implanted into tissue and bone. It is often this protein layer, rather than the pristine biomaterial surface, that is subsequently encountered by colonizing bacteria or attaching tissue cells. Thus, to study this important initial protein adsorption from human saliva and serum and how it might be influenced through chemical modification of the biomaterial surface, we have measured the amount of protein adsorbed and analyzed the composition of the adsorbed protein layer using gel electrophoresis and western blotting. Here, we have developed an in vitro model system based on silica surfaces, chemically modified with 7 silane-based self-assembled monolayers that span a broad range of physicochemical properties, from hydrophilic to hydrophobic surfaces (water contact angles from 15° to 115°), low to high surface free energy (12 to 57 mN/m), and negative to positive surface charge (zeta potentials from –120 to +40 mV at physiologic pH). We found that the chemical surface functionalities exerted a substantial effect on the total amounts of proteins adsorbed; however, no linear correlation of the adsorbed amounts with the physicochemical surface parameters was observed. Only the adsorption behavior of a few singular protein components, from which physicochemical data are available, seems to follow physicochemical expectations. Examples are albumin in serum and lysozyme in saliva; in both, adsorption was favored on countercharged surfaces. We conclude from these findings that in complex biofluids such as saliva and serum, adsorption behavior is dominated by the overall protein-binding capacity of the surface rather than by specific physicochemical interactions of single protein entities with the surface

Enhancement of Intracellular Calcium Ion Mobilization by Moderately but Not Highly Positive Material Surface Charges

Electrostatic forces at the cell interface affect the nature of cell adhesion and function; but there is still limited knowledge about the impact of positive or negative surface charges on cell-material interactions in regenerative medicine. Titanium surfaces with a variety of zeta potentials between -90 mV and +50 mV were generated by functionalizing them with amino polymers, extracellular matrix proteins/peptide motifs and polyelectrolyte multilayers. A significant enhancement of intracellular calcium mobilization was achieved on surfaces with a moderately positive (+1 to +10 mV) compared with a negative zeta potential (-90 to -3 mV). Dramatic losses of cell activity (membrane integrity, viability, proliferation, calcium mobilization) were observed on surfaces with a highly positive zeta potential (+50 mV). This systematic study indicates that cells do not prefer positive charges in general, merely moderately positive ones. The cell behavior of MG-63s could be correlated with the materials' zeta potential; but not with water contact angle or surface free energy. Our findings present new insights and provide an essential knowledge for future applications in dental and orthopedic surgery

Integrating ship movement scheduling and tug assignment within a canal harbor

In this paper we address the in-port ship scheduling and tug assignment problem. This problem aims to determine a schedule of ship movements, and their escorting tugs, within a canal harbor. We formulate the problem as a Boolean satisfiability problem. In particular, we deal with canal-harbors, as this kind of harbors present strict constraints, e.g., on safety distance. We consider the Port of Venice, a medium size Italian harbor, as a case stud

No clinically relevant CYP3A induction after St. John’s wort with low hyperforin content in healthy volunteers

Objective Induction of CYP3A by St. John’s wort (SJW) products with high hyperforin content is well described. Since CYP3A induction is mediated by hyperforin in a concentration-dependent manner, and SJW preparations differ significantly in hyperforin content, the aim of the study was to evaluate the effect of an SJW powder with low hyperforin content on CYP3A function. Methods Twenty healthy male volunteers received an SJW powder with low hyperforin content for 2 weeks. Midazolam plasma concentration time profiles were characterized after a single oral dose of 7.5 mg midazolam on the day before and on the 14th day of SJW medication. Results Midazolam AUC0–∞ slightly decreased from 124.0 ± 62.5 ng/ml·h at baseline to 105.6 ± 53.2 ng/ml·h after SJW (P < 0.05), representing a mean 11.3% decrease (95% CI: −22.8 to 0.21). No significant change in midazolam Cmax, t1/2 and tmax was observed. For all pharmacokinetic parameters, the 90% CI for the geometric mean ratio of treatment over baseline were within the no-effect boundaries of 0.70–1.43. Conclusion Administration of an SJW product with low hyperforin content resulted in a mild induction of CYP3A not considered clinically relevant