Protein-Resistant Surfaces through Mild Dopamine Surface Functionalization

The synthesis and evaluation of new dopamine-based catechol anchors coupled to poly(ethylene glycol) (PEG) for surface modification of TiO2 are reported. Dopamine is modified by dimethylamine-methylene or trimethylammonium- methylene groups, and the preparation of mPEG-Glu didopamine polymer 11 is presented. All these PEG polymers allow stable adlayers on TiO2 to be generated through mild dip-and-rinse procedures, as evaluated both by variable angle spectroscopic ellipsometry and X-ray photoelectron spectroscopy. The resulting surfaces substantially reduced protein adsorption upon exposure to full human serum

Domestic elites and external actors in post-conflict democratisation: mapping interactions and their impact

Following the end of the Cold War, post-conflict democratisation has rarely occurred without a significant international involvement. This contribution argues that an explanation of the outcomes of post-conflict democratisation requires more than an examination of external actors, their mission mandates or their capabilities and deficiencies. In addition, there is a need to study domestic elites, their preferences and motivations, as well as their perceptions of and their reactions to external interference. Moreover, the patterns of external–internal interactions may explain the trajectory of state-building and democracy promotion efforts. These issues deserve more attention from both scholars and practitioners in the fields of peace- and state-building, democracy promotion, regime transition and elite research. Analyses of external actors and domestic elites in post-conflict democratisation should therefore address three principal issues: (1) the identification of relevant domestic elites in externally induced or monitored state-building and democratisation processes, (2) the dynamics of external–domestic interactions and (3) the impact of these interactions on the outcomes of post-conflict democratisation

Catechol functionalized polymers and method for preparing them

Described are compounds that are capable of forming adlayers, said compounds comprising at least one headgroup A, an optional linker B, a polymer C, a terminal group D and an optionally present crosslinking group R, wherein the headgroup A is a compound of the following formula wherein X is independently from each other selected from an acidic group, such as OH, SH, phosphate, phosphornate and N+R2H, Y is a group derived from a convenient coupling group, in particular NL3, or N+(L3)2, Z1, Z3, and Z4 are C or N+ Z2, Z5 and Z6 are C-L1 or N+-L, wherein L1 is H or an electron withdrawing group, L is C1-C6 alkyl, in particular C1-C4 alkyl L2 and L3 are independently selected from H or C1-C6 alkyl, preferably C1-C4 alkyl, or L2 may form together with L1 or L of Z6 a heterocycle, in particular a positively charged heterocycle, n is 0, or 1, or 2, or 3, m is 0 or 1 with the proviso that at most one of Z1 to Z6 is N+ and that in case that Z1 is N+, L2 may additionally be an ester, an amide, or a heterocycle

Biomimetic Surface Modifications Based on the Cyanobacterial Iron Chelator Anachelin

Siderophores are natural iron chelators that have been evolutionarily selected to bind to Fe ions with very high binding consts. We utilize these unique properties to bind to metal oxide surfaces using a fragment of the cyanobacterial siderophore anachelin. The resulting poly(ethylene glycol) conjugate forms stable adlayers on TiO2 as has been shown by variable angle spectroscopic ellipsometry and XPS. Moreover, these coated surfaces are highly protein-resistant against the adsorption of full human serum

Functionality, growth and accelerated aging of tissue engineered living autologous vascular grafts

Living autologous tissue engineered vascular-grafts (TEVGs) with growth-capacity may overcome the limitations of contemporary artificial-prostheses. However, the multi-step invitro production of TEVGs requires extensive exvivo cell-manipulations with unknown effects on functionality and quality of TEVGs due to an accelerated biological age of the cells. Here, the impact of biological cell-age and tissue-remodeling capacity of TEVGs in relation to their clinical long-term functionality are investigated. TEVGs were implanted as pulmonary-artery (PA) replacements in juvenile sheep and followed for up to 240 weeks (∼4.5years). Telomere length and telomerase activity were compared amongst TEVGs and adjacent native tissue. Telomerase-activity of invitro expanded autologous vascular-cells prior to seeding was <5% as compared to a leukemic cell line, indicating biological-aging associated with decreasing telomere-length with each cellular-doubling. Up to 100 weeks, the cells in the TEVGs had consistently shorter telomeres compared to the native counterpart, whereas no significant differences were detectable at 240 weeks. Computed tomography (CT) analysis demonstrated physiological wall-pressures, shear-stresses, and flow-pattern comparable to the native PA. There were no signs of degeneration detectable and continuous native-analogous growth was confirmed by vessel-volumetry. TEVGs exhibit a higher biological age compared to their native counterparts. However, despite of this tissue engineering technology related accelerated biological-aging, growth-capacity and long-term functionality was not compromised. To the contrary, extensive in-vivo remodeling processes with substantial endogenous cellular turnover appears to result in "TEVG rejuvenation" and excellent clinical performance. As these large-animal results can be extrapolated to approximately 20 human years, this study suggests long-term clinical-safety of cardiovascular in vitro tissue engineering and may contribute to safety-criteria as to first-in-man clinical-trials

Copy, edit, and paste: natural product approaches to biomaterials and neuroengineering

Progress in the chemical sciences has formed the world we live in, both on a macroscopic and on a nanoscopic scale. The last century witnessed the development of high performance materials that interact with humans on many layers, from clothing to construction, from media to medical devices. On a molecular level, natural products and their derivatives influence many biological processes, and these compounds have enormously contributed to the health and quality of living of humans. Although coatings of stone materials with oils or resins (containing natural products) have led to improved tools already millennia ago, in contrast today, natural product approaches to designer materials, that is, combining the best of both worlds, remain scarce. In this Account, we will summarize our recent research efforts directed to the generation of natural product functionalized materials, exploiting the strategy of “copy, edit, and paste with natural products”. Natural products embody the wisdom of evolution, and only total synthesis is able to unlock the secrets enshrined in their molecular structure. We employ total synthesis (“copy”) as a scientific approach to address problems related to molecular structure, the biosynthesis of natural products, and their bioactivity. Additionally, the fundamental desire to investigate the mechanism of action of natural products constitutes a key driver for scientific inquiry. In an emerging area of relevance to society, we have prepared natural products such as militarinone D that can stimulate neurite outgrowth and facilitate nerve regeneration. This knowledge obtained by synthetic organic chemistry on complex natural products can then be used to design structurally simplified compounds that retain the biological power of the parent natural product (“edit”). This process, sometimes referred to as function-oriented synthesis, allows obtaining derivatives with better properties, improving their chemical tractability and reducing the step count of the synthesis. Along these lines, we have demonstrated that militarinone D can be truncated to yield structurally simplified analogs with improved activity. Finally, with the goal of designing bioactive materials, we have immobilized functionally optimized, neuritogenic natural products (“paste”). These materials could facilitate nerve regeneration, act as nerve guidance conduits, or lead to new approaches in neuroengineering. Based on the surface-adhesive properties of electron-deficient catecholates and the knowledge gathered on neuritogenic natural product derivatives, two mechanistically different design principles have been applied to generate neuritogenic materials. In conclusion, natural products, and their functionally optimized analogs, present a large, mostly untapped reservoir of powerful modulators of biological systems, and their hybridization with materials can lead to new approaches in various fields, from biofilm prevention to neuroengineering