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Ein biomimetischer Ansatz liegt der Selbstorganisation eines helikalen Poly(para ‐ aryltriazol) ‐ Foldamers um ein Templat zugrunde. Diese solvophobe Faltung ergibt Helices, die sich weiterhin zu langen Nanoröhren zusammenlagern (siehe Bild; Maßstab: 100 nm). Konstrukte einer bestimmten Länge und Chiralität werden mit dem Poly(γ ‐ benzyl ‐ L ‐ glutamat) ‐ Gerüst unter geeigneten Bedingungen erhalten, wie beim selbstorganisierten Aufbau von Tabakmosaikviren. [ABSTRACT FROM AUTHOR]

Over the past 50 years, numerous roads towards carbon-based materials have been explored, all of them being paved using mainly one functional group as the brick: acetylene. The acetylene group, or the carbon–carbon triple bond, is one of the oldest and simplest functional groups in chemistry, and although not present in any of the naturally occurring carbon allotropes, it is an essential tool to access their synthetic carbon-rich family. In general, two strategies towards the synthesis of π-conjugated carbon-rich structures can be employed: (a) either the acetylene group serves as a building blockto access acetylene-derived structures or (b) it serves as a synthetic toolto provide other, usually benzenoid, structures. The recently discovered copper-catalysed azide–alkyne cycloaddition (CuAAC) reaction, however, represents a new powerful alternative: it transforms the acetylene group into a five-membered heteroaromatic 1H-1,2,3-triazole (triazole) ring and this gives rise to new opportunities. Compared with all-carbon aromatic non-functional rings, the triazole ring possesses three nitrogen atoms and, thus, can serve as a ligand to coordinate metals, or as a hydrogen bond acceptor and donor. This Feature Article summarises examples of using the triazole ring to construct conjugation- and/or function-related heteroaromatic materials, such as tuneable multichromophoric covalent ensembles, macrocyclic receptors or responsive foldamers. These recent examples, which open a new sub-field within organic materials, started to appear only few years ago and represent “a few more bricks” on the road to carbon-rich functional materials. [ABSTRACT FROM AUTHOR]

We describe a novel modular approach to a series of luminescent iridium complexes bearing triazole–pyridine-derived ligands that were conveniently prepared by using “click” chemistry. One, two or three triazole–pyridine units were effectively built into the heteroaromatic macromolecule using versatile acetylene- and azide-functionalised precursors. Using this approach, a series of iridium-derived molecules, that differ in the number of iridium centres, the structural characteristics of the cyclometalating ligand and the backbone, were synthesised. The preliminary photophysical properties of the prepared complexes indicate that there is only limited interaction (through space or through the backbone) between the iridium centres within one molecule and that each iridium centre retains its individual properties. The results show that our approach can be generally applied towards covalently linked multichromophoric systems with potential application, for instance, in the design and preparation of tunable light emitters. As a demonstration of this concept, a single molecule white-light emitter, constructed from two iridium centres (yellow emission) and a fluorene unit (blue emission), is presented. [ABSTRACT FROM AUTHOR]

A novel, elegant, and significantly improved protocol for the synthesis of a protected octaacetylene phthalocyanine is described. Inexpensive, mild, and environmentally benign iodination of 1,2-dibromobenzene and subsequent optimized chemoselective palladium-catalyzed cyanation are employed to effectively build up the key intermediate 4,5-dibromophthalonitrile in two steps. Introduction of the tert-butyldimethylsilyl-protected acetylene moieties via a Sonogashira cross-coupling provides the desired phthalonitrile precursor that, after cyclization, yielded the protected octaacetylene phthalocyanine. Subsequently, in situ deprotection and "clicking" are employed as a highly efficient and quantitative route to a novel class of octatriazole-functionalized phthalocyanines. The ability of such triazole-derived phthalocyanines to form well-defined supramolecular structures upon doping with zinc(lI) triflate is demonstrated. [ABSTRACT FROM AUTHOR]

We have investigated the effect of structure modification of various discotic liquid crystal side chain polymers on their phase transitions and the resulting dynamics. This has resulted in a better understanding of the structure of the various nematic phases that can be formed, in particular giving rise to the identification of supramolecular thermotropic nematic phases where the fundamental units comprise assemblies of molecules. In addition we have examined the dynamics of field-induced order parameters in the isotropic phase of calamitic side chain polymers using dielectric relaxation spectroscopy and dynamic Kerr effect measurements. [ABSTRACT FROM AUTHOR]

A series of novel mesogens have been prepared by a five-fold Sonogashira reaction of terminal acetylenes with a functionalized pentabromophenol. The corresponding side chain polymers were prepared by a polymer analogous substitution reaction. The mesogens differ in the nature of the substituents, linking five hexyl tails to the aromatic core, i.e. CH2, O, S, SO2 and CONH groups. A wide range of mesophases and corresponding transition temperatures has been detected, ranging from low melting nematic phases to highly stable columnar phases. The widely variable phase behavior is described in terms of specific intermolecular interactions. [ABSTRACT FROM AUTHOR]

Various core materials have been introduced at the terminal end of a discotic mesogen (based on a pentakis(methylphenylethynyl) phenoxy core), resulting in the formation of liquid crystalline ‘monomers’ and ‘dimers.’ The mesomorphic properties of this series of derivatives were investigated as a function of the attached core material. It is shown that the clearing temperatures of the mesogens are dependent on: (i) the fraction of rigid mesogen, (ii) the presence of any linkages between the mesogens and (iii) the presence of any H-bonding interactions. In some materials extra stabilisation of the phase or, indeed, higher ordered mesophases were observed due to the end-group interactions. In addition, we report the investigations to prepare DAB-Am based dendrimers. [ABSTRACT FROM AUTHOR]

Nature uses discrete molecular building blocks to form polymers that assemble into multicomponent, multi-dynamic networks, inside (cytoskeleton) and outside (extracellular matrix) the cell. Both the intra-fibrous molecular dynamics and interactions between fibers dictate (non)linear mechanics, such as stress stiffening and relaxation, and ultimately biological function. Current synthetic systems capture only one dynamic process. Here, we present multi-dynamic hydrogels by uniting a stress-stiffening polymer with supramolecular polymers. Crucial is the molecular dynamics of the supramolecular polymers: They dictate the interaction strength with the stress-stiffening polymer and the subsequent dynamic mechanical properties of the mixed networks. The biological relevance of our multi-dynamic hydrogels is demonstrated by their ability to support fibroblast cell spreading. Future work may address the display of various dynamically presented bioactive cues to cells. [ABSTRACT FROM AUTHOR]

Fibrosis is characterized by the formation of fibrous connective tissue in response to primary injury. As a result, an affected organ may lose part of its functionality due to chronic, organ-specific tissue damage. Since fibrosis is a leading cause of death worldwide, targeting fibrotic diseases with antifibrotic hydrogels can be a lifesaving therapeutic strategy. This study developed a novel hybrid antifibrotic hydrogel by combining the synthetic polyisocyanide (PIC) with hyaluronic acid (HA). Gels of PIC are highly tailorable, thermosensitive, and strongly biomimetic in architecture and mechanical properties, whereas HA is known to promote non-fibrotic fetal wound healing and inhibits inflammatory signaling. The developed HA-PIC hybrids were biocompatible with physical properties comparable to those of the PIC gels. The antifibrotic nature of the gels was assessed by 3D cultures of human foreskin fibroblasts in the presence (or absence as control) of TGFβ1 that promotes differentiation into myofibroblasts, a critical step in fibrosis. Proliferation and macroscopic contraction assays and studies on the formation of stress fibers and characteristic fibrosis markers all indicate a strong antifibrotic nature of HA-PIC hydrogel. We showed that these effects originate from both the lightly crosslinked architecture and the presence of HA itself. The hybrid displaying both these effects shows the strongest antifibrotic nature and is a promising candidate for use as in vivo treatment for skin fibrosis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PHJ Kouwer reports financial support was provided by Netherlands Ministry of Education Culture and Science. none., (Copyright © 2023. Published by Elsevier B.V.)

In pelvic organ prolapse (POP) patients, the uterus, bladder and/or rectum descends into vagina due to weakened support tissues. High recurrence rates after POP surgery suggest an urgent need for improved surgical outcomes. Our aim is to promote connective tissue healing that results in stimulated tissue support functions by surgically applying a hydrogel functionalized with biological cues. We used known vaginal wound healing promoting factors (basic fibroblast growth factor, β-estradiol, adipose-derived stem cells) in the biomimetic and injectable polyisocyanide (PIC) hydrogel, which in itself induces regenerative vaginal fibroblast behavior. The regenerative capacity of injected PIC hydrogel, and the additional pro-regenerative effects of these bioactive factors was evaluated in abdominal wounds in rabbits. Assessment of connective tissue healing (tensile testing, histology, immunohistochemistry) revealed that injection with all PIC formulations resulted in a statistically significant stiffness and collagen increase over time, in contrast to sham. Histological evaluation indicated new tissue growth with moderate to mild immune activity at the hydrogel - tissue interface. The results suggest that PIC injection in an abdominal wound improves healing towards regaining load-bearing capacity, which encourages us to investigate application of the hydrogel in a more translational vaginal model for POP surgery in sheep., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Surgical outcomes of pelvic organ prolapse (POP) surgery are poor, resulting in a 20% recurrence risk. Following the hypothesis that impaired wound healing is the main determinant of recurrent POP, growth factors have the potential to promote wound healing and may improve surgical outcomes. In this study, we systematically reviewed the effect of growth factors on vaginal wound healing in both in vitro and animal studies. For each independent comparison, the standardized mean difference and 95% CI were calculated using the Hedges' g correction. Of the 3858 retrieved studies, seven studies were included, of which six were included in meta-analysis (three in vitro studies and four in vivo studies). In vitro , basic fibroblast growth factor (bFGF) promotes proliferation, differentiation, and collagen types I and III production. Epidermal growth factor stimulates proliferation and connective tissue growth factor promotes Tenascin-C expression. These effects, however, are less pronounced in vivo ; only bFGF slightly promotes collagen production. The review shows that growth factors, particularly bFGF, are able to promote vaginal wound healing in vitro . The uncertain in vivo findings suggest that preclinical models should be improved. The ultimate goal is to develop effective growth factor-supplemented therapies that improve surgical outcomes for POP.

Pelvic organ prolapse (POP) is the descent of the bladder, uterus, and/or rectum into the vagina. POP is associated with altered vaginal fibroblast functionality and connective tissue composition in the vaginal wall. The results of surgical intervention are poor, which may be related to the lack of true restoration of the connective tissue. An innovative treatment addresses tissue repair after surgery by the introduction of a bioactive supplement that enhances the healing process through collagen and elastin deposition. As a novel strategy, we first studied the effects in an in vitro model. Here, we investigate how the presence of cell binding GRGDS (RGD) peptides on the highly biomimetic polyisocyanide (PIC) gel facilitates and promotes the function of primary vaginal fibroblasts isolated from a POP patient. Fibroblast function was analyzed in terms of morphology, proliferation, and extracellular matrix (ECM) deposition and remodeling. RGD modification of the gel facilitated cell spread and proliferation. Quantitative outcomes of the ECM content indicated increased production of collagen and elastin by fibroblasts on gels with the highest RGD density. The in vitro results suggest that PIC-RGD hydrogel application may translate into improved connective tissue healing in the pelvic floor, which is essential for its use as a regeneration promoting additive in surgery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Three-dimensional (3D) matrix models using hydrogels are powerful tools to understand and predict cell behavior. The interactions between the cell and its matrix, however is highly complex: the matrix has a profound effect on basic cell functions but simultaneously, cells are able to actively manipulate the matrix properties. This (mechano)reciprocity between cells and the extracellular matrix (ECM) is central in regulating tissue functions and it is fundamentally important to broadly consider the biomechanical properties of the in vivo ECM when designing in vitro matrix models. This manuscript discusses two commonly used biopolymer networks, i.e. collagen and fibrin gels, and one synthetic polymer network, polyisocyanide gel (PIC), which all possess the characteristic nonlinear mechanics in the biological stress regime. We start from the structure of the materials, then address the uses, advantages, and limitations of each material, to provide a guideline for tissue engineers and biophysicists in utilizing current materials and also designing new materials for 3D cell culture purposes., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)

In periodontal treatment, topical adjunctive therapy with antimicrobials or anti-inflammatory agents is frequently applied. However, currently available drug carrier biomaterials often exhibit poor perfusion into small crevices, such as the deep and irregular periodontal pockets, due to relatively high viscosity. Moreover, high polymer concentrations of the polymer can potentially be cytotoxic upon confined local administration. This study aimed to formulate an antimicrobial and anti-inflammatory treatment option, by incorporating doxycycline (DOX) and/or lipoxin A 4 (LXA 4 ) into 0.5 wt% thermo-reversible polyisocyanopeptide (PIC). PIC can form hydrogels upon low polymer concentration, and we hypothesized that the thermo-reversible nature of the material would allow for application into the periodontal pocket. The formulations were characterized in vitro and finally tested in dogs with naturally occurring periodontitis, which were not euthanized afterward. Results showed that PIC/DOX/LXA 4 hydrogel could be easily prepared and injected into periodontal pockets. The PIC hydrogel facilitated the release of DOX or LXA 4 for around 4 days in vitro. When applied in dogs, the hydrogel exerted no local or systemic adverse effects. Gels loaded with LXA 4 and/or DOX reduced the subgingival bacterial load and pro-inflammatory interleukin-8 level. In addition, PIC-DOX and PIC-DOX+LXA 4 improved gingival clinical attachment by 0.6 mm compared with conventional periodontal treatment alone (i.e. mechanical debridement). In conclusion, the thermo-reversible PIC hydrogel is a safe and effective vehicle for periodontal drug delivery., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2020. Published by Elsevier Ltd.)

In periodontal treatment, patient differences in disease phenotype and treatment responses are well documented. Therefore, therapy duration and dosage should be tailored to the requirements of individual patients. To facilitate such personalized medication, a tunable and controllable system is needed to deliver drugs directly into the diseased periodontal pockets. The current study established a system to achieve different drug release rates and periods by incorporating bioactive agents into poly(lactic-co-glycolic acid) (PLGA) microspheres dispersed into a novel thermo-reversible polyisocyanopeptide (PIC) hydrogel. Specifically, two drugs, i.e. doxycycline and lipoxin, were separately loaded into acid-terminated and ester-capped PLGA by electrospraying. Different formulations were developed by loading the two kinds of PLGA microspheres with different mass ratios in the PIC gels. The results demonstrated that the PIC-PLGA vehicle exhibited appropriate injectability, long-term structural stability, and no obvious in vivo inflammatory response for the desired clinical application. Furthermore, the release profiles of drugs could be manipulated by adjusting the loaded mass ratio of acid- and ester- terminated PLGA microspheres in the PIC gels. The more ester-capped PLGA was used, the slower the release rate and the longer the release period, and vice versa. Additionally, the released drugs still preserved their bio-efficacy. This PIC-PLGA system can be further developed and tested in translational studies to demonstrate the final clinical benefit., Competing Interests: Declaration of Competing Interest This work was financially supported by the Dutch Research Council (NWO) Domain Applied and Engineering Sciences (project number 13844) and the Chinese Scholarship Council (project number 201509370020 and 201506170058). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Adequate sterilization procedures for soft biomaterials such as hydrogels are known to be challenging. These materials are delicate in structure, making them sensitive to harsh conditions and prone to damage. In this study, a suitable sterilization method for hydrogels composed of tri(ethylene glycol)-functionalized polyisocyanopeptides (PIC) was explored. These high biomimetic hydrogels are temperature and strain sensitive and have been presented as novel cell culturing matrices, wound dressings, and drug carriers. The methods that were investigated include autoclaving, γ-irradiation, ultraviolet (UV) light irradiation, and supercritical CO 2 (scCO 2 ) treatment. The results show that autoclaving and γ-irradiation have deleterious effects on the gelation behavior and mechanical characteristics of PIC. For γ-irradiation, cooling the gels on dry ice alleviated this negative impact, but not sufficiently enough to make the method viable. In contrast, UV light and scCO 2 treatment do not affect the mechanical properties of the PIC gels. Studies with gels inoculated with 10 7 CFU/mL Gram-positive bacteria Staphylococcus aureus show that only scCO 2 is capable of successfully sterilizing PIC hydrogels by achieving a 6-log reduction in bacterial load. It was concluded that, within the range of tested techniques, the sterilization of PIC is limited to scCO 2 .

Changing wound dressings inflicts pain and may disrupt wound repair. Novel synthetic thermosensitive hydrogels based on polyisocyanopeptide (PIC) offer a solution. These gels are liquid below 16 °C and form gels beyond room temperature. The architecture and mechanical properties of PIC gels closely resemble collagen and fibrin, and include the characteristic stiffening response at high strains. Considering the reversible thermo-responsive behavior, we postulate that PIC gels are easy to apply and remove, and facilitate healing without eliciting foreign body responses or excessive inflammation. Biocompatibility may be higher in RGD-peptide-functionalized PIC gels due to enhanced cell binding capabilities. Full-thickness dorsal skin wounds in mice were compared to wounds treated with PIC gel and PIC-RGD gel for 3 and 7 days. No foreign body reactions and similar wound closure rates were found in all groups. The level of macrophages, myofibroblasts, epithelial migration, collagen expression, and blood vessels did not significantly differ from controls. Surprisingly, granulocyte populations in the wound decreased significantly in the PIC gel-treated groups, likely because foreign bacteria could not penetrate the gel. RGD-peptides did not further improve any effect observed for PIC. The absence of adverse effects, ease of application, and the possibilities for bio-functionalization make the biomimetic PIC hydrogels suitable for development into wound dressings., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Ionic liquid crystals are materials that combine the classes of liquid crystals and ionic liquids. The first one is based on the multi-billion-dollar flat panel display industry, whilst the latter quickly developed in the past decades into a family of highly-tunable non-volatile solvents. The combination yields materials with a unique set of properties, but also with many challenges ahead. In this review, we provide an overview of the key concepts in ionic liquid crystals, particularly from a molecular perspective. What are the important molecular parameters that determine the phase behavior? How should they be introduced into the molecules? Finally, which other tools does one have to realize specific properties in the material?

A biomimetic approach has been used for the templated self-assembly of a helical poly(para-aryltriazole) foldamer. The solvophobic folding process yields helices that further self-assemble into long nanotubes (see picture; scale bar: 100 nm). Constructs of controlled length and chirality can be generated by applying a poly(γ-benzyl-l-glutamate) scaffold at the appropriate assembly conditions, mimicking tobacco mosaic virus self-assembly., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We describe the synthesis of a series of phthalocyanine (Pc)-perylenediimide (PDI)(8) "octad" molecules, in which eight PDI moieties are attached to a Pc core through alkyl-chain linkers. There is clear spectroscopic evidence that these octads can exist as non-aggregated "monomers" or form aggregates along the Pc cores, depending on the type of Pc and the solvent medium. In the low dielectric constant solvents, into which the octads are soluble, photoexcitation of the PDI units leads to rapid energy transfer to the Pc centre, rather than a charge separation between moieties. In octad monomers, the Pc singlet excited-state decays within tens of ps, whereas the excitons are stabilised in the aggregated form of the molecules, typically with lifetimes in the order of 1-10 ns. By contrast, in an octad design in which pi-pi interactions are suppressed by the steric hindrance of a corona of incompatible glycol tails around the molecule, a more straightforward photophysical interaction of Förster energy transfer between the PDI moieties and Pc core may be inferred. We consider these molecules as prototypical multichromophoric aggregates, giving delocalised states with considerable flexibility of design.