A Molecular Rheology Dynamics Study on 3D Printing of Liquid Crystal Elastomers.

This work presents a rheological study of a biocompatible and biodegradable liquid crystal elastomer (LCE) ink for three dimensional (3D) printing. These materials have shown that their structural variations have an effect on morphology, mechanical properties, alignment, and their impact on cell response. Within the last decade LCEs are extensively studied as potential printing materials for soft robotics applications, due to the actuation properties that are produced when liquid crystal (LC) moieties are induced through external stimuli. This report utilizes experiments and coarse-grained molecular dynamics to study the macroscopic rheology of LCEs in nonlinear shear flow. Results from the shear flow simulations are in line with the outcomes of these experimental investigations. This work believes the insights from these results can be used to design and print new material with desirable properties necessary for targeted applications.

Nanoconfined Crystallization in Poly(lactic acid) (PLA) and Poly(ethylene terephthalate) (PET) Induced by Various Forms of Premelt-Deformation.

The processing-structure-property relationship using poly(lactic acid) (PLA) and poly(ethylene terephthalate) (PET) is explored. Specifically, both pre-extension and preshear of amorphous PLA and PET above their glass transition temperatures Tg , carried out in the affine deformation limit, can induce a specific type of cold crystallization during annealing, i.e., nanoconfined crystallization (NCC) where crystal sizes are limited to a nanoscopic scale in all dimensions so as to render the processed PLA and PET optically transparent. The new polymer structure after premelt deformation can show considerably enhanced mechanical properties. For example, premelt stretching produces geometric condensation of the chain network. This structural alternation can profoundly change the mechanical characteristics, e.g., turning brittle PLA ductile. In contrast, after preshear of amorphous PLA above Tg , the NCC containing PLA remains brittle, showing the importance to have geometric condensation from processing. Both AFM imaging and SAXS measurements are performed to verify that premelt deformation of PLA and PET indeed results in NCC from annealing that permits the strain-induced cold crystallization to take place on the length scale of the mesh size of the deformed chain network.

Macromolecular Engineering and Additive Manufacturing of Polyisobutylene-Based Thermoplastic Elastomers. II. The Poly(styrene-b-isobutylene-b-styrene)/Poly(phenylene oxide) System.

This series of publications describes research rendering soft polyisobutylene (PIB)-based thermoplastic elastomers 3D printable by blending with rigid chemically compatible thermoplastics. The molecular structure, morphology, physical properties, and 3D printability of such blends have been systematically investigated. The authors' first report was concerned with the rendering of soft poly(styrene-b-isobutylene-b-styrene) (SIBS) 3D printable by blending with rigid polystyrene (PS). Here they report the macromolecular engineering of SIBS/polyphenylene oxide (PPO) blends for 3D printing. PPO, a rigid high-performance thermoplastic, is compatible with the hard PS block in SIBS; however, neither PPO nor SIBS can be directly 3D printed. The microphase-separated structures and physical properties of SIBS/PPO blends are systematically tuned by controlling blending ratios and molecular weights. Suitable composition ranges and desirable properties of SIBS/PPO blends for 3D printing are optimized. The morphology and properties of SIBS/PPO blends are characterized by an ensemble of techniques, including atomic force microscopy, small-angle X-ray scattering, and thermal and mechanical properties testing. The elucidation of processing-structure-property relationship of SIBS/PPO blends is essential for 3D printing and advanced manufacturing of high-performance polymer systems.

Missing Link between Helical Nano- and Microfilaments in B4 Phase Bent-Core Liquid Crystals, and Deciphering which Chiral Center Controls the Filament Handedness.

The range of possible morphologies for bent-core B4 phase liquid crystals has recently expanded from helical nanofilaments (HNFs) and modulated HNFs to dual modulated HNFs, helical microfilaments, and heliconical-layered nanocylinders. These new morphologies are observed when one or both aliphatic side chains contain a chiral center. Here, the following questions are addressed: which of these two chiral centers controls the handedness (helicity) and which morphology of the nanofilaments is formed by bent-core liquid crystals with tris-biphenyl diester core flanked by two chiral 2-octyloxy side chains? The combined results reveal that the longer arm of these nonsymmetric bent-core liquid crystals controls the handedness of the resulting dual modulated HNFs. These derivatives with opposite configuration of the two chiral side chains now feature twice as large dimensions compared to the homochiral derivatives with identical configuration. These results are supported by density functional theory calculations and stochastic dynamic atomistic simulations, which reveal that the relative difference between the para- and meta-sides of the described series of compounds drives the variation in morphology. Finally, X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM) data also uncover the new morphology for B4 phases featuring p2/m symmetry within the filaments and less pronounced crystalline character.

3D Porous Liquid Crystal Elastomer Foams Supporting Long-term Neuronal Cultures.

3D liquid crystal elastomer (3D-LCE) foams are used to support long-term neuronal cultures for over 60 days. Sequential imaging shows that cell density remains relatively constant throughout the culture period while the number of cells per observational area increases. In a subset of samples, retinoic acid is used to stimulate extensive neuritic outgrowth and maturation of proliferated neurons within the LCEs, inducing a threefold increase in length with cells displaying morphologies indicative of mature neurons. Designed LCEs' micro-channels have a similar diameter to endogenous parenchymal arterioles, ensuring that neurons throughout the construct have constant access to growth media during extended experiments. Here it is shown that 3D-LCEs provide a unique environment and simple method to longitudinally study spatial neuronal function, not possible in conventional culture environments, with simplistic integration into existing methodological pipelines.

Voltage-driven photoluminescence modulation of liquid-crystalline hybridized ZnO nanoparticles.

Liquid-crystalline hybrid nanomaterials have been obtained by grafting mesogenic units around luminescent ZnO nanocrystals of 5 nm in diameter. Modifying the mesogenic density around the inorganic core allows the modulation of the liquid-crystalline behavior and its miscibility in commercial liquid crystal (LC). The strong blue photoluminescence observed for the hybrids can be modulated by applying a voltage on a LC cell containing commercial LC and 10 wt % of hybrid.

Thermotropic luminescent clustomesogen showing a nematic phase: a combination of experimental and molecular simulation studies.

Octahedral Mo6 nanoclusters are functionalized with two organic ligands containing cyanobiphenyl (CB) units, giving luminescent hybrid liquid crystals (LC). Although the mesogenic density around the bulky inorganic core is constant, the two hybrids show different LC properties. Interestingly, one of them shows a nematic phase, which is particularly rare for this kind of supermolecular system. This surprising result is explained by using large-scale molecular dynamic simulations.

Organic chiral nano- and microfilaments: types, formation, and template applications.

Organic chiral nanofilaments are part of an important class of nanoscale chiral materials that has recently been receiving significant attention largely due to their potential use in applications such as optics, photonics, metameterials, and potentially a range of medical as well as sensing applications. This review will focus on key examples of the formation of such nano- and micro-filaments based on carbon nanofibers, polymers, synthetic oligo- and polypeptides, self-assembled organic molecules, and one prominent class of liquid crystals. The most critical aspects discussed here are the underlying driving forces for chiral filament formation, potentially answering why specific sizes and shapes are formed, what molecular design strategies are working equally well or rather differently among these materials classes, and what uses and applications are driving research in this fascinating field of materials science.

Controlling the Structure and Morphology of Organic Nanofilaments Using External Stimuli.

In our continuing pursuit to generate, understand, and control the morphology of organic nanofilaments formed by molecules with a bent molecular shape, we here report on two bent-core molecules specifically designed to permit a phase or morphology change upon exposure to an applied electric field or irradiation with UV light. To trigger a response to an applied electric field, conformationally rigid chiral (S,S)-2,3-difluorooctyloxy side chains were introduced, and to cause a response to UV light, an azobenzene core was incorporated into one of the arms of the rigid bent core. The phase behavior as well as structure and morphology of the formed phases and nanofilaments were analyzed using differential scanning calorimetry, cross-polarized optical microscopy, circular dichroism spectropolarimetry, scanning and transmission electron microscopy, UV-vis spectrophotometry, as well as X-ray diffraction experiments. Both bent-core molecules were characterized by the coexistence of two nanoscale morphologies, specifically helical nanofilaments (HNFs) and layered nanocylinders, prior to exposure to an external stimulus and independent of the cooling rate from the isotropic liquid. The application of an electric field triggers the disappearance of crystalline nanofilaments and instead leads to the formation of a tilted smectic liquid crystal phase for the material featuring chiral difluorinated side chains, whereas irradiation with UV light results in the disappearance of the nanocylinders and the sole formation of HNFs for the azobenzene-containing material. Combined results of this experimental study reveal that in addition to controlling the rate of cooling, applied electric fields and UV irradiation can be used to expand the toolkit for structural and morphological control of suitably designed bent-core molecule-based structures at the nanoscale.

Physical Models from Physical Templates Using Biocompatible Liquid Crystal Elastomers as Morphologically Programmable Inks For 3D Printing.

Advanced manufacturing has received considerable attention as a tool for the fabrication of cell scaffolds however, finding ideal biocompatible and biodegradable materials that fit the correct parameters for 3D printing and guide cells to align remain a challenge. Herein, a photocrosslinkable smectic-A (Sm-A) liquid crystal elastomer (LCE) designed for 3D printing is presented, that promotes cell proliferation but most importantly induces cell anisotropy. The LCE-based bio-ink allows the 3D duplication of a highly complex brain structure generated from an animal model. Vascular tissue models are generated from fluorescently stained mouse tissue spatially imaged using confocal microscopy and subsequently processed to create a digital 3D model suitable for printing. The 3D structure is reproduced using a Digital Light Processing (DLP) stereolithography (SLA) desktop 3D printer. Synchrotron Small-Angle X-ray Diffraction (SAXD) data reveal a strong alignment of the LCE layering within the struts of the printed 3D scaffold. The resultant anisotropy of the LCE struts is then shown to direct cell growth. This study offers a simple approach to produce model tissues built within hours that promote cellular alignment.

Both plant and bacterial nitrate reductases contribute to nitric oxide production in Medicago truncatula nitrogen-fixing nodules.

Nitric oxide (NO) is a signaling and defense molecule of major importance in living organisms. In the model legume Medicago truncatula, NO production has been detected in the nitrogen fixation zone of the nodule, but the systems responsible for its synthesis are yet unknown and its role in symbiosis is far from being elucidated. In this work, using pharmacological and genetic approaches, we explored the enzymatic source of NO production in M. truncatula-Sinorhizobium meliloti nodules under normoxic and hypoxic conditions. When transferred from normoxia to hypoxia, nodule NO production was rapidly increased, indicating that NO production capacity is present in functioning nodules and may be promptly up-regulated in response to decreased oxygen availability. Contrary to roots and leaves, nodule NO production was stimulated by nitrate and nitrite and inhibited by tungstate, a nitrate reductase inhibitor. Nodules obtained with either plant nitrate reductase RNA interference double knockdown (MtNR1/2) or bacterial nitrate reductase-deficient (napA) and nitrite reductase-deficient (nirK) mutants, or both, exhibited reduced nitrate or nitrite reductase activities and NO production levels. Moreover, NO production in nodules was found to be inhibited by electron transfer chain inhibitors, and nodule energy state (ATP-ADP ratio) was significantly reduced when nodules were incubated in the presence of tungstate. Our data indicate that both plant and bacterial nitrate reductase and electron transfer chains are involved in NO synthesis. We propose the existence of a nitrate-NO respiration process in nodules that could play a role in the maintenance of the energy status required for nitrogen fixation under oxygen-limiting conditions.

Highly Tunable Circularly Polarized Emission of an Aggregation-Induced Emission Dye Using Helical Nano- and Microfilaments as Supramolecular Chiral Templates.

Aggregation-induced emission (AIE)-based circularly polarized luminescence (CPL) has been recognized as a promising pathway for developing chiroptical materials with high luminescence dissymmetry factors (|glum|). Here, we propose a method for the construction of a thermally tunable CPL-active system based on a supramolecular self-assembly approach that utilizes helical nano- or microfilament templates in conjunction with an AIE dye. The CPL properties of the ensuing ensembles are predominantly determined by the intrinsic geometric differences among the various filament templates such as their overall dimensions (width, height, and helical pitch) and the area fraction of the exposed aromatic segments or sublayers. The proposed mechanism is based on the collective data acquired by absorption, steady state and time-resolved fluorescence, absolute quantum yield, and CPL measurements. The highest |glum| value for the most promising dual-modulated helical nanofilament templates in the present series was further enhanced, reaching up to |glum| = 0.25 by confinement in the appropriate diameter of anodized aluminum oxide (AAO) nanochannels. It is envisioned that this methodology will afford new insights into the design of temperature-rate indicators or anti-counterfeiting tags using a combination of structural color by the nano- and microfilament templates and the AIE property of the guest dye.

Molecular Conformation of Bent-Core Molecules Affected by Chiral Side Chains Dictates Polymorphism and Chirality in Organic Nano- and Microfilaments.

The coupling between molecular conformation and chirality is a cornerstone in the construction of supramolecular helical structures of small molecules across various length scales. Inspired by biological systems, conformational preselection and control in artificial helical molecules, polymers, and aggregates has guided various applications in optics, photonics, and chiral sorting among others, which are frequently based on an inherent chirality amplification through processes such as templating and self-assembly. The so-called B4 nano- or microfilament phase formed by some bent-shaped molecules is an exemplary case for such chirality amplification across length scales, best illustrated by the formation of distinct nano- or microscopic chiral morphologies controlled by molecular conformation. Introduction of one or more chiral centers in the aliphatic side chains led to the discovery of homochiral helical nanofilament, helical microfilament, and heliconical-layered nanocylinder morphologies. Herein, we demonstrate how a priori calculations of the molecular conformation affected by chiral side chains are used to design bent-shaped molecules that self-assemble into chiral nano- and microfilament as well as nanocylinder conglomerates despite the homochiral nature of the molecules. Furthermore, relocation of the chiral center leads to formation of helical as well as flat nanoribbons. Self-consistent data sets from polarized optical as well as scanning and transmission electron microscopy, thin-film and solution circular dichroism spectropolarimetry, and synchrotron-based X-ray diffraction experiments support the progressive and predictable change in morphology controlled by structural changes in the chiral side chains. The formation of these morphologies is discussed in light of the diminishing effects of molecular chirality as the chain length increases or as the chiral center is moved away from the core-chain juncture. The type of phase (B1-columnar or B4) and morphology of the nano- or microfilaments generated can further be controlled by sample treatment conditions such as by the cooling rate from the isotropic melt or by the presence of an organic solvent in the ensuing colloidal dispersions. We show that these nanoscale morphologies can then organize into a wealth of two- and three-dimensional shapes and structures ranging from flower blossoms to fiber mats formed by intersecting flat nanoribbons.

Liquid Crystal Elastomers-A Path to Biocompatible and Biodegradable 3D-LCE Scaffolds for Tissue Regeneration.

The development of appropriate materials that can make breakthroughs in tissue engineering has long been pursued by the scientific community. Several types of material have been long tested and re-designed for this purpose. At the same time, liquid crystals (LCs) have captivated the scientific community since their discovery in 1888 and soon after were thought to be, in combination with polymers, artificial muscles. Within the past decade liquid crystal elastomers (LCE) have been attracting increasing interest for their use as smart advanced materials for biological applications. Here, we examine how LCEs can potentially be used as dynamic substrates for culturing cells, moving away from the classical two-dimensional cell-culture nature. We also briefly discuss the integration of a few technologies for the preparation of more sophisticated LCE-composite scaffolds for more dynamic biomaterials. The anisotropic properties of LCEs can be used not only to promote cell attachment and the proliferation of cells, but also to promote cell alignment under LCE-stimulated deformation. 3D LCEs are ideal materials for new insights to simulate and study the development of tissues and the complex interplay between cells.

Synthesis of Biocompatible Liquid Crystal Elastomer Foams as Cell Scaffolds for 3D Spatial Cell Cultures.

Here, we present a step-by-step preparation of a 3D, biodegradable, foam-like cell scaffold. These scaffolds were prepared by cross-linking star block co-polymers featuring cholesterol units as side-chain pendant groups, resulting in smectic-A (SmA) liquid crystal elastomers (LCEs). Foam-like scaffolds, prepared using metal templates, feature interconnected microchannels, making them suitable as 3D cell culture scaffolds. The combined properties of the regular structure of the metal foam and of the elastomer result in a 3D cell scaffold that promotes not only higher cell proliferation compared to conventional porous templated films, but also better management of mass transport (i.e., nutrients, gases, waste, etc.). The nature of the metal template allows for the easy manipulation of foam shapes (i.e., rolls or films) and for the preparation of scaffolds of different pore sizes for different cell studies while preserving the interconnected porous nature of the template. The etching process does not affect the chemistry of the elastomers, preserving their biocompatible and biodegradable nature. We show that these smectic LCEs, when grown for extensive time periods, enable the study of clinically relevant and complex tissue constructs while promoting the growth and proliferation of cells.

Mitochondrial DNA depletion in adipose tissue of HIV-infected patients with peripheral lipoatrophy.

BACKGROUND: NRTI-induced host toxicity is proposed to involve cellular mitochondrial DNA (mtDNA) depletion. Determinants of cellular mtDNA copy number from HIV-infected patients receiving HAART and HIV-seronegative controls were investigated from subcutaneous fat samples, and relation with antiretroviral regimen was studied. STUDY DESIGN: HIV-infected patients receiving HAART (n = 50), HIV-infected patients not currently under HAART regimen (n = 2) and HIV-seronegative controls (n = 9) of similar age and BMI were enrolled prospectively when undergoing Coleman's lipostructure for correction of facial lipoatrophy or plastic surgery, respectively. After centrifugation, abdominal fat tissue was collected and stored at -80 degrees C. MtDNA analysis was blindly performed after a total DNA extraction from adipose tissue, followed by a real-time PCR quantification. The log of mtDNA copies/cell in adipose tissue [log(DNA)] was compared between groups by means of analysis of variance. RESULTS: The log(DNA) in adipose tissue of HIV-infected patients was significantly lower than in the HIV-seronegative control group (P < 0.0001). In HIV-infected patients, log(DNA) was significantly reduced in the 50 NRTI-treated patients (P < 0.01), but not when considering mtDNA level according to the use of PI or NNRTI in current HAART regimen. In NRTI-treated patients, only stavudine (n = 20) and didanosine (n=14) were significantly and independently associated with reduced mtDNA level (P < 0.0001 and <0.05, respectively). Currently stavudine or didanosine-treated patients had a significant reduced mtDNA level compared to past users (P < 0.0001 and <0.05, respectively). Other clinical, biological, and immuno-virological variables than NRTI did not correlate significantly to adipocyte mtDNA level. CONCLUSION: This study supports that current treatment by NRTI is a main determinant of mtDNA depletion in adipose tissue of HIV-seropositive patients with peripheral fat wasting. Stavudine or didanosine current intake is significantly associated with mtDNA depletion in vivo, that could be reversible after the discontinuation of these molecules, when considering mtDNA level according to current use versus past use of these molecules.

Evaluation of Coleman lipostructure for treatment of facial lipoatrophy in patients with human immunodeficiency virus and parameters associated with the efficiency of this technique.

OBJECTIVE: To evaluate the efficiency of Coleman lipostructure in patients infected with human immunodeficiency virus (HIV). DESIGN: Open-label study and survey. SETTING: Ambulatory dermatosurgery department of a university hospital. PATIENTS: Thirty-three consecutive HIV-infected patients undergoing Coleman lipostructure between 2000 and 2001. INTERVENTIONS: Clinical examination, blood tests, and standardized photographs at baseline and 1 year after the lipostructure. MEAN OUTCOME MEASURES: Efficiency was assessed by the agreement of 3 independent medical specialists on facial lipodystrophy improvement after surgery and by patient satisfaction. RESULTS: Facial lipoatrophy was improved in 12 patients (36%; 95% confidence interval, 20%-52%) as judged by all 3 evaluators. Quantity of fat injected (P = .01) and a low serum triglyceride level before surgery (P = .03) were significantly associated with improvement of facial lipoatrophy. Of the 33 patients, 14 (43%) were very satisfied, 17 (50%) were partly satisfied, and 27 (81%) had a better quality of life. The most common comment was that the patient looked better and appeared less ill. CONCLUSION: Our 1-year evaluation of Coleman lipostructure for correction of facial lipoatrophy in HIV-infected patients proved the efficiency of this treatment when measured conservatively by agreement on improvement by 3 independent specialists and demonstrated a patient satisfaction rate of 93%.