Bottom-Up Preparation of Phase-Separated Polymersomes.

A bottom-up approach to fabricating monodisperse, two-component polymersomes that possess phase-separated ("patchy") chemical topology is presented. This approach is compared with already-existing top-down preparation methods for patchy polymer vesicles, such as film rehydration. These findings demonstrate a bottom-up, solvent-switch self-assembly approach that produces a high yield of nanoparticles of the target size, morphology, and surface topology for drug delivery applications, in this case patchy polymersomes of a diameter of ≈50 nm. In addition, an image processing algorithm to automatically calculate polymersome size distributions from transmission electron microscope images based on a series of pre-processing steps, image segmentation, and round object identification is presented.

Biocompatible Short-Peptides Fibrin Co-assembled Hydrogels.

Fibrin hydrogels made by self-assembly of fibrinogen obtained from human plasma have shown excellent biocompatible and biodegradable properties and are widely used in regenerative medicine. The fibrinogen self-assembly process can be triggered under physiological conditions by the action of thrombin, allowing the injection of pregel mixtures that have been used as cell carriers, wound-healing systems, and bio-adhesives. However, access to fibrinogen from human plasma is expensive and fibrin gels have limited mechanical properties, which make them unsuitable for certain applications. One solution to these problems is to obtain composite gels made of fibrin and other polymeric compounds that improve their mechanical properties and usage. Herein, we prepared composite hydrogels made by the self-assembly of fibrinogen together with Fmoc-FF (Fmoc-diphenylalanine) and Fmoc-RGD (Fmoc-arginine-glycine-aspartic acid). We have shown that the mixture of these three peptides co-assembles and gives rise to a unique type of supramolecular fiber, whose morphology and mechanical properties can be modulated. We have carried out a complete characterization of these materials from chemical, physical, and biological points of view. Composite gels have improved mechanical properties compared to pure fibrin gels, as well as showing excellent biocompatibility ex vivo. In vivo experiments have shown that these gels do not cause any type of inflammatory response or tissue damage and are completely resorbed in short time, which would enable their use as vehicles for cell, drug, or growth factor release.

One-Pot Synthesis of Oxidation-Sensitive Supramolecular Gels and Vesicles.

Polypeptide-based nanoparticles offer unique advantages from a nanomedicine perspective such as biocompatibility, biodegradability, and stimuli-responsive properties to (patho)physiological conditions. Conventionally, self-assembled polypeptide nanostructures are prepared by first synthesizing their constituent amphiphilic polypeptides followed by postpolymerization self-assembly. Herein, we describe the one-pot synthesis of oxidation-sensitive supramolecular micelles and vesicles. This was achieved by polymerization-induced self-assembly (PISA) of the N-carboxyanhydride (NCA) precursor of methionine using poly(ethylene oxide) as a stabilizing and hydrophilic block in dimethyl sulfoxide (DMSO). By adjusting the hydrophobic block length and concentration, we obtained a range of morphologies from spherical to wormlike micelles, to vesicles. Remarkably, the secondary structure of polypeptides greatly influenced the final morphology of the assemblies. Surprisingly, wormlike micellar morphologies were obtained for a wide range of methionine block lengths and solid contents, with spherical micelles restricted to very short hydrophobic lengths. Wormlike micelles further assembled into oxidation-sensitive, self-standing gels in the reaction pot. Both vesicles and wormlike micelles obtained using this method demonstrated to degrade under controlled oxidant conditions, which would expand their biomedical applications such as in sustained drug release or as cellular scaffolds in tissue engineering.

Combinatorial entropy behaviour leads to range selective binding in ligand-receptor interactions.

From viruses to nanoparticles, constructs functionalized with multiple ligands display peculiar binding properties that only arise from multivalent effects. Using statistical mechanical modelling, we describe here how multivalency can be exploited to achieve what we dub range selectivity, that is, binding only to targets bearing a number of receptors within a specified range. We use our model to characterise the region in parameter space where one can expect range selective targeting to occur, and provide experimental support for this phenomenon. Overall, range selectivity represents a potential path to increase the targeting selectivity of multivalent constructs.

Modulation of Higher-order Behaviour in Model Protocell Communities by Artificial Phagocytosis.

Collective behaviour in mixed populations of synthetic protocells is an unexplored area of bottom-up synthetic biology. The dynamics of a model protocell community is exploited to modulate the function and higher-order behaviour of mixed populations of bioinorganic protocells in response to a process of artificial phagocytosis. Enzyme-loaded silica colloidosomes are spontaneously engulfed by magnetic Pickering emulsion (MPE) droplets containing complementary enzyme substrates to initiate a range of processes within the host/guest protocells. Specifically, catalase, lipase, or alkaline phosphatase-filled colloidosomes are used to trigger phagocytosis-induced buoyancy, membrane reconstruction, or hydrogelation, respectively, within the MPE droplets. The results highlight the potential for exploiting surface-contact interactions between different membrane-bounded droplets to transfer and co-locate discrete chemical packages (artificial organelles) in communities of synthetic protocells.

Molecular bionics - engineering biomaterials at the molecular level using biological principles.

Life and biological units are the result of the supramolecular arrangement of many different types of molecules, all of them combined with exquisite precision to achieve specific functions. Taking inspiration from the design principles of nature allows engineering more efficient and compatible biomaterials. Indeed, bionic (from bion-, unit of life and -ic, like) materials have gained increasing attention in the last decades due to their ability to mimic some of the characteristics of nature systems, such as dynamism, selectivity, or signalling. However, there are still many challenges when it comes to their interaction with the human body, which hinder their further clinical development. Here we review some of the recent progress in the field of molecular bionics with the final aim of providing with design rules to ensure their stability in biological media as well as to engineer novel functionalities which enable navigating the human body.

Effect of functionalized PHEMA micro- and nano-particles on the viscoelastic properties of fibrin-agarose biomaterials.

Two types of PHEMA-based particles, exhibiting either carboxyl or tertiary ammine functional groups, were incorporated to fibrin-agarose (FA) hydrogels, and the effect of the addition of these synthetic particles on the viscoelastic and microstructural properties of the biomaterials was evaluated. Experimental results indicated that the incorporation of both types of polymeric particles to FA scaffolds was able to improve the biomechanical properties of the biomaterials under steady state and oscillatory shear stresses, resulting in scaffolds characterized by higher values of the storage, loss, and shear moduli. In addition, the microstructural evaluation of the scaffolds showed that the nanoparticles exhibiting carboxyl functional groups were homogeneously distributed across the fibrous network of the hydrogels. The addition of both types of artificial polymeric particles was able to enhance the viscoelastic properties of the FA hydrogels, allowing the biomaterials to reach levels of mechanical consistency under shear stresses in the same range of some human native soft tissues, which could allow these biomaterials to be used as scaffolds for new tissue engineering applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 738-745, 2018.

Phagocytosis-inspired behaviour in synthetic protocell communities of compartmentalized colloidal objects.

The spontaneous assembly of micro-compartmentalized colloidal objects capable of controlled interactions offers a step towards rudimentary forms of collective behaviour in communities of artificial cell-like entities (synthetic protocells). Here we report a primitive form of artificial phagocytosis in a binary community of synthetic protocells in which multiple silica colloidosomes are selectively ingested by self-propelled magnetic Pickering emulsion (MPE) droplets comprising particle-free fatty acid-stabilized apertures. Engulfment of the colloidosomes enables selective delivery and release of water-soluble payloads, and can be coupled to enzyme activity within the MPE droplets. Our results highlight opportunities for the development of new materials based on consortia of colloidal objects, and provide a novel microscale engineering approach to inducing higher-order behaviour in mixed populations of synthetic protocells.

Biocompatible magnetic core-shell nanocomposites for engineered magnetic tissues.

The inclusion of magnetic nanoparticles into biopolymer matrixes enables the preparation of magnetic field-responsive engineered tissues. Here we describe a synthetic route to prepare biocompatible core-shell nanostructures consisting of a polymeric core and a magnetic shell, which are used for this purpose. We show that using a core-shell architecture is doubly advantageous. First, gravitational settling for core-shell nanocomposites is slower because of the reduction of the composite average density connected to the light polymer core. Second, the magnetic response of core-shell nanocomposites can be tuned by changing the thickness of the magnetic layer. The incorporation of the composites into biopolymer hydrogels containing cells results in magnetic field-responsive engineered tissues whose mechanical properties can be controlled by external magnetic forces. Indeed, we obtain a significant increase of the viscoelastic moduli of the engineered tissues when exposed to an external magnetic field. Because the composites are functionalized with polyethylene glycol, the prepared bio-artificial tissue-like constructs also display excellent ex vivo cell viability and proliferation. When implanted in vivo, the engineered tissues show good biocompatibility and outstanding interaction with the host tissue. Actually, they only cause a localized transitory inflammatory reaction at the implantation site, without any effect on other organs. Altogether, our results suggest that the inclusion of magnetic core-shell nanocomposites into biomaterials would enable tissue engineering of artificial substitutes whose mechanical properties could be tuned to match those of the potential target tissue. In a wider perspective, the good biocompatibility and magnetic behavior of the composites could be beneficial for many other applications.

Optimizing the magnetic response of suspensions by tailoring the spatial distribution of the particle magnetic material.

We report an experimental enhancement of the magnetic susceptibility of suspensions of particles that is related to the spatial distribution of the magnetic phase in the particles. At low field, the susceptibility of suspensions of nickel-coated diamagnetic spheres was approximately 75% higher than that of suspensions of solid nickel spheres with the same nickel content. This result was corroborated by magnetostatics theory and simulation. The distribution of the magnetic phase in a shell also led to an improvement of the field-induced rheological response of the suspensions.

Colloids on the frontier of ferrofluids. Rheological properties.

This paper is devoted to the steady-state rheological properties of two new kinds of ferrofluids. One of these was constituted by CoNi nanospheres of 24 nm in diameter, whereas the other by CoNi nanofibers of 56 nm in length and 6.6 nm in width. These ferrofluids were subjected to shear rate ramps under the presence of magnetic fields of different intensity, and the corresponding shear stress values were measured. From the obtained rheograms (shear stress vs shear rate curves) the values of both the static and the dynamic yield stresses were obtained as a function of the magnetic field. The magnetoviscous effect was also obtained as a function of both the shear rate and the magnetic field. The experimental results demonstrate that upon magnetic field application these new ferrofluids develop yield stresses and magnetoviscous effects much greater than those of conventional ferrofluids, based on nanospheres of approximately 10 nm in diameter. Besides some expected differences, such as the stronger magnetorheological effect in the case of ferrofluids based on nanofibers, some intriguing differences are found between the rheological behaviors of nanofiber ferrofluids and nanosphere ferrofluid. First, upon field application the rheograms of nanofiber ferrofluids present N-shaped dependence of the shear stress on the shear rate. The decreasing part of the rheograms takes place at low shear rate. These regions of negative differential viscosity, and therefore, unstable flow is not observed in the case of nanosphere ferrofluids. The second intriguing difference concerns the curvature of the yield stress vs magnetic field curves. This curvature is negative in the case of nanosphere ferrofluid, giving rise to saturation of the yield stress at medium field, as expected. However, in the case of nanofiber ferrofluid this curvature is positive, which means a faster increase of the yield stress with the magnetic field the higher the magnitude of the latter. These interesting differences may be due to the existence of strong interparticle solid friction in the case of nanofiber ferrofluids. Finally, theoretical models for the static yield stress of the ferrofluids were developed. These models consider that upon field application the ferrofluid nanoparticles are condensed in drops of dense phase. These drops tend to be aligned along the field direction, opposing the flow of the ferrofluids and being responsible for the static quasielastic deformation and the yield-stress phenomena. By considering the existence of interparticle dry friction only in the case of nanofiber ferrofluids, the developed models predicted quite well not only the magnitude of the static yield stress but also the differences in curvature of the yield stress vs magnetic field curves.

Stability and magnetorheological behaviour of magnetic fluids based on ionic liquids.

This paper reports the preparation of magnetic fluids consisting of magnetite nanoparticles dispersed in an ionic liquid. Different additives were used in order to stabilize the fluids. Colloidal stability was checked by magnetic sedimentation, centrifugation and direct observation. The results of these tests showed that a true ferrofluid was only obtained when the nanoparticles were coated with a layer of surfactant compatible with the ionic liquid. These experiments also showed that stability could not be reached just by electrostatic repulsion. The conclusions of the stability tests were confirmed by calculations of the interparticle energies of interaction. The rheological behaviour of the magnetic fluids upon magnetic field application was also investigated. The experimental magnetoviscous response was fitted by a microstructural model. The model considered that the fluids consisted of two populations of particles, one with a magnetic core diameter of 9 nm, and another with a larger diameter. Upon field application chain-like structures are supposed to be induced. According to estimations particles of 9 nm are too small to aggregate upon field application. The results of the calculations showed that the intensity of the magnetoviscous response depends on the concentration and size of the large particles, and on the thickness of the surfactant layers.

Steric repulsion as a way to achieve the required stability for the preparation of ionic liquid-based ferrofluids.

With this work we would like to emphasize the necessity of steric repulsion to stabilize novel ionic liquid-based ferrofluids. For this purpose, we prepared a suspension of magnetite nanoparticles coated with a double layer of oleic acid, dispersed in 1-ethyl-3-methylimidazolium ethylsulphate ([EMIM][EtSO(4)]). For comparison, a suspension of bare magnetite nanoparticles in [EMIM][EtSO(4)] was also prepared. The stability of these suspensions was checked by magnetic sedimentation and centrifugation processes. Furthermore, their yield stress was measured as a function of the applied magnetic field, which gave additional information on their stability. The results of these experiments showed that the suspension of bare nanoparticles was rather unstable, whereas the suspension of double layer coated nanoparticles gave rise to a true (stable) ferrofluid.