Hydrophobically modified complex coacervates for designing aqueous pressure-sensitive adhesives.

The rheology of complex coacervates can be elegantly tuned via the design and control of specific non-covalent hydrophobic interactions between the complexed polymer chains. The well-controlled balance between elasticity and energy dissipation makes complex coacervates perfect candidates for pressure-sensitive adhesives (PSAs). In this work, the polyanion poly(3-sulfopropyl methacrylate) (PSPMA) and the polycation quaternized poly(4-vinylpyridine) (QP4VP) were used to prepare complex coacervates in water. Progressive increase of hydrophobicity is introduced to the polyanion via partial deprotection of the protected precursor. Hence, the polymer chains in the complex coacervates can interact via both electrostatic (controlled by the amount of salt) and hydrophobic (controlled by the deprotection degree) interactions. It was observed that: (i) a rheological time-salt-hydrophobicity superposition principle is applicable, and can be used as a predictive tool for rheology, (ii) the slowdown of the stress relaxation dynamics, due to the increase of hydrophobic stickers (lower deprotection degree), can be captured by the sticky-Rouse model, and (iii) the systematic variation of hydrophobic stickers, amount of salt, and molecular weight of the polymers, enables the identification of optimizing parameters to design aqueous PSA systems. The presented results offer new pathways to control the rheology of complex coacervates and their applicability as PSAs.

Charged Polypeptide Tail Boosts the Salt Resistance of Enzyme-Containing Complex Coacervate Micelles.

Encapsulation of proteins can have advantages for their protection, stability, and delivery purposes. One of the options to encapsulate proteins is to incorporate them in complex coacervate core micelles (C3Ms). This can easily be achieved by mixing aqueous solutions of the protein and an oppositely charged neutral-hydrophilic diblock copolymer. However, protein-containing C3Ms often suffer from salt-inducible disintegration due to the low charge density of proteins. The aim of this study is to improve the salt stability of protein-containing C3Ms by increasing the net charge of the protein by tagging it with a charged polypeptide. As a model protein, we used CotA laccase and generated variants with 10, 20, 30, and 40 glutamic acids attached at the C-terminus of CotA using genetic engineering. Micelles were obtained by mixing the five CotA variants with poly(N-methyl-2-vinyl-pyridinium)-block-poly(ethylene oxide) (PM2VP128-b-PEO477) at pH 10.8. Hydrodynamic radii of the micelles of approximately 31, 27, and 23 nm for native CotA, CotA-E20, and CotA-E40, respectively, were determined using dynamic light scattering (DLS) and fluorescence correlation spectroscopy (FCS). The encapsulation efficiency was not affected using enzymes with a polyglutamic acid tail but resulted in more micelles with a smaller number of enzyme molecules per micelle. Furthermore, it was shown that the addition of a polyglutamic acid tail to CotA indeed resulted in improved salt stability of enzyme-containing C3Ms. Interestingly, the polyglutamic acid CotA variants showed an enhanced enzyme activity. This study demonstrates that increasing the net charge of enzymes through genetic engineering is a promising strategy to improve the practical applicability of C3Ms as enzyme delivery systems.

Enhanced stability of complex coacervate core micelles following different core-crosslinking strategies.

Complex coacervate core micelles (C3Ms) are formed by mixing aqueous solutions of a charged (bio)macromolecule with an oppositely charged-neutral hydrophilic diblock copolymer. The stability of these structures is dependent on the ionic strength of the solution; above a critical ionic strength, the micelles will completely disintegrate. This instability at high ionic strengths is the main drawback for their application in, e.g., drug delivery systems or protein protection. In addition, the stability of C3Ms composed of weak polyelectrolytes is pH-dependent as well. The aim of this study is to assess the effectiveness of covalent crosslinking of the complex coacervate core to improve the stability of C3Ms. We studied the formation of C3Ms using a quaternized and amine-functionalized cationic-neutral diblock copolymer, poly(2-vinylpyridine)-block-poly(ethylene oxide) (QP2VP-b-PEO), and an anionic homopolymer, poly(acrylic acid) (PAA). Two different core-crosslinking strategies were employed that resulted in crosslinks between both types of polyelectrolyte chains in the core (i.e., between QP2VP and PAA) or in crosslinks between polyelectrolyte chains of the same type only (i.e., QP2VP). For these two strategies we used the crosslinkers 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and dimethyl-3,3'-dithiopropionimidate dihydrochloride (DTBP), respectively. EDC provides permanent crosslinks, while DTBP crosslinks can be broken by a reducing agent. Dynamic light scattering showed that both approaches significantly improved the stability of C3Ms against salt and pH changes. Furthermore, reduction of the disulphide bridges in the DTBP core-crosslinked micelles largely restored the original salt-stability profile. Therefore, this feature provides an excellent starting point for the application of C3Ms in controlled release formulations.

The Unfolded Protein Response Sensor PERK Mediates Stiffness-Dependent Adaptation in Glioblastoma Cells.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults. In addition to genetic causes, the tumor microenvironment (TME), including stiffening of the extracellular matrix (ECM), is a main driver of GBM progression. Mechano-transduction and the unfolded protein response (UPR) are essential for tumor-cell adaptation to harsh TME conditions. Here, we studied the effect of a variable stiff ECM on the morphology and malignant properties of GBM stem cells (GSCs) and, moreover, examined the possible involvement of the UPR sensor PERK herein. For this, stiffness-tunable human blood plasma (HBP)/alginate hydrogels were generated to mimic ECM stiffening. GSCs showed stiffness-dependent adaptation characterized by elongated morphology, increased proliferation, and motility which was accompanied by F-Actin cytoskeletal remodeling. Interestingly, in PERK-deficient GSCs, stiffness adaptation was severely impaired, which was evidenced by low F-Actin levels, the absence of F-Actin remodeling, and decreased cell proliferation and migration. This impairment could be linked with Filamin-A (FLN-A) expression, a known interactor of PERK, which was strongly reduced in PERK-deficient GSCs. In conclusion, we identified a novel PERK/FLNA/F-Actin mechano-adaptive mechanism and found a new function for PERK in the cellular adaptation to ECM stiffening.

Complex coacervation and metal-ligand bonding as synergistic design elements for aqueous viscoelastic materials.

The application of complex coacervates in promising areas such as coatings and surgical glues requires a tight control of their viscous and elastic behaviour, and a keen understanding of the corresponding microscopic mechanisms. While the viscous, or dissipative, aspect is crucial at pre-setting times and in preventing detachment, elasticity at long waiting times and low strain rates is crucial to sustain a load-bearing joints. The independent tailoring of dissipative and elastic properties proves to be a major challenge that can not be addressed adequately by the complex coacervate motif by itself. We propose a versatile model of complex coacervates with customizable rheological fates by functionalization of polyelectrolytes with terpyridines, which provide transient crosslinks through complexation with metals. We show that the rheology of the hybrid complexes shows distinct footprints of both metal-ligand and coacervate dynamics, the former as a contribution very close to pure Maxwell viscoelasticity, the latter approaching a sticky Rouse fluid. Strikingly, when the contribution of metal-ligand bonds is dominant at long times, the relaxation of the overall complex is much slower than either the "native" coacervate relaxation time or the dissociation time of a comparable non-coacervate polyelectrolyte-metal-ligand complex. We recognize this slowing-down of transient bonds as a synergistic effect that has important implications for the use of complementary transient bonding in coacervate complexes.

Balancing Enzyme Encapsulation Efficiency and Stability in Complex Coacervate Core Micelles.

Encapsulation of charged proteins into complex coacervate core micelles (C3Ms) can be accomplished by mixing them with oppositely charged diblock copolymers. However, these micelles tend to disintegrate at high ionic strength. Previous research showed that the addition of a homopolymer with the same charge sign as the protein improved the stability of protein-containing C3Ms. In this research, we used fluorescence correlation spectroscopy (FCS) and dynamic light scattering (DLS) to study how the addition of the homopolymer affects the encapsulation efficiency and salt stability of the micelles. We studied the encapsulation of laccase spore coat protein A (CotA), a multicopper oxidase, using a strong cationic-neutral diblock copolymer, poly(N-methyl-2-vinyl-pyridinium iodide)-block-poly(ethylene oxide) (PM2VP128-b-PEO477), and a negatively charged homopolymer, poly(4-styrenesulfonate) (PSS215). DLS indeed showed an improved stability of this three-component C3M system against the addition of salt compared to a two-component system. Remarkably, FCS showed that the release of CotA from a three-component C3M system occurred at a lower salt concentration and over a narrower concentration range than the dissociation of C3Ms. In conclusion, although the addition of the homopolymer to the system leads to micelles with a higher salt stability, CotA is excluded from the C3Ms already at lower ionic strengths because the homopolymer acts as a competitor of the enzyme for encapsulation.

Tuning the Interactions in Multiresponsive Complex Coacervate-Based Underwater Adhesives.

In this work, we report the systematic investigation of a multiresponsive complex coacervate-based underwater adhesive, obtained by combining polyelectrolyte domains and thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) units. This material exhibits a transition from liquid to solid but, differently from most reactive glues, is completely held together by non-covalent interactions, i.e., electrostatic and hydrophobic. Because the solidification results in a kinetically trapped morphology, the final mechanical properties strongly depend on the preparation conditions and on the surrounding environment. A systematic study is performed to assess the effect of ionic strength and of PNIPAM content on the thermal, rheological and adhesive properties. This study enables the optimization of polymer composition and environmental conditions for this underwater adhesive system. The best performance with a work of adhesion of 6.5 J/m2 was found for the complex coacervates prepared at high ionic strength (0.75 M NaCl) and at an optimal PNIPAM content around 30% mol/mol. The high ionic strength enables injectability, while the hydrated PNIPAM domains provide additional dissipation, without softening the material so much that it becomes too weak to resist detaching stress.

Tree frog attachment: mechanisms, challenges, and perspectives.

Tree frogs have the remarkable ability to attach to smooth, rough, dry, and wet surfaces using their versatile toe pads. Tree frog attachment involves the secretion of mucus into the pad-substrate gap, requiring adaptations towards mucus drainage and pad lubrication. Here, we present an overview of tree frog attachment, with focus on (i) the morphology and material of the toe pad; (ii) the functional demands on the toe pad arising from ecology, lifestyle, and phylogenetics; (iii) experimental data of attachment performance such as adhesion and friction forces; and (iv) potential perspectives on future developments in the field. By revisiting reported data and observations, we discuss the involved mechanisms of attachment and propose new hypotheses for further research. Among others, we address the following questions: Do capillary and hydrodynamic forces explain the strong friction of the toe pads directly, or indirectly by promoting dry attachment mechanisms? If friction primarily relies on van der Waals (vdW) forces instead, how much do these forces contribute to adhesion in the wet environment tree frogs live in and what role does the mucus play? We show that both pad morphology and measured attachment performance suggest the coaction of several attachment mechanisms (e.g. capillary and hydrodynamic adhesion, mechanical interlocking, and vdW forces) with situation-dependent relative importance. Current analytical models of capillary and hydrodynamic adhesion, caused by the secreted mucus and by environmental liquids, do not capture the contributions of these mechanisms in a comprehensive and accurate way. We argue that the soft pad material and a hierarchical surface pattern on the ventral pad surface enhance the effective contact area and facilitate gap-closure by macro- to nanoscopic drainage of interstitial liquids, which may give rise to a significant contribution of vdW interactions to tree frog attachment. Increasing the comprehension of the complex mechanism of tree frog attachment contributes to a better understanding of other biological attachment systems (e.g. in geckos and insects) and is expected to stimulate the development of a wide array of bioinspired adhesive applications.

Heparin as a Bundler in a Self-Assembled Fibrous Network of Functionalized Protein-Based Polymers.

Nature shows excellent control over the mechanics of fibrous hydrogels by assembling protein fibers into bundles of well-defined dimensions. Yet, obtaining artificial materials displaying controlled bundling remains a challenge. Here, we developed genetically engineered protein-based polymers functionalized with heparin-binding KRSR domains and show controlled bundling using heparin as a binder. The protein polymer forms fibers upon increasing the pH to physiological values and at higher concentrations fibrous gels. We show that addition of heparin to the protein polymer with incorporated KRSR domains, induces bundling, which results in faster gel formation and stiffer gels. The interactions are expected to be primarily electrostatic and fiber bundling has an optimum when the positive charges of KRSR are approximately in balance with the negative charges of the heparin. Our study suggests that, generally, a straightforward method to control the properties of fibrous gels is to prepare a fiber former with specific binding domains and then simply adding an appropriate amount of binder.

Jack of all trades: versatile catechol crosslinking mechanisms.

Catechols play an important role in many natural systems. They are known to readily interact with both organic (e.g., amino acids) and inorganic (e.g., metal ions, metal oxides) compounds, thereby providing a powerful system for protein curing. Catechol crosslinked protein networks, such as sclerotized cuticle and byssal threads of the mussel, have been shown to exhibit excellent mechanical properties. A lot of effort has been devoted to mimicking the natural proteins using synthetic catechol-functionalized polymers. Despite the success in developing catechol-functionalized materials, the crosslinking chemistry of catechols is still a subject of debate. To develop materials with controlled and superior properties, a clear understanding of the crosslinking mechanism of catechols is of vital importance. This review describes the crosslinking pathways of catechol and derivatives in both natural and synthetic systems. We discuss existing pathways of catechol crosslinking and parameters that affect the catechol chemistry in detail. This overview will point towards a rational direction for further investigation of the complicated catechol chemistry.

Structure-Property Relationships of Granular Hybrid Hydrogels Formed through Polyelectrolyte Complexation.

Hybrid hydrogels are hydrogels that exhibit heterogeneity in the network architecture by means of chemical composition and/or microstructure. The different types of interactions, together with structural heterogeneity, which can be created on different length scales, determine the mechanical properties of the final material to a large extent. In this work, the microstructure-mechanical property relationships for a hybrid hydrogel that contains both electrostatic and covalent interactions are investigated. The hybrid hydrogel is composed of a microphase-separated polyelectrolyte complex network (PEC) made of poly(4-styrenesulfonate) and poly(diallyldimethylammonium chloride) within a soft and elastic polyacrylamide hydrogel network. The system exhibits a granular structure, which is attributed to the liquid-liquid phase separation into complex coacervate droplets induced by the polymerization and the subsequent crowding effect of the polyacrylamide chains. The coacervate droplets are further hardened into PEC granules upon desalting the hydrogel. The structure formation is confirmed by a combination of electron microscopic imaging and molecular dynamics simulations. The interpenetration of both networks is shown to enhance the toughness of the resulting hydrogels due to the dissipative behavior of the PEC through the rupture of electrostatic interactions. Upon cyclic loading-unloading, the hydrogels show recovery of up to 80% of their original dissipative behavior in less than 300 s of rest with limited plasticity. The granular architecture and the tough and self-recoverable properties of the designed hybrid networks make them good candidates for applications, such as shape-memory materials, actuators, biological tissue mimics, and elastic substrates for soft sensors.

Effect of Polyelectrolyte Charge Density on the Linear Viscoelastic Behavior and Processing of Complex Coacervate Adhesives.

It is well-known that the phase behavior and physicochemical and adhesive properties of complex coacervates are readily tuneable with the salt concentration of the medium. For toxicity reasons, however, the maximum applicable salt concentration in biomedical applications is typically low. Consequently, other strategies must be implemented in order to optimize the properties of the resulting complex coacervates. In this work, the effect of the charge density of a strong polyanion on the properties of complex coacervates was studied. To control this charge density, statistical anionic/charge-neutral hydrophilic copolymers were synthesized by means of an elegant protection/deprotection strategy and subsequently complexed with a strong polycation. The resulting complexes were observed to have an increasing water content as well as faster relaxation dynamics, with either increasing salt concentration or decreasing charge density. Time-salt and time-salt-charge density superpositions could be performed and showed that the relaxation mechanism of the complex coacervates remained unchanged. When the charge density was decreased, lower salt concentration complexes became suitable for viscoelastic adhesion with improved injectability. Such complex coacervates are promising candidates for injectable biomedical adhesives.

A silica sol-gel design strategy for nanostructured metallic materials.

Batteries, fuel cells and solar cells, among many other high-current-density devices, could benefit from the precise meso- to macroscopic structure control afforded by the silica sol-gel process. The porous materials made by silica sol-gel chemistry are typically insulators, however, which has restricted their application. Here we present a simple, yet highly versatile silica sol-gel process built around a multifunctional sol-gel precursor that is derived from the following: amino acids, hydroxy acids or peptides; a silicon alkoxide; and a metal acetate. This approach allows a wide range of biological functionalities and metals--including noble metals--to be combined into a library of sol-gel materials with a high degree of control over composition and structure. We demonstrate that the sol-gel process based on these precursors is compatible with block-copolymer self-assembly, colloidal crystal templating and the Stöber process. As a result of the exceptionally high metal content, these materials can be thermally processed to make porous nanocomposites with metallic percolation networks that have an electrical conductivity of over 1,000 S cm(-1). This improves the electrical conductivity of porous silica sol-gel nanocomposites by three orders of magnitude over existing approaches, opening applications to high-current-density devices.

Bioinspired Processing of Keratin into Upcycled Fibers through pH-Induced Coacervation.

Keratin is an important byproduct of the animal industry, but almost all of it ends up in landfills due to a lack of efficient recycling methods. To make better use of keratin-based natural resources, the current extraction and processing strategies need to be improved or replaced by more sustainable and cost-effective processes. Here, we developed a simple and environmentally benign method to process extracted keratin, using HCl to induce the formation of a coacervate, a separate aqueous phase with a very high protein concentration. Remarkably, this pH-induced coacervation did not result in the denaturation of keratin, and we could even observe an increase in the amount of ordered secondary structures. The low-pH coacervates could be extruded and wet-spun into high-performance keratin fibers, without requiring heating or any organic solvents. The secondary structure of keratin was largely conserved in these regenerated fibers, which exhibited excellent mechanical performance. The process developed in this study represents a simple and environmentally friendly strategy to upcycle waste keratin into high-performance materials.

One-Pot Synthesis of Strong Anionic/Charge-Neutral Amphiphilic Block Copolymers.

Despite the ever more versatile polymerization techniques that are becoming available, the synthesis of macromolecules with tailored functionalities can remain a lengthy endeavor. This becomes more conspicuous when the implementation of incompatible chemistries (i.e., strong polyelectrolytes) within sequence-controlled polymers is desired, often requiring (i) polymerization, (ii) chain extension, and (iii) postpolymerization modification. Herein, we explore the production of strong anionic/charge-neutral block copolymers (BCPs) in a one-pot fashion. This straightforward three-step process includes the synthesis of a macroinitiator and chain extension via rapid and efficient photomediated atom transfer radical polymerization, followed by in situ deprotection to expose the polyanionic domains. The resulting BCPs, which are strong amphiphiles by nature, are capable of self-assembly in aqueous media, as evidenced by dynamic light scattering, small-angle X-ray scattering, ζ-potential measurements, and transmission electron microscopy. We further demonstrate the versatility of our methodology by producing several BCPs through sampling of a single reaction mixture, enabling the straightforward production of strong polymer amphiphiles.

Bioinspired Processing: Complex Coacervates as Versatile Inks for 3D Bioprinting.

3D bioprinting is a powerful fabrication technique in biomedical engineering, which is currently limited by the number of available materials that meet all physicochemical and cytocompatibility requirements for biomaterial inks. Inspired by the key role of coacervation in the extrusion and spinning of many natural materials, hyaluronic acid-chitosan complex coacervates are proposed here as tunable biomaterial inks. Complex coacervates are obtained through an associative liquid-liquid phase separation driven by electrostatic attraction between oppositely charged macromolecules. They offer bioactive properties and facile modulation of their mechanical properties through mild physicochemical changes in the environment, making them attractive for 3D bioprinting. Fine-tuning the salt concentration, pH, and molecular weight of the constituent polymers results in biomaterial inks that are printable in air and water. The biomaterial ink, initially a viscoelastic fluid, transitions into a viscoelastic solid upon printing due to dehydration (for printing in air) or due to a change in pH and ionic composition (for printing in solution). Consequently, scaffolds printed using the complex coacervate inks are stable without the need for post-printing processing. Fabricated cell culture scaffolds are cytocompatible and show long-term topological stability. These results pave the way to a new class of easy-to-handle tunable biomaterials for biofabrication.

Toward Effective and Adsorption-Based Antifouling Zipper Brushes: Effect of pH, Salt, and Polymer Design.

The undesired spontaneous deposition and accumulation of matter on surfaces, better known as fouling, is a problematic and often inevitable process plaguing a variety of industries. This detrimental process can be reduced or even prevented by coating surfaces with a dense layer of end-grafted polymer: a polymer brush. Producing such polymer brushes via adsorption presents a very attractive technique, as large surfaces can be coated in a quick and simple manner. Recently, we introduced a simple and scalable two-step adsorption strategy to fabricate block copolymer-based antifouling coatings on hydrophobic surfaces. This two-step approach involved the initial adsorption of hydrophobic-charged diblock copolymer micelles acting as a primer, followed by the complexation of oppositely charged-antifouling diblock copolymers to form the antifouling brush coating. Here, we significantly improve this adsorption-based zipper brush via systematic tuning of various parameters, including pH, salt concentration, and polymer design. This study reveals several key outcomes. First of all, increasing the hydrophobic/hydrophilic block ratio of the anchoring polymeric micelles (i.e., decreasing the hydrophilic corona) promotes adsorption to the surface, resulting in the most densely packed, uniform, and hydrophilic primer layers. Second, around a neutral pH and at a low salt concentration (1 mM), complexation of the weak polyelectrolyte (PE) blocks results in brushes with the best antifouling efficacy. Moreover, by tuning the ratio between these PE blocks, the brush density can be increased, which is also directly correlated to the antifouling performance. Finally, switching to different antifouling blocks can increase the internal density or strengthen the bound hydration layer of the brush, leading to an additional enhancement of the antifouling properties (>99% lysozyme, 87% bovine serum albumin).

Scalable Fabrication of Reversible Antifouling Block Copolymer Coatings via Adsorption Strategies.

Fouling remains a widespread challenge as its nonspecific and uncontrollable character limits the performance of materials and devices in numerous applications. Although many promising antifouling coatings have been developed to reduce or even prevent this undesirable adhesion process, most of them suffer from serious limitations, specifically in scalability. Whereas scalability can be particularly problematic for covalently bound antifouling polymer coatings, replacement by physisorbed systems remains complicated as it often results in less effective, low-density films. In this work, we introduce a two-step adsorption strategy to fabricate high-density block copolymer-based antifouling coatings on hydrophobic surfaces, which exhibit superior properties compared to one-step adsorbed coatings. The obtained hybrid coating manages to effectively suppress the attachment of both lysozyme and bovine serum albumin, which can be explained by its dense and homogeneous surface structure as well as the desired polymer conformation. In addition, the intrinsic reversibility of the adhered complex coacervate core micelles allows for the successful triggered release and regeneration of the hybrid coating, resulting in full recovery of its antifouling properties. The simplicity and reversibility make this a unique and promising antifouling strategy for large-scale underwater applications.

Electrically Conductive and Highly Stretchable Piezoresistive Polymer Nanocomposites via Oxidative Chemical Vapor Deposition.

Electrically conductive polymer nanocomposites have been the subject of intense research due to their promising potential as piezoresistive biomedical sensors, leveraging their flexibility and biocompatibility. Although intrinsically conductive polymers such as polypyrrole (PPy) and polyaniline have emerged as lucrative candidates, they are extremely limited in their processability by conventional solution-based approaches. In this work, ultrathin nanostructured coatings of doped PPy are realized on polyurethane films of different architectures via oxidative chemical vapor deposition to develop stretchable and flexible resistance-based strain sensors. Holding the substrates perpendicular to the reactant flows facilitates diffusive transport and ensures excellent conformality of the interfacial integrated PPy coatings throughout the 3D porous electrospun fiber mats in a single step. This allows the mechanically robust (stretchability > 400%, with fatigue resistance up to 1000 cycles) nanocomposites to elicit a reversible change of electrical resistance when subjected to consecutive cycles of stretching and releasing. The repeatable performance of the strain sensor is linear due to dimensional changes of the conductive network in the low-strain regime (ε ≤ 50%), while the evolution of nano-cracks leads to an exponential increase, which is observed in the high-strain regime, recording a gauge factor as high as 46 at 202% elongational strain. The stretchable conductive polymer nanocomposites also show biocompatibility toward human dermal fibroblasts, thus providing a promising path for use as piezoresistive strain sensors and finding applications in biomedical applications such as wearable, skin-mountable flexible electronics.

Effect of Dynamically Arrested Domains on the Phase Behavior, Linear Viscoelasticity and Microstructure of Hyaluronic Acid - Chitosan Complex Coacervates.

Complex coacervates make up a class of versatile materials formed as a result of the electrostatic associations between oppositely charged polyelectrolytes. It is well-known that the viscoelastic properties of these materials can be easily altered with the ionic strength of the medium, resulting in a range of materials from free-flowing liquids to gel-like solids. However, in addition to electrostatics, several other noncovalent interactions could influence the formation of the coacervate phase depending on the chemical nature of the polymers involved. Here, the importance of intermolecular hydrogen bonds on the phase behavior, microstructure, and viscoelasticity of hyaluronic acid (HA)-chitosan (CHI) complex coacervates is revealed. The density of intermolecular hydrogen bonds between CHI units increases with increasing pH of coacervation, which results in dynamically arrested regions within the complex coacervate, leading to elastic gel-like behavior. This pH-dependent behavior may be very relevant for the controlled solidification of complex coacervates and thus for polyelectrolyte material design.