Sculpting tissues by phase transitions.

Biological systems display a rich phenomenology of states that resemble the physical states of matter - solid, liquid and gas. These phases result from the interactions between the microscopic constituent components - the cells - that manifest in macroscopic properties such as fluidity, rigidity and resistance to changes in shape and volume. Looked at from such a perspective, phase transitions from a rigid to a flowing state or vice versa define much of what happens in many biological processes especially during early development and diseases such as cancer. Additionally, collectively moving confluent cells can also lead to kinematic phase transitions in biological systems similar to multi-particle systems where the particles can interact and show sub-populations characterised by specific velocities. In this Perspective we discuss the similarities and limitations of the analogy between biological and inert physical systems both from theoretical perspective as well as experimental evidence in biological systems. In understanding such transitions, it is crucial to acknowledge that the macroscopic properties of biological materials and their modifications result from the complex interplay between the microscopic properties of cells including growth or death, neighbour interactions and secretion of matrix, phenomena unique to biological systems. Detecting phase transitions in vivo is technically difficult. We present emerging approaches that address this challenge and may guide our understanding of the organization and macroscopic behaviour of biological tissues.

A Biosynthetic Hybrid Spidroin-Amyloid-Mussel Foot Protein for Underwater Adhesion on Diverse Surfaces.

Strong underwater adhesives are attractive materials for biomedical healing and underwater repair, but their success in applications has been limited, owing to challenges with underwater setting and with balancing surface adhesion and cohesion. Here, we applied synthetic biology approaches to overcome these challenges through design and synthesis of a novel hybrid protein consisting of the zipper-forming domains of an amyloid protein, flexible spider silk sequences, and a dihydroxyphenylalanine (DOPA)-containing mussel foot protein (Mfp). This partially structured, hybrid protein can self-assemble into a semi-crystalline hydrogel that exhibits high strength and toughness as well as strong underwater adhesion to a variety of surfaces, including difficult-to-adhere plastics, tendon, and skin. The hydrogel allows selective debonding by oxidation or iron-chelating treatments. Both the material design and the biosynthetic approach explored in this study will inspire future work for a wide range of hybrid protein-based materials with tunable properties and broad applications.

Ultra-light poly(lactic acid)/SiO2 aerogel composite foam: A fully biodegradable and full life-cycle sustainable insulation material.

In this study, a fully biodegradable ultra-light poly(lactic acid)/silicon dioxide (PLA/SiO2) aerogel nanocomposite with ultra-low thermal conductivity was successfully fabricated. PLA used was a produced from lactic acid, where the lactic acid has been produced from carbohydrates. The rheological properties of PLA were enhanced by diphenylmethane diisocyanate (MDI). The foaming properties, cell density, cell size uniformity, mechanical properties and thermal conductivity and thermal diffusivity of PLA were further improved by SiO2 aerogel, and finally the ultra-low density foamed material was prepared by supercritical CO2. The density of PLA foam can be as low as 0.02 g/cm3 and the thermal conductivity as low as 0.02628 W/m·K. The PLA-based composites can be used in many fields such as thermal insulation, vibration damping and packaging, and can be fully biodegradable and sustainable throughout their life cycle, which meets the global trend of energy saving and emission reduction.

Chondrus crispus treated with ultrasound as a polysaccharides source with improved antitumoral potential.

Ultrasound-assisted extraction was used to recover gelling biopolymers and antioxidant compounds from Chondrus crispus with improved biological potential. The optimal processing conditions were evaluated using a Box-Behnken design, and the impact on the biological and thermo-rheological properties of the carrageenan fraction and on the bioactive features of the soluble extracts were studied. The optimum extraction parameters were defined by extraction time of ~34.7 min; solid liquid ratio of ~2.1 g/100 g and ultrasound amplitude of ~79.0% with a maximum power of 1130 W. The dependent variables exhibited maximum carrageenan yields (44.3%) and viscoelastic modulus (925.9 Pa) with the lowest gelling temperatures (38.7 °C) as well as maximum content of the extract in protein (22.4 mg/g), gallic acid (13.4 mg/g) and Trolox equivalents antioxidant capacity (182.4 mg TEAC/g). Tested hybrid carrageenans exhibited promising biological activities (% of growth inhibition around 91% for four human cancer cellular lines: A549; A2780; HeLa 229; HT-29).

Emulsifying capacity of peanut polysaccharide: Improving interfacial property through the co-dissolution of protein during extraction.

The co-dissolution of residual protein from byproduct (PPSI) was employed to improve the interfacial property of peanut polysaccharide (PPS). Protein content in the PPSI and PPS were 16.89% and 2.58%, respectively. The convent bonding and intermolecular interaction maintained the complex structure in PPSI. More protein promoted the shift from linear chain conformation to spherical particle, weakened surface charge, induced stronger intermolecular attraction and wettability, which facilitated interfacial adsorption of PPSI. Concomitantly, the linear chain after adsorbing the O/W interface was observed in PPSI-polystyrene, promoting the cross-linking between adsorption layers and thereby forming the elastic interfacial film. Consequently, the emulsion borne smaller size. Subsequently, the particles in continuous phase moved to the adsorption layer via intermolecular interaction and then formed a gel, enhancing stability against oil coalescence, the thermal and refrigerated treatments. Additionally, the acidified (pH 3.0) PPSI further strengthened the emulsion structure and improved its creaming and freeze-thaw stability.

Pastable, Adhesive, Injectable, Nanofibrous, and Tunable (PAINT) Biphasic Hybrid Matrices as Versatile Therapeutic Carriers.

A critical challenge in many pharmaceutical fields is developing versatile adjuvant devices that can reduce the off-target delivery of therapeutic materials to target lesions. Herein, a biphasic hybrid fibrous system that can manipulate the spatial and temporal delivery of various therapeutic agents to target lesions by integrating multiple distinct systems and technologies such as fluffy coaxial electrospun polycaprolactone (PCL)/polystyrene (PS) fibers, cyclohexane-mediated leaching to remove PS layers selectively, amine display on PCL fibers, conjugation of naturally occurring adhesive gallol molecules onto hyaluronic acid (HA-g), and electrostatically complexing the aminated PCL fibers with the gallol-conjugated HA. In the context of "paintable" systems on target lesions, the resulting system is called a PAINT matrix (abbreviated according to the initial letter of its features: pastable, adhesive, injectable, nanofibrous, and tunable). Its viscoelastic property, which was attributed by coalescing aminated PCL fibers with viscous HA-g, enabled it to be noninvasively injected and fit into any cavity in the body with various morphologies, manually pasted on tissue surfaces, and adhered onto moisture-rich surfaces to ensure the secure delivery of therapeutics toward the target lesions. The PAINT matrix efficiently supplied immunomodulatory human neural stem cells (hNSCs) at rat hemisectioned spinal cord injury (SCI) sites and promoted both locomotive and sensory recovery in SCI models, presumably by protecting hNSCs against host immunosurveillance. The PAINT matrix will be broadly utilized for efficiently delivering therapeutics to difficult-to-reach target lesions by direct infusion or conventional biomaterial-mediated approaches due to their locations, wet surfaces, or complicated ambient environments.

The influence of alkaline treatment on the mechanical and structural properties of bacterial cellulose.

The unique mechanical properties of hydrated bacterial cellulose make it suitable for biomedical applications. This study evaluates the effect of concentrated sodium hydroxide treatment on the structural and mechanical properties of bacterial cellulose hydrogels using rheological, tensile, and compression tests combined with mathematical modelling. Bacterial cellulose hydrogels show a concentration-dependent and irreversible reduction in shear moduli, compression, and tensile strength after alkaline treatment. Applying a poroelastic biphasic model to through-thickness compressive stress-relaxation tests showed the alkaline treatment to induce no significant change in axial compression, an effect was observed in the radial direction, potentially due to the escape of water from within the hydrogel. Scanning electron microscopy showed a more porous structure of bacterial cellulose. These results show how concentration-dependent alkaline treatment induces selective weakening of intramolecular interactions between cellulose fibres, allowing the opportunity to precisely tune the mechanical properties for specific biomedical application, e.g., faster-degradable materials.

Self-Healing, Self-Adhesive Silk Fibroin Conductive Hydrogel as a Flexible Strain Sensor.

Flexible and wearable hydrogel strain sensors have attracted tremendous attention for applications in human motion and physiological signal monitoring. However, it is still a great challenge to develop a hydrogel strain sensor with certain mechanical properties and tensile deformation capabilities, which can be in conformal contact with the target organ and also have self-healing properties, self-adhesive capability, biocompatibility, antibacterial properties, high strain sensitivity, and stable electrical performance. In this paper, an ionic conductive hydrogel (named PBST) is rationally designed by proportionally mixing polyvinyl alcohol (PVA), borax, silk fibroin (SF), and tannic acid (TA). SF can not only be a reinforcement to introduce an energy dissipation mechanism into the dynamically cross-linked hydrogel network to stabilize the non-Newtonian behavior of PVA and borax but it can also act as a cross-linking agent to combine with TA to reduce the dissociation of TA on the hydrogel network, improving the mechanical properties and viscoelasticity of the hydrogel. The combination of SF and TA can improve the self-healing ability of the hydrogel and realize the adjustable viscoelasticity of the hydrogel without sacrificing other properties. The obtained hydrogel has excellent stretchability (strain > 1000%) and shows good conformal contact with human skin. When the hydrogel is damaged by external strain, it can rapidly self-repair (mechanical and electrical properties) without external stimuli. It shows adhesiveness and repeatable adhesiveness to different materials (steel, wood, PTFE, glass, iron, and cotton fabric) and biological tissues (pigskin) and is easy to peel off without residue. The obtained PBST conductive hydrogel also has a wide strain-sensing range (>650%) and reliable stability. The hydrogel adhered to the skin surface can monitor large strain movements such as in finger joints, wrist joints, knee joints, and so on and detect swallowing, smiling, facial bulging and calming, and other micro-deformation behaviors. It can also distinguish physical signals such as light smile, big laugh, fast and slow breathing, and deep and shallow breathing. Therefore, the PBST conductive hydrogel material with multiple synergistic functions has great potential as a flexible wearable strain sensor. The PBST hydrogel has antibacterial properties and good biocompatibility at the same time, which provides a safety guarantee for it as a flexible wearable strain sensor. This work is expected to provide a new way for people to develop ideal wearable strain sensors.

Nonlinear dynamics and acoustic emissions of interacting cavitation bubbles in viscoelastic tissues.

The cavitation-mediated bioeffects are primarily associated with the dynamic behaviors of bubbles in viscoelastic tissues, which involves complex interactions of cavitation bubbles with surrounding bubbles and tissues. The radial and translational motions, as well as the resultant acoustic emissions of two interacting cavitation bubbles in viscoelastic tissues were numerically investigated. Due to the bubble-bubble interactions, a remarkable suppression effect on the small bubble, whereas a slight enhancement effect on the large one were observed within the acoustic exposure parameters and the initial radii of the bubbles examined in this paper. Moreover, as the initial distance between bubbles increases, the strong suppression effect is reduced gradually and it could effectively enhance the nonlinear dynamics of bubbles, exactly as the bifurcation diagrams exhibit a similar mode of successive period doubling to chaos. Correspondingly, the resultant acoustic emissions present a progressive evolution of harmonics, subharmonics, ultraharmonics and broadband components in the frequency spectra. In addition, with the elasticity and/or viscosity of the surrounding medium increasing, both the nonlinear dynamics and translational motions of bubbles were reduced prominently. This study provides a comprehensive insight into the nonlinear behaviors and acoustic emissions of two interacting cavitation bubbles in viscoelastic media, it may contribute to optimizing and monitoring the cavitation-mediated biomedical applications.

Agarose Stearate-Carbomer940 as Stabilizer and Rheology Modifier for Surfactant-Free Cosmetic Formulations.

Some commonly used surfactants in cosmetic products raise concerns due to their skin-irritating effects and environmental contamination. Multifunctional, high-performance polymers are good alternatives to overcome these problems. In this study, agarose stearate (AS) with emulsifying, thickening, and gel properties was synthesized. Surfactant-free cosmetic formulations were successfully prepared from AS and carbomer940 (CBM940) mixed systems. The correlation of rheological parameter with skin feeling was determined to study the usability of the mixed systems in cosmetics. Based on rheological analysis, the surfactant-free cosmetic cream (SFC) stabilized by AS-carbomer940 showed shear-thinning behavior and strongly synergistic action. The SFC exhibited a gel-like behavior and had rheological properties similar to commercial cosmetic creams. Scanning electron microscope images proved that the AS-CBM940 network played an important role in SFC's stability. Oil content could reinforce the elastic characteristics of the AS-CBM940 matrix. The SFCs showed a good appearance and sensation during and after rubbing into skin. The knowledge gained from this study may be useful for designing surfactant-free cosmetic cream with rheological properties that can be tailored for particular commercial cosmetic applications. They may also be useful for producing medicine products with highly viscous or gel-like textures, such as some ointments and wound dressings.

Potato starch altered the rheological, printing, and melting properties of 3D-printable fat analogs based on inulin emulsion-filled gels.

Plant-based oil inks that imitate the texture and melting behavior of traditional animal fats using 3D printing have been developed. The influence of the incorporation of potato starch and the type of oil on rheology and meltability was investigated. The results showed that the dynamic modulus and hardness of fat analogs increased, whereas fat analog meltability decreased with an increase in potato starch content. Coconut oil and soybean oil-containing fat analogs incorporated with proper potato starch levels exhibited good printability and similar meltability to commercial beef and pork fats. The addition of potato starch suppressed fat analog meltability as it disrupted the inulin matrix. Fat analogs containing coconut oil could be texturized at temperatures lower than those required for their soybean oil counterparts. The fat analogs were solid at room temperature, demonstrated good printability, and imitated the melting behavior of fat contained in real meat throughout the cooking process.

Viscoelastic behaviour of rapid and slow self-healing hydrogels formed by densely branched arabinoxylans from Plantago ovata seed mucilage.

We report rheological characterisation of hydrogels formed by highly substituted brush-like arabinoxylans from Plantago ovata seed mucilage. Two arabinoxlyan fractions with similar molecular weight and linkage compositions are chosen to form gels with distinct rheological properties but a similar network structure. Small and large amplitude oscillatory shear rheology is used to characterise the sol-gel transition as a function of temperature and concentration. Differences in rheology and gelation of the two hydrogels are found to be associated with the different proportion of 'slow'- and 'fast'-dissociating junctions stabilised by hydrogen bonds, with the 'fast'-dissociating junctions playing an important role in rapid self-healing of the gel. Based on the temperature dependence of storage modulus and time-temperature superposition principle in combination with the Arrhenius equation, the activation energies of junction zone dissociation are estimated to be 402-480 kJ/mol and 97-144 kJ/mol for the 'slow' and 'fast' junction types, respectively.

Chemical modification strategies for viscosity-dependent processing of gellan gum.

Recently, the hydrogel-forming polysaccharide gellan gum (GG) has gained popularity as a versatile biomaterial for tissue engineering purposes. Here, we examine the modification strategies suitable for GG to overcome processing-related limitations. We emphasize the thorough assessment of the viscoelastic and mechanical properties of both precursor solutions and final hydrogels. The investigated modification strategies include purification, oxidation, reductive chain scission, and blending. We correlate polymer flow and hydrogel forming capabilities to viscosity-dependent methods including casting, injection and printing. Native GG and purified NaGG are shear thinning and feasible for printing, being similar in gelation and compression behavior. Oxidized GGox possesses reduced viscosity, higher toughness, and aldehydes as functional groups, while scissored GGsciss has markedly lower molecular weight. To exemplify extrudability, select modification products are printed using an extrusion-based bioprinter utilizing a crosslinker bath. Our robust modification strategies have widened the processing capabilities of GG without affecting its ability to form hydrogels.

Flowering in bursting bubbles with viscoelastic interfaces.

The lifetime of bubbles, from formation to rupture, attracts attention because bubbles are often present in natural and industrial processes, and their geometry, drainage, coarsening, and rupture strongly affect those operations. Bubble rupture happens rapidly, and it may generate a cascade of small droplets or bubbles. Once a hole is nucleated within a bubble, it opens up with a variety of shapes and velocities depending on the liquid properties. A range of bubble rupture modes are reported in literature in which the reduction of a surface energy drives the rupture against inertial and viscous forces. The role of surface viscoelasticity of the liquid film in this colorful scenario is, however, still unknown. We found that the presence of interfacial viscoelasticity has a profound effect in the bubble bursting dynamics. Indeed, we observed different bubble bursting mechanisms upon the transition from viscous-controlled to surface viscoelasticity-controlled rupture. When this transition occurs, a bursting bubble resembling the blooming of a flower is observed. A simple modeling argument is proposed, leading to the prediction of the characteristic length scales and the number and shape of the bubble flower petals, thus paving the way for the control of liquid formulations with surface viscoelasticity as a key ingredient. These findings can have important implications in the study of bubble dynamics, with consequences for the numerous processes involving bubble rupture. Bubble flowering can indeed impact phenomena such as the spreading of nutrients in nature or the life of cells in bioreactors.

Silk Hydrogel Substrate Stress Relaxation Primes Mesenchymal Stem Cell Behavior in 2D.

Tissue-mimetic silk hydrogels are being explored for diverse healthcare applications, including stem cell delivery. However, the impact of stress relaxation of silk hydrogels on human mesenchymal stem cell (MSC) biology is poorly defined. The aim of this study was to fabricate silk hydrogels with tuned mechanical properties that allowed the regulation of MSC biology in two dimensions. The silk content and stiffness of both elastic and viscoelastic silk hydrogels were kept constant to permit direct comparisons. Gene expression of IL-1ß, IL-6, LIF, BMP-6, BMP-7, and protein tyrosine phosphatase receptor type C were substantially higher in MSCs cultured on elastic hydrogels than those on viscoelastic hydrogels, whereas this pattern was reversed for insulin, HNF-1A, and SOX-2. Protein expression was also mechanosensitive and the elastic cultures showed strong activation of IL-1ß signaling in response to hydrogel mechanics. An elastic substrate also induced higher consumption of glucose and aspartate, coupled with a higher secretion of lactate, than was observed in MSCs grown on viscoelastic substrate. However, both silk hydrogels changed the magnitude of consumption of glucose, pyruvate, glutamine, and aspartate, and also metabolite secretion, resulting in an overall lower metabolic activity than that found in control cells. Together, these findings describe how stress relaxation impacts the overall biology of MSCs cultured on silk hydrogels.

Modulating storage stability of binary gel by adjusting the ratios of starch and kappa-carrageenan.

This study aimed to investigate the interaction mechanism of the waxy starch and kappa carrageenan (KC) gel with different ratios during co-gelatinization and storage. Water distributions, mobilities and rheological properties of the mixture gels were studied. When KC concentration was low (0.5%KC and 4% starch), the starch dominated the system, and the gel strength was the lowest. When KC concentration increased to 0.75%, the gel had the lowest change rate of fracture force, and the most homogeneous network of the freeze-dried gel was observed. When KC concentration increased to 1.0%, the gel strength was high, but the uneven structure led to the instability of the gel. Overall, the gel with 0.75%KC and 4% starch was the most stable during storage, and the exclusion of the two components to each other was the weakest, resulting in the uniform structure of the gel.

Characterization of covalent, feruloylated polysaccharide gels by pulsed field gradient-stimulated echo (PFG-STE)-NMR.

Translational mobility of guest molecules such as water and glucose in gels that are based on feruloylated polysaccharides appears to be critical to understand their nutritional and functional properties. Here, the applicability of PFG-STE-NMR on feruloylated gels was proven, and relationships to rheological data were studied. Arabinoxylans and pectins were extracted from by-products using varying conditions. Laccase induced coupling of these chemically characterized polymers resulted for most of the feruloylated polysaccharides in homogeneous gels. Rheological studies confirmed that polysaccharide composition affects viscoelastic properties of the resulting gels. Generally, diffusion of water and glucose is hindered in gels. In the feruloylated polysaccharide gels, both polysaccharide concentration and extraction conditions affect the diffusion behavior of these molecules. A simple correlation between rheological data and mobility of guest molecules has not generally been found: although long time acid extracted pectins form highly elastic gels, water diffusion in these gels is less hindered.

Viscoelastic surface electrode arrays to interface with viscoelastic tissues.

Living tissues are non-linearly elastic materials that exhibit viscoelasticity and plasticity. Man-made, implantable bioelectronic arrays mainly rely on rigid or elastic encapsulation materials and stiff films of ductile metals that can be manipulated with microscopic precision to offer reliable electrical properties. In this study, we have engineered a surface microelectrode array that replaces the traditional encapsulation and conductive components with viscoelastic materials. Our array overcomes previous limitations in matching the stiffness and relaxation behaviour of soft biological tissues by using hydrogels as the outer layers. We have introduced a hydrogel-based conductor made from an ionically conductive alginate matrix enhanced with carbon nanomaterials, which provide electrical percolation even at low loading fractions. Our combination of conducting and insulating viscoelastic materials, with top-down manufacturing, allows for the fabrication of electrode arrays compatible with standard electrophysiology platforms. Our arrays intimately conform to the convoluted surface of the heart or brain cortex and offer promising bioengineering applications for recording and stimulation.

Polypseudorotaxane and polydopamine linkage-based hyaluronic acid hydrogel network with a single syringe injection for sustained drug delivery.

Polypseudorotaxane structure and polydopamine bond-based crosslinked hyaluronic acid (HA) hydrogels including donepezil-loaded microspheres were developed for subcutaneous injection. Both dopamine and polyethylene glycol (PEG) were covalently bonded to the HA polymer for catechol polymerization and inclusion complexation with alpha-cyclodextrin (α-CD), respectively. A PEG chain of HA-dopamine-PEG (HD-PEG) conjugate was threaded with α-CD to make a polypseudorotaxane structure and its pH was adjusted to 8.5 for dopamine polymerization. Poly(lactic-co-glycolic acid) (PLGA)/donepezil microsphere (PDM) was embedded into the HD-PEG network for its sustained release. The HD-PEG/α-CD/PDM 8.5 hydrogel system exhibited an immediate gelation pattern, injectability through single syringe, self-healing ability, and shear-thinning behavior. Donepezil was released from the HD-PEG/α-CD/PDM 8.5 hydrogel in a sustained pattern. Following subcutaneous injection, the weight of excised HD-PEG/α-CD/PDM 8.5 hydrogel was higher than the other groups on day 14. These findings support the clinical feasibility of the HD-PEG/α-CD/PDM 8.5 hydrogel for subcutaneous injection.

Direct ink writing of aloe vera/cellulose nanofibrils bio-hydrogels.

Direct-ink-writing (DIW) of hydrogels has become an attractive research area due to its capability to fabricate intricate, complex, and highly customizable structures at ambient conditions for various applications, including biomedical purposes. In the current study, cellulose nanofibrils reinforced aloe vera bio-hydrogels were utilized to develop 3D geometries through the DIW technique. The hydrogels revealed excellent viscoelastic properties enabled extruding thin filaments through a nozzle with a diameter of 630 µm. Accordingly, the lattice structures were printed precisely with a suitable resolution. The 3D-printed structures demonstrated significant wet stability due to the high aspect ratio of the nano- and microfibrils cellulose, reinforced the hydrogels, and protected the shape from extensive shrinkage upon drying. Furthermore, all printed samples had a porosity higher than 80% and a high-water uptake capacity of up to 46 g/g. Altogether, these fully bio-based, porous, and wet stable 3D structures might have an opportunity in biomedical fields.