Mimicking Dynamic Adhesiveness and Strain-Stiffening Behavior of Biological Tissues in Tough and Self-Healable Cellulose Nanocomposite Hydrogels.

Although self-healing gels with structural resemblance to biological tissues attract great attention in biomedical fields, it remains a dilemma for combination between fast self-healing properties and high mechanical toughness. On the basis of the design of dynamic reversible cross-links, we incorporate rigid tannic acid-coated cellulose nanocrystal (TA@CNC) motifs into the poly(vinyl alcohol) (PVA)-borax dynamic networks for the fabrication of a high toughness and rapidly self-healing nanocomposite (NC) hydrogel, together with dynamically adhesive and strain-stiffening properties that are particularly indispensable for practical applications in soft tissue substitutes. The results demonstrate that the obtained NC gels present a highly interconnected network, where flexible PVA chains wrap onto the rigid TA@CNC motifs and form the dynamic TA@CNC-PVA clusters associated by hydrogen bonds, affording the critical mechanical toughness. The synergetic interactions between borate-diol bonds and hydrogen bonds impart a typical self-healing behavior into the NC gels, allowing the dynamic cross-linked networks to undergo fast rearrangement in the time scale of seconds. Moreover, the obtained NC hydrogels not only mimic the main feature of biological tissues with the unique strain-stiffening behavior but also display unique dynamic adhesiveness to nonporous and porous substrates. It is expected that this versatile approach opens up a new prospect for the rational design of multifunctional cellulosic hydrogels with remarkable performance to expand their applications.

Design of diversified self-assembly systems based on a natural rosin-based tertiary amine for doxorubicin delivery and excellent emulsification.

A novel rosin-based ester tertiary amine (RETA) with three hydrophilic groups and a rigid hydrophobic group was synthesized from rosin by Diels-Alder addition, acylation and esterification reactions. RETA was characterized by infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance spectroscopy (13C NMR). Results from testing surface tension, zeta potential, and transmission electron spectroscopy showed that RETA had unique pH responsiveness. RETA self-assembled into worm-like micelles, spherical micelles 130 nm in diameter and big spherical worm-like aggregates with diameter of 2 µm at pH = 5.76, 8.04 and 9.38, respectively. The critical micelle concentration (CMC) of RETA was 0.42 mmol/L, and the surface tension at CMC (γcmc) was 38.73 mN/m when pH was 8.04. The RETA had a potential application in delivering doxorubicin hydrochloride (DOX) due to the pH responsiveness. Self-assembly mixed systems of RETA and rosin-based phosphoric acid (DDPD) were designed to improve emulsification. The mixed systems had obvious synergistic effects and unexpected emulsification. The γcmc and CMC of mixtures were 41.74 mN/m and 0.20 mmol/L, the size of mixture micelles increased up to 300 nm in the optimum molar ratio of RETA/DDPD (7:3) by TEM and cryo-TEM. It was worth noting that the mixture system formed vesicles in the RETA/DDPD molar ratio of 5:5. The stability time of emulsion with RETA and DDPD as emulsifier were only 63 s and 52 s respectively, but the stability time increased to 234 s in the optimum molar ratio. In addition, the formation mechanisms of micelles at different pH and in various mixtures were discussed in detail. What's more, cytotoxicity results showed that the toxicity of RETA was lower significantly than that of lecithin, a food ingredient in egg yolk and soybean. The cell viability was more than 83% in the high concentration of RETA (4000 µg/ml).

Metal Ion Mediated Cellulose Nanofibrils Transient Network in Covalently Cross-linked Hydrogels: Mechanistic Insight into Morphology and Dynamics.

Utilization of reversible interactions as sacrificial bonds in biopolymers is critical for the integral synthesis of mechanically superior biological materials. In this work, cellulose nanofibrils (CNFs) reinforced covalent polyacrylamide (PAAm) composite hydrogels are immersed into multivalent cation (Ca2+, Zn2+, Al3+, and Ce3+) aqueous solution to form ionic association among CNFs, leading to the ionic-covalent cross-linked hydrogels. The cations promote the formation of porous networks of nanofibrils by screening the repulsive negative charges on CNF surface and dominate the mechanical properties and self-recovery efficiency of the hydrogels, resulting in mechanically reinforced ionic hydrogels with stiff (Young's modulus 257 kPa) and tough properties (fracture toughness 386 kJ/m3). The in situ Raman spectroscopy during stretching corroborates the stress transfer medium of CNF, and the microscopic morphologies of stable crack propagation validates that the multiple toughening mechanisms occur in a balanced energy dissipation manner, enabling synergistic combination of stiffness and toughness. Moreover, the depth-sensing instrumentation by indentation test also demonstrates that the CNF ionic coordination contributes simultaneous improvement in hardness and elasticity by as much as 600% compared to those pristine gels. This work demonstrates a facile way to transfer nanoscale building blocks to bulk elastomers with tunable dynamic properties and may provide a new prospect for the rational design of CNF reinforced hydrogels for applications where high-bearing capability is needed.

Self-assembled structures and excellent surface properties of a novel anionic phosphate diester surfactant derived from natural rosin acids.

A novel anionic rosin-based phosphate diester sodium (DDPDS) was successfully synthesized from raw dehydroabietic acid, a natural raw material, via four-step reactions: acylation, esterification, phosphorylation and neutralization. Nuclear magnetic resonance (13C NMR) and Fourier transform infrared spectroscopy (FT-IR) were used to characterize the structure of target products. The aggregation behaviors in aqueous-ethanol solution and surface properties of DDPDS and its mixed systems were investigated by transmission electron microscopy (TEM), automatic tensiometer and contact angle measuring instrument. The results showed that DDPDS had high surface activity, unexpected emulsification and excellent wettability. The critical micelle concentration (CMC) of 1.35g∗L-1, the minimum surface tension (γcmc) of 31.75mN∗m-1, emulsifying power of 153s and the minimum contact angle of 13.4° were determined for DDPDS. Spherical vesicles with diameter about 50nm and 5µm were self-assembled respectively in aqueous-ethanol solution when DDPDS concentration is about 1 CMC and 5 CMC. Two surfactant ionic self-assembly systems were constructed by mixing DDPDS with sodium dodecylbenzenesulfonate (SDBS) and cetyltrimethylammonium bromide (CTAB), which forms 40nm and 20nm spherical micelles in 1 CMC aqueous-ethanol solution. Possible formation mechanisms of surfactant ionic self-assembly systems on a combination of ionic interactions between DDPDS and SDBS or CTAB are discussed. It was found that there were an obvious synergistic effect of foam stability in DDPDS/SDBS mixed system and an obvious synergistic effect of foam capability in DDPDS/CTAB mixed system.

Simple approach to reinforce hydrogels with cellulose nanocrystals.

The physical crosslinking of colloidal nanoparticles via dynamic and directional non-covalent interactions has led to significant advances in composite hydrogels. In this paper, we report a simple approach to fabricate tough, stretchable and hysteretic isotropic nanocomposite hydrogels, where rod-like cellulose nanocrystals (CNCs) are encapsulated by flexible polymer chains of poly(N,N-dimethylacrylamide) (PDMA). The CNC-PDMA colloidal clusters build a homogeneously cross-linked network and lead to significant reinforcing effect of the composites. Hierarchically structured CNC-PDMA clusters, from isolated particles to an interpenetrated network, are observed by transmission electron microscopy measurements. Dynamic shear oscillation measurements are applied to demystify the differences in network rheological behaviors, which were compared with network behaviors of chemically cross-linked PDMA counterparts. Tensile tests indicate that the hybrid hydrogels possess higher mechanical properties and a more efficient energy dissipation mechanism. In particular, with only 0.8 wt% of CNC loading, a 4.8-fold increase in Young's modulus, 9.2-fold increase in tensile strength, and 5.8-fold increase in fracture strain are achieved, which is ascribed to a combination of CNC reinforcement in the soft matrix and CNC-PDMA colloidal cluster conformational rearrangement under stretching. Physical interactions within networks serve as reversible sacrificial bonds that dissociate upon deformation, exhibiting large hysteresis as an energy dissipation mechanism via cluster mobility. This result contrasts with the case of chemically cross-linked PDMA counterparts where the stress relaxation is slow due to the permanent cross-links and low resistance against crack propagation within the covalent network.

In situ grafting silica nanoparticles reinforced nanocomposite hydrogels.

Highly flexible nanocomposite hydrogels were prepared by using silica nanoparticles (SNPs) as fillers and multi-functional cross-links to graft hydrophilic poly(acrylic acid) (PAA) by free radical polymerization from an aqueous solution. The SNPs were collected by neighboring polymer chains and dispersed uniformly within a PAA matrix. The mechanical properties of the nanocomposite hydrogels were tailored by the concentration of SNPs according to the percolation model. It was proposed that covalent bonds of adsorbed chains on the filler surface resulted in the formation of a shell of an immobilized glassy layer and trapped entanglements, where the glassy polymer layer greatly enhanced the elastic modulus and the release of trapped entanglements at deformation contributed to the viscoelastic properties.

Mechanical and viscoelastic properties of cellulose nanocrystals reinforced poly(ethylene glycol) nanocomposite hydrogels.

The preparation and mechanical properties of elastomeric nanocomposite hydrogels consisting of cellulose nanocrystals (CNCs) and poly(ethylene glycol) (PEG) are reported. The aqueous nanocomposite CNC/PEG precursor solutions covalently cross-linked through a one-stage photocross-linking process. The mechanical properties of nanocomposite hydrogels, including Young's modulus (E), fracture stress (σ), and fracture strain (ε), were measured as a function of CNC volume fraction (φCNC, 0.2-1.8%, v/v) within polymeric matrix. It was found that the homogeneously dispersed nanocomposite hydrogels can be prepared with φCNC being less than 1.5%, whereas the heterogeneous nanocomposite hydrogels were obtained with φCNC being higher than 1.5%. The nanocomposite hydrogels exhibited higher strengths and flexibilities when compared with neat PEG hydrogels, where the modulus, fracture stress, and fracture strain enhanced by a factor of 3.48, 5, and 3.28, respectively, over the matrix material alone at 1.2% v/v CNC loading. Oscillatory shear data indicated the CNC-PEG nanocomposite hydrogels were more viscous than the neat PEG hydrogels and were efficient at energy dissipation due to the reversible interactions between CNC and PEG polymer chains. It was proposed that the strong gel viscoelastic behavior and the mechanical reinforcement were related to "filler network", where the temporary interactions between CNC and PEG interfered with the covalent cross-links of PEG.