Rheological study on rapid recovery of hydrogel based on oligomeric electrolyte

The hydrogel consisting of an oligomeric electrolyte, poly[pyridinium-1,4-diyl-iminocarbonyl-1,4-phenylenemethylene chloride] ( 1-Cl) underwent self-healing at temperatures lower than its gelation temperature after destruction of the gel network in a shear flow. The self-healing mechanism was investigated by rheological measurements on three different kinds of gels including a low-molecular weight organogelator and a polymeric hydrogelator. Although all of the three gels exhibited thermo-reversible hysteresis loops in the shear moduli, only 1-Cl hydrogel recovered its mechanical properties after vigorous agitation. It is conjectured that the self-healing is due to formation of network structure via a chlorine ion mediated hydrogen bond for which the activation energy is on the order of 10 kJ/mol.     

Mussel-inspired chemistry in producing mechanically robust and bioactive hydrogels as skin dressings

The development of hydrogels as skin dressings demonstrates a great potential in real life applications. To achieve this, the hydrogel has to conquer its natural poor mechanical strength, and to prolong its lifetime, antifatigue and self-healing properties originating from dynamic interactions are also required. As skin dressings, the hydrogel needs to maintain its ductility while pursuing the above mentioned properties. In this work, poly(ethylene glycol) diacrylate is used to produce skin dressings by reinforcing poly(ethylene glycol) diacrylate/alginate double network hydrogels with a crosslinker from mussel-inspired chemistry, which is 3,4-dihydroxy-l-phenylalanine. This crosslinking methodology significantly improved mechanical strength of the hydrogel, with 11,200% increase in compressive failure strength; it endowed the hydrogel with outstanding antifatigue and training strengthening properties that makes its mechanical strength increasing in a 50 cycles compressive test; the hydrogel showed excellent self-healing properties that in rheological characterization; it also displayed enhanced storage modulus after withstanding a shear strain up to 1100%; meanwhile, the hydrogel exhibited extreme ductility with an elastic modulus of only 10.90–16.53 kPa. 3,4-dihydroxy-l-phenylalanine also renders the hydrogel its inherent antioxidant activity, conductivity, and bioadhesiveness. Together with the highly transparent appearance, the hydrogels possess a great potential and practibility in the fields of skin dressings.     

Injectable and self-healing hydrogels with tissue adhesiveness and antibacterial activity as wound dressings for infected wound healing

The design of wound dressings with excellent self-healing ability, adequate adhesion, good biocompatibility, and potential antibacterial ability is of great significance for the healing of infected wounds arising from human activities. Herein, a series of multi-functional hydrogel dressings, poly(ionized isocyanoethyl methacrylate-glutamine)/poly(hexamethylene guanidine) (iG_x/PHMG_y) hydrogels, were obtained through homopolymerization of fully ionized isocyanoethyl methacrylate-glutamine (iIEM-Gln) in the presence of poly(hexamethylene guanidine) (PHMG), in which strong hydrogen bonds were formed among urea groups in the P (iIEM-Gln) chain to form a stable hydrogel network. The prepared iG_x/PHMG_y hydrogels exhibited adequate self-healing ability and tissue adhesion, which could be firmly adhered to the wound surface and remained intact during application. In addition, the presence of PHMG imparted good antibacterial activity to the hydrogels for the effective promotion of the wound healing in S. aureus infected skin wound on mice. Overall, this multi-functional hydrogel provides a facile and effective strategy for the design of infected wound dressings, and may show great potential in clinical applications.     

Preparation and Characterization of Attractive Poly(amino acid)Hydrogels Based on 2-Ureido-4[1H]-pyrimidinone

Self-healing hydrogels with the shear-thinning property are novel injectable materials and are superior to traditional injectable hydrogels.The self-healing hydrogels based on 2-ureido-4[1 H]-pyrimidinone(UPy)have recently received extensive attention due to their dynamic reversibility of UPy dimerization.However,generally,UPy-based self-healing hydrogels exhibit poor stability,cannot degrade in vivo and can hardly be excreted from the body,which considerably limit their bio-application.Here,using poly(l-glutamic acid)(PLGA)as biodegradable matrix,branchingα-hydroxy-ω-amino poly(ethylene oxide)(HAPEO)as bridging molecule to introduce UPy,and ethyl acrylate polyethylene glycol(MAPEG)to introduce double bond,the hydrogel precursors(PMHU)are prepared.A library of the self-healing hydrogels has been achieved with well self-healable and shear-thinning properties.With the increase of MAPEG grafting ratio,the storage modulus of the self-healing hydrogels decreases.The self-healing hydrogels are stable in solution only for 6 h,hard to meet the requirements of tissue regeneration.Consequently,ultraviolet(UV)photo-crosslinking is involved to obtain the dual crosslinking hydrogels with enhanced mechanical properties and stability.When MAPEG grafting ratio is 35.5%,the dual crosslinking hydrogels can maintain the shape in phosphate-buffered saline solution(PBS)for at least 8 days.Loading with adipose-derived stem cell spheroids,the self-healing hydrogels are injected and self-heal to a whole,and then they are crosslinked in situ via UV-irradiation,obtaining the dual crosslinking hydrogels/cell spheroids complex with cell viability of 86.7%±6.0%,which demonstrates excellent injectability,subcutaneous gelatinization,and biocompatibility of hydrogels as cell carriers.The novel PMHU hydrogels crosslinked by quadruple hydrogen bonding and then dual photo-crosslinking of double bond are expected to be applied for minimal invasive surgery or therapies in tissue engineering.     

Functional Polyion Complex Micelles for Potential Targeted Hydrophobic Drug Delivery

Polyion complex (PIC) micelles have gained an increasing interest, mainly as promising nano-vehicles for the delivery of various hydrophilic charged (macro)molecules such as DNA or drugs to the body. The aim of the present study is to construct novel functional PIC micelles bearing cell targeting ligands on the surface and to evaluate the possibility of a hydrophobic drug encapsulation. Initially, a pair of functional oppositely charged peptide-based hybrid diblock copolymers were synthesized and characterized. The copolymers spontaneously co-assembled in water into nanosized PIC micelles comprising a core of a polyelectrolyte complex between poly(L-aspartic acid) and poly(L-lysine) and a biocompatible mixed shell of disaccharide-modified poly(ethylene glycol) and poly(2-hydroxyethyl methacrylate). Depending on the molar ratio between the oppositely charged groups, PIC micelles varying in surface charge were obtained and loaded with the natural hydrophobic drug curcumin. PIC micelles’ drug loading efficiency, in vitro drug release profiles and antioxidant activity were evaluated. The preliminary results indicate that PIC micelles can be successfully used as carriers of hydrophobic drugs, thus expanding their potential application in nanomedicine.     

Gold nanoparticles reinforce self-healing microgel multilayers

We report on the finding that absorption of citrate-stabilized Au nanoparticles into microgel/polyelectrolye multilayer thin films results in an increase in the resistance of those films to strain-induced damage in the dry state while maintaining the remarkable self-healing properties of the films following rehydration. Films were fabricated atop elastomeric poly(dimethylsiloxane) substrates by a centrifuge-assisted layer-by-layer technique using anionic hydrogel microparticles (microgels) and cationic linear polymers as the building blocks. Gold nanoparticles were embedded into swollen hydrogel films by a simple immersion method wherein the Coulombic interactions between the anionic Au particles and the polycation are likely important. After drying, the mechanical properties of films were inferred from the observation of cracks/wrinkles formed during stretching of the elastomeric substrate. As-prepared (no Au) hydrogel films revealed the presence of damage perpendicular to the stretching direction (10% strain), as observed previously. However, Au nanoparticle-doped films displayed significantly reduced damage under identical stretching conditions while forming cracks and wrinkles under higher strains (20?C30%). Importantly, all films displayed excellent self-healing behavior upon rehydration regardless of Au content, suggesting that the nanoparticle toughening effect does not interfere with the film mobility required to achieve autonomic repair.     

基于动态共价键的自愈性水凝胶及其在医学领域的应用

自愈性水凝胶作为一种新型仿生智能材料受到了科研人员的广泛关注.近年来,人们利用动态共价键、超分子作用,发展了一系列自愈性水凝胶,并将其应用于药物控释、细胞三维培养、组织工程等生物医用领域.本文总结和评述了基于动态共价键的自愈性水凝胶及这些水凝胶作为药物载体的相关研究,并展望了基于动态化学的自愈性水凝胶的未来发展.     

Self-healing mineralized hydrogel scaffolds for stretch-triggered dye release

Hydrogels, with self-healing properties that can self-repair spontaneously when subjected to mechanical stress, are gaining popularity in the biomedical field. Numerous attempts have been made to create distinctive hydrogels with self-healing properties, along with stimuli-responsiveness and biocompatibility. Several techniques exist for fabricating hydrogels, including physical and chemical crosslinking via the creation of covalent bonds, and so on. Here, we prepared self-healing, stimuli-responsive, mineralized hydrogel by simply dissolving Kollidon 90-F, sodium chloride (NaCl), and potassium carbonate (K₂CO₃) in an aqueous solution. The dissociated CO₃²⁻ replaces the water molecules from the Kollidon 90-F polymer backbone and facilitates the cross-linking of the polymer chain, resulting in hydrogel formation. In addition, the in-situ produced sodium carbonate (Na₂CO₃) strengthens the hydrogel network. We optimized the mineralized hydrogels by taking various metal salts and different concentrations of K₂CO₃. The optimized hydrogel showed good stability over a period of time, was able to maintain viscoelastic properties, possessed good self-healing ability, and showed a shape retention ability. The shear-thinning property demonstrated by the optimized hydrogel could open a ray of hope in the bioprinting or 3D printing industry. Further, the stretch-responsive release of dye from the Self-healing mineralized hydrogel (SHMH) matrix confirms the mechanoresponsive behavior of the hydrogel. Overall, the findings could be utilized in the future to fabricate a stable drug delivery system that can autonomously release the drug molecules when stretched by daily processes such as joint movements.     

Chitosan-based self-healing hydrogel for bioapplications

A chitosan-based biocompatible self-healing hydrogel has been facilely prepared and used for bioapplications.     

Cell-Encapsulating Hydrogel Puzzle: Polyrotaxane-Based Self-Healing Hydrogels

Slide-ring hydrogels using polyrotaxanes have been developed as highly tough soft materials. However, they have never been used as biomaterials because of the lack of biocompatibility. Meanwhile, self-healing hydrogels are expected to improve fatigue resistance and extend the period of use. However, owing to the lack of high mechanical strength, they are limited in their use as biomaterials. Here we first developed a biocompatible self-healing/slide-ring hydrogel using glycol chitosan and a water-soluble polyrotaxane. We obtained excellent mechanical toughness and biocompatibility to promote the proliferation of human umbilical vein endothelial cells (HUVECs) encapsulated in the hydrogel. Owing to the rapid self-healing property, the cell-encapsulating gels adjusted arbitrarily, maintaining good cell proliferation function. Therefore, slide-ring hydrogels enable the use of biomaterials for soft-tissue engineering.     

Multi-bond network hydrogels with robust mechanical and self-healable properties

Multi-bond network(MBN) which contains a single network with hierarchical cross-links is a suggested way to fabricate robust hydrogels. In order to reveal the roles of different cross-links with hierarchical bond energy in the MBN, here we fabricate poly(acrylic acid) physical hydrogels with dual bond network composed of ionic cross-links between carboxylFe3+ interactions and hydrogen bonds, and compare these dually cross-linked hydrogels with singly and ternarily cross-linked hydrogels. Simple models are employed to predict the tensile property, and the results confirm that the multi-bond network with hierarchical distribution in the bond energy of cross-links endows hydrogel with effective energy-dissipating mechanism. Moreover, the dually cross-linked MBN gels exhibit excellent mechanical properties(tensile strength up to 500 k Pa, elongation at break ~ 2400%) and complete self-healing after being kept at 50 °C for 48 h. The factors on promoting self-healing are deeply explored and the dynamic multi-bonds are regarded to trigger the self-healing along with the mutual diffusion of long polymer chains and ferric ions.     

氢键型水凝胶自修复行为的Monte Carlo模拟

基于氢键型自修复水凝胶的结构特征构建了其横截面的格气模型, 并利用Monte Carlo模拟方法对其自修复行为进行研究. 首先根据自修复过程中的比热峰值确定了氢键的临界联结分数, 然后重点考察了氢键强度、 合作效应以及平均断面间距对其自修复行为的影响. 在此基础上, 进一步研究了氢键型凝胶的动态修复过程, 讨论了相关因素对自修复时间等动态性质的影响. 结果表明, 氢键型凝胶的自修复在本质上归属于一级热力学相变, 且氢键强度是自修复过程中的最关键因素. 同时, 初始断面间距和格子间的合作效应也可显著影响凝胶的自修复行为.     

Development of a novel self-healing dental nanocomposite containing PUF nanocapsules and nanoclay

The aims of this research were to develop the first self-healing dental nanocomposite and to evaluate mechanical properties (compressive and flexural strength), crack-healing, and self-healing longevity after 90 days of water aging. The principal reasons for failure are microcracks formed by polymerization shrinkage, recurrent dynamic mechanical stress, water sorption, and thermal fatigue. N, N-dihydroxyethyl p-toluidine and triethylene glycol dimethacrylate (DEPT-TEGDMA) nanocapsules were synthesized as they have been proven previously to be biocompatible for dental materials. Nanoclay was used as a filler to improve the mechanical properties of self-healing tooth nanocomposites. Nanocapsules were prepared by in situ emulsion polymerization of poly urea-formaldehyde (PUF) shells. The synthesized PUF shells were characterized by FTIR, SEM, and DLS analyses. The results showed that incorporating nanocapsules at a 7.5% mass fraction into the nanocomposite increased the mechanical properties. A good self-healing efficiency ranging from 54.06 to 58% recovery was obtained. The 90 days of water-aging compared to 1 day did not reduce the self-healing efficiency (p > 0.1), showing water-aging did not damage the nanocapsules.     

Thermal-responsive self-healing hydrogel based on hydrophobically modified chitosan and vesicle

High-performance polymer materials with stimulus-responsive, self-healing and controllable features are expected to have diverse applications. In this paper, we report a novel, thermal-switchable self-healing hydrogel which can be obtained simply by mixing the hydrophobically modified chitosan (hm-chitosan) with the thermal-responsive vesicle composed of 5-methyl salicylic acid (5mS) and dodecyltrimethylammonium bromide (DTAB). Temperature stimuli points to a sol–gel phase transition in the supramolecular hydrogel and such transition can be reversibly performed for several cycles. In particular, the gelation temperature can be easily controlled by varying the ratio of DTAB to 5mS. Aside from the temperature responsive ability, the original feature highlighted in this work is that such a vesicle-based hydrogel exhibits interesting self-healing feature in a matter of seconds through the autonomic reconstruction without the use of healing agent. Thus, hydrogels based on hm-chitosan and functional vesicle may have potential application in a wide range of areas.     

Oxidized Xanthan Gum Crosslinked NOCC: Hydrogel System and Their Biological Stability from Oxidation Levels of the Polymer

Dynamic hydrogel systems from N,O-carboxymethyl chitosan (NOCC) are investigated in the past years, which has facilitated their widespread use in many biomedical engineering applications. However, the influence of the polymer's oxidation levels on the hydrogel biological properties is not fully investigated. In this study, chitosan is converted into NOCC and introduced to react spontaneously with oxidized xanthan gum (OXG) to form several injectable hydrogels with controlled degradability. Different oxidation levels of xanthan gum, as well as NOCC/OXG volume ratios, are trialed. The infrared spectroscopy spectra verify chemical modification on OXG and successful crosslinking. With increasing oxidation levels, more dialdehyde groups are introduced into the OXG, resulting in changes in physical properties including gelation, swelling, and self-healing efficiency. Under different volume ratios, the hydrogel shows a stable structure and rigidity with higher mechanical properties, and a slower degradation rate. The shear-thinning and self-healing properties of the hydrogels are confirmed. In vitro assays with L929 cells show the biocompatibility of all formulations although the use of a high amount of OXG15 and OXG25 limited the cell proliferation capacity. Findings in this study suggested a suitable amount of OXG at different oxidation levels in NOCC hydrogel systems for tissue engineering applications.     

交联壳聚糖水凝胶填充层状微胶囊的制备与性能

在甲基丙烯酸和乳酸接枝修饰的水溶性壳聚糖(CML)存在下, 合成了尺寸均匀的球形CML杂化碳酸钙微粒. 通过层层组装(LBL)技术在该微粒表面形成了聚苯乙烯磺酸钠(PSS)/聚烯丙基胺盐酸盐(PAH)多层膜, 去除碳酸钙微粒后得到内部含有CML的聚电解质微胶囊. 进一步采用紫外光引发CML聚合, 将CML转化为CML微凝胶, 得到内部填充凝胶的微胶囊. 通过扫描电镜、光学显微镜和透射电镜等技术表征了微胶囊的结构. 与传统的LBL微胶囊不同, 凝胶填充的微胶囊干燥时尺寸收缩, 但仍可保持球形; 再次水化后, 能够膨胀恢复其原有尺寸和形态. 各种具有不同电荷性质、分子量和亲疏水性的染料分子及蛋白质均可有效地装载到微胶囊内.     

Conductive Tough Hydrogel for Bioapplications

Biocompatible conductive tough hydrogels represent a new class of advanced materials combining the properties of tough hydrogels and biocompatible conductors. Here, a simple method, to achieve a self‐assembled tough elastomeric composite structure that is biocompatible, conductive, and with high flexibility, is reported. The hydrogel comprises polyether‐based liner polyurethane (PU), poly(3,4‐ethylenedioxythiophene) (PEDOT) doped with poly(4‐styrenesulfonate) (PSS), and liquid crystal graphene oxide (LCGO). The polyurethane hybrid composite (PUHC) containing the PEDOT:PSS, LCGO, and PU has a higher electrical conductivity (10 × ), tensile modulus (>1.6 × ), and yield strength (>1.56 × ) compared to respective control samples. Furthermore, the PUHC is biocompatible and can support human neural stem cell (NSC) growth and differentiation to neurons and supporting neuroglia. Moreover, the stimulation of PUHC enhances NSC differentiation with enhanced neuritogenesis compared to unstimulated cultures. A model describing the synergistic effects of the PUHC components and their influence on the uniformity, biocompatibility, and electromechanical properties of the hydrogel is presented.     

Preparation of thermoresponsive and pH-sensitivity polymer magnetic hydrogel nanospheres as anticancer drug carriers

In this work, a novel thermo and pH responsive magnetic hydrogel nanosphere poly(N-isopropylacrylamide-co-acrylic acid)/Fe(3)O(4) (poly(NIPAAm-co-AA)/Fe(3)O(4)) has been successfully prepared. The magnetic hydrogel nanospheres with thermo and pH-sensitivity were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared-spectrometer (FT-IR), UV-vis absorption spectroscopy, and vibrating sample magnetometer (VSM). The magnetic hydrogel nanospheres exhibited uniform sphere structures and superparamagnetic property. Finally, the drug loading capacities and the releasing behavior of the magnetic hydrogel nanospheres were investigated with doxorubicin hydrochloride (DOX) as an anticancer drug model. The resulting magnetic hydrogel nanospheres exhibited high encapsulation efficiency (95%) to DOX under an appropriate condition. In vitro release experiments revealed that release was faster at pH 5.3 (37°C) than at pH 7.4 (25°C) or pH 7.4 (37°C). The DOX-loaded magnetic hydrogel nanospheres also showed enhanced anticancer effect compared with the free drug in vitro. These presented results suggested that the magnetic hydrogel nanospheres have a potential as tumor targeting drug carrier.     

Highly stretchable,self-adhesive,and self-healable double network hydrogel based on alginate/polyacrylamide with tunable mechanical properties

A number of synthetic hydrogels suffer from low mechanical strength. Despite of the recent advances in the fabrication of tough hydrogels, it is still a great challenge to simultaneously construct high stretchability, and self-adhesive and self-healing capability in a hydrogel. Herein, a new type of double network hydrogel was prepared based on irreversible cross-linking of polyacrylamide chains and Schiff-base reversible cross-linking between glycidyl methacrylate-grafted ethylenediamine and oxidized sodium alginate (OSA). The combination of both cross-linkings and their synergistic effect provided a novel hydrogel with high strength, stretchable, rapid self-healing, and self-adhesiveness to different material. Besides, the hydrogels with diverse OSA content could maintain their original shapes after loading–unloading tensile test. The resulting hydrogel has a great potential in various fields for supporting and load-bearing substance.     

An Injectable and Antifouling Supramolecular Polymer Hydrogel with Microenvironment-Regulatory Function to Prevent Peritendinous Adhesion and Promote Tendon Repair

The imbalance of extrinsic and intrinsic healing of tendon is thought to be the main cause of peritendinous adhesions. In this work, an injectable supramolecular poly(N-(2-hydroxypropyl) acrylamide) (PHPAm) hydrogel is prepared merely via side chain hydrogen-bonding crosslinks. This PHPAm exhibits good antifouling and self-healing properties. The supramolecular hydrogel simultaneously loaded with Prussian blue (PB) nanoparticles and platelet lysate (PL) is explored as a functional physical barrier, which can significantly resist the adhesion of fibrin and fibroblasts, attenuate the local inflammatory response, and enhance the tenocytes activity, thus balancing extrinsic and intrinsic healing. The PHPAm hydrogel is shown to prevent peritendinous adhesions considerably by inhibiting NF-κB inflammatory pathway and TGF-β1/Smad3-mediated fibrosis pathway, thereby significantly improving tendon repair by releasing bioactive factors to regulate the tenocytes behavior. This work provides a new strategy for developing physical barriers to prevent peritendinous adhesions and promote tissue repair effectively.