Self-assembly in magnetic supramolecular hydrogels

Most recent advances in the synthesis of supramolecular hydrogels based on low molecular weight gelators (LMWGs) have focused on the development of novel hybrid hydrogels, combining LMWGs and different additives. The dynamic nature of the noncovalent interactions of supramolecular hydrogels, together with the specific properties of the additives included in the formulation, allow these novel hybrid hydrogels to present interesting features, such as stimuli-responsiveness, gel-sol reversibility, self-healing and thixotropy, which make them very appealing for multiple biomedical and biotechnological applications. In particular, the inclusion of magnetic nanoparticles in the hydrogel matrix results in magnetic hydrogels, a particular type of stimuli-responsive materials that respond to applied magnetic fields. This review focuses on the recent advances in the development of magnetic supramolecular hydrogels, with special emphasis in the role of the magnetic nanoparticles in the self-assembly process, as well as in the exciting applications of these materials.     

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.     

Build in seconds: Small-molecule hydrogels of self-assembled tryptophan derivatives

Small-molecule hydrogels based on amino acid derivatives have promising applications in many biological fields, including cell culture, drug delivery, and tissue engineering. Although these hydrogels have been widely reported to have low cytotoxicity, biocompatibility, and tunable bioactivity, problems such as harsh preparation conditions and complex material design hinder their application. Herein, by adjusting pH to induce non-covalent interactions between small-molecule tryptophan derivatives (N-[(phenylmethoxy)carbonyl]-l-tryptophan, Mw: 338.35), we developed a self-assembled three-dimensional network hydrogel that can be rapidly formed in seconds. And the supramolecular self-assembly mechanism of the hydrogels was also investigated in detail through experimental characterizations and density functional theory calculation. As-prepared hydrogels also exhibit reversible pH-stimulated response and self-healing properties. This study details a research process for the simple and rapid preparation of tryptophan derivative-based hydrogels, which provides more reference ideas for the future development of materials based on other amino acid derivatives.     

强韧型自愈合水凝胶的研究进展

水凝胶作为一种由大量水和与众不同的三维网状结构构成的智能软材料,已经广泛应用于许多领域,如药物输送、软骨修复、废物处理及电子设备等。然而,水凝胶不良的机械性能及自愈合性极大地限制了它们的潜在应用。目前已报道的韧性水凝胶通常不具有或只有很弱的自修复性,而自修复水凝胶通常机械性能非常弱。因此,研发具有高效自修复性能和优异机械性能的水凝胶材料,无论是从学术角度还是工业角度都是非常重要的。本文总结了近些年来强韧型自愈合水凝胶的最新研究进展,从其制备方法、性能等方面进行了简要介绍,并对未来的发展前景进行了展望。     

Surfactant-induced healing of tough hydrogels formed via hydrophobic interactions

Different reversible molecular interactions have been used in the past few years to generate self-healing in synthetic hydrogels. However, self-healing hydrogels synthesized so far suffer from low mechanical strength which may limit their use in any stress-bearing applications. Here, we present a simple technique to heal mechanically strong polyacrylamide hydrogels formed via hydrophobic interactions between stearyl groups. A complete healing in the hydrogels was achieved by the treatment of the damaged areas with an aqueous solution of wormlike sodium dodecyl sulfate micelles. The micelles in the healing agent solubilize the hydrophobes in the cut surfaces, so that they easily find their partners in the other cut surface due to the hydrophobic interactions. Surfactant-induced healing produces high toughness (～1 MPa) gels withstanding 150 kPa of stress at a deformation ratio of 1,100 %. The healing technique developed here is generally applicable to the physical gels formed by hydrophobic associations.     

Supramolecular polymeric hydrogels

The supramolecular crosslinking of polymer chains in water by specific, directional and dynamic non-covalent interactions has led to the development of novel supramolecular polymeric hydrogels. These aqueous polymeric networks constitute an interesting class of soft materials exhibiting attractive properties such as stimuli-responsiveness and self-healing arising from their dynamic behaviour and that are crucial for a wide variety of emerging applications. We present here a critical review summarising the formation of dynamic polymeric networks through specific non-covalent interactions, with a particular emphasis on those systems based on host-guest complex formation, as well as the characterisation of their physical characteristics. Aqueous supramolecular chemistry has unlocked a versatile toolbox for the design and fine-tuning of the material properties of these hydrogels (264 references).     

双重响应性生物基自修复凝胶的制备及其性能

为拓宽多重响应性凝胶在生物医学领域中的应用,本文基于生物大分子构筑具有pH响应、糖响应性的可自修复性水凝胶。 本文选用3-氨基苯硼酸(APBA)和2,3-环氧丙基三甲基氯化铵(CHGTA)分别对聚谷氨酸(γ-PGA)和瓜尔胶(GG)进行改性制备了聚谷氨酸-g-氨基苯硼酸(γ-PGA-g-APBA)和阳离子瓜尔胶,在此基础上,对γ-PGA-g-APBA和阳离子瓜尔胶进行物理共混制备生物基凝胶。 通过傅里叶变换红外光谱仪(FTIR)、核磁共振波谱仪(¹H NMR)和流变仪对聚合物化学结构、接枝率、流变性能和力学性能进行表征,并考察了凝胶在不同pH值及糖浓度下刺激响应性。 结果表明,凝胶具有自修复性,修复效率可达100%;具有pH响应性,在环境pH值较高时更易形成凝胶,且凝胶强度随pH值升高而增大;同时所制凝胶具有糖响应性,在4 g/L的葡萄糖溶液中浸泡后即可导致凝胶解体。 这些结果说明功能基团APBA的引入可赋予凝胶多重响应性。 所制的双重响应性生物基凝胶具有良好的生物相容性,有望应用于生物医学、功能器件、传感等领域。     

Antibacterial Broad-Spectrum Dendritic/Gellan Gum Hybrid Hydrogels with Rapid Shape-Forming and Self-Healing for Wound Healing Application

Treating wound infections is a difficult task ever since pathogenic bacteria started to develop resistance to common antibiotics. The present study develops hybrid hydrogels based on the formation of a polyelectrolyte complex between the anionic charges of dopamine-functionalized Gellan Gum (GG-DA) and the cationic moieties of the TMP-G2-alanine dendrimer. The hydrogels thus obtained can be doubly crosslinked with CaCl₂, obtaining solid hydrogels. Or, by oxidizing dopamine to GG-DA, possibly causing further interactions such as Schiff Base and Michael addition to take place, hydrogels called injectables can be obtained. The latter have shear-thinning and self-healing properties (efficiency up to 100%). Human dermal fibroblasts (HDF), human epidermal keratinocytes (HaCaT), and mouse monocyte cells (RAW 264.7), after incubation with hydrogels, in most cases show cell viability up to 100%. Hydrogels exhibit adhesive behavior on various substrates, including porcine skin. At the same time, the dendrimer serves to crosslink the hydrogels and endows them with excellent broad-spectrum microbial eradication activity within four hours, evaluated using Staphylococcus aureus 2569 and Escherichia coli 178. Using the same GG-DA/TMP-G2-alanine ratios hybrid hydrogels with tunable properties and potential for wound dressing applications can be produced.     

The design,mechanism and biomedical application of self-healing hydrogels

Current advances made in self-healing hydrogels relating to the design strategies, self-healing mechanism, testing methods and biomedical application in vivo were extensively reviewed in this article.     

One-step synthesis of self-healable hydrogels by the spontaneous phase separation of linear multi-block copolymers during the emulsion copolymerization

Self-healable polyacrylamide-based hydrogels were prepared at room temperature via a one-step emulsion copolymerization of acrylamide(AM),dodecyl 2-methacryIate(DM),and 5-acetylaminopentyl acrylate(AAPA) using sodium dodecyl sulfonate(SDS) as the emulsifier and ammonium persulfate(APS)as the initiator.The produced linear multi-block copolymer chains are composed of randomly-linked hydrophilic polyacrylamide segments(PAM) and hydrophobic segments constituted by DM and AAPA units(P(DM-co-AAPA)).The P(DM-co-AAPA) segments will self-aggregate into hydrophobic microdomains during the polymerization process driven by the hydrophobic interactions,and finally separate from water phase,acting as the crosslinks and leading to the formation of strong hydrogels with a storage modulus as high as 400 Pa.These hydrophobic microdomains will be dissolved in water when the temperature increases to 70℃,resulting in a temperature-responsive reversible sol-gel transition of the prepared hydrogels.Furthermore,the prepared hydrogels have excellent self-healing ability.The broken hydrogels can be automatically healed into a body with a same strength within 2-min's contact.This work provides a new simple way to prepare reversible physical crosslinked hydrogel with high strength and self-healing efficiency.     

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.     

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.     

Ultrahigh-water-content supramolecular hydrogels exhibiting multistimuli responsiveness

Hydrogels are three-dimensional networked materials that are similar to soft biological tissues and have highly variable mechanical properties, making them increasingly important in a variety of biomedical and industrial applications. Herein we report the preparation of extremely high water content hydrogels (up to 99.7% water by weight) driven by strong host-guest complexation with cucurbit[8]uril (CB[8]). Cellulosic derivatives and commodity polymers such as poly(vinyl alcohol) were modified with strongly binding guests for CB[8] ternary complex formation (K(eq) = 10(12) M(-2)). When these polymers were mixed in the presence of CB[8], whereby the overall solid content was 90% cellulosic, a lightly colored, transparent hydrogel was formed instantaneously. The supramolecular nature of these hydrogels affords them with highly tunable mechanical properties, and the dynamics of the CB[8] ternary complex cross-links allows for rapid self-healing of the materials after damage caused by deformation. Moreover, these hydrogels display responsivity to a multitude of external stimuli, including temperature, chemical potential, and competing guests. These materials are easily processed, and the simplicity of their preparation, their availability from inexpensive renewable resources, and the tunability of their properties are distinguishing features for many important water-based applications.     

Hydrophobic association and ionic coordination dual crossed-linked conductive hydrogels with self-adhesive and self-healing virtues for conformal strain sensors

As a promising functional material, conductive hydrogel has attracted extensive attention, especially in flexible sensor field. Despite the recent developments, current hydrogels still experience several issues, such as limited stretchability, lack of self-recovery and self-healing capability, and insufficient self-adhesion. Herein, dual cross-linked (DC) poly (AA-co-LMA)_SDS/Fe³⁺ hydrogels are fabricated subtly on the basis of ionic coordination interactions and the poly (AA-co-LMA)_SDS hydrophobic association networks, which may provide one plausible routine to compensate the mentioned drawback of hydrogels. The hydrophobic association and ionic coordination networks work synergistically to endow the hydrogels remarkable stretchability (>1200%), high-fracture strength (≈ 820 kPa), and excellent self-healing capability. In addition, the DC hydrogel-based strain sensors displayed a broad sensing range (0 ∼ 900%), conspicuous sensitivity (strain 0% ∼ 200%, gauge factor = 0.53; strain 200% ∼ 500%, gauge factor = 1.23; strain 500% ∼ 900%, gauge factor = 2.09), and pronounced durability. What's more, the self-adhesive feature ensures the strain sensor always forming a good conformal contact with the skin during human movements and displaying remarkable bidirectional detection capability.     

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.     

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.     

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.     

Double-Network Heparin Dynamic Hydrogels: Dynagels as Anti-bacterial 3D Cell Culture Scaffolds

Double cross-linked dynamic hydrogels, dynagels, have been prepared through reversible imine bonds and supramolecular interactions, which showed good pH responsiveness, injectability, self-healing property and biocompatibility. With the further encapsulation of heparin, the obtained hydrogels exhibited good anti-bacterial activity and promotion effects for 3D cell culture.     

Self-healing Polymeric Hydrogels: Toward Multifunctional Soft Smart Materials

The concept of self-healing that involves a built-in ability to heal in response to damage wherever and whenever it occurs in a material,analogous to the healing process in living organisms, has emerged a couple of decades ago. Driven primarily by the demands for life-like materials and soft smart materials, therefore, the development of self-healing polymeric hydrogels has continually attracted the attention of the scientific community. Here, this review is intended to give an in-depth overview...