Search

Sodium aescinate (SA) shows great potential for treating lymphedema since it can regulate the expression of cytokines in M1 macrophages, however, it is commonly administered intravenously in clinical practice and often accompanied by severe toxic side effects and short metabolic cycles. Herein, SA-loaded chiral supramolecular hydrogels are prepared to prove the curative effects of SA on lymphedema and enhance its safety and transdermal transmission efficiency. In vitro studies demonstrate that SA- loaded chiral supramolecular hydrogels can modulate local immune responses by inhibiting M1 macrophage polarization. Typically, these chiral hydrogels can significantly increase the permeability of SA with good biocompatibility due to the high enantioselectivity between chiral gelators and stratum corneum and L-type hydrogels are found to have preferable drug penetration over D-type hydrogels. In vivo studies show that topical delivery of SA via chiral hydrogels results in dramatic therapeutic effects on lymphedema. Specifically, it can downregulate the level of inflammatory cytokines, reduce the development of fibrosis, and promote the regeneration of lymphatic vessels. This study initiates the use of SA for lymphedema treatment and for the creation of an effective chiral biological platform for improved topical administration., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Tissue engineering (TE), as a new interdisciplinary discipline, aims to develop biological substitutes for repairing damaged tissues and organs. For the success of tissue regeneration, such biomaterials need to support the physiological activities of cells and allow the growth and maturation of tissues. Naturally, this regulation is achieved through the dynamic remodeling of the extracellular matrix (ECM) of cells. In recent years, chiral supramolecular hydrogels have shown higher application potential in the TE field than traditional polymer hydrogels due to their dynamic noncovalent interactions, adjustable self-assembly structure, and good biocompatibility. These advantages make it possible to construct hydrogels under physiological conditions with structure and function similar to those of the natural ECM. Meanwhile, the chiral characteristics of hydrogels play an important role in regulating cellular activities such as differentiation, adhesion, and proliferation, which is beneficial for tissue formation. In this review, a brief introduction is presented to highlight the importance of chiral fiber supramolecular hydrogels for TE at first. Afterward, the considerations for chiral supramolecular hydrogel design, as well as the influence of external stimuli on chiral hydrogel construction, are discussed. Finally, the potential application prospects of these materials in TE and the significant contribution made by our group in this field are summarized. This review not only helps to reveal the importance of chiral properties in TE but also provides new strategies for TE research based on chiral bionic microenvironments. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Biology-Inspired Nanomaterials > Peptide-Based Structures Nanotechnology Approaches to Biology > Cells at the Nanoscale Therapeutic Approaches and Drug Discovery > Emerging Technologies., (© 2022 Wiley Periodicals LLC.)

Chronic wounds, such as diabetic foot ulcers (DFU), are a serious clinical problem. It is a challenge for the conventional wound dressings to achieve the desirable therapeutic efficacy due to the lack of biomimetic structural environment for rapid re-epithelization. Inspired by the naturally existing chiral structures in skin, a novel amino acid-based chiral hydrogel dressing is developed, consisting of left-handed or right-handed helical fibers self-assembled by l/d-phenylalanine derivatives. Compared to the levorotatory chiral hydrogel (LH), the dextral chiral hydrogel (DH) shows the ability to enhance cell adhesion, proliferation, and migration, and strongly promotes diabetic wound healing and re-epithelialization with a drug-free mode. Interestingly, the dextral chiral hydrogel is able to actively increase adsorption of type I collagen and promote proliferation and migration of keratinocyte in an integrin and YAP-mediated manner. This study not only provides a novel strategy for treatment of chronic wounds by utilizing dextral chiral hydrogel dressings, but also unveils the molecular mechanism for effect of dextral chiral structures on the promoted proliferation of keratinocyte., (© 2022 Wiley-VCH GmbH.)

Chirality exits from molecular-level, supramolecular, and nanoscaled helical structures to the macroscopic level in biological life. Among these various levels, as the central structural motifs in living systems (e.g., double helix in DNA, α-helix, β-sheet in proteins), supramolecular helical systems arising from the asymmetrical spatial stacking of molecular units play a crucial role in a wide diversity of biochemical reactions (e.g., gene replication, molecular recognition, ion transport, enzyme catalysis, and so on). However, the importance of supramolecular chirality and its potential biofunctions has not yet been fully explored. Thus, generating chiral assembly to transfer nature's chiral code to artificial biomaterials is expected to be utilized for developing novel functional biomaterials. As one of the most commonly used biomaterials, supramolecular hydrogels have attracted considerable research interest due to their resemblance to the structure and function of the native extracellular matrix (ECM). Therefore, the performance and manipulation of chiral assembled nanoarchitectures in supramolecular hydrogels may provide useful insights into understanding the role of supramolecular chirality in biology.In this Account, recent progress on chiral supramolecular hydrogels is presented, including how to construct and regulate assembled chiral nanostructures in hydrogels with controllable handedness and then use them to develop chiral hydrogels that could be applied in biology, biochemistry, and medicine. First, a brief introduction is provided to present the basic concept related to supramolecular chirality and the importance of supramolecular chirality in living systems. The chiral assemblies in supramolecular hydrogels are strongly driven by noncovalent interactions between molecular building blocks (such as hydrogen bonding, π-π stacking, hydrophobic, and van der Waals interactions). Consequently, the handedness of these chiral assemblies can be regulated by many extra stimuli including solvents, temperature, pH, metal ions, enzymes, and photoirradiation, which is presented in the second section. This manipulation of the chirality of nanoarchitectures in supramolecular hydrogels can result in the development of potential biofunctions. For example, specific supramolecular chirality-induced biological phenomena (such as controlled cell adhesion, proliferation, differentiation, apoptosis, protein adsorption, drug delivery, and antibacterial adhesion) are presented in detail in the third section. Finally, the outlook of open challenges and future developments of this rapidly evolving field is provided. This account that highlights the diverse chirality-dependent biological phenomena not only helps us to understand the importance of chirality in life but also provides new ideas for designing and preparing chiral materials for more bioapplications.

A generally applicable strategy to obtain mechanically robust hydrogels for the incorporation and containment of functional reporter bacteria for the microarray and microparticle-based detection and signaling of N-acyl homoserine lactone autoinducers (3OC 12 HSL) at relevant concentrations is reported. For reinforcing hydrogels of 1,4-bi(phenylalanine-diglycol)-benzene (PDB), a hybrid hydrogel is formed by the combination of PDB self-assembly with Ca 2+ mediated alginate crosslinking. The different assembly mechanisms are shown not to interfere with each other and despite the more than four-fold increased moduli of the hydrogels, diffusion of autoinducers into the gels remains efficient and Escherichia coli pLuxR-green fluorescent protein (GFP) reporter bacteria are proliferating. Templating affords reporter bacteria-loaded hydrogels with controllable shape and size. Upon exposure to 3OC 12 HSL, the embedded bacteria exhibit an up to 12 ± 3 times increase in fluorescence intensity due to autoinducer-triggered GFP expression. This approach can serve as a potentially generally applicable strategy to sensitively detect bacteria via their secreted autoinducers., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A multi-functional gelator precursor with high photosensitivity is rationally designed, which can not only selectively target hepatocellular carcinoma (HCC) cells, but also form intracellular self-assembly triggered by light and subsequently inducing cell death. The study develops a methodology to design biological targets of supramolecular self-assembly under external stimuli for cancer research.

For CH···O hydrogen bonds in assembled structures and the applications, one of the critical issues is how molecular spatial structures affect their interaction modes as well as how to translate the different modes into the macroscopic properties of materials. Herein, coumarin-derived isomeric hydrogelators with different spatial structures are synthesized, where only nitrogen atoms locate at the ortho, meso, or para position in the pyridine ring. The gelators can self-assemble into single crystals and nanofibrous networks through CH···O interactions, which are greatly influenced by nitrogen spatial positions in the pyridine ring, leading to the different self-assembly mechanisms, packing modes, and properties of the nanofibrous networks. Typically, different cell proliferation rates are obtained on the different CH···O bonds driving nanofibrous structures, implying that tiny variation of the stereo-position of nitrogen atoms can be sensitively detected by cells. The study paves a novel way to investigate the influence of isomeric molecular assembly on macroscopic properties and functions of materials.

A new family of coumarin-based supramolecular hydrogelators without conventional gelating motifs have been designed and synthesized in a one-step reaction. Fluorescent nanofibers self-assembled from these hydrogelators could be used as potential scaffolds for better visualization of the interaction between substrates and cells.

Amino acid-derived self-assembled nanofibers comprising supramolecular chiral hydrogels with unique physiochemical characteristics are highly demanded biomaterials for various biological applications. However, their narrow functionality often limits practical use, necessitating the development of biomaterials with multiple features within a single system. Herein, chiral co-assembled hybrid hydrogel systems termed LPH-EGCG and DPH-EGCG were constructed by co-assembling L/DPFEG gelators with epigallocatechin gallate (EGCG) followed by cross-linking with polyvinyl alcohol (PVA) and hyaluronic acid (HA). The developed hybrid hydrogels exhibit superior mechanical strength, self-healing capabilities, and adhesive properties, owing to synergistic non-covalent interactions. Integrating hydrophilic polymers enhances the system's capacity to demonstrate favorable swelling characteristics. Furthermore, the introduction of EGCG facilitated the hybrid gels to display notable antibacterial properties against both Gram-positive and Gram-negative bacterial strains, alongside showcasing strong antioxidant capabilities. In vitro investigation demonstrated enhanced cell adhesion and migration with the LPH-EGCG system in comparison to DPH-EGCG, thus emphasizing the promising prospects of these hybrid hydrogels in advanced tissue engineering applications. [ABSTRACT FROM AUTHOR]

Chirality, a fundamental design feature at all levels of life organization, has shown great capability in guiding cell‐fate determination and tissue regeneration. Chirality‐directed differentiation programs involve remarkable changes in transcriptional networks, yet whether epigenetic regulatory events are also required is less well understood. Herein, by combining high‐throughput m6A MeRIP sequencing, RIP‐qPCR, and gene modulation techniques, it is demonstrated that biomimetic chiral nanofibrils can bidirectionally regulate wilms tumor 1 associated protein (WTAP)‐mediated m6A RNA methylation to guide macrophages polarization for tissue regeneration. The biomimic chiral nanofibril hydrogels are fabricated using a self‐assembly approach based on C2‐symmetric phenylalanine derivatives. In vitro and in vivo studies indicated that the L‐nanofibrils exhibit a greater propensity to promote M2‐macrophage polarization than D‐nanofibrils, thereby favoring osteogenesis. Then, m6A‐MeRIP sequencing revealed a unique chirality‐dependent m6A methylation level in macrophages, which was gated by a competitive pair of CCM3‐FAK through enantioselectively integrin recognition. L‐nanofibrils considerably suppressed WTAP‐mediated m6A methylation by promoting Itgα3‐FAK expression and paxillin‐driven mechanotransduction, whereas D‐nanofibrils induced WTAP‐mediated m6A methylation by favoring ItgαV‐CCM3 expression and suppressing mechanotransduction. Furthermore, the gain‐of‐function and loss‐of‐function experiments and RIP‐qPCR demonstrate that the WTAP expression could direct macrophage polarization via manipulating the functional molecule B7‐H3 (CD276). Thus, a mechano‐epigenetic mechanism of chirality‐mediated cell‐fate determination is unveiled, which holds remarkable promise in the realm of assisted regenerative material design. [ABSTRACT FROM AUTHOR]

To comprehend the significance of improved conductive properties in C2‐symmetric hydrogels, it is vital to investigate how non‐gelating achiral functional group isomers influence the conductivity of such supramolecular hydrogels, whereas understanding the major driving forces behind this regulatory process is first and foremost. Herein, we report a hydrogel system containing tryptophan‐conjugated NDI as the backbone (L/D‐NTrp), enabling effective supramolecular assembly with the bipyridyl functional group isomers. This co‐assembly behavior results in materials with exceptional mechanical properties and high conductivities, surpassing most previously reported C2‐symmetrical hydrogels, as well as the ability to form controlled morphologies. Notably, the co‐hydrogels displayed an eight‐fold increase in mechanical strength, making them more robust and resistant to deformation compared to the original gel. Additionally, all hydrogels exhibited favorable electrical conductivity, with the co‐assembled hydrogels showcasing notable performance, making them a promising candidate for use in electronic devices and sensors. This report lays the foundation for further investigation into the properties and potential applications of L/D‐NTrp compound in the range of fields, including drug delivery, tissue engineering, and electronics. [ABSTRACT FROM AUTHOR]

Cancer recurrence remains a major challenge after primary tumor excision, and the inflammation of tumor-caused wounds can hinder wound healing and potentially promote tumor growth. Herein, a chiral L-phenylalanine-based (LPFEG) supramolecular hydrogel system encapsulated with polydopamine nanoparticles (PDA-NPs) has been developed in order to prevent tumor relapse after surgery and promote wound repair. PDA-NPs allow for near-infrared (NIR) light-triggered photothermal therapy, especially, it can scavenge free radicals in the surgical wound. LPFEG can mimic native extracellular matrix (ECM) structure to create a chiral microenvironment that enhances fibroblast adhesion, proliferation, and new tissue regeneration. With anticancer drug doxorubicin (DOX) loaded into the composite hydrogel, the antitumor effect is significantly enhanced by the integration of chemo-photothermal therapy both in vitro and in vivo. The PDA-based chiral supramolecular composite hydrogel as an effective postoperative adjuvant possesses promising applicable prospects in inhibiting tumor recurrence and accelerating wound healing after operation. After primary tumor excision, cancer recurrence remains a severe concern, and the inflammation induced by tumor-related wounds can delay wound healing. Herein, we designed a chiral L-phenylalanine-based (LPFEG) supramolecular hydrogel platform that was co-assembled with polydopamine nanoparticles (PDA-NPs). Among them, PDA-NPs can offer photothermal therapy and scavenge free radicals in surgical wounds. LPFEG can create a chiral microenvironment that promotes fibroblast adhesion, proliferation, and new tissue regeneration. Furthermore, with anticancer drug doxorubicin (DOX) loaded into the composite hydrogel, the antitumor effect is considerably boosted. Therefore, the PDA-based chiral supramolecular hydrogel shows high application potential as a postoperative adjuvant in preventing tumor relapse as well as accelerating wound healing after surgery. [Display omitted] [ABSTRACT FROM AUTHOR]

Despite clinical applications of the first‐generation tissue adhesives and hemostats, the correlation among microstructure and hemostasis of hydrogels with wound healing is less understood and it is elusive to design high‐performance hydrogels to meet worldwide growing demands in wound closure, hemostasis, and healing. Inspired by the microstructure of extracellular matrix and mussel‐mimetic chemistry, two kinds of coordinated and covalent glycopolypeptide hydrogels are fabricated, which present tunable tissue adhesion strength (14.6–83.9 kPa) and microporous structure (8–18 µm), and lower hemolysis <1.5%. Remarkably, the microporous size mainly controls the hemostasis, and those hydrogels with larger pores of 16–18 µm achieve the fastest hemostasis of ≈14 s and the lowest blood loss of ≈6% than fibrin glue and others. Moreover, both biocompatibility and hemostasis affect wound healing performance, as assessed by hemolysis, cytotoxicity, subcutaneous implantation, and hemostasis and healing assays. Importantly, the glycopolypeptide hydrogel‐treated rat‐skin defect model achieves full wound closure and regenerates thick dermis and epidermis with some hair follicles on day 14. Consequently, this work not only establishes a versatile method for constructing glycopolypeptide hydrogels with tunable adhesion and microporous structure, fast hemostasis, and superior healing functions, but also discloses a useful rationale for designing high‐performance hemostatic and healing hydrogels. [ABSTRACT FROM AUTHOR]

Hydrogel as a carrier for drug delivery system has been developed, but it is hard to change the load and release of drugs through a simple way. Herein, the authors report a novel pH-sensitive supramolecular binary hydrogel based on Phe-Gly derivative gelator (LPPG) and 4,4′-dipyridine disulfide (DPDS). Fourier transform infrared spectroscopy, circular dichroism, and 1H NMR confirm that the driving force for the coassembly process is intermolecular hydrogen bonds. The composite hydrogel can improve the dye adsorption capacity relative to LPPG hydrogel. Moreover, the controllable absorption of the dyes is studied by varying the pH and concentration of dye solutions. LPPG-DPDS hydrogel can also release of entrapped dyes at physiological pH. The two-component hydrogel should be a promising system for controllable drug delivery. [ABSTRACT FROM AUTHOR]

Syneresis property limits the further application of Kappa-carrageenan (κ-CG) in cell culture scaffold. To address this problem, κ-CG hydrogel is tailored by blending with a C2-symmetric benzene-based supramolecular gelator (B2). Scanning electron microscope (SEM) and Fourier transform infrared (FT-IR) spectroscopy confirm the semi­interpenetrating (semi-IPN) structure of the blended hydrogels and their wettability or thermal stability is also found to be improved. Based on the reduced syneresis, the growth and proliferation of the cultured HCT 116 cells on the blended hydrogels is enhanced compared with pure κ-CG hydrogels. This study paves an easy and feasible way to achieve stable and biocompatible κ-CG/B2 blended hydrogels with high water retention and it helps broaden the promising applications of κ-CG hydrogels in tissue engineering. [ABSTRACT FROM AUTHOR]

In this paper, a new type of low molecular weight gelators (LMWGs), C2-symmetric benzene-based hydrogel (C2-BHG) with a 1,4-dimine benzene was self-assembled on glassy carbon electrode (GCE) and mica surface based on the hydrogen bond or hydrophobic interaction. Atomic force microscopy (AFM) characterization demonstrated the formation process of the C2-BHG hydrogel layer from particles to clusters, and finally to interconnected fiber network gel. The C2-BHG hydrogel layer resulted in the increase of the hydrophilicity of GCE surface. The C2-BHG modified GCEs (C2-BHG/GCE) with different assembly time were studied by cyclic voltammetry and electrochemical impedance spectroscopy in the presence of Fe(CN) 6 4−/3− redox probe. The rich amide and hydroxyl groups in the gel film make the C2-BHG/GCE suitable as ultrasensitive sensor for the detection of Cu(II) ions by stripping voltammetry with the limit of detection of 5×10 −10 g/L (S/N>3). Under the optimal conditions, the two linear ranges of Cu(II) ions were found to be 1×10 −9 ∼1×10 −7 g/L and 1×10 −7 ∼1×10 −4 g/L. The strong coordination interaction of C2-BHG with Cu(II) ions was confirmed by UV-Visible characterization. This new type of C2-BHG modified electrode was promising for highly sensitive Cu(II) ions sensor application due to high stability and excellent selectivity of the analytical signal. [ABSTRACT FROM AUTHOR]

In recent years, C 2 -symmetric supramolecular chiral gelators have emerged as a powerful tool for the construction of functional nanostructures to be applied in different fields. Myriad applications of these nanoscale architectures, in fields such as cell culture, dye adhesion and release, bacterial adhesion, tissue engineering, drug delivery, and chiroptical switches are being envisaged. This review attempts to present a succinct overview of the current state of research on functional nano-scale systems, the design, synthesis, and applications of self-assembled C 2 -symmetric supramolecular chiral gelators "engineered" to carry out precise functions, with an emphasis on the design on the basis of different cores for supramolecular self-assembly. This highlight gives a brief flavor of the development of C 2 -symmetric supramolecular chiral gelators broadly from the first decade of the 2000 s up to now. A particular theme is the emergence of C 2 -symmetric supramolecular chiral gels and increasing hi-tech niche application areas with respect to design and synthesis. Control and exploitation of design of C 2 -symmetric supramolecular chiral gels form a huge part of the grand challenge of directed assembly of extended structures with targeted properties and applications. [ABSTRACT FROM AUTHOR]

• A new method of selectively recognizing melamine and cyanuric acid by supramolecular interactions of gelation. • Chirality inversion and amplification was observed for LPF-co-CA and LPF-co-MA systems respectively. • Highly stable LPF-co-MA and LPF-co-CA gels were obtained in comparison to the LPF alone. Molecular recognition of achiral structural analogues, a remaining challenge for materials scientists and chemists, is the key to manipulating the applications and properties of supramolecular chiral materials. Herein, we report the molecular recognition of two harmful structural analogues i.e. melamine (MA) and cyanuric acid (CA) by using C 2 -symmetric phenylalanine chiral hydrogelators. Two distinct molecular recognition events between hydrogelator fibrils and triazine based achiral molecules are demonstrated: phenylalanine-co-melamine (PF-co-MA) gels showed chirality amplification while chirality inversion was observed for phenylalanine-co-cyanuric acid (PF-co-CA) gels. Moreover, viscoelastic properties and twist pitch were also regulated under the influence of the achiral molecules. Such phenomenon is mainly mediated by H-bonding among the two components, which may subtly change the arrangement of the molecules, in turn, the self-assembled nanostructures. This method of using C 2 -symmetric phenylalanine based gelators in the recognition of the achiral molecules may be broadly applicable for a wide variety of molecular recognition partners such as sugars. [ABSTRACT FROM AUTHOR]