Chirality Evolution of Supramolecular Helices by Electron Transfer Assisted Secondary Nucleation.

Chirality evolution is ubiquitous and important in nature, but achieving it in artificial systems is still challenging. Herein, the chirality evolution of supramolecular helices based on l-phenylalanine derivative (LPF) and naphthylamide derivate (NDIAPY) is achieved by the strategy of electron transfer (ET) assisted secondary nucleation. ET from LPF to NDIAPY can be triggered by 5 s UV irradiation on left-handed LPF-NDIAPY co-assemblies, leading to NDIAPY radical anions and partial disassembly of the helices.

Simultaneous Fabrication of P and M Helices in One-Component Chiral System by Methanol-Water Mediated Dual Assembly Pathway.

The synergetic evolution of multiple chiral structures stemmed from same building units is ubiquitous in nature and vital to living systems, but achieving it in artificial systems remains a challenge. Herein, we report a methanol-water mediated dual assembly pathway strategy for simultaneous construction of P and M helices in one-component chiral system. The conformation of l-phenylaniline derivates (LBpyF) is controlled to folded state in CHOH due to the hydrogen bonds as well as C-H⋅⋅⋅π interaction between LBpyF and CHOH.

Bilayer Scaffolds Synergize Immunomodulation and Rejuvenation via Layer-Specific Release of CK2.1 and the "Exercise Hormone" Lac-Phe for Enhanced Osteochondral Regeneration.

Repairing osteochondral defects necessitates the intricate reestablishment of the microenvironment. The cartilage layer consists of a porous gelatin methacryloyl hydrogel (PGelMA) covalently crosslinked with the chondroinductive peptide CK2.1 via a "linker" acrylate-PEG-N-hydroxysuccinimide (AC-PEG-NHS).

Chiral Hydrogel Nerve Conduit Boosts Peripheral Nerve Regeneration via Regulation of Schwann Cell Reprogramming.

The Schwann cell (SC) is essential in peripheral nerve regeneration by reprogramming into a stem-like "repair Schwann cell" (rSC) phenotype; however, maintaining the rSC stemness remains an unmet challenge. Chirality is a fundamental factor controlling cell fate, and its potential role in regulation of SC reprogramming has long been ignored and remains poorly understood. Herein, inspired by natural chiral components in the SC microenvironment, chiral hydrogel nerve conduits are prepared by supramolecular assembly of l/d-phenylalanine derivatives (l/d-Phe) in polymeric chitosan-gelatin conduits.

Chiral Supramolecular Nanofibers Regulated Tumor-Derived Exosomes Secretion for Constructing an Anti-Tumor Extracellular Microenvironment.

Tumor-derived exosomes (TDEs) induced extracellular microenvironment has recently been validated to be critical for tumor progression and metastasis, however, remodeling it for oncotherapy still remains a major challenge due to difficulty in regulation of TDEs secretion. Herein, the supramolecular chiral nanofibers, composed of -phenylalanine derivates (L/D-Phe) and linear hyaluronic acid (HA), are successfully employed to construct TDEs induced anti-tumor extracellular microenvironment. The left-handed L-Phe @HA nanofibers significantly inhibit TDEs secretion into extracellular microenvironment, which results in suppression of tumor proliferation and metastasis in vitro and vivo.

Amino acid-based supramolecular chiral hydrogels promote osteogenesis of human dental pulp stem cells via the MAPK pathway.

Critical-size defects (CSDs) of the craniofacial bones cause aesthetic and functional complications that seriously impact the quality of life. The transplantation of human dental pulp stem cells (hDPSCs) is a promising strategy for bone tissue engineering. Chirality is commonly observed in natural biomolecules, yet its effect on stem cell differentiation is seldom studied, and little is known about the underlying mechanism.

Chiral Supramolecular Hydrogel Enhanced Transdermal Delivery of Sodium Aescinate to Modulate M1 Macrophage Polarization Against Lymphedema.

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.

Chiral Supramolecular Assemblies: Controllable Construction and Biological Activity.

Chiral supramolecular assemblies with helical structures (e. g., proteins with α-helix, DNA with double helix, collagen with triple-helix) as the central structure motifs in biological systems play a crucial role in various physiological activities of living organisms.

Unique Chirality Selection in Neural Cells for D-Matrix Enabling Specific Manipulation of Cell Behaviors.

Manipulating neural cell behaviors is a critical issue to various therapies for neurological diseases and damages, where matrix chirality has long been overlooked despite the proven adhesion and proliferation improvement of multiple non-neural cells by L-matrixes. Here, it is reported that the D-matrix chirality specifically enhances cell density, viability, proliferation, and survival in four different types of neural cells, contrasting its inhibition in non-neural cells. This universal impact on neural cells is defined as "chirality selection for D-matrix" and is achieved through the activation of JNK and p38/MAPK signaling pathways by the cellular tension relaxation resulting from the weak interaction between D-matrix and cytoskeleton proteins, particularly actin.

Realizing Abundant Chirality Inversion of Supramolecular Nanohelices by Multiply Manipulating the Binding Sites in Molecular Blocks.

The induction of diverse chirality regulation in nature by multiple binding sites of biomolecules is ubiquitous and plays an essential role in determining the biofunction of biosystems. However, mimicking this biological phenomenon and understanding at a molecular level its mechanism with the multiple binding sites by establishing an artificial system still remains a challenge. Herein, abundant chirality inversion is achieved by precisely and multiply manipulating the co-assembled binding sites of phenylalanine derivatives (D/LPPF) with different naphthalene derivatives (NA, NC, NP, NF).

Infected Diabetic Wound Regeneration Using Peptide-Modified Chiral Dressing to Target Revascularization.

Revascularization plays a critical role in the healing of diabetic wounds. Accumulation of advanced glycation end products (AGEs) and refractory multidrug resistant bacterial infection are the two major barriers to revascularization, directly leading to impaired healing of diabetic wounds. Here, an artfully designed chiral gel dressing is fabricated (named as HA-LM2-RMR), which consists of l-phenylalanine and cationic hexapeptide coassembled helical nanofibers cross-linked with hyaluronic acid via hydrogen bonding.

Assembly of Helical Nanostructures: Solvent-Induced Morphology Transition and Its Effect on Cell Adhesion.

Being able to precisely manipulate both the morphology and chiroptical signals of supramolecular assemblies will help to better understand the natural biological self-assembly mechanism. Two simple l/d-phenylalanine-based derivatives (L/DPFM) have been designed, and their solvent-dependent morphology evolutions are illustrated. It was found that, as the content of H O in aqueous ethanol solutions was increased, LPFM self-assembles first into right-handed nanofibers, then flat fibrous structures, and finally inversed left-handed nanofibers.

Kinetic Co-assembly Pathway Induced Chirality Inversion Along with Morphology Transition.

Kinetic co-assembly pathway induced chirality inversion along with morphology transition is of importance to understand biological processes, but still remains a challenge to realize in artificial systems. Herein, helical nanofibers consisting of phenylalanine-based enantiomers (L/DPF) successfully transform into kinetically trapped architectures with opposite helicity through a kinetic co-assembly pathway. By contrast, the co-assemblies obtained by a thermodynamic pathway exhibit non-helical structures.

Polydopamine-doped supramolecular chiral hydrogels for postoperative tumor recurrence inhibition and simultaneously enhanced wound repair.

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.

Chiral Hydrogel Accelerates Re-Epithelization in Chronic Wounds via Mechanoregulation.

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.

A chiral microenvironment promotes retinal progenitor cell proliferation by activating the Akt and ERK pathways.

Retinal progenitor cell (RPC) transplantation has been proposed as a potential strategy for the treatment of retinal degeneration, which is a leading cause of vision loss. However, a major obstacle is the poor proliferation of RPCs. Accumulating evidence suggests that the chiral features of the extracellular microenvironment are closely related to cell proliferation.

Inversion of Supramolecular Chirality by In Situ Hydrolyzation of Achiral Diethylene Glycol Motifs.

Chiral inversion of supramolecular assemblies is of great research interest due to its broad practical applications. However, chiral structure transition induced by in situ regulation of building molecules has remained a challenge. Herein, left-handed fibrous assemblies were constructed by -symmetic lphenylalanine coupled with diethylene glycol (LPFEG) molecules.

Use of Electrospun Phenylalanine/Poly-ε-Caprolactone Chiral Hybrid Scaffolds to Promote Endothelial Remodeling.

The fabrication of tissue-engineered vascular grafts to replace damaged vessels is a promising therapy for cardiovascular diseases. Endothelial remodeling in the lumen of TEVGs is critical for successful revascularization. However, the construction of well-functioning TEVGs remains a fundamental challenge.

Three-Dimensional Chiral Supramolecular Microenvironment Strategy for Enhanced Biocatalysis.

How the three-dimensional (3D) chiral environment affects the biocatalysis remains an important issue, thereby inspiring the development of a microenvironment that highly mimics the natural features of enzyme to guarantee enhanced biocatalysis. In this study, two gelators bearing d/l-phenylalanine as chiral centers are designed to construct the 3D chiral catalytic microenvironment for enhancing the biocatalysis of lipase. Such a microenvironment is programmed through chiral transmission of chirality from molecular chirality to achiral polymers.

Rational Fabrication of Multiple Dimensional Assemblies from Tryptophan-Based Racemate.

Fabricating structural complex assemblies from simple amino acid-based derivatives is attracting great research interests due to their easy accessibility and preparation. However, the morphological regulation of racemates (an equimolar mixture of enantiomers) were largely overlooked. In this work, through rational modulation of kinetic and thermodynamic parameters, we achieved multiple dimensional architectures employing tryptophan-based racemate (RPWM).

Induction of Chirality in Supramolecular Coassemblies Built from Achiral Precursors.

The emergence, transference, amplification, and memory of chiroptical activity in supramolecular assemblies, including circularly polarized absorbance and circularly polarized luminescence, remain significant challenges. Herein, an achiral pyridine-substituted coumarin derivative and chiral additives can coassemble into helical nanostructures with fine chiroptical activity via subtle hydrogen-bonding interactions. The resulting supramolecular assemblies remain optically active even after the removal of chiral additives, demonstrating supramolecular chirality can be remembered in the assemblies.

Effect of Stereochemistry on Chirality and Gelation Properties of Supramolecular Self-Assemblies.

Although chiral nanostructures have been fabricated at various structural levels, the transfer and amplification of chirality from molecules to supramolecular self-assemblies are still puzzling, especially for heterochiral molecules. Herein, four series of C -symmetrical dipeptide-based derivatives bearing various amino acid sequences and different chiralities are designed and synthesized. The transcription and amplification of molecular chirality to supramolecular assemblies are achieved.

Redox-Driven Helix Reversal of Graphene-Based Hydrogels.

Controlling the handedness of dynamic helical nanostructures of supramolecular assemblies by external stimuli is of great fundamental significance with appealing morphology-dependent applications. Significantly, access to chirality transformation of dynamic multistimuli-responsive systems can provide channels for real-time monitoring of the transfer processes in biological systems. However, efforts to achieve helix inversion in an all-gel-state and to comprehend the phenomena at a molecular scale are scarce.

Solvent-Controlled Topological Evolution from Nanospheres to Superhelices.

Supramolecular assemblies with diverse morphologies are crucial in determining their biochemical or physical properties. However, the topological evolution and self-assembly intermediates as well as the mechanism remain elusive. Herein, a dynamic morphological evolution from solid nanospheres to superhelical nanofibers is revealed via self-assembly of a minimal l-tryptophan-based derivative (LPWM) with various mixed solvent combinations, including the formation of solid nanospheres, the fusion of nanospheres into pearling necklace, the disintegration of necklace into short nanofibers, the distortion of nanofibers into nanotwists, and the entanglement of nanotwists into superhelices.