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. Right-handed l-Phe fibers within hydrogel conduits maintain the stemness of rSC through enhanced stereoselective interaction between collagen IV and l-Phe fibers triggered by collagen IV-Integrin α1ß1, MAPK, and YAP/TAZ signaling pathways and finally activate the key regulator of SC reprogramming, the c-Jun pathway. In the rat model of a sciatic nerve defect, the l-Phe hydrogel nerve conduit significantly enhances nerve regeneration, exhibiting markedly improved histological, electrophysiological, and functional outcomes. The findings reveal the chirality-dependent regulation of SC reprogramming in a pioneering way, offering potential strategies for nerve regeneration therapies.

Enhancing Biocatalysis through Chiral Supramolecular Scaffolds: Insights into the Structural Adaptability of Lipase.

How to maintain high catalytic activity and stability in the process of biocatalysis is crucial, inspiring strategies to construct an appropriate catalytic microenvironment. Considering the lipase's inherent chirality and the necessity for a delicate hydrophilic-hydrophobic equilibrium, we crafted a chiral, nonaqueous catalytic microenvironment via the in situ coassembly of Boc-FLFL-NHNH2 (Bfl) and lipase. Benefiting from the chirality and distinct Bfl-lipase interactions, the lipase@Bfl supramolecular hybrid amplifies biological functionalities and can serve as a versatile and highly efficient catalyst. Kinetic investigations and molecular docking simulations uncover the strong lipase-substrate affinity and lipase-Bfl interactions, explaining the enhanced biological effects, catalytic activity, and stability. Our study establishes a suitable microenvironment to address the chirality and hydrophobicity during catalysis and highlights the potential of artificial chiral scaffolds and catalytic medium for enhancing lipase activity.

Supramolecular Polymer Co-Assembled Multifunctional Chiral Hybrid Hydrogels with Adhesive, Self-Healing and Antibacterial Properties.

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.

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 L/D-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. Biological assays and theoretical modeling reveal that these results are mainly attributed to strong adsorption of the key exosomes transporters (Ras-related protein Rab-27A and synaptosome-associated protein 23) on left-handed L-Phe @HA nanofibers via enhanced stereoselective interaction, leading to degradation and phosphorylated dropping of exosomes transporters. Subsequently, transfer function of exosomes transporters is limited, which causes remarkable inhibition of TDEs secretion. These findings provide a promising novel insight of chiral functional materials to establish an anti-tumor extracellular microenvironment via regulation of TDEs secretion.

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. In this study, supramolecular chiral hydrogels were constructed using L/d-phenylalanine (L/D-Phe) derivatives. The results of alkaline phosphatase expression analysis, alizarin red S assay, as well as quantitative real-time polymerase chain reaction and western blot analyses suggest that right-handed D-Phe hydrogel fibers significantly promoted osteogenic differentiation of hDPSCs. A rat model of calvarial defects was created to investigate the regulation of chiral nanofibers on the osteogenic differentiation of hDPSCs in vivo. The results of the animal experiment demonstrated that the D-Phe group exhibited greater and faster bone formation on hDPSCs. The results of RNA sequencing, vinculin immunofluorescence staining, a calcium fluorescence probe assay, and western blot analysis indicated that L-Phe significantly promoted adhesion of hDPSCs, while D-Phe nanofibers enhanced osteogenic differentiation of hDPSCs by facilitating calcium entry into cells and activate the MAPK pathway. These results of chirality-dependent osteogenic differentiation offer a novel therapeutic strategy for the treatment of CSDs by optimising the differentiation of hDPSCs into chiral nanofibers.

An Ultrasound-Triggered STING Pathway Nanoagonist for Enhanced Chemotherapy-Induced Immunogenic Cell Death.

Although chemotherapy has the potential to induce tumor immunotherapy via immunogenic cell death (ICD) effects, how to control the intensity of the immune responses still deserves further exploration. Herein, a controllable ultrasound (US)-triggered chemo-immunotherapy nanoagonist is successfully synthesized by utilizing the pH and reactive oxygen species (ROS) dual-responsive PEG-polyphenol to assemble sonosensitizer zinc oxide (ZnO) and doxorubicin (DOX). The PZnO@DOX nanoparticles have an intelligent disassembly to release DOX and zinc ions in acidic pH conditions. Notably, US irradiation generates ROS by sonodynamic therapy and accelerates the drug release process. Interestingly, after the PZnO@DOX+US treatment, the injured cells release double-stranded DNA (dsDNA) from the nucleus and mitochondria into the cytosol. Subsequently, both the dsDNA and zinc ions bind with cyclic GMP-AMP synthase and activate the stimulator of interferon genes (STING) pathway, resulting in the dendritic cell maturation, ultimately promoting DOX-induced ICD effects and antigen-specific T cell immunity. Therefore, chemotherapy-induced immune responses can be modulated by non-invasive control of US.

Multi-Omics Reveals the Genetic and Metabolomic Architecture of Chirality Directed Stem Cell Lineage Diversification.

Chirality-directed stem-cell-fate determination involves coordinated transcriptional and metabolomics programming that is only partially understood. Here, using high-throughput transcriptional-metabolic profiling and pipeline network analysis, the molecular architecture of chirality-guided mesenchymal stem cell lineage diversification is revealed. A total of 4769 genes and 250 metabolites are identified that are significantly biased by the biomimetic chiral extracellular microenvironment (ECM). Chirality-dependent energetic metabolism analysis has revealed that glycolysis is preferred during left-handed ECM-facilitated osteogenic differentiation, whereas oxidative phosphorylation is favored during right-handed ECM-promoted adipogenic differentiation. Stereo-specificity in the global metabolite landscape is also demonstrated, in which amino acids are enriched in left-handed ECM, while ether lipids and nucleotides are enriched in right-handed ECM. Furthermore, chirality-ordered transcriptomic-metabolic regulatory networks are established, which address the role of positive feedback loops between key genes and central metabolites in driving lineage diversification. The highly integrated genotype-phenotype picture of stereochemical selectivity would provide the fundamental principle of regenerative material design.

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. 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.

NDI based C2-symmetric Chiral Supramolecular Hydrogels Towards Enhanced Conductivity.

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.

3D Chiral Self-Assembling Matrixes for Regulating Polarization of Macrophages and Enhance Repair of Myocardial Infarction.

The regulation of inflammatory response at the site of injury and macrophage immunotherapy is critical for tissue repair. Chiral self-assemblies are one of the most ubiquitous life cues, which is closely related to biological functions, life processes, and even the pathogenesis of diseases. However, the role of supramolecular chiral self-assemblies in the regulation of immune functions in the internal environment of tissues has not been fully explored yet. Herein, 3D supramolecular chiral self-assembling matrixes are prepared to regulate the polarization of macrophages and further enhance the repair of myocardial infarction (MI). Experiments studies show that M-type (left-handed) self-assembling matrixes significantly inhibit inflammation and promote damaged myocardium repair by upregulating M2 macrophage polarization and downstream immune signaling compared with P-type (right-handed), and R-type (non-chirality) self-assembling matrixes. Classical molecular dynamics (MD) simulation demonstrates that M-type self-assembling matrixes display higher stereo-affinity to cellular binding, which enhances the clustering of mechanosensitive integrin ß1 (Itgß1) and activates focal adhesion kinase (FAK) and Rho-associated protein kinase (ROCK), as well as downstream PI3K/Akt1/mTOR signaling axes to promote M2 polarization. This study of designing a 3D chiral self-assembling matrixes microenvironment suitable for regulating the polarization of macrophages will provide devise basis for immunotherapy with biomimetic materials.

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. Variations in chiral structure can cause many abnormal physiological activities. To gain insight into the construction, structural transition, and related physiological functions of these complex helix in natural systems, it is necessary to fabricate artificial supramolecular assemblies with controllable helix orientation as research platform. This review discusses recent advances in chiral supramolecular assembly, including the precise construction and regulation of assembled chiral nanostructures with tunable chirality. Chiral structure-dependent biological activities, including cell proliferation, cell differentiation, antibacterial activity and tissue regeneration, are also discussed. This review not only contributes to further understanding of the importance of chirality in the physiological environment, but also plays an important role in the development of chiral biomedical materials for the treatment of diseases (e. g., tissue engineering regeneration, stem cell transplantation therapy).

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. Also, D-matrix promotes sciatic nerve repair effectively, both with or without non-neural stem cell implantation, by improving the population, function, and myelination of autologous Schwann cells. D-matrix chirality, as a simple, safe, and effective microenvironment cue to specifically and universally manipulate neural cell behaviors, holds extensive application potential in addressing neurological issues such as nerve regeneration, neurodegenerative disease treatment, neural tumor targeting, and neurodevelopment.

Molecular Polarizability Regulated Piezoelectricity of Organic Materials from Single-Molecular Level.

Although molecular piezoelectric materials are ideal constituents for next-generation electronic microdevices, their weak piezoelectric coefficients which restrict their practical applications need to be enhanced by some strategies. Herein, a series of d-phenylalanine derivatives are synthesized and an increased molecular piezoelectric coefficient of their assemblies is achieved by acid doping. The acid doping can increase the asymmetric distribution of charges in the molecules and in turn molecular polarizability, leading to the enhanced molecular piezoelectricity of assemblies. The effective piezoelectric coefficients can be promoted up to 38.5 pm V-1 and four times those without doping, which is also higher than those obtained by the reported methods. Moreover, the piezoelectric energy harvesters can generate voltage up to 3.4 V and current up to 80 nA. This practical strategy can enhance piezoelectric coefficients without varying the crystal structures of the assemblies, which may inspire future molecular design of organic functional materials.

Mxene-Based Supramolecular Composite Hydrogels for Antioxidant and Photothermal Antibacterial Activities.

Bacterial infections and oxidative damage caused by various reactive oxygen species (ROS) pose a significant threat to human health. It is highly desirable to find an ideal biomaterial system with broad spectrum antibacterial and antioxidant capabilities. A new supramolecular antibacterial and antioxidant composite hydrogel made of chiral L-phenylalanine-derivative (LPFEG) as matrix and Mxene (Ti3 C2 Tx ) as filler material is presented. The noncovalent interactions (H-bonding and π-π interactions) in between LPFEG and Mxene and the inversion of LPFEG chirality are verified by Fourier transform infrared and circular dichroism spectroscopy. The composite hydrogels show improved mechanical properties revealed by rheological analysis. The composite hydrogel system exhibits photothermal conversion efficiency (40.79%), which enables effective photothermal broad-spectrum antibacterial activities against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria. Furthermore, the Mxene also enables the composite hydrogel to exhibit excellent antioxidant activity by efficiently scavenging free radicals like DPPH•, ABTS•+, and •OH. These results indicate that the Mxene-based chiral supramolecular composite hydrogel, with improved rheological, antibacterial, and antioxidant properties has a great potential for biomedical applications.

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). The amide and hydroxy group of naphthalene derivatives prefer to bind with the carboxy group of LPPF, while carboxylic groups and fluoride atoms tend to bind with the amide moiety of LPPF. All these diverse interaction modes can precisely trigger helicity inversion of LPPF nanofibers. In addition, synergistically manipulating the carboxy and amide binding sites from a single LPPF molecule to simultaneously interact with different naphthalene derivatives leads to chirality regulation. Typically, varying the solvent may switch the interaction modes and the switched new interaction modes can be employed to further regulate the chirality of the LPPF nanofibers. This study may provide a novel approach to explore chirality diversity in artificial systems by regulating the intermolecular binding sites.

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. This chiral gel possesses abundant chiral and cationic sites, not only effectively reducing AGEs via stereoselective interaction but also specifically killing multidrug resistant bacteria rather than host cells since cationic hexapeptides selectively interact with negatively charged microbial membrane. Surprisingly, the HA-LM2-RMR fibers present an attractive ability to activate sprouted angiogenesis of Human Umbilical Vein Endothelial Cells by upregulating VEGF and OPA1 expression. In comparison with clinical Prontosan Wound Gel, the HA-LM2-RMR gel presents superior healing efficiency in the infected diabetic wound with respect to angiogenesis and re-epithelialization, shortening the healing period from 21 days to 14 days. These findings for chiral wound dressing provide insights for the design and construction of diabetic wound dressings that target revascularization, which holds great potential to be utilized in tissue regenerative medicine.

Aniline dimers serving as stable and efficient transfer units for intermolecular charge-carrier transmission.

Because any perturbation in the number of oxidation sites associated with the polymeric backbone can cause changes in the electrical properties, the stability of electrical properties has strongly prevented the wide adoption of most conducting polymers for commercialization, e.g., polyanilines (PANI). Herein, we showed that aniline dimers (AD) had more stable conductivity during redox due to their determinately separate oxidization or reduction units. Instead of intramolecular charge transfer as PANI, AD could serve as effective transfer units to facilitate intermolecular charge-carrier transmission due to low band-gap formation induced by the J-aggregation of AD, ensuring efficient conductivity. Typically, the electrical properties of AD-derived materials will still be stable after 10,000 redox cycles under a high operating voltage, far surpassing PANI under equivalent conditions. Meanwhile, the AD-derived materials could act as effective conducting and sensing layers with good stability. This approach opened an avenue for improving the stability of conductive polymers.

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 H2 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. Assemblies in ethanol and H2 O exhibit opposite conformations and circular dichroism (CD) signals even though they are constructed from the same molecules. Thus, the morphology-dependent cell adhesion and proliferation behaviors are further characterized. Left-handed nanofibers are found to be more favorable for cell adhesion than right-handed nanostructures. Quantitative AFM analysis showed that the L929 cell adhesion force on left-handed LPFM fibers is much higher than that on structures with inversed handedness. Moreover, the value of cell Young's modulus is lower for left-handed nanofibrous films, which indicates better flexibility. The difference in cell-substrate interactions might lead to different effects on cell behavior.

Chiral fiber supramolecular hydrogels for tissue engineering.

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.

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. 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. STATEMENT OF SIGNIFICANCE: 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.