Hydrogel System Research Articles

Biochemical Signal-Induced Supramolecular Hydrogelation for Structured Free-Standing Soft Material Formation.

Cells coordinate their activity and regulate biological processes in response to chemical signals. Mimicking natural processes, control over the formation of artificial supramolecular materials is of high interest for their application in biology and medicine. Supramolecular material that can form in response to chemical signals is important for the development of autonomously responsive materials. Herein, a supramolecular hydrogel system is reported enabling in situ generation of hydrogelators in response to a specific chemical signal. Using self-immolative chemistry, spatial control over the formation of supramolecular hydrogel material and structured free-standing hydrogel objects via providing H2O2 locally is demonstrated. In addition, a hybrid system is developed enabling in situ generation of the H2O2 by the action of an enzyme and glucose, providing an extra handle for the development of an intelligent soft material. This generic design should enable the use of various (chemical)stimuli that can be obtained via coupling different stimuli and various chemical and/or biological markers and appears a versatile approach for the design of smart artificial soft materials that can find application in theranostic purposes.

Polydopamine-modified MXene-integrated photothermal responsive hydrogel for constructing rapid photothermal and self-sensing gradi- ent hydrogel actuators

Abstract PNIPAm-based stimuli-responsive hydrogel actuators have made significant progress. By introducing responsive modules such as photothermal nanoparticles, the hydrogel can respond to environmental changes and construct anisotropic structures, allowing the hydrogel actuators to quickly bend and realize complex shape deformation. How-ever, there remains a need to enhance the mechanical properties of these hydrogels to accommodate multiple deformation actions and different application scenarios, and enhance the compatibility between nanoparticles and the hydrogels to improve the comprehensive performance of materials are still issues that need to be solved. In this study, we modified two-dimensional MXene nanosheets with polydopamine (PDA) to obtain P-MXene, which served as a photothermal agent and can be stably dispersed within the hydrogel system. We copolymerized thermosensitive N-isopropylacrylamide (NIPAm) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) in situ and used a direct current (DC) electric field to induce a concentration gradient distribution of P-MXene nanosheets within the hydrogel, resulting in the preparation of anisotropic gradient hydrogel actuators with good stretchability and conductivity. The hydrogel structure was characterized using scanning electron microscopy (SEM) and the Fourier transform infrared (FTIR) spectra. The swelling properties, mechani-cal properties and conductivity of the hydrogel were studied. The actuation behavior of P(NIPAm-DMAEMA)/P-MXene gradient hydrogel actuators under different thickness and electric field intensity was investigated. Additionally, the sensitivity and stability of the conductive hydrogel actuators were tested. and the functions of monitoring human health and information transmission were realized. It integrated with rapid photo responsiveness and self-sensing capabilities to monitor the defor-mation process of the actuators through real-time relative resistance changes during the actuations. This work is expected to expand the application field of soft hydrogel actuators and provide new insights into the design of a new generation of soft robots.

Minimally Invasive Syringe-Injectable Hydrogel with Angiogenic Factors for Ischemic Stroke Treatment.

Ischemic stroke (IS) accounts for most stroke incidents and causes intractable damage to brain tissue. This condition manifests as diverse aftereffects, such as motor impairment, emotional disturbances, and dementia. However, a fundamental approach to curing IS remains unclear. This study proposes a novel approach for treating IS by employing minimally invasive and injectable jammed gelatin-norbornene nanofibrous hydrogels (GNF) infused with growth factors (GFs). The developed GNF/GF hydrogels are administered to the motor cortex of a rat IS model to evaluate their therapeutic effects on IS-induced motor dysfunction. GNFs mimic a natural fibrous extracellular matrix architecture and can be precisely injected into a targeted brain area. The syringe-injectable jammed nanofibrous hydrogel system increased angiogenesis, inflammation, and sensorimotor function in the IS-affected brain. For clinical applications, the biocompatible GNF hydrogel has the potential to efficiently load disease-specific drugs, enabling targeted therapy for treating a wide range of neurological diseases.

Photochemical Patterning and Characterization of Mechanical Properties on Soft Materials

AbstractAlthough different chemistries for the spatio‐temporal localization of molecules and gradients of chemical signals within soft materials are now available, the achievement of spatio‐temporal patterns of mechanical properties in such materials and their characterization remain considerable challenges. This study presents the syntheses of two novel photo‐sensitive and thermoresponsive hydrogel systems, a photo‐stiffening and a photo‐softening hydrogel. Their potential for fabricating soft materials with patterned mechanical properties is then demonstrated by fabricating an actuator whose higher‐order bending properties can be switched on with light, and by encoding mechanical properties for digital information encryption and storage. Microindentation and a custom‐made data analysis software are essential for the characterization of all the materials. From a general perspective, this work opens a route to the fabrication of soft materials with patterned mechanical properties, addressing an important emerging challenge in soft materials science with applications in soft robotics and information encryption and storage.

A drug-loaded nano chitosan/hyaluronic acid hydrogel system as a cartilage tissue engineering scaffold for drug delivery

Cartilage lesions, especially osteoarthritis (OA), usually arise from aging, trauma, or obesity and require medical intervention due to the damaged site's inflammation and the cartilage tissue's poor self-healing capacity. This study aimed to prepare a drug-loaded nanoparticle hydrogel system with anti-inflammatory and chondroprotective effects to treat OA. First, hyaluronic acid (HA) was oxidized to create aldehyde functional groups and then cross-linked with adipic acid dihydrazide (ADH) to form a hydrogel. Next, chitosan nanoparticles (CS NPs) loaded with an anti-inflammatory molecule (fisetin) and or a chondrogenic and chondroprotective agent (kartogenin) were incorporated into the hyaluronan hydrogel to improve the release profile of the drug and increase its retention time in the joint cavity. Incorporating drug-loaded NPs into the hyaluronan hydrogel provided the hydrogel with controlled release features and improved properties. In addition, the real-time PCR (Polymerase chain reaction) results showed that the hyaluronan hydrogel containing both drug-loaded NPs performed better than either constituent alone on an in vitro model of OA. Finally, based on the results of in vitro evaluation, this drug-loaded nanoparticle hydrogel system can be a promising technique for treating OA by rapidly suppressing inflammation and supporting cartilage regeneration and requires further investigation in an animal model of OA. Meanwhile, this study investigated, for the first time, the effect of the simultaneous use of fisetin and kartogenin together with a nano CS/HA hydrogel system to treat OA.

Engineered biomimetic nanovesicles-laden multifunctional hydrogel enhances targeted therapy of diabetic wound

Angiogenesis is essential for diabetic wound healing. Endothelial progenitor cell-derived extracellular vesicles (EPC-EVs) are known to promote wound healing by enhancing angiogenesis, while the low yield and lack of effective targeting strategies limit their therapeutic efficacy. Here, the biomimetic nanovesicles (NVs) prepared from EPC (EPC-NV) through an extrusion approach were reported, which functioned as EV mimetics to deliver contents from EPC to the wound. Besides, the cRGD peptide was coupled to the surface of EPC-NV (mEPC-NV) to achieve active endothelial cells (ECs)-targeting. Furthermore, we developed a dual hydrogel network by combining Fe3+@ Protocatechualdehyde (PA) complex-modified Acellular Dermal Matrix (ADM) with light-cured gelatin (GelMA), to enrich and sustainably release mEPC-NV. The hydrogel system with antioxidant and antibacterial properties also made up for the deficiency of mEPC-NV, reducing reactive oxygen species (ROS) and inhibiting infection in diabetic wound. Taken together, this study established a novel bioactive delivery system with angiogenesis, antioxidant and antibacterial activities, which might be a promising strategy for the treatment of diabetic wound.

Injectable hyaluronate-based hydrogel with a dynamic/covalent dual-crosslinked architecture for bone tissue engineering: Enhancing osteogenesis and immune regulation

In orthopedic practice, accommodating irregular defects caused by trauma or surgery with traditional preformed bone graft substitutes is often challenging. As a result, injectable hydrogels with seed cells have garnered significant interest in bone repair due to their adaptability and minimally invasive properties. However, they cannot simultaneously achieve injectability and mechanical properties, providing a biophysical and biochemical environment for cell support. In this study, a novel injectable hydrogel system (OA hydrogel) loaded with aspirin and bone mesenchymal stem cells (BMSCs) was developed to enhance osteogenesis and immune regulation in small irregular bone defects. OA hydrogels possessed self-healing and shear-thinning properties due to dynamic/covalent hydrazone bonds between aldehyde-modified hyaluronic acid methacrylate (ADH-HAMA) and oxidized hyaluronic acid (OHA). By photopolymerization of the enclosed HAMA, the OADC hydrogel was further reinforced, making it more suitable for cell proliferation. In vitro, composite hydrogels improved the osteogenic differentiation of BMSCs. Additionally, it promoted the M2 polarization of human monocytic leukemia (THP-1) cells. In vivo, the synergistic effect of acetylsalicylic acid (ASA) and BMSCs encapsulated within the OADC hydrogel promoted new bone formation in rat calvaria through increased recruitment and polarization of M2 macrophages. These findings underscore the significant promise of hydrogels for bone tissue engineering applications.

Folic Acid - Based Hydrogels Co-assembled with Protocatechuic Acid for Enhanced Treatment of Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) presents a significant therapeutic challenge due to the need for oral drug delivery systems that withstand acidic environment of stomach while effectively targeting intestinal inflammation. To address this issue, we created a novel hydrogel system based on a folic acid (FA)-dopamine (DA) conjugate, co-assembled with protocatechuic acid (PCA), to form F-DP hydrogels. These hydrogels demonstrated robust anti-gastric acid, mucosal adhesive, and injectable properties, enhancing their efficacy for targeted delivery. In DSS-induced colitis mouse models, treatment with F-DP hydrogels resulted in significant therapeutic improvements, including increased body weight, reduced disease activity index (DAI), and maintained colon length. Biochemical assays revealed that F-DP hydrogels significantly enhanced antioxidant enzyme activities (GSH and SOD) and reduced oxidative stress markers (NO and MDA). Histological assessments confirmed effective repair of the colonic mucosal barrier, restoration of tight junction protein ZO-1, and reduction of inflammatory lesions. Furthermore, immunofluorescence staining indicated that F-DP hydrogels facilitated macrophages polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, thereby reducing inflammation and promoting tissue repair. Our study demonstrates that F-DP hydrogels show significant potential for improving IBD treatment through enhanced gastric resistance, intestinal adhesion, and synergistic anti-inflammatory effects, warranting further investigation for clinical applications.

An adaptive bionic sensor: enhancing ankle joint tracking with high sensitivity and superior cushioning performance

Flexible sensors are renowned for their rapid responsiveness, high flexibility, and outstanding mechanical properties, making them ideal for applications in wearable devices, sports and health monitoring, and human-machine interfaces. To enhance the sensing performance of these flexible sensors, researchers have drawn inspiration from nature, creating various bionic microstructures. However, these structures often manifest in the macroscopic form of thin films, which do little to improve impact resistance and joint protection. In response, this work achieves a highly sensitive and impact-resistant pressure sensor by integrating bionic principles at both micro and macro levels. Specifically, at the micro level, a muscle-like hydrogel system consisting of MXene nanosheets incorporated into the double network of polyvinyl alcohol and sodium alginate matrix is selected. At the macro level, the bionic prototypes of mimosa leaves and durian spikes with good energy absorption structure, together with octopus’ sucker with good adsorption capacity are selected, and the synergistic construction of the three structures is realized through 3D printing methods. The obtained sensor has an appropriate response range, sensitivity and stability. More importantly, the displacement deformation of the hydrogel can be reduced by 91.22%, while its adhesion strength can be increased by 57.5% compared to the unstructured hydrogel. As a proof-of-concept, the proposed bionic flexible sensor can be used to monitor the motion status of the human ankle joint in real-time, thereby assisting users in making real-time judgments on gait health.

Losartan-based nanocomposite hydrogel overcomes chemo-immunotherapy resistance by remodeling tumor mechanical microenvironment

Preclinical studies demonstrating high cure rates with PD1/PD-L1 combinations have led to numerous clinical trials, but emerging results are disappointing. These combined immunotherapies are commonly employed for patients with refractory tumors following prior treatment with cytotoxic agents. Here, we uncovered that the post-chemotherapy tumor presents a unique mechanical microenvironment characterized by an altered extracellular matrix (ECM) elasticity and increased stiffness, which facilitate the development of aggressive tumor phenotypes and confer resistance to checkpoint blocking therapy. As thus, we rationally designed an in situ nanocomposite hydrogel system, LOS&FeOX@Gel, which enabled effective and specific delivery of the therapeutic payloads (losartan [LOS] and oxaliplatin [OX]) into tumor. We demonstrate that sustained release of LOS effectively remodels the tumor mechanical microenvironment (TMM) by reducing ECM deposition and its associated “solid stress”, thereby augmenting the efficacy of OX and its immunological effects. Importantly, this hydrogel system greatly sensitized post-chemotherapy tumor to checkpoint blocking therapy, showing synergistic therapeutic effects against cancer metastasis. Our study provides mechanistic insights and preclinical rationale for modulating TMM as a potential neoadjuvant regimen for tumor to optimize the benefits of chemo-immunotherapy, which lays the groundwork for leveraging “mechanical-immunoengineering” strategies to combat refractory tumors.Graphical

Exos-Loaded Gox-Modified Smart-Response Self-Healing Hydrogel Improves the Microenvironment and Promotes Wound Healing in Diabetic Wounds.

Wound management has always been a challenge in the clinical treatment of diabetes. In this study, glucose oxidase (GOx) is grafted onto natural pullulan polysaccharides, and oxidization is carried out to form a self-healing hydrogel using carboxymethyl chitosan by means of reversible Schiff base covalent bonding. The smart-response drug release properties of this natural self-healing hydrogel are demonstrated in diabetic wounds by taking advantage of two key factors, namely the pH-responsive nature of Schiff base bonding and the fact that GOx reduces the pH in diabetic wounds. To further enhance the biological functions of the hydrogel dressing, exosomes (Exos) are introduced into the hydrogel system. The GOx present in the hydrogel system improves the high-glucose microenvironment of diabetic wounds, releasing H2O2 to impart antimicrobial effects, and ensuring that the hydrogel realizes a smart-response function. The carboxymethyl chitosan component used to construct the hydrogel plays an effective antibacterial role. Moreover, the Exos loaded into the hydrogel effectively promotes neovascularization of the wound. The Exos also regulates macrophage polarization and reduces the levels of persistent inflammation in diabetic wounds. These results suggest that this smart responsive, multifunctional, and self-healing hydrogel dressing is ideal for the management of diabetic wounds.

Chitosan-based self-healing thermosensitive hydrogel loaded with siHMGB1 for treatment of rheumatoid arthritis via macrophage repolarization.

Rheumatoid arthritis (RA) is a prevalent autoimmune disease marked by immune cell activation, particularly macrophages. An imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages causes synovial inflammation and joint damage, worsening RA. This study presents a biomacromolecular hydrogel delivery system with apoferritin nanoparticles for effective delivery of small interfering high mobility group protein (siHMGB1). The system was designed to promote the polarization of M1 macrophages to the M2 phenotype by downregulating the HMGB1/TLR4/NF-κB-p65 signaling pathway, offering a potential therapeutic approach for the treatment of RA. The oxidized chondroitin sulfate - chitosan - sodium glycerol β - phosphate - Fn/siHMGB1 (OCF/siHMGB1) hydrogel system possessed temperature-sensitive and self-healing properties, enabling the sustained, stable, and efficient release of siHMGB1 at the affected joint. After effective uptake by macrophages, siHMGB1 could effectively repolarize M1-phenotype macrophages to M2-phenotype via the HMGB1/TLR4/NF-κB-p65 signaling pathway both in vitro and in vivo. Additionally, it suppressed the release of pro-inflammatory cytokines and upregulated anti-inflammatory cytokines, which significantly blocked the TLR4/p65-mediated inflammatory signaling. In conclusion, the siHMGB1-loaded hydrogel delivery system designed in this study is effective in treating RA and highlights the potential of gene therapy to induce repolarization of M1 to M2 macrophages for RA treatment.

Wearable Multifunctional Hydrogel for Oral Microenvironment Visualized Sensing Coupled with Sonodynamic Bacterial Elimination and Tooth Whitening.

Bacterial-driven dental caries and tooth discoloration are growing concerns as the most common oral health problems. Current diagnostic methods and treatment strategies hardly allow simultaneous early detection and non-invasive treatment of these oral diseases. Herein, a wearable multifunctional double network hydrogel combined with polyaniline and barium titanate (PANI@BTO) nanoparticles is developed for oral microenvironment visualized sensing and sonodynamic therapy. Due to the colorimetric properties of polyaniline, the hydrogel displays a highly sensitive and selective response for visualized sensing of oral acidic microenvironment. Meanwhile, the barium titanate in the hydrogel efficiently generates reactive oxygen species (ROS) under ultrasound irradiation, realizing non-invasive treatment in the oral cavity. Through bacterial elimination experiments and tooth whitening studies, the hydrogel can achieve the dual effect of effectively inhibiting the growth of cariogenic bacteria and degrading tooth surface pigments. Owing to the visualized sensing of the oral acidic microenvironment and efficient sonodynamic therapy function, the proposed hydrogel system offers a solution for the prevention of caries and tooth whitening, which is promising in developing the biomedical system targeting the simultaneous sensing and therapy for oral diseases.

The Role of Pectin Hydrogel Systems Plus Iodine and Phyto Extract in Second-Degree Burn in Rats

The Role of Pectin Hydrogel Systems Plus Iodine and Phyto Extract in Second-Degree Burn in Rats

Tailoring smart hydrogels through manipulation of heterogeneous subdomains

The mechanical interactions among integrated cellular structures in soft tissues dictate the mechanical behaviors and morphogenetic deformations observed in living organisms. However, replicating these multifaceted attributes in synthetic soft materials remains a challenge. In this work, we develop a smart hydrogel system featuring engineered stiff cellular patterns that induce strain-driven heterogeneous subdomains within the hydrogel film. These subdomains arise from the distinct mechanical responses of the pattern and film domains under applied mechanical forces. Unlike previous studies that incorporate reinforced inclusions into soft matrices to tailor material properties, our method manipulates the localization, integration, and interaction of these subdomain building blocks within the soft film. This enables extensive tuning of both local and global behaviors. Notably, we introduce a subdomain-interface mechanism that allows for the concurrent customization and decoupling of mechanical properties and shape transformations within a single material system—an achievement rarely accomplished with current synthetic soft materials. Additionally, our use of in-situ imaging characterizations, including full-field strain mapping via digital imaging correlation and reciprocal-space patterns through fast Fourier transform analysis of real-space pattern domains, provides rapid real-time monitoring tools to uncover the underlying principles governing tailored multiscale heterogeneities and intricate behaviors.

Regenerative Outcomes of Combining siCOL1A2 Hydrogel with Acupuncture in a Rat Model of Chronic Intervertebral Disc Degeneration

Intervertebral disc degeneration (IVDD) is a significant cause of chronic pain and disability, necessitating innovative therapeutic strategies. This study investigates the combined effect of a novel siCOL1A2-encapsulated hydrogel and acupuncture on IVDD in a rat model. We developed a hydrogel system, siCOL1A2-encapsulated G5-PBA hydrogel (siCOL1A2@G5-PBA@Gel), designed for sustained siRNA delivery to the degenerated discs and assessed its therapeutic efficacy alongside acupuncture treatment. Key inflammatory genes were identified through RNA-seq analysis, with COL1A2 highlighted as a crucial regulator of inflammatory responses in IVDD. Our in vivo experiments involved treating rats with hydrogel alone, acupuncture alone, and combining both. The treatments were evaluated through behavioral pain assessments, imaging techniques (X-ray and MRI), and histological analyses. Results indicated that the combination therapy significantly alleviated pain, reduced inflammation, and promoted disc regeneration more effectively than individual treatments. The hydrogel proved biocompatible and facilitated targeted gene silencing, while acupuncture enhanced therapeutic outcomes by improving local blood circulation and modulating inflammatory responses. These findings suggest that integrating siCOL1A2 hydrogel with acupuncture offers a promising approach to treating IVDD.

Recent Progress of Organic Room‐Temperature Phosphorescent Hydrogels

Organic room‐temperature phosphorescent (RTP) materials have garnered significant attention owing to their unique photophysical properties. Traditionally, the stabilization of triplet excitons in RTP materials necessitates a crystalline matrix or rigid polymer chain, which limits their use in flexible materials. In contrast, hydrogels offer biocompatibility, softness, and ease of processing. Therefore, incorporating phosphorescent molecules into hydrogel systems can expand the application potential of RTP materials. This concept summarizes recent advancements in RTP hydrogels, emphasizing their synthetic strategies and diverse applications.

Controlled TPCA-1 delivery engineers a pro-tenogenic niche to initiate tendon regeneration by targeting IKKβ/NF-κB signaling

Tendon repair remains challenging due to its poor intrinsic healing capacity, and stem cell therapy has emerged as a promising strategy to promote tendon regeneration. Nevertheless, the inflammatory environment following acute tendon injuries disrupts stem cell differentiation, leading to unsatisfied outcomes. Our study recognized the critical role of NF-κB signaling in activating inflammation and suppressing tenogenic differentiation of stem cells after acute tendon injury via multiomics analysis. TPCA-1, a selective inhibitor of IKKβ/NF-κB signaling, efficiently restored the impaired tenogenesis of stem cells in the inflammatory environment. By developing a microsphere-incorporated hydrogel system for stem cell delivery and controlled release of TPCA-1, we successfully engineered a pro-tenogenic niche to initiate tenogenesis for tendon regeneration. Collectively, we recognize NF-κB signaling as a critical target to tailor a pro-tenogenic niche and propose the combined delivery of stem cells and TPCA-1 as a potential strategy for acute tendon injuries.

Emerging Strategies for Local Delivery of Immune Checkpoint Inhibitors to Potentiate Cancer Immunotherapy: Current Status and Future Prospects.

Cancer constitutes a significant threat to patients' lives worldwide. Immunotherapy, particularly immune checkpoint inhibitors (ICIs) that boost antitumor immunity by targeting immune checkpoint components, has emerged as a promising strategy for its treatment in recent years. However, the objective response rates of the ICIs are unsatisfactory. As the primary route, systemic administration of ICIs is often accompanied by immune-related adverse events. Local delivery of ICIs serves as a potential therapeutic strategy that can improve the efficacy while simultaneously reducing side effects through precise drug release at the tumor site. Initial validation of direct local application of ICIs for tumors in clinical trials has indicated reduced side effects and improved efficacy, while low bioavailability remains a challenge. Furthermore, research on various carriers, including nanoparticles, microneedles, hydrogels, combined platforms, and implantable devices for local release of ICIs has exhibited applying potential in treating murine tumors, among which combined platforms such as combined hydrogel system hold the highest promise due to their encompassment of the advantages of multiple carriers. These carriers, by incorporating ICIs and other therapeutics, could manage cancers more potently, which needs to be confirmed in clinical trials after the refinement of their biocompatibility. This review summarizes the latest research advancements regarding local administration of ICIs, with a particular focus on the carriers for local delivery as well as the combination therapies, thus providing novel insights and research guidance for scholars to enhance the efficacy of locally delivered ICIs on managing multiple cancers in the future.

Eugenol-Loaded Lipid Nanoparticles-Derived Hydrogels Ameliorate Psoriasis-like Skin Lesions by Lowering Oxidative Stress and Modulating Inflammation.

Psoriasis is a chronic T-cell-mediated autoimmune skin disorder characterized by excessive epidermal thickening, overproliferation of keratinocyte, disruption of epidermal cell differentiation, and increased blood vessel growth in the dermal layer. Despite the common use of corticosteroids in psoriasis treatment, their limited efficacy and numerous side effects pose significant challenges. This research introduces a promising alternative approach by encapsulating eugenol (EU) in soya phosphatidylcholine (SPC) nanoparticles (EUNPs) which showed spherical shape nanoparticles with a hydrodynamic size of approximately 200 nm, polydispersity index 0.23, encapsulation efficiency of 85% having good colloidal stability indicated by ζ-potential of -27 mV. Later on, these EUNPs were formulated into a topical hydrogel system by using Carbopol 974P (EUNPGel), which exhibited superior drug loading, enhanced release kinetics for 48 h, long-term stability, and the ability to scavenge reactive oxygen species (ROS). Furthermore, EUNPs inhibited keratinocyte proliferation, induced apoptosis, and augmented the uptake of IL-6-mediated inflammation in human keratinocyte cells. Application of EUNPs-loaded gels (EUNPGel) to imiquimod-induced psoriatic lesions demonstrated effective dermal penetration, suppressed keratinocyte hyperplasia and restored epidermal growth. This led to a remarkable reduction in the Psoriasis Area and Severity Index (PASI) score from 3.75 to 0.5 within 5 days. This novel approach enhances ROS scavenging capacity, improves cellular uptake, facilitates skin penetration and retention, reduces the activity of hyperactive immune cells, and suggests potential applications for treating other immune-related disorders such as acne and atopic dermatitis.