Hydrogel System Research Articles

Blood-responsive mussel-inspired hydrogels for hemostasis, antibacterial action, and wound healing

Rapid hemostasis, potent antimicrobial activity, and efficient wound management are critical factors in enhancing the survival of trauma patients. Chitosan, as a green and sustainable biomaterial with low cost, degradability and biocompatibility, is widely used in the biomedical field. However, chitosan dissolves in an acidic environment, which is not conducive to wound healing. In this study, chitosan was chemically modified to address this limitation. A mussel-inspired hydrogel composed of caffeic acid-grafted chitosan, gallic acid-grafted chitosan, and oxidized microcrystalline cellulose (CHI-C/CSG/OMCC) was designed. This hydrogel exhibits blood-responsive gelation behavior and offers a synergistic combination of tissue adhesion, antimicrobial properties, and tissue repair capabilities. The carboxyl, hydroxyl, phenolic hydroxyl and aldehyde groups within the hydrogel system endowed the hydrogel with excellent adhesion properties (53.1 kPa adhesion strength to porcine skin-adherent tissues), biocompatibility, and excellent antimicrobial properties. Surprisingly, this hydrogel not only achieved rapid and effective hemostasis, but also effectively promoted wound healing in a mouse skin injury model. In addition, its remarkable efficacy in stopping bleeding within approximately 2 min without rebleeding was demonstrated in a porcine model of acute gastrointestinal hemorrhage in the esophagus, stomach, and intestines. This blood-responsive ternary hydrogel offers a promising alternative to wound management materials due to its excellent overall performance and superior efficacy in all phases of wound healing.

Application of Physically Crosslinked Hyaluronic Acid Hydrogel in the Treatment of Radiation‐Induced Skin Injury

AbstractWounds caused by radiation exposure are often hard to heal. The functional hydrogel can be used as a wound treatment material of multiple dimensions according to patients' needs. Hyaluronic acid hydrogel can be used to create a moist environment conducive to wound healing. In this study, new complex hydrogels based on physically crosslinked hyaluronic acid are investigated, which adopt the freeze‐thaw technique, loaded with small molecule drugs deferoxamine and retinoic acid, and effectively promote the healing of radiation‐induced skin ulcers. The combined application of deferoxamine and retinoic acid can improve skin injury after radiation, promoting angiogenesis, reducing inflammation, and protecting skin appendages. In vitro and in vivo results show enhanced cell viability and biological function, significantly accelerate healing of the irradiated wounds, and improve collagen deposition in the skin of the irradiated rats. Also, the skin appendages, such as hair follicles, are protected to a certain extent, implying functionally repairing the skin. Considering the ease of use of the hydrogel system in clinical applications, complex hydrogels can be considered a suitable candidate for treating radiation‐induced skin injury.

Exploring the potential of nanoparticles-based polydopamine for effective treatment of refractory keratitis: Mild photothermal loop therapy

Keratitis is the leading cause of blindness worldwide. In refractory cases, it can even lead to eyeball enucleation. The critical challenges of refractory keratitis are the drug-resistant bacteria and bacterial biofilms formation. Therefore, we established an innovative therapeutic approach for keratitis based on mild photothermal loop (MPL) therapy. First, we analyzed the bactericidal effect of methicillin-resistant Staphylococcus aureus (MRSA) under various loops and temperature durations to determine the optimal condition. Then, RAN-seq was applied to explore the underlying mechanisms. Additionally, we formulated a dual-purpose polyvinyl alcohol-polydopamine (PDA/PVA) hydrogel system and explored its effects on the reactive oxygen species (ROS) scavenging capability, antibacterial properties, and anti-inflammatory properties in vitro, as well as its effect in vivo. The results indicated substantial bactericidal properties after exposure in four loops, each lasting 10 min at 45 °C. RNA-seq revealed the altered genes related to virulence and biofilm formation. In addition to good photothermal performance, the PDA/PVA system could effectively eliminate MRSA, reduce ROS, inhibit biofilm formation, and decrease inflammatory factors expression. Moreover, the in vivo results demonstrated the potential of MPL for bacterial keratitis. This study serves as the first attempt to use MPL therapy for refractory keratitis, offering a new approach for clinical practice.

Effects of Nucleophilic Catalysts on the Self‐Assembly of Hydrazone‐Based Supramolecular Hydrogels

AbstractCatalytic control over molecular self‐assembly provides a powerful approach to regulate the structures as well as the functionalities of supramolecular materials. Revealing how the catalysts affect the molecular self‐assembly process is crucial for rational design and control of the supramolecular self‐assembly systems. Herein, relying on a hydrazone‐based dynamic supramolecular hydrogel system, the effects of various nucleophilic catalysts on the self‐assembly of the hydrogels are investigated, demonstrating that the catalyst influences the hydrogelators self‐assembly via facilitating both the reaction and hydrogelators nucleation processes. The catalyst with higher catalytic activity accelerates the formation thereon the self‐assembly of hydrazone‐based hydrogelators, leading to hydrogels with more branched networks and higher stiffness. Importantly, we also verify that the catalysts, depending on the molecular structure, can also accelerate the self‐assembly process by affecting the hydrogelators nucleation process. These findings not only add more details to the effects of nucleophilic catalysts on the hydrazone‐based hydrogelation system, but also suggest that both the catalysis activity and chemical structures should be considered for catalytically controlled molecular self‐assembly.

Design and Evaluation of Inorganic/Organic Hybrid Bio-composite for Site-Specific Oral Delivery of Darifenacin

Benign hyperplasia (BHP) is a common disorder that affects men over the age of 60 years. Transurethral resection of the prostate (TURP) is the gold standard for operative treatment, but a range of drugs are also available to improve quality of life and to reduce BHP-associated urinary tract infections and complications. Darifenacin, an anti-muscarinic agent, has been found effective for relieving symptoms of overactive bladder associated with BHP, but the drug has poor solubility and bioavailability, which are major challenges in product development. An inorganic/organic bio-composite with gastric pH-resistant property was synthesized for the targeted oral delivery of Darifenacin to the lower gastrointestinal tract (GIT). This development was accomplished through co-precipitation of calcium carbonate in quince seed-based mucilage. The FTIR, XRD, DSC, and TGA results showed good drug-polymer compatibility, and the SEM images showed calcite formation in the quince hydrogel system. After 72 h, the drug release of 34% and 75% were observed in acidic (0.1N HCl) and 6.8 pH phosphate buffer, respectively. A restricted/less drug was permeated through gastric membrane (21.8%) as compared to permeation through intestinal membrane (65%.) The developed composite showed significant reduction in testosterone-induced prostatic hyperplasia (2.39 ± 0.12***) as compared to untreated diseased animal group. No sign of organ toxicity was observed against all the developed composites. In this study, we developed an inorganic–organic composite system that is highly biocompatible and effective for targeting the lower GIT, thereby avoiding the first-pass metabolism of darifenacin.Graphical

Prolonged, staged, and self-regulated methotrexate release coupled with ROS scavenging in an injectable hydrogel for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) remains a formidable healthcare challenge due to its chronic nature and potential for irreversible joint damage. Methotrexate (MTX) is a cornerstone treatment for RA but carries significant risks of adverse effects with repeated administration, necessitating the exploration of alternative delivery methods. Injectable hydrogels loaded with MTX for intra-articular injection present a promising solution, allowing sustained drug release directly into affected joints. However, current hydrogel systems often lack extended therapeutic periods and the ability to self-regulate drug release according to disease state. Furthermore, RA is associated with excessive production of reactive oxygen species (ROS), which exacerbates inflammation and joint damage. Herein, we developed an advanced injectable hydrogel (MPDANPs/MTX HA-PEG gel) based on “bio-orthogonal chemistry”, combining hyaluronic acid and polyethylene glycol (PEG) matrices co-loaded with mesoporous polydopamine nanoparticles (MPDANPs) and MTX. MPDANPs/MTX HA-PEG gel achieved prolonged, staged, and self-regulated MTX release, coupled with ROS scavenging capabilities for enhanced therapeutic efficacy. Due to its optimized MTX release behavior and significant ROS scavenging function, MPDANPs/MTX HA-PEG gel exhibited potent anti-inflammatory effects in collagen-induced arthritis (CIA) rats following a single intra-articular injection. Our findings highlight the potential of MPDANPs/MTX HA-PEG gel as a highly effective treatment strategy for RA, offering a promising avenue for improving patient outcomes.

Shear-thinning hydrogel for allograft cell transplantation and externally controlled transgene expression

This work establishes the design of a fully synthetic, shear-thinning hydrogel platform that is injectable and can isolate engineered, allogeneic cell therapies from the host. We utilized RAFT to generate a library of linear random copolymers of N,N-dimethylacrylamide (DMA) and 2-vinyl-4,4-dimethyl azlactone (VDMA) with variable mol% VDMA and degree of polymerization. Poly(DMA-co-VDMA) copolymers were subsequently modified with either adamantane (Ad) or β-cyclodextrin (Cd) through amine-reactive VDMA to prepare hydrogel precursor macromers containing complementary guest-host pairing pendant groups that, when mixed, form shear-thinning hydrogels. Rheometric evaluation of the hydrogel library enabled identification of lead macromer structures comprising 15 mol% pendants (Ad or Cd) and a degree of polymerization of 1000; mixing of these Ad and Cd functionalized precursors yielded hydrogels possessing storage modulus above 1000 Pa, tan(δ) values below 1 and high yield strain, which are target characteristics of robust but injectable shear-thinning gels. This modular system proved amenable to nanoparticle integration with surface-modified nanoparticles displaying Ad. The addition of the Ad-functionalized nanoparticles simultaneously improved mechanical properties of the hydrogels and enabled extended hydrogel retention of a model small molecule in vivo. In studies benchmarking against alginate, a material traditionally used for cell encapsulation, the lead hydrogel showed significantly less fibrous encapsulation in a subcutaneous implant site. Finally, this platform was utilized to encapsulate and extend in vivo longevity of inducible transgene-engineered mesenchymal stem cells in an allogeneic transplant model. The hydrogels remained intact and blocked infiltration by host cells, consequently extending the longevity of grafted cell function relative to a benchmark, shear-thinning hyaluronic acid-based gel. In sum, the new synthetic, shear-thinning hydrogel system presented here shows potential for further development as an injectable platform for delivery and in situ drug modulation of allograft and engineered cell therapies.

Antibacterial and Anticorrosive Hydrogel Coating Based on Complementary Functions of Sodium Alginate and g-C3N4.

Graphitic carbon nitride (g-C3N4, CN) has emerged as a promising photocatalytic material due to its inherent stability, antibacterial properties, and eco-friendliness. However, its tendency to aggregate and limited dispersion hinder its efficacy in practical antibacterial applications. To address these limitations, this study focuses on developing a composite hydrogel coating, in which sodium alginate (SA) molecules interact electrostatically and through hydrogen bonding to anchor CN, thereby significantly improving its dispersion. The optimal CN loading of 35% results in a hydrogel with a tensile strength of 120 MPa and an antibacterial rate of 99.87% within 6 h. The enhanced mechanical properties are attributed to hydrogen bonding between the -NH2 groups of CN and the -OH groups of SA, while the -OH groups of SA facilitate the attraction of photogenerated holes from CN, promoting carrier transfer and separation, thereby strengthening the antibacterial action. Moreover, the hydrogel coating exhibits excellent antibacterial and corrosion resistance capabilities against Pseudomonas aeruginosa on 316L stainless steel (316L SS), laying the foundation for advanced antimicrobial and anticorrosion hydrogel systems.

Gelatin-carboxymethyl cellulose/iron-based metal-organic framework nanocomposite hydrogel as a promising biodegradable fertilizer release system: Synthesis, characterization, and fertilizer release studies

Application of fertilizers is a routine method in agriculture to increase the fertility of plants However, conventional fertilizers have raised serious health and environmental problems in recent years. Therefore, the development of biodegradable superabsorbent hydrogels based on natural polymers with the capability for fertilizer controlled release has attracted much interest. In the current research, a novel nanocomposite hydrogel based on gelatin and carboxymethyl cellulose polymers enriched with an iron based metal- organic framework (MIL-53 (Iron)) was prepared. The prepared nanocomposite hydrogel was loaded with NPK fertilizer to obtain a slow release fertilizer system. The structural properties of the nanocomposite hydrogel were investigated using FTIR, XRD, and SEM techniques. The swelling and fertilizer release behavior of the nanocomposite hydrogel were evaluated in conditions. Results showed that by adding iron-based metal organic framework to the hydrogel matrix, the water absorption capacity of the hydrogel system was increased to 345.8 (g/g). Fertilizer release studies revealed that the release of fertilizer from the nanocomposite matrix has a slow and continuous release pattern. Therefore, the synthesized nanocomposite has an appropriate strength and high potential to be used as a slow-release fertilizer system.

Metal Halide Perovskite Nanocrystals-Intermediated Hydrogel for Boosting the Biosensing Performance.

Metal-halide perovskites have become attractive nanomaterials for advanced biosensors, yet the structural design remains challenging due to the trade-off between environmental stability and sensing sensitivity. Herein, a trinity strategy is proposed to address this issue by integrating Mn (II) substitution with CsPb2Cl5 inert shell and NH2-PEG-COOH coating for designing Mn2+-doped CsPbCl3/CsPb2Cl5 core/shell hetero perovskite nanocrystals (PMCP PNCs). The trinity strategy isolates the emissive Mn2+-doped CsPbCl3 core from water and the Mn2+ d-d transition generates photoluminescence with a long lifetime, endowing the NH2-PEG-COOH capped Mn2+-doped CsPbCl3/CsPb2Cl5 PNCs with robust water stability and oxygen-sensitive property. Given the structural integration, photoluminescent hydrogel biosensors are designed by embedding the PMCP PNCs into the hydrogel system to deliver on-site pesticide information on food products. Impressively, benefiting from the dual enzyme triggered-responsive property of PMCP PNCs, the hydrogel biosensor is endowed with ultra-high sensitivity toward chlorpyrifos pesticide at the nanogram per milliliter level. Such a robust PMCP PNCs-based hydrogel sensor can provide accurate pesticide information while guiding the construction of photoluminescent biosensors for upcoming on-site applications.

Enhancing Wound Healing With Sprayable Hydrogel Releasing Multi Metallic Ions: Inspired by the Body's Endogenous Healing Mechanism.

In the pursuit of new wound care products, researchers are exploring methods to improve wound healing through exogenous wound healing products. However, diverging from this conventional approach, this work has developed an endogenous support system for wound healing, drawing inspiration from the body's innate healing mechanisms governed by the sequential release of metal ions by body at wound site to promote different stages of wound healing. This work engineers a multi-ion-releasing sprayable hydrogel system, to mimic this intricate process, representing the next evolutionary step in wound care products. It comprises Alginate (Alg) and Fibrin (Fib) hydrogel infused with Polylactic acid (PLA) polymeric microcarriers encapsulating multi (calcium, copper, and zinc) nanoparticles (Alg-Fib-PLA-nCMB). Developed sprayable Alg-Fib-PLA-nCMB hydrogel show sustained release of beneficial multi metallic ions at wound site, offering a range of advantages including enhanced cellular function, antibacterial properties, and promotion of crucial wound healing processes like cell migration, ROS mitigation, macrophage polarization, collagen deposition, and vascular regeneration. In a comparative study with a commercial product (Midstress spray), developed Alg-Fib-PLA-nCMB hydrogel demonstrates superior wound healing outcomes in a rat model, indicating its potential for next generation wound care product, addressing critical challenges and offering a promising avenue for future advancements in the wound management.

Encapsulation of human natural killer cells into novel gelatin-based polymeric hydrogel networks.

In the innate immune system, natural killer (NK) cells are effector lymphocytes which control several tumor types and microbial infections by limiting disease spread and tissue damage. With tumor cell killing abilities, with no priming or prior activation, NKs are potential anti-cancer therapies. In clinical practice, NKs are used in intravenous injections as they typically grow as suspension, similar to other blood cells. In this study, we designed a novel and effective biomaterial-based platform for NK cell delivery, which included in-situ NK cell encapsulation into three-dimensional (3D) biocompatible polymeric scaffolds for potential anti-cancer treatments. Depending on physical cross-linking between an alginate (ALG) polymer and a divalent cation, two natural polymers (gelatin (GEL) and hyaluronic acid (HA)) penetrated into pores and generated an inter-penetrating hydrogel system with improved mechanical properties and stability. After extensive characterization of hydrogels, NK cells were encapsulated inside using our in-situ gelation procedure to provide a biomimetic microenvironment.&#xD.

Small dop of comonomer, giant shift of dynamics: α-methyl-regulated viscoelasticity of poly(methacrylamide) hydrogels

α-Methyl groups play significant roles in the regulation of water molecules within both small molecular systems and bio-macromolecular systems. Systematically studying the influence of α-methyl on the dynamics of water molecules within hydrogel systems is therefore worthwhile. In this study, we prepared a series of hydrogen-bonded (H-bonded) hydrogels with varying densities of α-methyl groups by copolymerizing methacrylamide (MAm) with its α-methyl-absent analogue, acrylamide (Am). Introducing a small amount of Am (≤6 mol%) into the polymer chain resulted in significant shifts in the viscoelasticity of the hydrogels. The hydrogels exhibit a “time-temperature-α-methyl equivalence”, meaning that introduction of α-methyl-absent monomer has effects similar to elevating temperature and prolonging observation time on the dynamic properties. Based on low-field nuclear magnetic resonance spectroscopy and Raman scattering, a “hydrophilic defects-assisted H-bonds dissociation” mechanism is proposed, depicting that the α-methyl-absent monomer can disturb the rearrangement of water molecules surrounding the polymer chain and accelerate chain dissociation. These findings enabled the copolymer hydrogels with functions such as fast self-healing and tunable interface adhesion.

Experimental evaluation of a hydrogel composite desiccant wheel for dehumidification with high water uptake and low regeneration temperature

Rotary dehumidification, a key method for continuous solid adsorption dehumidification, is extensively utilised in various industrial and practical applications. The performance of the adsorbent within the desiccant wheel is a major determinant of its energy efficiency in practical applications. While studies on Metal Organic Frameworks (MOFs) and polymer desiccant wheels exist, the majority of rotary dehumidification systems continue to employ traditional adsorbents like silica gel and zeolite, which are plagued by low dehumidification capacity and high energy consumption issues. Super hygroscopic hydrogel, enhanced with a hygroscopic agent, has gained prominence in air treatment because of its outstanding hygroscopicity and low regeneration temperature. With the goal of integrating advanced materials into practical engineering applications and mitigating the heat and mass transfer loss and adsorption/desorption performance degradation due to volume expansion and viscous agglomeration post-water uptake in large-scale super hygroscopic hydrogel applications, this study successfully developed a hydrogel wheel, measuring 350 mm in diameter and 200 mm in thickness, using a honeycomb-shaped glass fibre paper substrate. Experimental findings demonstrate that the hydrogel desiccant wheel outperforms both the MOF and commercial low-temperature silica gel wheels under all tested environmental conditions. This advantage is particularly noticeable at 15 °C and 30 % Relative Humidity (RH), where the moisture content differential (Δd) in the hydrogel system is 2.96 g/kg, 1.89 times greater than the MOF system’s 1.56 g/kg and 5.19 times higher than the silica gel’s 0.57 g/kg. Furthermore, the controlled variable method was used to assess the impact of each operational parameter on the hydrogel wheel’s performance in both low and high moisture conditions, offering design insights for engineering applications.

Regulation of thermal migration channel in cellulose hydrogel to enhance thermopower

Ionic thermoelectric material is gaining increasing attention, and many attempts have been devoted to obtain huge ionic thermopower, which remains a big challenge. Herein, the idea of “ion thermal migration channel” was propose, and a high ionic thermopower was achieved by regulating the thermal migration channel in cellulose hydrogel system. It is found that the channels size as well as the channel-ion interaction played dominant roles. Initially, the channel size in cellulose/KCl hydrogel were optimized to enlarge the channel-Cl− interactions via counter-ion condensation effect, which improved the thermopower from 2.45 mV·K−1 to 8.13 mV·K−1. Then, sodium alginate as polyanion was doped and multi-valance ion cross-linking was carried out, to further enhance the channel-Cl− interaction, and a high thermopower of 22.09 mV·K−1 was realized. In addition, the cellulose based ionic thermoelectric hydrogel displayed viable basis for energy harvesting and temperature sensing as wearable flexible devices. The present work not only provides a systematic strategy for the thermopower regulation, but also supplies an applicable approach for the preparation of sustainable thermoelectric materials with biomass resources, demonstrating great potential in sustainability and green energy.

Gelatin methacryloyl biomaterials and strategies for trophoblast research

Rising maternal mortality rates in the U.S. are a significant public health issue that must be addressed; however, much of the basic science information required to target pregnancy-related pathologies have not yet been defined. Placental and blastocyst implantation research are challenging to perform in humans because of the early time frame of these processes in pregnancy and limited access to first trimester tissues. As a result, there is a critical need to develop model systems capable of studying these processes in increasing mechanistic detail. With the recent passing of the FDA Modernization Act 2.0 and advances in tissue engineering methods, three-dimensional microphysiological model systems offer an exciting opportunity to model early stages of placentation. Here, we detail the synthesis, characterization, and application of gelatin methacryloyl (GelMA) hydrogel platforms for studying trophoblast behavior in three-dimensional hydrogel systems. Photopolymerization strategies to fabricate GelMA hydrogels render the hydrogels homogeneous in terms of structure and stable under physiological temperatures, allowing for rigorous fabrication of reproducible hydrogel variants. Unlike other natural polymers that have minimal opportunity to tune their properties, GelMA hydrogel properties can be tuned across many axes of variation, including polymer degree of functionalization, gelatin bloom strength, light exposure time and intensity, polymer weight percent, photoinitiator concentration, and physical geometry. In this work, we aim to inspire and instruct the field to utilize GelMA biomaterial strategies for future placental research. With enhanced microphysiological models of pregnancy, we can now generate the basic science information required to address problems in pregnancy.

A dendritic cell-recruiting, antimicrobial blood clot hydrogel for melanoma recurrence prevention and infected wound management

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.

Neurophilic peptide-reinforced dual-fiber-network bioactive hydrogels for spinal cord injury repair

Spinal cord injury (SCI) is a challenging central nervous system disorder that characterized by microenvironmental disturbances following injury, which can be addressed by simulating the microenvironment of the spinal cord regeneration. Herein, we report the design and synthesis of bioactive hydrogels with a dual-fiber-network (DFN) porous structure, using self-assembled peptide nanofibers (PNFs) and natural cellulose nanofibers (CNFs). A neurophilic peptide is further introduced to enhance nervous regeneration capability of the pre-prepared PNF/CNF hydrogels, which then exhibit excellent neuro-affinity, self-healing ability, biodegradability, and biocompatibility, facilitating targeted SCI repair and regeneration through the hydrogel injection. The in vitro experiments reveal that the DFN hydrogel can enhance the proliferation and migration of bone marrow mesenchymal stem cells, and induce neural stem cell (NSC) proliferation with enhanced neuronal differentiation and axonal growth. Additionally, the in vivo studies validate that the hydrogel attenuates the post-SCI inflammation, inhibits reactive astrocyte proliferation, and facilitates endogenous NSC proliferation and migration, as well as promotes neuronal growth and axonal regeneration. The potential mechanism of SCI repair is ascribed to the hydrogel-induced activation of the PI3K/AKT/mTOR pathway, which alleviates inflammatory response, inhibits excessive reactive response of glial cells, and promotes NSC differentiation into neurons. This neurophilic peptide-reinforced DFN bioactive hydrogel system, with its comprehensive approach to SCI repair, holds great potential for clinical applications.

Intraoperative Cavity Local Delivery System with NETs-Specific Drug Release for Post-Breast Cancer Surgery Recurrence Correction.

Postoperative breast cancer recurrence is tricky due to the limited therapeutic options. Transforming growth factors-β (TGF-β) is vital in promoting postoperative tumor recurrence. However, conventional blocking strategies fail to satisfy both bio-safety and sufficient relapse correction. Neutrophil extracellular traps (NETs) are essential for the spatiotemporal dynamics of TGF-β at tumor-resection sites, whose unique mechanism for local TGF-β amplification could remarkably increase the risk of relapse after surgery. Herein, the principle of NETs formation is ingeniously utilized to construct a surgical residual cavity hydrogel that mimics NETs formation. The hydrogel is prepared based on the electrostatic interaction between histidine (His) and sodium alginate (Alg). Then, arginine deiminase 4 (PAD4) protein is released during NETs formation. Simultaneously, the electrical property of His in hydrogel changes automatically, which further lead to promising localized release of anti-TGF-β. The hydrogel system can realize specific and selective drug release at targeted NETs site over a prolonged period while exhibiting excellent biocompatibility. Superior breast cancer recurrence inhibition is achieved by suppressing TGF-β and related indicators, impeding epithelial-mesenchymal transition (EMT) progression, and rectifying the locally exacerbated immunosuppressive environment within NETs. The novel NETs local microenvironment drug release functional hydrogel will provide inspiration for postoperative recurrence correction strategies.

Glucose Oxidase-Coated Calcium Peroxide Nanoparticles as an Innovative Catalyst for In Situ H2O2-Releasing Hydrogels.

In situ forming and hydrogen peroxide (H2O2)-releasing hydrogels have been considered as attractive matrices for various biomedical applications. Particularly, horseradish peroxidase (HRP)-catalyzed crosslinking reaction serves efficient method to create in situ forming hydrogels due to its advantageous features, such as mild reaction conditions, rapid gelation rate, tunable mechanical strength, and excellent biocompatibility. Herein, a novel HRP-crosslinked hydrogel system is reported that can produce H2O2 in situ for long-term applications, using glucose oxidase-coated calcium peroxide nanoparticles (CaO2@GOx NPs). In this system, CaO2 gradually produced H2O2 to support the HRP-mediated hydrogelation, while GOx further catalyzed the oxidation of glucose for in situ H2O2 generation. As the hydrogel is formed rapidly is expected and the H2O2 release behavior is prolonged up to 10 days. Interestingly, hydrogels formed by HRP/CaO2@GOx-mediated crosslinking reaction provided a favorable 3D microenvironment to support the viability and proliferation of fibroblasts, compared to that of hydrogels formed by either HRP/H2O2 or HRP/CaO2/GOx-mediated crosslinking reaction. Furthermore, HRP/CaO2@GOx-crosslinked hydrogel enhanced the angiogenic activities of endothelial cells, which is demonstrated by the in vitro tube formation test and in ovo chicken chorioallantoic membrane model. Therefore, HRP/CaO2@GOx-catalyzed hydrogels is suggested as potential in situ H2O2-releasing materials for a wide range of biomedical applications.