Oral delivery of Sunitinib malate using carboxymethyl cellulose/poly(acrylic acid-itaconic acid)/Cloisite 30B nanocomposite hydrogel as a pH-responsive carrier.

This work aimed to fabricate a Cloisite 30B-incorporated carboxymethyl cellulose graft copolymer of acrylic acid and itaconic acid hydrogel (Hyd) via a free radical polymerization method for controlled release of Sunitinib malate anticancer drug. The synthesized samples were characterized by FTIR, XRD, TEM, and SEM-dot mapping analyses. The encapsulation efficiency of Hyd and Hyd/Cloisite 30B (6 wt%) was 81 and 93%, respectively, showing the effectiveness of Cloisite 30B in drug loading. An in vitro drug release study showed that drug release from all samples in a buffer solution with pH 7.4 was higher than in a buffer solution with pH 5.5. During 240 min, the cumulative drug release from Hyd/Cloisite 30B (94.97% at pH 7.4) is lower than Hyd (53.71% at pH 7.4). Also, drug-loaded Hyd/Cloisite 30B (6 wt%) demonstrated better antibacterial activity towards S. Aureus bacteria and E. Coli. High anticancer activity of Hyd/Cloisite 30B against MCF-7 human breast cancer cells was shown by the MTT assay, with a MCF-7 cell viability of 23.82 ± 1.23% after 72-hour incubation. Our results suggest that Hyd/Cloisite 30B could be used as a pH-controlled carrier to deliver anticancer Sunitinib malate.

Intelligent Hydrogel with Physiologically Dependent Capacities of Photothermal Conversion and Nanocatalytic Medicine to Integratively Inhibit Bacteria and Inflammation for On-Demand Treatment of Infected Wound.

Although chemodynamic therapy (CDT) and photothermal therapy (PTT) based on a variety of nanoparticles have been developed to achieve effective anti-bacterial therapy, the limited therapeutic efficiency of CDT alone, as well as the undifferentiated damage of PTT to both bacteria and surrounding healthy tissue are still challenges for their clinical application of infected wounds treatments. In addition, during the CDT and PTT-mediated antimicrobial processes, the endogenous macrophages would be easily converted to pro-inflammatory macrophages (M1 phenotype) under local ROS and hyperthermia to promote inflammation, resulting in unexpected suppression of tissue regeneration and possible wound deterioration. To address these problems, a biodegradable sodium alginate/hyaluronic acid hydrogel loaded with functional CeO2-Au nano-alloy (AO@ACP) is fabricated to not only achieve precise and efficient antibacterial activity through infection-environment dependent photothermal-chemodynamic therapy but also rapidly eliminate the excess reactive oxygens (ROS) in the M1 type macrophage at the infected area to induce their polarization to M2 type for significant inhibition of inflammation and remarkable enhancement of tissue regeneration, hopefully developing an effective strategy to treat infected wound.

A novel ZIF-8@IL-MXene/poly (N-isopropylacrylamide) nanocomposite hydrogel toward multifunctional adsorption.

Phenols, dyes, and metal ions present in industrial wastewater can adversely affect the environment and leach biological carcinogens. Given that the current research focuses only on the removal of one or two of those categories. Herein, this work reports a novel ZIF-8@IL-MXene/Poly(N-isopropylacrylamide) (NIPAM) nanocomposite hydrogel that can efficiently and conveniently absorb and separate multiple pollutants from industrial wastewater. Ionic liquid (IL) was grafted onto MXene surfaces using a one-step method, and then incorporated into NIPAM monomer solutions to obtain the IL-MXene/PNIPAM composite hydrogel via in-situ polymerization. ZIF-8@IL-MXene/PNIPAM nanocomposite hydrogels were obtained by in-situ growth of ZIF-8 on the pore walls of composite hydrogels. As-prepared nanocomposite hydrogel showed excellent mechanical properties and can withstand ten repeated compressions without any damage, the specific surface area increased by 100 times, and the maximum adsorption capacities for p-nitrophenol (4-NP), crystal violet (CV), and copper ion (Cu2+) were 198.40, 325.03, and 285.65 mg g-1, respectively, at room temperature. The VPTTs of all hydrogels ranged from 33 to 35 °C, so the desorption process can be achieved in deionized water at 35-40 °C, and its adsorption capacities after five adsorption-desorption cycles decreased to 79%, 91%, and 29% for 4-NP, CV, and Cu2+, respectively. The adsorption data fitting results follow pseudo-second-order kinetics and Freundlich models, which is based on multiple interactions between the functional groups contained in hydrogels and adsorbent molecules. The hydrogel is the first to realize the high-efficiency adsorption of phenols, dyes and metal ions in industrial wastewater simultaneously, and the preparation process of hydrogels is environmentally friendly. Also, giving hydrogel multifunctional adsorption is beneficial to promote the development of multifunctional adsorption materials.

Injectable ultrasound-powered bone-adhesive nanocomposite hydrogel for electrically accelerated irregular bone defect healing.

The treatment of critical-size bone defects with irregular shapes remains a major challenge in the field of orthopedics. Bone implants with adaptability to complex morphological bone defects, bone-adhesive properties, and potent osteogenic capacity are necessary. Here, a shape-adaptive, highly bone-adhesive, and ultrasound-powered injectable nanocomposite hydrogel is developed via dynamic covalent crosslinking of amine-modified piezoelectric nanoparticles and biopolymer hydrogel networks for electrically accelerated bone healing. Depending on the inorganic-organic interaction between the amino-modified piezoelectric nanoparticles and the bio-adhesive hydrogel network, the bone adhesive strength of the prepared hydrogel exhibited an approximately 3-fold increase. In response to ultrasound radiation, the nanocomposite hydrogel could generate a controllable electrical output (-41.16 to 61.82 mV) to enhance the osteogenic effect in vitro and in vivo significantly. Rat critical-size calvarial defect repair validates accelerated bone healing. In addition, bioinformatics analysis reveals that the ultrasound-responsive nanocomposite hydrogel enhanced the osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. Overall, the present work reveals a novel wireless ultrasound-powered bone-adhesive nanocomposite hydrogel that broadens the therapeutic horizons for irregular bone defects.

Targeting SUMOylation with an injectable nanocomposite hydrogel to optimize radiofrequency ablation therapy for hepatocellular carcinoma.

BACKGROUND: Incomplete radiofrequency ablation (iRFA) in hepatocellular carcinoma (HCC) often leads to local recurrence and distant metastasis of the residual tumor. This is closely linked to the development of a tumor immunosuppressive environment (TIME). In this study, underlying mechanisms and potential therapeutic targets involved in the formation of TIME in residual tumors following iRFA were explored. Then, TAK-981-loaded nanocomposite hydrogel was constructed, and its therapeutic effects on residual tumors were investigated. RESULTS: This study reveals that the upregulation of small ubiquitin-like modifier 2 (Sumo2) and activated SUMOylation is intricately tied to immunosuppression in residual tumors post-iRFA. Both knockdown of Sumo2 and inhibiting SUMOylation with TAK-981 activate IFN-1 signaling in HCC cells, thereby promoting dendritic cell maturation. Herein, we propose an injectable PDLLA-PEG-PDLLA (PLEL) nanocomposite hydrogel which incorporates self-assembled TAK-981 and BSA nanoparticles for complementary localized treatment of residual tumor after iRFA. The sustained release of TAK-981 from this hydrogel curbs the expansion of residual tumors and notably stimulates the dendritic cell and cytotoxic lymphocyte-mediated antitumor immune response in residual tumors while maintaining biosafety. Furthermore, the treatment with TAK-981 nanocomposite hydrogel resulted in a widespread elevation in PD-L1 levels. Combining TAK-981 nanocomposite hydrogel with PD-L1 blockade therapy synergistically eradicates residual tumors and suppresses distant tumors. CONCLUSIONS: These findings underscore the potential of the TAK-981-based strategy as an effective therapy to enhance RFA therapy for HCC.

Nanoparticle-Reinforced Tough Hydrogel as a Versatile Platform for Pharmaceutical Drug Delivery: Preparation and in Vitro Characterization.

Natural polymer-based hydrogels are excellent for encapsulating hydrophilic drugs, but they are mechanically weak and degrade easily. In this communication, we exploit the electrostatic interaction between nanosilicates (nSi) and gelatin methacrylate (GelMA) to form a mechanically tough nanocomposite hydrogel for pharmaceutical drug delivery. These hydrogels, prepared at subzero temperatures to form cryogels, displayed macroporous structures, which favors cell infiltration. The designed tough cryogel also showed a slower rate of degradation. Furthermore, we encapsulated the small molecule metformin and sustained the drug release under physiological conditions. Cryogel-loaded metformin reduced the effect of endothelial cell injury caused by nutrient deprivation in vitro. Finally, we hypothesize that this versatile nanocomposite material will find use in diverse biomedical applications.

Nanocomposite Hydrogel Engineered Janus Membrane for Membrane Distillation with Robust Fouling, Wetting, and Scaling Resistance.

Membrane distillation (MD) is considered to be rather promising for high-salinity wastewater reclamation. However, its practical viability is seriously challenged by membrane wetting, fouling, and scaling issues arising from the complex components of hypersaline wastewater. It remains extremely difficult to overcome all three challenges at the same time. Herein, a nanocomposite hydrogel engineered Janus membrane has been facilely constructed for desired wetting/fouling/scaling-free properties, where a cellulose nanocrystal (CNC) composite hydrogel layer is formed in situ atop a microporous hydrophobic polytetrafluoroethylene (PTFE) substrate intermediated by an adhesive layer. By the synergies of the elevated membrane liquid entry pressure, inhibited surfactant diffusion, and highly hydratable surface imparted by the hydrogel/CNC (HC) layer, the resultant HC-PTFE membrane exhibits robust resistance to surfactant-induced wetting and oil fouling during 120 h of MD operation. Meanwhile, owing to the dense and hydroxyl-abundant surface, it is capable of mitigating gypsum scaling and scaling-induced wetting, resulting in a high normalized flux and low distillate conductivity at a concentration factor of 5.2. Importantly, the HC-PTFE membrane enables direct desalination of real hypersaline wastewater containing broad-spectrum foulants with stable vapor flux and robust salt rejection (99.90%) during long-term operation, demonstrating its great potential for wastewater management in industrial scenarios.

Ag nanocomposite hydrogels with immune and regenerative microenvironment regulation promote scarless healing of infected wounds.

BACKGROUND: Bacterial infection, complex wound microenvironment and persistent inflammation cause delayed wound healing and scar formation, thereby disrupting the normal function and appearance of skin tissue, which is one of the most problematic clinical issues. Although Ag NPs have a strong antibacterial effect, they tend to oxidize and form aggregates in aqueous solution, which reduces their antibacterial efficacy and increases their toxicity to tissues and organs. Current research on scar treatment is limited and mainly relies on growth factors and drugs to reduce inflammation and scar tissue formation. Therefore, there is a need to develop methods that effectively combine drug delivery, antimicrobial and anti-inflammatory agents to modulate the wound microenvironment, promote wound healing, and prevent skin scarring. RESULTS: Herein, we developed an innovative Ag nanocomposite hydrogel (Ag NCH) by incorporating Ag nanoparticles (Ag NPs) into a matrix formed by linking catechol-modified hyaluronic acid (HA-CA) with 4-arm PEG-SH. The Ag NPs serve dual functions: they act as reservoirs for releasing Ag/Ag+ at the wound site to combat bacterial infections, and they also function as cross-linkers to ensure the sustained release of basic fibroblast growth factor (bFGF). The potent antibacterial effect of the Ag NPs embedded in the hydrogel against S.aureus was validated through comprehensive in vitro and in vivo analyses. The microstructural analysis of the hydrogels and the in vitro release studies confirmed that the Ag NCH possesses smaller pore sizes and facilitates a slower, more sustained release of bFGF. When applied to acute and infected wound sites, the Ag NCH demonstrated remarkable capabilities in reshaping the immune and regenerative microenvironment. It induced a shift from M1 to M2 macrophage polarization, down-regulated the expression of pro-inflammatory factors such as IL-6 and TNF-α, and up-regulated the expression of anti-inflammatory IL-10. Furthermore, the Ag NCH played a crucial role in regulating collagen deposition and alignment, promoting the formation of mature blood vessels, and significantly enhancing tissue reconstruction and scarless wound healing processes. CONCLUSIONS: We think the designed Ag NCH can provide a promising therapeutic strategy for clinical applications in scarless wound healing and antibacterial therapy.

Safranin-O cationic dye removal from wastewater using carboxymethyl cellulose-grafted-poly(acrylic acid-co-itaconic acid) nanocomposite hydrogel.

Copolymer of acrylic acid (AA) and itaconic acid (IA) grafted onto sodium carboxymethyl cellulose hydrogel (CMC-g-poly (AA-co-IA)) was successfully synthesized as an adsorbent to remove safranin-O from wastewater. The swelling and removal efficiencies of CMC-g-poly (AA-co-IA) were enhanced by increasing IA/AA molar ratio as well as by incorporation of montmorillonite clay nano-sheets (MMT). The surface area of MMT, CMC-g-poly (AA-co-IA), and CMC-g-poly (AA-co-IA) samples was 15.632, 0.61452, and 0.66584 m2/g, respectively, indicating the effectiveness of MMT nano-sheets in improving hydrogel surface area. The maximum removal efficiency of CMC-g-poly (AA-co-IA)/MMT under optimum conditions i.e., pH of 8, initial concentration of 10 mg/L, adsorbent dose of 2 g/L, and contact time of 40 min was ascertained 99.78% using a response surface methodology-central composite design (RSM-CCD). Pseudo-second-order and Langmuir models giving the maximum monolayer adsorption capacity of 18.5185 mg/g and 19.1205 mg/g for CMC-g-poly (AA-co-IA) and CMC-g-poly (AA-co-IA)/MMT samples, respectively are the best-fitted models for kinetic and equilibrium data. Thermodynamically, safranin-O decontamination was spontaneous, exothermic, and entropy decreasing. Moreover, ad (de)sorption behavior study showed that CMC-g-poly (AA-co-IA)/MMT performance was not changed after multiple recovery steps. Therefore, CMC-g-poly (AA-co-IA)/MMT was considered as a highly potential adsorbent for safranin-O removal from wastewater.

Nanocomposite Hydrogel of Pd@ZIF-8 and Laponite® : Size-Selective Hydrogenation Catalyst under Mild Conditions.

The composite hydrogel of a nanoscale metal-organic framework (NMOF) and nanoclay has emerged as a new soft-material with advanced properties and applications. Herein, we report a facile synthesis of a hydrogel nanocomposite by charge-assisted self-assembly of Pd@ZIF-8 nanoparticles with Laponite® nanoclay which coat the surface of Pd@ZIF-8 nanoparticles. Such surface coating significantly enhanced the thermal stability of the ZIF-8 compared to the pristine framework. Further, the Pd@ZIF-8+LP hydrogel nanocomposite shows better size-selective catalytic hydrogenation of olefins than Pd@ZIF-8 nanoparticles based on selective diffusion of the substrate.

Fabrication of chitosan-aminopropylsilane graphene oxide nanocomposite hydrogel embedded PES membrane for improved filtration performance and lead separation.

In the present study chitosan-aminopropylsilane graphene oxide (CS-APSGO) nanocomposite hydrogel was synthesized and utilized as a hydrophilic additive in different dosages (0.5, 1, 2 and 5 wt%) in fabrication of porous polyethersulfone (PES) membranes via the phase inversion induced process by immersion precipitation method for heavy metal ion and dye removal. The modified membranes were characterized using ATR-FTIR, AFM, SEM, water contact angle, overall porosity and mean pore radius evaluations and zeta potential measurement. The addition of CS-APSGO nanocomposite hydrogel to PES doping solutions enhanced membranes hydrophilicity and consequently pure water flux permeability. Filtration performance of the CS-APSGO embedded membranes showed promising antifouling properties during BSA filtration test (FRR> 90%) and 1 wt% membranes showed the highest pure water flux of 123.8 L/m2 h with BSA rejection more than 98% and removal capability more than 82% for lead (II) ion, 90.5% and 98.5% for C.I. Reactive Blue 50 and C.I. Reactive Green 19, respectively. Therefore, the CS-APSGO nanocomposite hydrogel blending in order to modification of PES-based membranes have a noticeable potential in improving filtration performance of blended membranes.

Overview of Polyvinyl Alcohol Nanocomposite Hydrogels for Electro-Skin, Actuator, Supercapacitor and Fuel Cell.

The properties of polyvinyl alcohol (PVA) nanocomposite hydrogels influenced by nanoparticles are reviewed. Various kinds of nanoparticles with excellent mechanical and electrical properties have been introduced into PVA hydrogel to produce stretchable and conductive PVA nanocomposite hydrogel. Understanding the mechanism between the matrix of PVA hydrogel and nanoparticles is therefore critical for the development of PVA nanocomposite hydrogels. This review focuses on the nanoparticles include carbon nanotubes, graphene oxide and metal nanoparticles, and describes the effects of nanoparticles on the mechanical and conductive properties of PVA nanocomposite hydrogels. A new promising area of soft stretchable PVA nanocomposite hydrogel is highlighted for possible applications. Finally, a brief outlook for future research is presented.

Highly Dynamic Nanocomposite Hydrogels Self-Assembled by Metal Ion-Ligand Coordination.

Hydrogels are emerging biomaterials with desirable physicochemical characteristics. Doping of metal ions such as Ca2+ , Mg2+ , and Fe2+ provides the hydrogels with unique attributes, including bioactivity, conductivity, and tunability. Traditionally, this doping is achieved by the interaction between metal ions and corresponding ligands or the direct incorporation of as-prepared metal-based nanoparticles (NPs). However, these approaches rely on a complex and laborious preparation and are typically restricted to few selected ion species. Herein, by mixing aqueous solutions of ligands (bisphosphonates, BPs), polymer grafted with ligands, and metal ions, a series of self-assembled metallic-ion nanocomposite hydrogels that are stabilized by the in situ formed ligand-metal ion (BP-M) NPs are prepared. Owing to the universal coordination between BPs and multivalent metal ions, the strategy is highly versatile and can be generalized for a wide array of metal ions. Such hydrogels exhibit a wide spectrum of mechanical properties and remarkable dynamic properties, such as excellent injectability, rapid stress relaxation, efficient ion diffusion, and triggered disassembly for harvesting encapsulated cells. Meanwhile, the hydrogels can be conveniently coated or patterned onto the surface of metals via electrophoresis. This work presents a universal strategy to prepare designer nanocomposite materials with highly tunable and dynamic behaviors.

Bioinorganic nanocomposite hydrogels formed by HRP-GOx-cascade-catalyzed polymerization and exfoliation of the layered composites.

The mild preparation of multifunctional nanocomposite hydrogels is of great importance for practical applications. We report that bioinorganic nanocomposite hydrogels, with calcium niobate nanosheets as cross-linkers, can be prepared by dual-enzyme-triggered polymerization and exfoliation of the layered composite. The layered HRP/calcium niobate composites (HRP=horseradish peroxidase) are formed by the assembly of the calcium niobate nanosheets with HRP. The dual-enzyme-triggered polymerization can induce the subsequent exfoliation of the layered composite and final gelation through the interaction between polymer chains and inorganic nanosheets. The self-immobilized HRP-GOx enzymes (GOx=glucose oxidase) within the nanocomposite hydrogel retain most of enzymatic activity. Evidently, their thermal stability and reusability can be improved. Notably, our strategy could be easily extended to other inorganic layered materials for the fabrication of other functional nanocomposite hydrogels.

C-di-GMP@ZIF-8 nanocomposite injectable hydrogel based on modified chitosan and hyaluronic acid for infected wound healing by activating STING signaling.

The treatment of infected wounds relies on antibiotics; however, increasing drug resistance has made therapeutic processes more difficult. Activating self-innate immune abilities may provide a promising alternative to treat wounds with bacterial infections. In this work, we constructed an immunogenic injectable hydrogel crosslinked by the Schiff base reaction of carboxymethyl chitosan (NOCC) and aldehyde hyaluronic acid (AHA) and encapsulated with stimulator of interferon genes (STING) agonist c-di-GMP loaded ZIF-8 nanoparticles (c-di-GMP@ZIF-8). Nanocubic ZIF-8 was screened as the most efficient intracellular drug delivery vector from five differently-shaped morphologies. The NOCC/AHA hydrogel released c-di-GMP@ZIF-8 more quickly (43 %) in acidic environment (pH = 5.5) of infected wounds compared with 34 % in non-infected wound environment (pH = 7.4) at 96 h due to pH-responsive degradation performance. The released c-di-GMP@ZIF-8 was found to activate the STING signaling of macrophages and enhance the secretion of IFN-ß, CCL2, and CXCL12 5.8-7.6 times compared with phosphate buffer saline control, which effectively inhibited S. aureus growth and promoted fibroblast migration. In rat models with infected wounds, the c-di-GMP@ZIF-8 nanocomposite hydrogels improved infected wound healing by promoting granulation tissue regeneration, alleviating S. aureus-induced inflammation, and improving angiogenesis. Altogether, this study demonstrated a feasible strategy using STING-targeted and pH-responsive hydrogels for infected wound management.

In situ fabricated ZnO nanostructures within carboxymethyl cellulose-based ternary hydrogels for wound healing applications.

Zinc oxide nanostructures (ZnO NS) were fabricated in situ within a ternary hydrogel system composed of carboxymethyl cellulose-agarose-polyvinylpyrrolidone (CAP@ZnO TNCHs) by a one-pot method employing moist-heat solution casting. The percentages of CMC and ZnO NS were varied in the CAP hydrogel films and then they were investigated by different techniques, such as ATR/FTIR, TGA, XRD, XPS, and FE-SEM analysis. Furthermore, the mechanical properties, hydrophilicity, swelling, porosity, and antibacterial activity of the CAP@ZnO TNCHs were studied. In-vitro biocompatibility assays were performed with skin fibroblast (CCD-986sk) cells. In-vitro culture of CCD-986sk fibroblasts showed that the ZnO NS facilitated cell adhesion and proliferation. Furthermore, the application of CAP@ZnO TNCHs enhanced cellular interactions and physico-chemical, antibacterial bacterial, and biological performance relative to unmodified CAP hydrogels. Also, an in vivo wound healing study verified that the CAP@ZnO TNCHs promoted wound healing significantly within 18 days, an effect superior to that of unmodified CAP hydrogels. Hence, these newly developed cellulose-based ZnO TNCHs are promising materials for wound healing applications.

Design and Self-Assembly of Peptide-Copolymer Conjugates into Nanoparticle Hydrogel for Wound Healing in Diabetes.

Background: Delayed wound healing in skin injuries has become a significant problem in clinics, seriously affecting and even threatening life and health. Recently, research interest has increased in developing wound dressings containing bioactive compounds capable of improving outcomes for complex healing needs. Methods: In this study, Puerarin-loaded nanoparticles (Pue-NPs) were prepared using the cell-penetrating peptide-poly (lactic-co-glycolic acid) (CPP-PLGA) as a drug carrier by the emulsified solvent evaporation method. Then, they were added into poly (acrylic acid) to obtain a self-assembled nanocomposite hydrogels (SANHs) drug delivery system using the co-polymerization method. The particle size, zeta potential, and micromorphology of Pue-NPs were measured; the appearance, mechanical properties, adhesive strength, and biological activity of SANHs were performed. Finally, the potential of SANHs for wound healing was further evaluated in streptozotocin-induced diabetic mice. Results: Pue-NPs were regularly spherical, with an average particle size of 134.57 ± 1.42 nm and a zeta potential of 2.14 ± 0.78 mV. SANHs was colorless and transparent with a honeycomb-like porous structure and had an excellent swelling ratio (917%), water vapor transmission rate (3077 g·m-2·day-1), mechanical properties (Young's modulus of 18 kPa, elongation at break of 307%), and adhesive strength (15.5 kPa). SANHs exhibited sustained release of Pue over 48h, with a cumulative release of 55.60 ± 6.01%. In vitro tests revealed that the SANHs presented a 92.22% antibacterial rate against Escherichia coli after 4h, and a 61.91% scavenging rate of 1.1-diphenyl-2-trinitrophenylhydrazine (DPPH) radical. In vivo experiments showed that SANHs accelerated wound repair by reducing the inflammatory response at the wound site, promoting angiogenesis, and facilitating epidermal regeneration and collagen deposition. Conclusion: In conclusion, we successfully prepared SANHs. Our results show that SANHs have excellent performance and improves wound healing in diabetic mice model, indicating that it can be used to develop an effective strategy for the treatment of diabetic wounds.

Nanocomposite Hydrogel for Real-Time Wound Status Monitoring and Comprehensive Treatment.

Current skin sensors or wound dressings fall short in addressing the complexities and challenges encountered in real-world scenarios, lacking adequate capability to facilitate wound repair. The advancement of methodologies enabling early diagnosis, real-time monitoring, and active regulation of drug delivery for timely comprehensive treatment holds paramount significance for complex chronic wounds. In this study, a nanocomposite hydrogel is devised for real-time monitoring of wound condition and comprehensive treatment. Tannins and siRNA containing matrix metalloproteinase-9 gene siRNA interference are self-assembled to construct a degradable nanogel and modified with bovine serum albumin. The nanogel and pH indicator are encapsulated within a dual-crosslinking hydrogel synthesized with norbornene dianhydride-modified paramylon. The hydrogel exhibited excellent shape adaptability due to borate bonding, and the click polymerization reaction led to rapid in situ curing of the hydrogel. The system not only monitors pH, temperature, wound exudate alterations, and peristalsis during wound healing but also exhibits hemostatic, antimicrobial, anti-inflammatory, and antioxidant properties, modulates macrophage polarization, and facilitates vascular tissue regeneration. This therapeutic approach, which integrates the monitoring of pathological parameters with comprehensive treatment, is anticipated to address the clinical issues and challenges associated with chronic diabetic wounds and infected wounds, offering broad prospects for application.

Porphyrin-based-MOF nanocomposite hydrogels for synergistic sonodynamic and gas therapy against tumor.

The glioma is one of the most aggressive tumors in humans, which is difficult to eradicate clinically. Therefore, we devised a porphyrin-based metal-organic frameworks (MOFs) crosslinking hyaluronic acid (HA) hydrogel nanocomposite through double-network (Cu-MOF-S-S-HA-Gel, CSSH-Gel), which is tumor responsive for enhanced gas therapy and sonodynamic therapy (SDT). Firstly, the hydrogels show extraordinary injectability and biocompatibility, which enables intratumor administration to circumvent the danger associated with surgery. The Cu-MOF-Cys and HA-Cys are interconnected through ether and disulfide bonds to establish a dual-network gel structure. The overexpressed glutathione (GSH) in tumor microenvironment (TME) reacts with disulfide bonds to release of the nanosensitizer (Cu-MOF). Subsequently, Cu-MOF generates reactive oxygen species (ROS) upon ultrasound irradiation for SDT, and releases L-cysteine(L-Cys) catalyzed by 3-mercapto pyruvate sulfotransferase (3-MST) to generate H2S for gas therapy. The CSSH-Gel obtained excellent synergistic anti-tumor effects (82.34 % inhibition ratio in vivo), which holds tremendous promise for the advancement of minimally invasive glioma therapies.

Enhancing the Mechanical Properties of Injectable Nanocomposite Hydrogels by Adding Boronic Acid/Boronate Ester Dynamic Bonds at the Nanoparticle-Polymer Interface.

Incorporating nanoparticles into injectable hydrogels is a well-known technique for improving the mechanical properties of these materials. However, significant differences in the mechanical properties of the polymer matrix and the nanoparticles can result in localized stress concentrations at the polymer-nanoparticle interface. This situation can lead to problems such as particle-matrix debonding, void formation, and material failure. This work introduces boronic acid/boronate ester dynamic covalent bonds (DCBs) as energy dissipation sites to mitigate stress concentrations at the polymer-nanoparticle interface. Once boronic acid groups were immobilized on the surface of SiO2 nanoparticles (SiO2-BA) and incorporated into an alginate matrix, the nanocomposite hydrogels exhibited enhanced viscoelastic properties. Compared to unmodified SiO2 nanoparticles, introducing SiO2 nanoparticles with boronic acid on their surface improved the structural integrity and stability of the hydrogel. In addition, nanoparticle-reinforced hydrogels showed increased stiffness and deformation resistance compared to controls. These properties were dependent on nanoparticle concentration. Injectability tests showed shear-thinning behavior for the modified hydrogels with injection force within clinically acceptable ranges and superior recovery.