Nanocomposite Hydrogel System Research Articles

An injectable nanocomposite hydrogel prevents postoperative tumor recurrence and wound infection via synergistic photothermal-chemo-therapy

HypothesisTumor recurrence, bacterial infection, and wound healing remain significant clinical challenges after skin-tumor resection. In this study, we tested the hypothesis that a multifunctional nanocomposite platform containing nanoparticles (NPs) with the photothermal agent IR820 and bioactive drug curcumin (Cur) would be able to prevent tumor recurrence, limit bacterial wound infections, and promote wound healing. ExperimentsIn this study, we developed a near-infrared light-activated nanocomposite hydrogel system (Hydrogel/Cur@IR820) by incorporating self-assembled NPs (Cur@IR820) in solutions containing Pluronic F127 modified with aldehyde groups (F127-CHO) and polyethyleneimine-grafted F127 (F127-PEI). FindingsThe Hydrogel/Cur@IR820 platform exhibited inherent multifunctional properties, including superior injectability, self-healing behavior, photothermal effects, and free radical scavenging ability. The Cur@IR820 NPs led to photonic hyperthermia and near-infrared (NIR)-triggered Cur release, which drove synergistic therapeutic effects against bacteria and tumor cells. Furthermore, the Hydrogel/Cur@IR820 system promoted wound repair and tissue regeneration by reducing inflammation through the antioxidant properties of Cur. Overall, the results of this study have clinical implications for inhibiting tumor growth, treating bacterial infections, and accelerating tissue regeneration.

Decoding Macrophage Subtypes to Engineer Modulating Hydrogels for the Alleviation of Intervertebral Disk Degeneration.

A major pathological basis for low back pain is intervertebral disk degeneration, which is primarily caused by the degeneration of nucleus pulposus cells due to imbalances in extracellular matrix (ECM) anabolism and catabolism. The phenotype of macrophages in the local immune microenvironment greatly influences the balance of ECM metabolism. Therefore, the control over the macrophage phenotype of the ECM is promising to repair intervertebral disk degeneration. Herein, the preparation of an injectable nanocomposite hydrogel is reported by embedding epigallocatechin-3-gallate-coated hydroxyapatite nanorods in O-carboxymethyl chitosan cross-linked with aldehyde hyaluronic acid that is capable of modulating the phenotype of macrophages. The bioactive components play a primary role in repairing the nucleus pulposus, where the hydroxyapatite nanorods can promote anabolism in the ECM through the nucleopulpogenic differentiation of mesenchymal stem cells. In addition, epigallocatechin-3-gallate can decrease catabolism in the ECM in nucleus pulposus by inducing M2 macrophage polarization, which exists in normal intervertebral disks and can alleviate degeneration. The nanocomposite hydrogel system shows promise for the minimally invasive and effective treatment of intervertebral disk degeneration by controlling anabolism and catabolism in the ECM and inhibiting the IL17 signaling pathway (M1-related pathway) in vitro and in vivo.

Thermoresponsive injectable self-healing hydrogel containing polydopamine-coated Fe/Mo-doped TiO2 nanoparticles for efficient synergistic sonodynamic-chemodynamic-photothermal-chemo therapy

A smart hydrogel loading multifunctional nanoparticles and anticancer drugs was designed to achieve synergistic therapy against tumors with high efficiency and specificity. The thermoresponsive injectable self-healing hydrogel was prepared through the Schiff base between aldehyde-functionalized poly(2-(2-methoxyethoxy) ethyl methacrylate)–co-oligo(ethylene glycol) methacrylate-co-2-hydroxyethyl methacrylate) (P(MEO2MA-co-OEGMA-co-HEMA), APMOH) and hydroxypropyl chitosan (HPCS). The polydopamine-coated Fe/Mo-doped titanium dioxide nanoparticles (PDA@dTiO2 NPs) were prepared and dispersed into the hydrogel with anticancer drug doxorubicin (DOX). PDA@dTiO2 NPs as sonosensitizers can convert oxygen into singlet oxygen (1O2) under ultrasound (US) irradiation, achieving sonodynamic therapy (SDT). They were also considered nanoenzymes, generating oxygen to supply an oxygen source for SDT, producing hydroxyl radical (·OH) to achieve chemodynamic therapy (CDT), and eliminating glutathione (GSH) to enhance the level of oxidative stress. After near-infrared (NIR) irradiation, the temperature of the hydrogel increased due to the photothermal ability of the polydopamine (PDA) layer. When the temperature reached the hydrogel's lower critical solution temperature (LCST), the hydrophilic-hydrophobic transformation occurred, and the hydrogel volume contracted. Consequently, the release rate of PDA@dTiO2 NPs and DOX increased, improving the therapeutic effects. The nanocomposite hydrogel system can achieve synergistic sonodynamic-chemodynamic-photothermal-chemo therapy (SDT-CDT-PTT-CT) for tumors, providing a novel platform for synergistic tumor treatment.

Self-healing and shape-adaptive nanocomposite hydrogels with anti-inflammatory, antioxidant, antibacterial activities and hemostasis for real-time visual regeneration of diabetic wounds

Diabetic severe wounds are difficult to heal and regenerate, and are extremely challenging to manage in clinical practice with common wound dressings. There is a need to develop multifunctional dressings that meet the requirements for efficient treatment of diabetic wounds. Therefore, the nanocomposite hydrogel with oxidized chondroitin sulfate (OCS), carboxymethyl chitosan (CMC), and phenol red-modified ε-poly-l-lysine (EPL-PR) as the backbones, encapsulated with chondroitin sulfate-modified selenium nanoparticles (CS@SeNPs) and infinite coordination polymer nanomedicine (ICPs) composed of procyanidins, berberine hydrochloride and Fe(III), was designed and fabricated. The prepared nanocomposite hydrogel system allows for rapid in situ gelation and complete coverage of irregular wounds. In vivo and in vitro investigations demonstrate that the nanocomposite hydrogel shows excellent tissue adhesion, antibacterial activities, biocompatibility and free radical scavenging properties. The rapid hemostasis of the nanocomposite hydrogel is confirmed through hemorrhage models of liver and caudal amputation. All the advantages enable the nanocomposite hydrogel to effectively induce skin tissue remodeling, promote vascular and hair follicle regeneration, remove free radicals from wounds, and accelerate wound healing. The nanocomposite hydrogel can also successfully monitor the pH range of 5–10, thus enabling real-time visual monitoring of the wound healing phase, facilitating wound management in clinical settings. This multifunctional wound dressing opens up ideas for the treatment and management of diabetic full-thickness wounds.

Design and fabrication of a Preformed Thixotropic-Viscoelastic Nanocomposite hydrogel system (PNCH) for controlling sand production in reservoirs

In this study, the performance of preformed dual crosslinked nanocomposite hydrogels (PNCH) consisting of acrylamide, 2-acrylamide-2-methylpropane sulfonic acid, maleic acid, and acrylic acid in sand control was investigated. Also, the effects of three nanoparticles (NPs) of iron (PNCH1), silicon (PNCH2), and bentonite (PNCH3) on the PNCH structure were studied. The morphology, equilibrium swelling ratio (ESR), rheology, thermal strength, zeta potential, and compressive strength were experimentally analyzed. According to the XRD results, the NPs were completely dispersed in all three samples. The results of SEM and EDS tests confirmed the presence of NPs within the PNCHs with a dense, homogeneous, and porous structure. The results of the ESR at distilled and formation water at ambient temperature for PNCHs (1), (2), and (3) were (13.9,4.55), (15.45, 6.35), and (12.9, 4.8), also at reservoir temperatures ESR results were reported (78, 17.5), (89, 13), and (70,12.9) respectively. From the TGA results, structure destruction of PNCHs starts at 222, 225, and 202 °C respectively so the addition of 1 wt% of NPs increased the structure destruction from nearly 80 °C to more than 200 °C. Based on the results of the strain sweep test, structures of PNCHs can cause viscoelastic behavior with the maximum elastic modulus of 29,000, 8430, and 10,800, and critical strain of (10%, 19.3%, and 10.8%) respectively. The loop test results confirmed the time-dependent viscoelastic properties of thixotropic in all structures. Finally, in compressive strength test revealed that adding 0.5 pore volume of 1 wt% of PNCH into the sandpack increased its strength by 980%.

Injectable heat-sensitive nanocomposite hydrogel for regulating gene expression in the treatment of alcohol-induced osteonecrosis of the femoral head.

For repairing lesions, it is important to recover physiological and cellular activities. Gene therapy can restore these activities by regulating the expression of genes in lesion cells; however, in chronic diseases, such as alcohol-induced osteonecrosis of the femoral head (ONFH), gene therapy has failed to provide long-term effects. In this study, we developed a heat-sensitive nanocomposite hydrogel system with a secondary nanostructure that can regulate gene expression and achieve long-term gene regulation in lesion cells. This nanocomposite hydrogel exists in a liquid state at 25 °C and is injectable. Once injected into the body, the hydrogel can undergo solidification induced by body heat, thereby gaining the ability to be retained in the body for a prolonged time period. With the gradual degradation of the hydrogel in vivo, the internal secondary nanostructures are continuously released. These nanoparticles carry plasmids and siRNA into lesion stem cells to promote the expression of B-cell lymphoma 2 (inhibiting the apoptosis of stem cells) and inhibit the secretion of peroxisome proliferators-activated receptors γ (PPARγ, inhibiting the adipogenic differentiation of stem cells). Finally, the physiological activity of the stem cells in the ONFH area was restored and ONFH repair was promoted. In vivo experiments demonstrated that this nanocomposite hydrogel can be indwelled for a long time, thereby providing long-term treatment effects. As a result, bone reconstruction occurs in the ONFH area, thus enabling the treatment of alcohol-induced ONFH. Our nanocomposite hydrogel provides a novel treatment option for alcohol-related diseases and may serve as a useful biomaterial for other gene therapy applications.

Mussel-Inspired Tantalum Nanocomposite Hydrogels for In Situ Oral Cancer Treatment.

Oral squamous cell carcinoma (OSCC) is one of the most common oral malignancies. Radiotherapy is the primary noninvasive treatment of OSCC for avoiding surgery-induced facial deformities and impaired oral function. However, the specificity of in situ OSCC limits radiotherapeutic effects because of the hypoxia-induced low radiosensitivity of tumors and the low radiation tolerance of surrounding normal tissues. Here, we design a highly efficient and low-toxic radiosensitization strategy. On the one hand, biocompatible poly(vinyl pyrrolidone)-modified tantalum nanoparticles (Ta@PVP NPs) not only have strong X-ray deposition capability to upregulate oxidative stress but also have photothermal conversion efficiency to improve hypoxia for tumor radiosensitivity. On the other hand, to optimize the spatial distribution of Ta@PVP NPs within tumors, mussel-inspired catechol with bioadhesive properties is grafted on tumor microenvironment-responsive sodium alginate (DAA) to form in situ hydrogels for precision radiotherapy. On this basis, we find that Ta@PVP-DAA hydrogels effectively inhibit OSCC development in mice under photothermal-assisted radiotherapy without facial deformities and damage to surrounding normal tissues. Overall, our work not only promotes the exploration of Ta@PVP NPs as new radiosensitizers for OSCC but also develops a nanocomposite hydrogel system strategy as a promising paradigm for the precision treatment of orthotopic tumors.

Synthesis, characterization, and rheological behavior of HPG graft poly (AM-co-AMPS)/GO nanocomposite hydrogel system for enhanced oil recovery

The purpose of this study is to investigate the synthesis of graft copolymer nanocomposite based on hydroxypropyl guar (HPG) graft acrylamide (AM) and 2-acryloamido-2-methyl propane sulfonic acid (AMPS), reinforced with graphene oxide (GO), and study its suitability for the development of the copolymer-based hydrogel systems by chromium triacetate crosslinker to use in oil recovery applications. The characterization outcomes acknowledged the grafting of AM and AMPS onto HPG in the attendance of the GO. The uniform dispersion of GO at 0.1 wt.% was observed in the morphology analysis. Moreover, not only the viscosity but also, the storage and loss modulus of graft copolymer nanocomposites hydrogel improved by adding GO. The effect of graft copolymer nanocomposite and crosslinker concentrations on the performance of hydrogel was also evaluated and optimized by a rheological test. These results showed the outstanding performance of crosslinked hydrogel structure of HPG-g-poly (AM-co-AMPS)/GO, owing to the linking of AM with AMPS and grafting on the HPG chains and the surface of GO in attendance of chromium triacetate. This makes the copolymer hydrogel system more stable against salinity, shearing, and high temperatures. Therefore, this nanocomposite hydrogel system is potentially useful for oil recovery applications.

An Injectable Nanocomposite Hydrogel Improves Tumor Penetration and Cancer Treatment Efficacy

Hydrogel as a local drug depot can increase drug concentration at the tumor site. However, conventional drug-loaded hydrogel is typically formed by direct dissolution of drug molecules inside the hydrogel, which usually suffers from limited drug retention and poor tumor penetration. In this study, a nanocomposite hydrogel consisting of oxaliplatin (OXA)-conjugated G5 polyamidoamine (G5-OXA) and oxidized dextran (Dex-CHO) is constructed to improve local drug delivery. The OXA-containing nanocomposite hydrogel (denoted as PDO gel) is injectable and could maintain in vivo up to more than three weeks, which increases drug retention in tumor tissues. More interestingly, G5-OXA released from the PDO gel show potent tumor penetration mainly through an active transcytosis process. In vivo antitumor studies in an orthotopic 4T1 tumor model show that PDO gel significantly inhibits primary tumor growth as well as the metastasis. In addition, the PDO gel can also activate the immunosuppressive tumor microenvironment through immunogenic cell death effect, and further improves therapeutic efficacy with the combination of PD-1 antibody. These results demonstrate that the nanocomposite hydrogel can simultaneously enhance the retention and penetration of chemotherapeutic drugs via the combination of both advantages of hydrogel and nanoparticles, which provides new insights for the design of local drug delivery systems. Statement of significanceHydrogel represents an important class of local drug delivery depot. However, conventional drug-loaded hydrogel is usually achieved by direct dissolution of small drug molecules inside the hydrogel, which typically suffers from limited drug retention and poor tumor penetration. Herein, we developed a nanocomposite hydrogel, which could gradually degrade and release drug-conjugated small nanoparticles (∼ 6 nm) for improved tumor penetration through the combination of an active transcytosis process and a passive diffusion process. This nanocomposite hydrogel system improved tumor penetration and retention of drug in primary tumors as well as the drug deposition in lymph nodes, which significantly suppressed tumor growth and metastasis.

Modulating the Properties of Poly(glycerol sebacate)-Based Polyurethane Hydrogels Using an Organoclay.

Elastomeric hydrogels are promising in soft tissue applications due to their biomimetic mechanical and physical behaviors. In this study, we design and synthesize a poly(glycerol sebacate)-based polyurethane-clay nanocomposite hydrogel system with controllable mechanical, swelling, drug release, and biodegradation behaviors. The polymer-clay nanocomposites are synthesized by in situ polymerization in the presence of a solvent, which facilitates the dispersion of clay within the polymer matrix and their bonding. The nanocomposite hydrogels exhibit higher water swelling ratios in comparison to the neat polymer. The fully swollen hydrogels are capable of enduring complex mechanical deformations such as stretching and knotting, while the tensile moduli of the hydrogels mimic various soft tissues in human body. The mechanical behavior of hydrogels is significantly enhanced by the addition of no more than 3 phr clay, showing higher stiffness, strength, ductility, and toughness. The drug loading and release behavior of the hydrogels is investigated with three model drugs, showing selective drug loading capacity and sustained release, based on the Coulombic interaction between the clay and drug molecules. Biodegradation tests under a simulated body condition reveal a highly tunable degradation rate by the clay content in the nanocomposite hydrogels. Good cytocompatibility by the cell metabolic assay with mouse fibroblasts in vitro is also demonstrated. Finally, three-dimensional microporous foam is manufactured as a proof-of-concept study.

Liposomal SDF-1 Alpha Delivery in Nanocomposite Hydrogels Promotes Macrophage Phenotype Changes and Skin Tissue Regeneration.

Skin regeneration in chronic wounds is often delayed due to persistent inflammation induced by underlying conditions such as diabetes. This effect is mediated, in part, by macrophages present in the wound, which can be stimulated to adopt either pro- or anti-inflammatory phenotypes depending on the status of the local microenvironment. In this work, the prohealing chemokine stromal cell-derived factor-1 alpha (SDF-1α) is controllably released from a hydrogel-based biomaterial to promote skin tissue regeneration and wound closure. This innovative nanocomposite hydrogel system releases liposomal stromal cell-derived factor-1 alpha (lipoSDF) as a new treatment approach for dorsal full-thickness skin wounds in wild-type and diabetic mice. Using this strategy, the recruitment and polarization of macrophages primarily of the anti-inflammatory phenotype were observed, along with a decreased amount of open wound surface area in diabetic mice after 28 days. This was accompanied by histological observations of increased epidermal stratification and dermal angiogenesis. These findings represent an important step of investigation distinctive in its field for developing immunomodulatory biomaterials that are able to influence macrophage phenotype and promote healing as hydrogel-based wound dressings.

Characterization, antioxidant activity, and biocompatibility of selenium nanoparticle-loaded thermosensitive chitosan hydrogels

In this study, we recruited chitosan (CS) both for selenium nanoparticles (SeNPs) synthesis and for the development of a thermoresponsive nanocomposite hydrogel with the addition of glycerol phosphate (GP). Considering that SeNPs are toxic at high concentrations, five different ingredients of the nanocomposite hydrogel system with low concentrations of SeNPs (1.25–20 μg/mL) were prepared. The gelation conditions, structural characteristics, and mechanical properties of SeNPs-loaded thermosensitive CS/GP hydrogels were investigated. We also evaluated their antioxidizing activities and biocompatibility of the CS/GP/SeNPs hydrogels. Our study demonstrated that the incorporation of SeNPs in the hydrogel improved its mechanical properties, antioxidant activity, and degree of swelling. According to the properties of SeNPs and CS/GP thermosensitive hydrogels, the combination of these two technologies in an appropriate manner would be a promising antioxidant system for drug delivery and tissue engineering.

Injectable and self-healing nanocomposite hydrogel loading needle-like nano-hydroxyapatite and graphene oxide for synergistic tumour proliferation inhibition and photothermal therapy.

Non-chemotherapeutic tumour treatment has received extensive attention due to its having fewer side effects as compared to chemotherapy. However, nanomaterials-based non-chemotherapy still faces limitations such as poor targeting and low retention. Therefore, a Schiff base cross-linked hydrogel was designed and prepared using aldehyde-modified polyethylene glycol (PEG) and carboxymethyl chitosan (CMC). This hydrogel has good injectable and self-healing properties and can carry graphene oxide (GO) as a photothermal agent and needle-like nano-hydroxyapatite (HAP) as a tumour inhibitor. Combined with tumour proliferation inhibition therapy and photothermal therapy, the nanocomposite hydrogel system can avoid the side effects of chemotherapy and improve the accuracy of tumour treatment. The PEG-CMC/HAP/GO nanocomposite hydrogel system has a porous structure, good injectability and self-healing properties to meet the mechanical requirements. In vitro cell characterization showed that GO is phototoxic to tumour cells, HAP can inhibit the proliferation of tumour cells, the nanocomposite hydrogel remained in the tumour site, and the encapsulated GO and HAP did not transfer to the normal site and cause cell damage. In the in vivo investigation, the breast cancer tumour-bearing mice, the model animals for tumour treatment, were treated with an intratumoral injection of the PEG-CMC/HAP/GO nanocomposite hydrogel. This functional self-healing hydrogel loaded with GO and HAP effectively inhibited tumour cell proliferation and realized the synergistic effect of photothermal therapy, which is expected to become a new effective treatment approach for tumours.

Gold Nanoparticle Promoted Formation and Biological Properties of Injectable Hydrogels.

Acceleration of gelation in the biological environment and improvement of overall biological properties of a hydrogel is of enormous importance. Biopolymer stabilized gold (Au) nanoparticles (NPs) exhibit cytocompatibility and therapeutic activity. Hence, in situ gelation and subsequent improvement in the property of a hydrogel by employing Au NPs is an attractive approach. We report that stable Au NPs accelerate the conventional nucleophilic substitution reaction of activated halide-terminated poly(ethylene glycol) and tertiary amine functional macromolecules, leading to the rapid formation of injectable nanocomposite hydrogels in vivo and ex vivo with improved modulus, cell adhesion, cell proliferation, and cytocompatibility than that of a pristine hydrogel. NP surfaces with low chain grafting density and good colloidal stability are crucial requirements for the use of these NPs in the hydrogel formation. Influence of the structure of the amine functional prepolymer, the spacer connecting the halide leaving groups of the substrate, and the structure of the stabilizer on the rate promoting activity of the NPs have been evaluated with model low-molecular-weight substrates and macromolecules by 1H NMR spectroscopy, rheological experiments, and density functional theory. Results indicate a significant effect of the spacer connecting the halide leaving group with the macromolecule. The Au nanocomposite hydrogels show sustained co-release of methotrexate, an anti-rheumatic drug, and the Au NPs. This work provides insights for designing an injectable nanocomposite hydrogel system with multifunctional property. The strategy of the use of cytocompatible Au NPs as a promoter provides new opportunity to obtain an injectable hydrogel system for biological applications.

A liposome/gelatin methacrylate nanocomposite hydrogel system for delivery of stromal cell-derived factor-1α and stimulation of cell migration

Chronic, non-healing skin and soft tissue wounds are susceptible to infection, difficult to treat clinically, and can severely reduce a patient's quality of life. A key aspect of this issue is the impaired recruitment of mesenchymal stem cells (MSCs), which secrete regenerative cytokines and modulate the phenotypes of other effector cells that promote healing. We have engineered a therapeutic delivery system that can controllably release the pro-healing chemokine stromal cell derived factor-1α (SDF-1α) to induce the migration of MSCs. In order to protect the protein cargo from hydrolytic degradation and control its release, we have loaded SDF-1α in anionic liposomes (lipoSDF) and embedded them in gelatin methacrylate (GelMA) to form a nanocomposite hydrogel. In this study, we quantify the release of SDF-1α from our hydrogel system and measure the induced migration of MSCs in vitro via a transwell assay. Lastly, we evaluate the ability of this system to activate intracellular signaling in MSCs by using Western blots to probe for the phosphorylation of key proteins in the mTOR pathway. To our knowledge, this is the first study to report the delivery of liposomal SDF-1α using a nanocomposite approach. The results of this study expand on our current understanding of factors that can be modified to affect MSC behavior and phenotype. Furthermore, our findings contribute to the development of new hydrogel-based therapeutic delivery strategies for clinical wound healing applications. Statement of SignificanceChronic, non-healing wounds promote an inflammatory environment that inhibits the migration of mesenchymal stem cells (MSCs), which secrete pro-healing and regenerative cytokines. The goal of this project is to apply principles of tissue engineering to achieve controllable release of the pro-healing chemokine SDF-1α to modulate the intracellular signaling and migratory behavior of MSCs. In this work, we introduce a nanocomposite strategy to tailor the release of SDF-1α using a liposome/gelatin methacrylate hydrogel approach. We are the first group to report the delivery of liposomal SDF-1α using this strategy. Our findings aim to further elucidate the role of MSCs in directing wound healing and guide the development of immunomodulatory and therapeutic delivery strategies for clinical wound healing applications.

Polymer/zeolite nano-composite hydrogels as promising water reservoir materials: effect of clinoptilolite content on physicochemical properties

In this work, with the aim of improving the water uptake behavior and mechanical properties, a novel nano-composite hydrogel system was synthesized using clinoptilolite as a semi-layered zeolite. Accordingly, the gelatin/SCMC-g-poly (AA-co-AAm)/clinoptilolite semi-IPN nano-composite hydrogel samples were synthesized and studied. The FTIR, XRD, SEM and EDX analysis were accomplished to confirm the successful synthesis of the nano-composite hydrogel samples. Additionally, to investigate the effect of clinoptilolite content on water uptake properties and gel characteristics of the synthesized nano-composite hydrogel samples, water absorption kinetics studies and rheological evaluations were carried out. It is obtained that, there is an optimum amount for additive content which can improve the hydrogel properties. Results showed that nano-composite hydrogel sample with 5% W/W of clinoptilolite with respect to the gelatin amount has the best efficiency from the point of view of the water absorption properties and gel characteristics. This phenomenon is related to the creation of physical cross linking in the hydrogels’ structure which leads to the creation of porous hydrogels.

Single-injecting, bioinspired nanocomposite hydrogel that can recruit host immune cells in situ to elicit potent and long-lasting humoral immune responses

Vaccination is an effective medical intervention for preventing disease. However, without an adjuvant, most subunit vaccines are poorly immunogenic. This work develops a bioinspired nanocomposite hyaluronic acid hydrogel system that incorporates N-trimethyl chitosan nanoparticles (TMC/NPs) that carry a model subunit vaccine ovalbumin (OVA) that can elicit a potent and prolonged antigen-specific humoral response. Experimental results indicate that the nanocomposite hydrogel system (NPs-Gel) can retain a large proportion of its TMC/NPs that are bonded by covalent/electrostatic interactions and extend the release of the encapsulated OVA, enabling their localization at the site of hydrogel injection. The positively charged TMC/NPs can be effectively internalized by dendritic cells, significantly augmenting their maturation, suggesting that TMC can function as an adjuvant-based OVA delivery system. Upon subcutaneous implantation in mice, the NPs-Gel acts as an in situ depot that recruits and concentrates immune cells. The TMC/NPs that do not have any specific interactions with the hydrogel network are released rapidly and internalized by the neighboring immune cells, providing a priming dose, while those retained inside the NPs-Gel are ingested by the recruited and concentrated immune cells over time, acting as a booster dose, eliciting high titers of OVA-specific antibody responses. These experimental results suggest particulate vaccines that are integrated in such a bioinspired hydrogel system may be used as single-injection prime-boost vaccines, enabling effective and persistent humoral immune responses.

Injectable in Situ Shape-Forming Osteogenic Nanocomposite Hydrogel for Regenerating Irregular Bone Defects.

The in situ forming injectable hydrogels are appealing for irregular bone defects because of the ease of administration and the addition of ceramics, molecules, and proteins into the hydrogel. We have developed in situ shape-forming hydrogel using oxidized alginate and gelatin as the hydrogel matrix. Whitlockite bioceramic nanoparticles (WH NPs) were incorporated, as they provide enhanced osteogenic stimulation compared to hydroxyapatite via providing higher local ion concentration. The drug simvastatin was also incorporated into the hydrogel system, as it increases the expression of BMP-2 thereby provide environment for bone regeneration. The presence of both WH nanoparticles and simvastatin would enhance bone regeneration potential. The whitlockite nanoparticles (80 ± 8 nm) were synthesized by precipitation method and were characterized. The nanocomposite hydrogel system was characterized by SEM, FTIR and rheologically. The gelation time of the in situ nanocomposite hydrogel was determined by rheological analysis as 28 s, whereas hydrogel alone showed 132 s. Addition of WH NPs not only shortened the gelation time but also increased the gel strength. The in vitro release of simvastatin from the nanocomposite hydrogel showed a release over a period of 28 days. The alkaline phosphatase (ALP) level also showed a significant increase. RUNX2 and BMP2 expressions showed that nanocomposite hydrogel enhanced the osteogenic differentiation. In vivo bone regeneration studies in mice cranial defect studies showed nanocomposite hydrogel was effective in regenerating the bone compared to controls. Thus, the simvastatin-incorporated oxidized alginate-gelatin/WH NPs hydrogel system has the potential to be used as a repairing and regenerative system in cranial bone defects.

Poly(vinyl alcohol)/chitosan/honey/clay responsive nanocomposite hydrogel wound dressing

ABSTRACTMany efforts have been made to develop modern wound dressings to overcome limitations of traditional ones. Smart nanocomposite hydrogels are appropriate candidates. In this work, a novel responsive nanocomposite hydrogel based on poly(vinyl alcohol)/chitosan/honey/clay was developed and evaluated as a novel wound dressing. The morphology and properties of synthesized nanocomposite hydrogels loaded with honey as a drug model were investigated. The exfoliated morphology of nanocomposite was confirmed by X‐ray diffractometry. Swelling studies were performed at 20 and 37 °C at various pH. The results showed that swelling increased as a result of temperature rise and maximum swelling occurred at a pH of 2. In vitro release of honey was also studied at the same conditions. Corresponding results indicated faster honey release rate at higher pH values. MTT results exhibited no cytotoxicity in nanocomposite hydrogel system. Investigation of antibacterial activity revealed more than 99% antibacterial activity for proposed system. In vivo results confirmed the wound healing ability of developed system. Generally, appropriate properties of proposed system made it ideal in wound dressing applications. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46311.

Controlled tuning of LCST based on poly (N-isopropylacrylamide)/Hydroxypropyl cellulose temperature-sensitive hydrogel by electron beam pre-radiation method

As a temperature-sensitive-discoloration hydrogel based on NIPAAm/HHPC was fabricated via two steps of electron beam radiation. Small nanomaterial such as GO and Fe2O3 were also added severally into the system of hydrogel as chromogenic agent. Different colors can be displayed in nanocomposite hydrogel system at the low, medium and high temperature respectively. The LCST of hydrogel system can be also adjusted precisely by the changes of irradiation dose of the prepolymer and composition ratio. Experimental results showed that the hydrogel can be changed quickly itself color in its near LCST. The microstructure and composition of nanocomposite hydrogel were characterized further by NMR, FTIR, TG, DSC, XRD, FE-SEM and XPS so as to reveal the mechanism of temperature-sensitive- discoloration. The novel NIPAAm/HHPC-based nanocomposite hydrogel is suitable especially to indicate different fever temperatures for fever patients and can be expected to as a new type of temperature-sensitive sensor and replace the traditional clinical thermometer.