pH responsive cross-linked polymeric matrices based on natural polymers: effect of process variables on swelling characterization and drug delivery properties.

PubMed

Naeem, Fahad; Khan, Samiullah; Jalil, Aamir; Ranjha, Nazar Muhammad; Riaz, Amina; Haider, Malik Salman; Sarwar, Shoaib; Saher, Fareha; Afzal, Samrin

2017-01-01

Introduction: The current work was aimed to design and synthesize novel crosslinked pH-sensitive gelatin/pectin (Ge/Pec) hydrogels using different polymeric ratios and to explore the effect of polymers and degree of crosslinking on dynamic, equilibrium swelling and in vitro release behavior of the model drug (Mannitol). Methods: The Ge/Pec based hydrogels were prepared using glutaraldehyde as the crosslinker. Various structural parameters that affect their release behavior were determined, including swelling study, porosity, sol-gel analysis, average molecular weight between crosslinks (Mc), volume fraction of polymer (V2,s), solvent interaction parameter (χ) and diffusion coefficient. The synthesized hydrogels were subjected to various characterization tools like Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and DSC differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Results: The hydrogels show highest water uptake and release at lower pH values. The FTIR spectra showed an interaction between Ge and Pec, and the drug-loaded samples also showed the drug-related peaks, indicating proper loading of the drug. DSC and TGA studies confirmed the thermal stability of hydrogel samples, while SEM showed the porous nature of hydrogels. The drug release followed non-Fickian diffusion or anomalous mechanism. Conclusion: Aforementioned characterizations reveal the successful formation of copolymer hydrogels. The pH-sensitive swelling ability and drug release behavior suggest that the rate of polymer chain relaxation and drug diffusion from these hydrogels are comparable which also predicts their possible use for site-specific drug delivery.

pH responsive cross-linked polymeric matrices based on natural polymers: effect of process variables on swelling characterization and drug delivery properties

PubMed Central

Naeem, Fahad; Khan, Samiullah; Jalil, Aamir; Ranjha, Nazar Muhammad; Riaz, Amina; Haider, Malik Salman; Sarwar, Shoaib; Saher, Fareha; Afzal, Samrin

2017-01-01

Introduction: The current work was aimed to design and synthesize novel crosslinked pH-sensitive gelatin/pectin (Ge/Pec) hydrogels using different polymeric ratios and to explore the effect of polymers and degree of crosslinking on dynamic, equilibrium swelling and in vitro release behavior of the model drug (Mannitol). Methods: The Ge/Pec based hydrogels were prepared using glutaraldehyde as the crosslinker. Various structural parameters that affect their release behavior were determined, including swelling study, porosity, sol-gel analysis, average molecular weight between crosslinks (Mc), volume fraction of polymer (V2,s), solvent interaction parameter (χ) and diffusion coefficient. The synthesized hydrogels were subjected to various characterization tools like Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and DSC differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Results:The hydrogels show highest water uptake and release at lower pH values. The FTIR spectra showed an interaction between Ge and Pec, and the drug-loaded samples also showed the drug-related peaks, indicating proper loading of the drug. DSC and TGA studies confirmed the thermal stability of hydrogel samples, while SEM showed the porous nature of hydrogels. The drug release followed non-Fickian diffusion or anomalous mechanism. Conclusion: Aforementioned characterizations reveal the successful formation of copolymer hydrogels. The pH-sensitive swelling ability and drug release behavior suggest that the rate of polymer chain relaxation and drug diffusion from these hydrogels are comparable which also predicts their possible use for site-specific drug delivery. PMID:29159145

Hydrogel-Based Fluorescent Dual pH and Oxygen Sensors Loaded in 96-Well Plates for High-Throughput Cell Metabolism Studies.

PubMed

Wu, Shanshan; Wu, Siying; Yi, Zheyuan; Zeng, Fei; Wu, Weizhen; Qiao, Yuan; Zhao, Xingzhong; Cheng, Xing; Tian, Yanqing

2018-02-13

In this study, we developed fluorescent dual pH and oxygen sensors loaded in multi-well plates for in-situ and high-throughput monitoring of oxygen respiration and extracellular acidification during microbial cell growth for understanding metabolism. Biocompatible PHEMA-co-PAM materials were used as the hydrogel matrix. A polymerizable oxygen probe (OS2) derived from PtTFPP and a polymerizable pH probe (S2) derived from fluorescein were chemically conjugated into the matrix to solve the problem of the probe leaching from the matrix. Gels were allowed to cure directly on the bottom of 96-well plates at room-temperature via redox polymerization. The influence of matrix's composition on the sensing behaviors was investigated to optimize hydrogels with enough robustness for repeatable use with good sensitivity. Responses of the dual sensing hydrogels to dissolved oxygen (DO) and pH were studied. These dual oxygen-pH sensing plates were successfully used for microbial cell-based screening assays, which are based on the measurement of fluorescence intensity changes induced by cellular oxygen consumption and pH changes during microbial growth. This method may provide a real-time monitoring of cellular respiration, acidification, and a rapid kinetic assessment of multiple samples for cell viability as well as high-throughput drug screening. All of these assays can be carried out by a conventional plate reader.

Preparation and properties of graphene oxide-regenerated cellulose/polyvinyl alcohol hydrogel with pH-sensitive behavior.

PubMed

Rui-Hong, Xie; Peng-Gang, Ren; Jian, Hui; Fang, Ren; Lian-Zhen, Ren; Zhen-Feng, Sun

2016-03-15

In this study, graphene oxide reinforced regenerated cellulose/polyvinyl alcohol (GO-RCE/PVA) ternary hydrogels were successfully prepared via a repeated freezing and thawing method in NaOH/urea aqueous solution. The effect of GO content on the mechanical properties, swelling behavior, water content of composite hydrogels was investigated. It was found that the mechanical properties of GO-RCE/PVA ternary hydrogels were largely enhanced relative to RCE/PVA hydrogels. With the addition of 1.0wt% GO, the tensile strength was increased by 40.4% from 0.52MPa to 0.73MPa, accompanied by the increase of the elongation at break (from 103% to 238%). Meanwhile, GO-RCE/PVA ternary hydrogels performed the excellent pH-sensitivity, and the higher pH leaded to higher swelling ratio. With 0.8wt% GO loading, the swelling ratio of GO-RCE/PVA ternary hydrogel was improved from 150% (pH=2) to 310% (pH=14). In addition, a slight increase in the water content of the ternary hydrogel was achieved with increasing concentrations of GO. It is believed that this novel ternary hydrogels is a promising material in the application of biomedical engineering and intelligent devices. Copyright © 2015 Elsevier Ltd. All rights reserved.

pH-sensitive Itaconic acid based polymeric hydrogels for dye removal applications.

PubMed

Sakthivel, M; Franklin, D S; Guhanathan, S

2016-12-01

A series of Itaconic Acid (IA) based pH-sensitive polymeric hydrogels were synthesized by condensation polymerization of Itaconic Acid (IA) with Ethylene Glycol (EG) in the presence of an acid medium resulted into pre-polymer. Further, pre-polymer were co-polymerized with Acrylic Acid (AA) through free radical polymerization using Potassium persulphate (KPS). The structural and surface morphological characterizations of the synthesized hydrogels were studied using FT-IR spectroscopy and Scanning Electron Microscope (SEM) respectively. The swelling and swelling equilibrium were performed at varies pH (4.0-10.0). Further, the effects of IA, EG and AA on swelling properties have also been investigated. Thermal stability of synthesized hydrogels have been investigated by TGA, DTA and DSC. The synthesized hydrogels have shown good ability to uptake a Cationic dye. The Methylene blue has been chosen as a model cationic dye. The results of dye removal using IA hydrogels found to have excellent dye removal capacity. Such kind of IA based hydrogels may be recommended for eco-friendly environmental application. viz., removal of dyes and metal ions and sewage water treatment, purification of water etc. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterization of pH-sensitive hydrogels by conductimetry and calorimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheppard, N.F. Jr.; Chen, Jey-Hsin; Lawson, H.C.

1993-12-31

The total and freezing water contents, and electrical conductivity of pH-sensitive hydrogels formed from poly(hydroxyethyl methacrylate - co - dimethylaminoethyl methacrylate) were measured as a function of copolymer composition and pH. For an 80/20 HEMA/DMAEMA gel (mole ratio), the water content increases from 37% at pH 10 of the bathing solution value at pH 10 to 90% at low pH. The difference between total and freezing water content in the gels is approximately 25%, consistent with values reported in the literature. An examination of the results in the context of the Yasuda free- volume model suggests that freezing water content,more » rather than total water content, may be suitable for modelling of hydrogel conductivity.« less

Xylan-Modified-Based Hydrogels with Temperature/pH Dual Sensitivity and Controllable Drug Delivery Behavior

PubMed Central

Kong, Wei-Qing; Gao, Cun-Dian; Hu, Shu-Feng; Ren, Jun-Li; Zhao, Li-Hong; Sun, Run-Cang

2017-01-01

Among the natural macromolecules potentially used as the scaffold material in hydrogels, xylan has aroused great interest in many fields because of its biocompatibility, low toxicity, and biodegradability. In this work, new pH and thermoresponsive hydrogels were prepared by the cross-linking polymerization of maleic anhydride-modified xylan (MAHX) with N-isopropylacrylamide (NIPAm) and acrylic acid (AA) under UV irradiation to form MAHX-g-P(NIPAm-co-AA) hydrogels. The pore volume, the mechanical properties, and the release rate for drugs of hydrogels could be controlled by the degree of substitution of MAHX. These hydrogels were characterized by swelling ability, lower critical solution temperature (LCST), Fourier-transform infrared (FTIR), and SEM. Furthermore, the cumulative release rate was investigated for acetylsalicylic acid and theophylline, as well as the cytocompatibility MAHX-based hydrogels. Results showed that MAHX-based hydrogels exhibited excellent swelling–deswelling properties, uniform porous structure, and the temperature/pH dual sensitivity. In vitro, the cumulative release rate of acetylsalicylic acid for MAHX-based hydrogels was higher than that for theophylline, and in the gastrointestinal sustained drug release study, the acetylsalicylic acid release rate was extremely slow during the initial 3 h in the gastric fluid (24.26%), and then the cumulative release rate reached to 90.5% after sustained release for 5 h in simulated intestinal fluid. The cytotoxicity experiment demonstrated that MAHX-based hydrogels could promote cell proliferation and had satisfactory biocompatibility with NIH3T3 cells. These results indicated that MAHX-based hydrogels, as new drug carriers, had favorable behavior for intestinal-targeted drug delivery. PMID:28772664

Facile fabrication and characterization of a novel oral pH-sensitive drug delivery system based on CMC hydrogel and HNT-AT nanohybrid.

PubMed

Hossieni-Aghdam, Seyed Jamal; Foroughi-Nia, Behrouz; Zare-Akbari, Zhila; Mojarad-Jabali, Solmaz; Motasadizadeh, Hamidreza; Farhadnejad, Hassan

2018-02-01

The main aim of the present study was to design pH-sensitive bionanocomposite hydrogel beads based on CMC and HNT-AT nanohybrid and evaluate whether prepared bionanocomposite beads have the potential to be used in drug delivery applications. Atenolol (AT), as a model drug, was incorporated into the lumen of HA nanotubes via the co-precipitation technique. HNT/AT nanohybrid and CMC/HNT-AT beads were characterized via XRD, SEM, TGA, and FT-IR techniques. Drug loading and encapsulation efficiency was found to be high for CMC/HNT3 beads. Moreover, the swelling and drug release properties of the prepared CMC/HA-AT beads were investigated, and showed a pH sensitive swelling behavior with maximum its content at pH 6.8. Also, it was found that the swelling ratio of CMC/HNT beads was lower than that of pristine CMC beads. Drug release behavior of CMC/HNT-AT bionanocomposite hydrogel beads were investigated. A more sustained and controlled drug releases were observed for CMC/HNT-AT beads. Copyright © 2017 Elsevier B.V. All rights reserved.

Flexible pH-Sensing Hydrogel Fibers for Epidermal Applications.

PubMed

Tamayol, Ali; Akbari, Mohsen; Zilberman, Yael; Comotto, Mattia; Lesha, Emal; Serex, Ludovic; Bagherifard, Sara; Chen, Yu; Fu, Guoqing; Ameri, Shideh Kabiri; Ruan, Weitong; Miller, Eric L; Dokmeci, Mehmet R; Sonkusale, Sameer; Khademhosseini, Ali

2016-03-01

Epidermal pH is an indication of the skin's physiological condition. For example, pH of wound can be correlated to angiogenesis, protease activity, bacterial infection, etc. Chronic nonhealing wounds are known to have an elevated alkaline environment, while healing process occurs more readily in an acidic environment. Thus, dermal patches capable of continuous pH measurement can be used as point-of-care systems for monitoring skin disorder and the wound healing process. Here, pH-responsive hydrogel fibers are presented that can be used for long-term monitoring of epidermal wound condition. pH-responsive dyes are loaded into mesoporous microparticles and incorporated into hydrogel fibers using a microfluidic spinning system. The fabricated pH-responsive microfibers are flexible and can create conformal contact with skin. The response of pH-sensitive fibers with different compositions and thicknesses are characterized. The suggested technique is scalable and can be used to fabricate hydrogel-based wound dressings with clinically relevant dimensions. Images of the pH-sensing fibers during real-time pH measurement can be captured with a smart phone camera for convenient readout on-site. Through image processing, a quantitative pH map of the hydrogel fibers and the underlying tissue can be extracted. The developed skin dressing can act as a point-of-care device for monitoring the wound healing process. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Injectable antibacterial conductive hydrogels with dual response to an electric field and pH for localized "smart" drug release.

PubMed

Qu, Jin; Zhao, Xin; Ma, Peter X; Guo, Baolin

2018-05-01

Injectable hydrogels with multistimuli responsiveness to electrical field and pH as a drug delivery system have been rarely reported. Herein, we developed a series of injectable conductive hydrogels as "smart" drug carrier with the properties of electro-responsiveness, pH-sensitivity, and inherent antibacterial activity. The hydrogels were prepared by mixing chitosan-graft-polyaniline (CP) copolymer and oxidized dextran (OD) as a cross-linker. The chemical structures, morphologies, electrochemical property, swelling ratio, conductivity, rheological property, in vitro and in vivo biodegradation, and gelation time of hydrogels were characterized. The pH-responsive behavior was verified by drug release from hydrogels in PBS solutions with different pH values (pH = 7.4 or 5.5) in an in vitro model. As drug carriers with electric-driven release, the release rate of the model drugs amoxicillin and ibuprofen loaded within CP/OD hydrogels dramatically increased when an increase in voltage was applied. Both chitosan and polyaniline with inherent antibacterial properties endowed the hydrogels with excellent antibacterial properties. Furthermore, cytotoxicity tests of the hydrogels using L929 cells confirmed their good cytocompatibility. The in vivo biocompatibility of the hydrogels was verified by H&E staining. Together, all these results suggest that these injectable pH-sensitive conductive hydrogels with antibacterial activity could be ideal candidates as smart drug delivery vehicles for precise doses of medicine to meet practical demand. Stimuli-responsive or "smart" hydrogels have attracted great attention in the field of biotechnology and biomedicine, especially on designing novel drug delivery systems. Compared with traditional implantable electronic delivery devices, the injectable hydrogels with electrical stimuli not only are easy to generate and control electrical field but also could avoid frequent invasive surgeries that offer a new avenue for chronic diseases. In addition, designing a drug carrier with pH-sensitive property could release drug efficiently in targeted acid environment, and it could reinforce the precise doses of medicine. Furthermore, caused by opportunistic microorganisms and rapid spread of antibiotic-resistant microbes, infection is still a serious threat for many clinical utilities. To overcome these barriers, we designed a series of injectable antibacterial conductive hydrogels based on chitosan-graft-polyaniline (CP) copolymer and oxidized dextran (OD), and we demonstrated their potential as "smart" delivery vehicles with electro-responsiveness and pH-responsive properties for triggered and localized release of drugs. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

An organic self-regulating microfluidic system.

PubMed

Eddington, D T; Liu, R H; Moore, J S; Beebe, D J

2001-12-01

In this paper we present an organic feedback scheme that merges microfluidics and responsive materials to address several limitations of current microfluidic systems. By using in situ fabrication and by taking advantage of microscale phenomena (e.g., laminar flow, short diffusion times), we have demonstrated feedback control of the output pH in a completely organic system. The system autonomously regulates an output stream at pH 7 under a range of input flow conditions. A single responsive hydrogel component performs the functionality of traditional feedback system components. Vertically stacked laminar flow is used to improve the time response of the hydrogel actuator. A star shaped orifice is utilized to improve the flow characteristics of the membrane/orifice valve. By changing the chemistry of the hydrogel component, the system can be altered to regulate flow based on hydrogels sensitive to temperature, light, biological/molecular, and others.

Synthesis and Swelling Behavior of pH-Sensitive Semi-IPN Superabsorbent Hydrogels Based on Poly(acrylic acid) Reinforced with Cellulose Nanocrystals

PubMed Central

Lim, Lim Sze; Rosli, Noor Afizah; Ahmad, Ishak; Mat Lazim, Azwan; Mohd Amin, Mohd Cairul Iqbal

2017-01-01

pH-sensitive poly(acrylic acid) (PAA) hydrogel reinforced with cellulose nanocrystals (CNC) was prepared. Acrylic acid (AA) was subjected to chemical cross-linking using the cross-linking agent MBA (N,N-methylenebisacrylamide) with CNC entrapped in the PAA matrix. The quantity of CNC was varied between 0, 5, 10, 15, 20, and 25 wt %. X-ray diffraction (XRD) data showed an increase in crystallinity with the addition of CNC, while rheology tests demonstrated a significant increase in the storage modulus of the hydrogel with an increase in CNC content. It was found that the hydrogel reached maximum swelling at pH 7. The potential of the resulting hydrogels to act as drug carriers was then evaluated by means of the drug encapsulation efficiency test using theophylline as a model drug. It was observed that 15% CNC/PAA hydrogel showed the potential to be used as drug carrier system. PMID:29156613

A composite hydrogels-based photonic crystal multi-sensor

NASA Astrophysics Data System (ADS)

Chen, Cheng; Zhu, Zhigang; Zhu, Xiangrong; Yu, Wei; Liu, Mingju; Ge, Qiaoqiao; Shih, Wei-Heng

2015-04-01

A facile route to prepare stimuli-sensitive poly(vinyl alcohol)/poly(acrylic acid) (PVA/PAA) gelated crystalline colloidal array photonic crystal material was developed. PVA was physically gelated by utilizing an ethanol-assisted method, the resulting hydrogel/crystal composite film was then functionalized with PAA to form an interpenetrating hydrogel film. This sensor film is able to efficiently diffract the visible light and rapidly respond to various environmental stimuli such as solvent, pH and strain, and the accompanying structural color shift can be repeatedly changed and easily distinguished by naked eye.

[Study on preparation of the pH sensitive hydroxyethyl chitin/poly (acrylic acid) hydrogel and its drug release property].

PubMed

Zhao, Yu; Chen, Guohua; Sun, Mingkun; Jin, Zhitao; Gao, Congjie

2006-04-01

Hydroxyethyl chitin (HECH) is a water soluble chitin derivative made by etherification of chitin, ethylene chlorohydrin was used as etherification reagent in this reaction. A novel interpenetrating polymer network (IPN) composed of HECH/PAA was prepared. The IR spectra confirmed that HECH/PAA was formed through chemical bond interaction. The sensitivity of this hydrogel to temperature and pH was studied. The swelling ratio of this hydrogel in artificial intestinal juice is much greater than that in artificial gastric juice. The IPN hydrogel exhibited a typical pH-sensitivity, and its degree of swelling ratio increased with the increase of temperature. The sustained-release drug system of Dichlofenac potassium was prepared by using HECH/PAA as the drug carrier. The release experiment showed a perfect release behavior in artificial intestinal juice. This IPN is expected to be used as a good drug delivery system of enteric medicine.

Preparation and characterization of a novel pH-sensitive hydrogel obtained from UV light-induced polymerization

NASA Astrophysics Data System (ADS)

Tian, R. Q.; Zhao, Y. G.; Cui, Y. Q.; Zhang, X. Y.; Zhang, J.; Liang, X. Y.; Shang, Q.

2015-05-01

The main aim of this study was to develop a novel pH-sensitive hydrogel prepared via an UV light-induced polymerization. Single-factor experiments were performed to acquire the optimum formula of final poly(MAA-co-PEGMA) hydrogel. Fourier transform infrared spectroscopy (FTIR) spectra were employed to confirm the successful preparation of the designed copolymers. Inner morphologies of the polymeric hydrogels were observed via an S-4800 scanning electron microscope (SEM). Swelling and reversible swelling-shrinking studies were carried out in different phosphate buffer solution (PBS) with various pH values. Drug-loading tests were performed with bovine serum albumin (BSA) as a model drug. The in vitro release profile was also investigated in PBS with the pH values of 1.2 and 7.4. FTIR spectra confirmed the preparation of the poly(MAA-co-PEGMA) copolymers without any residual monomers. The typical space grid structures were observed from the SEM photographs of hydrogels. The obtained hydrogel showed an excellent pH-sensibility and reversible swelling-shrinking property. The maximum drug-loading (40.9 %) was gained from the BSA concentration of 50.0 mg/mL. During the releasing process, only 5.8 ± 0.9 % of BSA was released at pH 1.2, but 82.1 ± 6.2 % was diffused at pH 7.4. These data suggested that such medicated hydrogel could deliver BSA to alkaline conditions (e.g., intestinal environments) site-specifically, which protected BSA from destroying by gastric acid or pepsase. Therefore, such hydrogel had a significant meaning in theoretical research and practical application.

Reinforcement of thermoplastic chitosan hydrogel using chitin whiskers optimized with response surface methodology.

PubMed

Sun, Guohui; Zhang, Xin; Bao, Zixian; Lang, Xuqian; Zhou, Zhongzheng; Li, Yang; Feng, Chao; Chen, Xiguang

2018-06-01

To strengthen the mechanical strength of thermo-sensitive hydroxybutyl chitosan (HBC) hydrogel, chitin whiskers were used as sticker to fabricate reinforced HBC (HBCW) hydrogel by using response surface methodology. Unlike the intrinsic network of HBC hydrogel, HBCW hydrogel showed a laminar shape with firm structure. The preparation condition was optimized by three-factor-three-level Box-Behnken design. The maximum mechanical strength (1011.11 Pa) was achieved at 50 °C, when the concentrations of HBC and chitin whiskers were 5.1 wt% and 2.0 wt%, respectively. The effects of temperature, pH value and NaCl concentration on mechanical strength of HBCW hydrogels were investigated via the oscillatory stress sweeps. The results showed that HBCW hydrogel could reach the maximum stiffness (∼1126 Pa) at 37 °C pH 12.0. Low pH and high salty ions could decrease the stability of hydrogel, while chitin whiskers could increase the stress tolerance and related ruptured strain of HBCW hydrogels. Copyright © 2018. Published by Elsevier Ltd.

Metabolic Study of Cancer Cells Using a pH Sensitive Hydrogel Nanofiber Light Addressable Potentiometric Sensor.

PubMed

Shaibani, Parmiss Mojir; Etayash, Hashem; Naicker, Selvaraj; Kaur, Kamaljit; Thundat, Thomas

2017-01-27

We report a simple, fast, and cost-effective approach that measures cancer cell metabolism and their response to anticancer drugs in real time. Using a Light Addressable Potentiometric Sensor integrated with pH sensitive hydrogel nanofibers (NF-LAPS), we detect localized changes in pH of the media as cancer cells consume glucose and release lactate. NF-LAPS shows a sensitivity response of 74 mV/pH for cancer cells. Cancer cells (MDA MB231) showed a response of ∼0.4 unit change in pH compared to virtually no change observed for normal cells (MCF10A). We also observed a drop in pH for the multidrug-resistant cancer cells (MDA-MB-435MDR) in the presence of doxorubicin. However, inhibition of the metabolic enzymes such as hexokinase and lactate dehydrogenase-A suggested an improvement in the efficacy of doxorubicin by decreasing the level of acidification. This approach, based on extracellular acidification, enhances our understanding of cancer cell metabolic modes and their response to chemotherapies, which will help in the development of better treatments, including choice of drugs and dosages.

Development and evaluation of a novel polymeric hydrogel of sucrose acrylate-co-polymethylacrylic acid for oral curcumin delivery.

PubMed

Huang, Sijin; Wang, Jialei; Shang, Qing

2017-02-01

A monomer of sucrose acrylate (AC-sucrose) was synthesized by conjugating starting compound sucrose with methyl acrylate (MA). The obtained AC-sucrose was characterized by mass spectrometry (MS) and Fourier transform infrared (FTIR) spectroscopy. AC-sucrose was selected as a monomer to fabricate a novel pH sensitive hydrogel via free radical polymerization. The inner morphology of the final hydrogel was observed with an S-4800 scanning electron microscope (SEM). The swelling and de-swelling behaviors of the hydrogel chips were also studied. Curcumin (CUR) was selected as a model drug and loaded into the final hydrogel. The release profiles of CUR were performed via dialysis method in pH 1.2, 6.8 and 7.4 buffers, respectively. Mass and FTIR spectra confirmed the synthesis of AC-sucrose. SEM photographs showed that poly(AC-sucrose-co-MAA) hydrogels had many 3D meshes. In pH 1.2 buffer, the hydrogel chips showed the biggest swelling ratio (SR) of 34.4 ± 1.9%. However, in pH 7.4 buffer, the SRs of the hydrogel chips reached to 368.7 ± 28.0%, which suggested that the hydrogel had an excellent pH sensibility. The releasing profiles showed that only 4.6 ± 0.4% of CUR was released in pH 1.2 buffer but 93.7 ± 4.7% of CUR was diffused into pH 7.4 buffer. These data suggested that the CUR-loaded poly (AC-sucrose-co-MAA) hydrogel could direct CUR to release in basic environments.

Impact of immobilizing of low molecular weight hyaluronic acid within gelatin-based hydrogel through enzymatic reaction on behavior of enclosed endothelial cells.

PubMed

Khanmohammadi, Mehdi; Sakai, Shinji; Taya, Masahito

2017-04-01

The hydrogels having the ability to promote migration and morphogenesis of endothelial cells (ECs) are useful for fabricating vascularized dense tissues in vitro. The present study explores the immobilization of low molecular weight hyaluronic acid (LMWHA) derivative within gelatin-based hydrogel to stimulate migration of ECs. The LMWHA derivative possessing phenolic hydroxyl moieties (LMWHA-Ph) was bound to gelatin-based derivative hydrogel through the horseradish peroxidase-catalyzed reaction. The motility of ECs was analyzed by scratch migration assay and microparticle-based cell migration assay. The incorporated LMWHA-Ph molecules within hydrogel was found to be preserved stably through covalent bonds during incubation. The free and immobilized LMWHA-Ph did not lose an inherent stimulatory effect on human umbilical vein endothelial cells (HUVECs). The immobilized LMWHA-Ph within gelatin-based hydrogel induced the high motility of HUVECs, accompanied by robust cytoskeleton extension, and cell subpopulation expressing CD44 cell receptor. In the presence of immobilized LMWHA-Ph, the migration distance and the number of existing HUVECs were demonstrated to be encouraged in dose-dependent and time-dependent manners. Based on the results obtained in this work, it was concluded that the enzymatic immobilization of LMWHA-Ph within gelatin-based hydrogel represents a promising approach to promote ECs' motility and further exploitation for vascular tissue engineering applications. Copyright © 2017 Elsevier B.V. All rights reserved.

A thermo- and pH-sensitive hydrogel composed of quaternized chitosan/glycerophosphate.

PubMed

Wu, Jie; Su, Zhi-Guo; Ma, Guang-Hui

2006-06-06

The quaternized chitosan was synthesized by the reaction of chitosan and glycidyltrimethylammonium chloride (GTMAC) and named as N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC). A novel hydrogel system composed of HTCC/glycerophosphate (HTCC/GP) with thermo- and pH-sensitivity was synthesized and used as an intelligent drug carrier. The formulation was solution below or at room temperature, which allowed it injectable and to incorporate living cells, proteins, enzymes or other therapeutic drugs easily. Once the surrounding temperature was up to 37 degrees C, the system was transformed to a non-flowing hydrogel, and the formed hydrogel can release the trapped drug as a function of pH values. The swelling behavior of the system and the release profiles of doxorubicin hydrochloride (DX) as a model drug at different pH values were investigated. At acidic condition the hydrogel dissolved and released drug quickly, while it absorbed water and released drug slowly at neutral or basic conditions. Hydrogel composed of chitosan hydrochloride and glycerophosphate (CS/GP) was also prepared to compare with HTCC/GP hydrogel. The HTCC/GP hydrogel in this study was transparent which made it suitable for some specific uses such as ocular drug formulation.

Novel levan and pNIPA temperature sensitive hydrogels for 5-ASA controlled release.

PubMed

Osman, Asila; Oner, Ebru Toksoy; Eroglu, Mehmet S

2017-06-01

Levan based cross-linker was successfully synthesized and used to prepare a series of more biocompatible and temperature responsive levan/N-isopropyl acrylamide (levan/pNIPA) hydrogels by redox polymerization at room temperature. Volume phase transition temperature (VPTT) of the hydrogels were precisely determined by derivative differential scanning calorimetry (DDSC). Incorporation of levan into the pNIPA hydrogel increased the VPTT from 32.8°C to 35.09°C, approaching to body temperature. Swelling behavior and 5-aminosalicylic acid (5-ASA) release of the hydrogels were found to vary significantly with temperature and composition. Moreover, a remarkable increase in thermal stability of levan within hydrogel with increase of pNIPA content was recorded. The biocompatibility of the hydrogels were tested against mouse fibroblast L929 cell line in phosphate buffer saline (PBS, pH 7.4). The hydrogels showed increasing biocompatibility with increasing levan ratio, indicating levan enhanced the hydrogel surface during swelling. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preparation and physico-chemical properties of hydrogels from carboxymethyl cassava starch crosslinked with citric acid

NASA Astrophysics Data System (ADS)

Boonkham, Sasikan; Sangseethong, Kunruedee; Chatakanon, Pathama; Niamnuy, Chalida; Nakasaki, Kiyohiko; Sriroth, Klanarong

2014-06-01

Recently, environmentally friendly hydrogels prepared from renewable bio-based resources have drawn significant attention from both industrial and academic sectors. In this study, chemically crosslinked hydrogels have been developed from cassava starch which is a bio-based polymer using a non-toxic citric acid as a crosslinking agent. Cassava starch was first modified by carboxymethylation to improve its water absorbency property. The carboxymethyl cassava starch (CMCS) obtained was then crosslinked with citric acid at different concentrations and reaction times. The gel fraction of hydrogels increased progressively with increasing citric acid concentration. Free swelling capacity of hydrogels in de-ionized water, saline solution and buffers at various pHs as well as absorption under load were investigated. The results revealed that swelling behavior and mechanical characteristic of hydrogels depended on the citric acid concentration used in reaction. Increasing citric acid concentration resulted in hydrogels with stronger network but lower swelling and absorption capacity. The cassava starch hydrogels developed were sensitive to ionic strength and pH of surrounding medium, showing much reduced swelling capacity in saline salt solution and acidic buffers.

Effects of Mechanical Constraint on the Performance of Fluorescent Hydrogel-based Fiber Optic Sensors

NASA Astrophysics Data System (ADS)

Jukl, Jennifer Marie

Although biosensor technology is a broad and well-studied field, the progress of many novel sensor technologies faces challenges. These challenges range from simple design considerations to fundamental issues with the concept or approach. One of the most active fields of sensor research integrates fiber optics with specially engineered fluorescent molecules. This type of sensor typically utilizes a porous polymer or porous glass substrate to entrap the fluorescent (or fluorescently-tagged) molecule. Porous polymer hydrogels are generally favored due to their ease of fabrication, low cost, adaptability, and biocompatibility. While hydrogels are ideal for both functional molecule suspension and fluid diffusion, their porosity and hydrophilicity are not always advantageous. The largest drawback of these properties is the hydrogel swelling they produce and the resulting geometric changes. This project investigated the limitations of fluorescent hydrogel-based sensors and the effects of unpredictable structural changes hydrogels undergo during typical, unrestrained swelling. The significance of covalent incorporation of the sensing fluorophore into the hydrogel matrix is also explored. Leaching tests were conducted using polyacrylamide (PAm) hydrogels which were impregnated with one of two pH sensitive fluorophores, one which bonded covalently with the hydrogel matrix during polymerization (fluorescein o-acrylate), and one which did not (fluorescein sodium). Once determined to be effective, the covalently bonding fluorophore was used to create constrained-dimension fluorescent pH sensors. These sensors were tested for effectiveness and reproducibility. All data was collected using a laboratory grade optical fibers, a USB spectrometer, and SpectraSuite software (Ocean Optics, 2010) unless otherwise specified.

Optical sensing properties of Au nanoparticle/hydrogel composite microbeads using droplet microfluidics

NASA Astrophysics Data System (ADS)

Li, Huilin; Men, Dandan; Sun, Yiqiang; Zhang, Tao; Hang, Lifeng; Liu, Dilong; Li, Cuncheng; Cai, Weiping; Li, Yue

2017-10-01

Uniform Au nanoparticle (NP)/poly (acrylamide-co-acrylic acid) [P(AAm-co-AA)] hydrogel microbeads were successfully prepared using droplet microfluidics technology. The microbeads exhibited a good stimuli-responsive behavior to pH value. Particularly in the pH value ranging from pH 2-pH 9, the composite microbead sizes gradually increased along with the increase of pH value. The homogeneous Au NPs, which were encapsulated in the P(AAm-co-AA) hydrogel microbeads, could transform the volume changes of hydrogel into optical signals by a tested single microbead with a microspectrometre system. The glucose was translated into gluconic acid by glucose oxidase. Thus, the Au NP/P(AAm-co-AA) hydrogel microbeads were used for detecting glucose based on pH effects on the composite microbeads. For this, the single Au NP/P(AAm-co-AA) hydrogel microbead could act as a good pH- or glucose-visualizing sensor.

Radiation-induced synthesis and swelling properties of p(2-hydroxyethyl methacrylate/itaconic acid/oligo (ethylene glycol) acrylate) terpolymeric hydrogels

NASA Astrophysics Data System (ADS)

Micic, M.; Stamenic, D.; Suljovrujic, E.

2012-09-01

Since it is presumed that by incorporation of pH-responsive (IA) and temperature-responsive (OEGA) co-monomers, it is possible to prepare P(HEMA/IA/OEGA) hydrogels with dual (pH and thermo) responsiveness, the main purpose of our study is to investigate the influence of different mole fractions of IA and especially OEGA on the diversity of the swelling properties of the obtained hydrogels. For that reason, a series of terpolymeric hydrogels with different mole ratios of 2-hydroxyethyl methacrylate (HEMA), itaconic acid (IA) and oligo(ethylene glycol) acrylates (OEGA) was synthesised by gamma radiation. The obtained hydrogels were characterised by swelling studies in the wide pH (2.2-9.0) and temperature range (20-70 °C), confirming dual (pH and thermo) responsiveness and a large variation in the swelling capability. It was observed that the equilibrium swelling of P(HEMA/IA/OEGA) hydrogels, for a constant amount of IA, increased progressively with an increase in OEGA share. On the other hand, the dissociation of carboxyl groups from IA occurs at pH>4; therefore, small mole fractions of IA render good pH sensitivity and a large increase in the swelling capacity of these hydrogels at higher pH values. Additional characterisation of structure and properties was conducted by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and mechanical measurements, confirming that the inherent properties of P(HEMA/IA/OEGA) hydrogels can be significantly tuned by variation in their composition. According to all presented, it seems that the obtained hydrogels can be a beneficial synergetic combination for controlled delivery of bioactive molecules such as drugs, peptides, proteins, etc.

Enzymatic regulation of functional vascular networks using gelatin hydrogels

PubMed Central

Chuang, Chia-Hui; Lin, Ruei-Zeng; Tien, Han-Wen; Chu, Ya-Chun; Li, Yen-Cheng; Melero-Martin, Juan M.; Chen, Ying-Chieh

2015-01-01

To manufacture tissue engineering-based functional tissues, scaffold materials that can be sufficiently vascularized to mimic the functionality and complexity of native tissues are needed. Currently, vascular network bioengineering is largely carried out using natural hydrogels as embedding scaffolds, but most natural hydrogels have poor mechanical stability and durability, factors that critically limit their widespread use. In this study, we examined the suitability of gelatin-phenolic hydroxyl (gelatin-Ph) hydrogels that can be enzymatically crosslinked, allowing tuning of the storage modulus and the proteolytic degradation rate, for use as injectable hydrogels to support the human progenitor cell-based formation of a stable and mature vascular network. Porcine gelatin-Ph hydrogels were found to be cytocompatible with human blood-derived endothelial colony-forming cells and white adipose tissue-derived mesenchymal stem cells, resulting in >87% viability, and cell proliferation and spreading could be modulated by using hydrogels with different proteolytic degradability and stiffness. In addition, gelatin was extracted from mouse dermis and murine gelatin-Ph hydrogels were prepared. Importantly, implantation of human cell-laden porcine or murine gelatin-Ph hydrogels into immunodeficient mice resulted in the rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, the degree of enzymatic crosslinking of the gelatin-Ph hydrogels could be used to modulate cell behavior and the extent of vascular network formation in vivo. Our report details a technique for the synthesis of gelatin-Ph hydrogels from allogeneic or xenogeneic dermal skin and suggests that these hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues. PMID:25749296

Thermosensitive chitosan/glycerophosphate-based hydrogel and its derivatives in pharmaceutical and biomedical applications.

PubMed

Supper, Stephanie; Anton, Nicolas; Seidel, Nina; Riemenschnitter, Marc; Curdy, Catherine; Vandamme, Thierry

2014-02-01

Thermogelling chitosan (CS)/glycerophosphate (GP) solutions have been reported as a new type of parenteral in situ forming depot system. These free-flowing solutions at ambient temperature turn into semi-solid hydrogels after parenteral administration. Formulation parameters such as CS physico-chemical characteristics, CS/gelling agent ratio or pH of the system, were acknowledged as key parameters affecting the solution stability, the sol/gel transition behavior and/or the final hydrogel structure. We discuss also the use of the standard CS/GP thermogels for various biomedical applications, including drug delivery and tissue engineering. Furthermore, this manuscript reviews the different strategies implemented to improve the hydrogel characteristics such as combination with carrier particles, replacement of GP, addition of a second polymer and chemical modification of CS. The recent advances in the formulation of CS-based thermogelling systems already overcame several challenges faced by the standard CS/GP system. Dispersion of drug-loaded carrier particles into the thermogels allowed achieving prolonged release profiles for low molecular weight drugs; incorporation of an additional polymer enabled to strengthen the network, while the use of chemically modified CS led to enhanced pH sensitivity or biodegradability of the matrix.

A novel hydrogel based piezoresistive pressure sensor platform for chemical sensing

NASA Astrophysics Data System (ADS)

Orthner, Michael P.

New hydrogel-based micropressure sensor arrays for use in the fields of chemical sensing, physiological monitoring, and medical diagnostics are developed and demonstrated. This sensor technology provides reliable, linear, and accurate measurements of hydrogel swelling pressures, a function of ambient chemical concentrations. For the first time, perforations were implemented into the pressure sensors piezoresistive diaphragms, used to simultaneously increase sensor sensitivity and permit diffusion of analytes into the hydrogel cavity. It was shown through analytical and numerical (finite element) methods that pore shape, location, and size can be used to modify the diaphragm mechanics and concentrate stress within the piezoresistors, thus improving electrical output (sensitivity). An optimized pore pattern was chosen based on these numerical calculations. Fabrication was performed using a 14-step semiconductor fabrication process implementing a combination of potassium hydroxide (KOH) and deep reactive ion etching (DRIE) to create perforations. The sensor arrays (2x2) measure approximately 3 x 5 mm2 and used to measure full scale pressures of 50, 25, and 5 kPa, respectively. These specifications were defined by the various swelling pressures of ionic strength, pH and glucose specific hydrogels that were targeted in this work. Initial characterization of the sensor arrays was performed using a custom built bulge testing apparatus that simultaneously measured deflection (optical profilometry), pressure, and electrical output. The new perforated diaphragm sensors were found to be fully functional with sensitivities ranging from 23 to 252 muV/V-kPa with full scale output (FSO) ranging from 5 to 80 mV. To demonstrate proof of concept, hydrogels sensitive to changes in ionic strength were synthesized using hydroxypropyl-methacrylate (HPMA), N,N-dimethylaminoethyl-methacrylate (DMA) and a tetra-ethyleneglycol-dimethacrylate (TEGDMA) crosslinker. This hydrogel quickly and reversibly swells when placed environments of physiological buffer solutions (PBS) with ionic strengths ranging from 0.025 to 0.15 M. Chemical testing showed sensors with perforated diaphragms have higher sensitivity than those with solid diaphragms, and sensitivities ranging from 53.3+/-6.5 to 271.47+/-27.53 mV/V-M, depending on diaphragm size. Additionally, recent experiments show sensors utilizing Ultra Violet (UV) polymerized glucose sensitive hydrogels respond reversibly to physiologically relevant glucose concentrations from 0 to 20 mM.

SYNTHESIS AND IN VITRO CHARACTERIZATION OF HYDROXYPROPYL METHYLCELLULOSE-GRAFT-POLY (ACRYLIC ACID/2-ACRYLAMIDO-2-METHYL-1-PROPANESULFONIC ACID) POLYMERIC NETWORK FOR CONTROLLED RELEASE OF CAPTOPRIL.

PubMed

Furqan Muhammad, Iqbal; Mahmood, Ahmad; Aysha, Rashid

2016-01-01

A super-absorbent hydrogel was developed by crosslinking of 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) and acrylic acid with hydroxypropyl methylcellulose (HPMC) for controlled release drug delivery of captopril, a well known antihypertensive drug. Acrylic acid and AMPS were polymerized and crosslinked with HPMC by free radical polymerization, a widely used chemical crosslinking method. N,N'-methylenebisacrylamide (MBA) and potassium persulfate (KPS) were added as cross-linker and initiator, respectively. The hydrogel formulation was loaded with captopril (as model drug). The concentration of captopril was monitored at 205 nm using UV spectrophotometer. Equilibrium swelling ratio was determined at pH 2, 4.5 and 7.4 to evaluate the pH responsiveness of the formed hydrogel. The super-absorbent hydrogels were evaluated by FTIR, SEM, XRD, and thermal analysis (DSC and TGA). The formation of new copolymeric network was determined by FTIR, XRD, TGA and DSC analysis. The hydrogel formulations with acrylic acid and AMPS ratio of 4: 1 and lower amounts of crosslinker had shown maximum swelling. Moreover, higher release rate of captopril was observed at pH 7.4 than at pH 2, because of more swelling capacity of copolymer with increasing pH of the aqueous medium. The present research work confirms the development of a stable hydrogel comprising of HPMC with acrylic acid and AMPS. The prepared hydrogels exhibited pH sensitive behav-ior. This superabsorbent composite prepared could be a successful drug carrier for treating hypertension.

The influence of the kinetics of self-assembly on the properties of dipeptide hydrogels.

PubMed

Cardoso, Andre Zamith; Alvarez, Ana Estefania Alvarez; Cattoz, Beatrice N; Griffiths, Peter C; King, Stephen M; Frith, William J; Adams, Dave J

2013-01-01

We discuss the effect of the kinetics of pH change on the mechanical properties of dipeptide hydrogels. Data from other peptide-based low molecular weight gelator (LMWG) systems suggest that the rheological properties are often highly dependent on the assembly rate. To examine kinetics here, we have used the hydrolysis of glucono-8-lactone (GdL). The hydrolysis of GdL to gluconic acid results in a decrease in pH, the rate of which is temperature sensitive. Hence, we can adjust the rate of pH decrease, whilst achieving the same absolute final pH. Our data shows that at all temperatures the rheological profile is very similar, with an increase to a plateau, followed by a second increase in moduli, despite very different kinetics of assembly. Surprisingly, the final mechanical properties are very similar in all cases. We also show that the structures formed at the plateau can be accessed by adjusting the pH using CO2. By carefully balancing the pKa. of the gelator with the pH achievable using CO2, flexible hydrogel membranes can be formed as opposed to a bulk gel. The rheological characteristics of the membranes are typical of a highly entangled polymer network. These membranes can be rigidified by post-addition of GdL to further lower the pH.

In-vitro investigations of a pH- and ionic-strength-responsive polyelectrolytic hydrogel using a piezoresistive microsensor

PubMed Central

Schulz, Volker; Guenther, Margarita; Gerlach, Gerald; Magda, Jules J.; Tathireddy, Prashant; Rieth, Loren; Solzbacher, Florian

2010-01-01

Environmental responsive or smart hydrogels show a volume phase transition due to changes of external stimuli such as pH or ionic strength of an ambient solution. Thus, they are able to convert reversibly chemical energy into mechanical energy and therefore they are suitable as sensitive material for integration in biochemical microsensors and MEMS devices. In this work, micro-fabricated silicon pressure sensor chips with integrated piezoresistors were used as transducers for the conversion of mechanical work into an appropriate electrical output signal due to the deflection of a thin silicon bending plate. Within this work two different sensor designs have been studied. The biocompatible poly(hydroxypropyl methacrylate-N,N-dimethylaminoethyl methacrylate-tetra-ethyleneglycol dimethacrylate) (HPMA-DMA-TEGDMA) was used as an environmental sensitive element in piezoresistive biochemical sensors. This polyelectrolytic hydrogel shows a very sharp volume phase transition at pH values below about 7.4 which is in the range of the physiological pH. The sensor's characteristic response was measured in-vitro for changes in pH of PBS buffer solution at fixed ionic strength. The experimental data was applied to the Hill equation and the sensor sensitivity as a function of pH was calculated out of it. The time-dependent sensor response was measured for small changes in pH, whereas different time constants have been observed. The same sensor principal was used for sensing of ionic strength. The time-dependent electrical sensor signal of both sensors was measured for variations in ionic strength at fixed pH value using PBS buffer solution. Both sensor types showed an asymmetric swelling behavior between the swelling and the deswelling cycle as well as different time constants, which was attributed to the different nature of mechanical hydrogel-confinement inside the sensor. PMID:21152365

Design, Optimization, and Evaluation of a Novel Metronidazole-Loaded Gastro-Retentive pH-Sensitive Hydrogel.

PubMed

El-Mahrouk, Galal M; Aboul-Einien, Mona H; Makhlouf, Amal I

2016-12-01

Floating pH-sensitive chitosan hydrogels containing metronidazole were developed for the eradication of Helicobacter pylori from the stomach. Hydrogels were prepared by crosslinking medium or high molecular weight chitosan in lyophilized solutions containing metronidazole using either citrate or tripolyphosphate (TPP) salts at 1% or 2% concentration. A 2 3 factorial design was developed to study the influence of formulation parameters on the physical characteristics of the prepared hydrogels. The interaction between hydrogel components was investigated. The morphology of the prepared hydrogels was inspected and their percentage swelling, release pattern, and moisture content were evaluated. The results revealed the absence of interaction between hydrogel components and their highly porous structure. Percentage swelling of the hydrogels was much higher, and drug release was faster in gastric pH compared with intestinal pH. The formula prepared using 2% high molecular weight chitosan and 2% TPP significantly swelled (700%) within the first 4 h and released the loaded drug over a period of 24 h. Its moisture content was not affected by storage at high relative humidity. Therefore, this formula was selected to be tested in dogs for its gastric retention (using X-ray radiography) and efficacy in the eradication of H. pylori (using histopathological and microbiological examination). The results revealed that the prepared hydrogel formula was retained in dog stomach for at least 48 h, and it was more effective against H. pylori than the commercially available oral metronidazole tablets (Flagyl®).

pH-responsive self-healing injectable hydrogel based on N-carboxyethyl chitosan for hepatocellular carcinoma therapy.

PubMed

Qu, Jin; Zhao, Xin; Ma, Peter X; Guo, Baolin

2017-08-01

Injectable hydrogels with pH-responsiveness and self-healing ability have great potential for anti-cancer drug delivery. Herein, we developed a series of polysaccharide-based self-healing hydrogels with pH-sensitivity as drug delivery vehicles for hepatocellular carcinoma therapy. The hydrogels were prepared by using N-carboxyethyl chitosan (CEC) synthesized via Michael reaction in aqueous solution and dibenzaldehyde-terminated poly(ethylene glycol) (PEGDA). Doxorubicin (Dox), as a model of water-soluble small molecule anti-cancer drug was encapsulated into the hydrogel in situ. Self-healing behavior of the hydrogels was investigated at microscopic and macroscopic levels, and the hydrogels showed rapid self-healing performance without any external stimulus owing to the dynamic covalent Schiff-base linkage between amine groups from CEC and benzaldehyde groups from PEGDA. The chemical structures, rheological property, in vitro gel degradation, morphology, gelation time and in vitro Dox release behavior from the hydrogels were characterized. Injectability was verified by in vitro injection and in vivo subcutaneous injection in a rat. pH-responsive behavior was verified by in vitro Dox release from hydrogels in PBS solutions with different pH values. Furthermore, the activity of Dox released from hydrogel matrix was evaluated by employing human hepatocellular liver carcinoma (HepG2). Cytotoxicity test of the hydrogels using L929 cells confirmed their good cytocompatibility. Together, these pH-responsive self-healing injectable hydrogels are excellent candidates as drug delivery vehicles for liver cancer treatment. STATEMENT OF SIGNIFICANCE: pH-responsive drug delivery system could release drug efficiently in targeted acid environment and minimalize the amount of drug release in normal physiological environment. pH-sensitive injectable hydrogels as smart anti-cancer drug delivery carriers show great potential application for cancer therapy. The hydrogels with self-healing property could prolong their lifetime during implantation and provide the advantage of minimally invasive surgery and high drug-loading ratio. This work reported the design of a series of pH-responsive self-healing injectable hydrogels based on N-carboxyethyl chitosan synthesized in aqueous solution and dibenzaldehyde-terminated poly(ethylene glycol) via a green approach, and demonstrated their potential as intelligent delivery vehicle of doxorubicin for hepatocellular carcinoma therapy via the pH-responsive nature of dynamic Schiff base. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Fabrication of poly(ethylene glycol) hydrogel microstructures using photolithography

NASA Technical Reports Server (NTRS)

Revzin, A.; Russell, R. J.; Yadavalli, V. K.; Koh, W. G.; Deister, C.; Hile, D. D.; Mellott, M. B.; Pishko, M. V.

2001-01-01

The fabrication of hydrogel microstructures based upon poly(ethylene glycol) diacrylates, dimethacrylates, and tetraacrylates patterned photolithographically on silicon or glass substrates is described. A silicon/silicon dioxide surface was treated with 3-(trichlorosilyl)propyl methacrylate to form a self-assembled monolayer (SAM) with pendant acrylate groups. The SAM presence on the surface was verified using ellipsometry and time-of-flight secondary ion mass spectrometry. A solution containing an acrylated or methacrylated poly(ethylene glycol) derivative and a photoinitiator (2,2-dimethoxy-2-phenylacetophenone) was spin-coated onto the treated substrate, exposed to 365 nm ultraviolet light through a photomask, and developed with either toluene, water, or supercritical CO2. As a result of this process, three-dimensional, cross-linked PEG hydrogel microstructures were immobilized on the surface. Diameters of cylindrical array members were varied from 600 to 7 micrometers by the use of different photomasks, while height varied from 3 to 12 micrometers, depending on the molecular weight of the PEG macromer. In the case of 7 micrometers diameter elements, as many as 400 elements were reproducibly generated in a 1 mm2 square pattern. The resultant hydrogel patterns were hydrated for as long as 3 weeks without delamination from the substrate. In addition, micropatterning of different molecular weights of PEG was demonstrated. Arrays of hydrogel disks containing an immobilized protein conjugated to a pH sensitive fluorophore were also prepared. The pH sensitivity of the gel-immobilized dye was similar to that in an aqueous buffer, and no leaching of the dye-labeled protein from the hydrogel microstructure was observed over a 1 week period. Changes in fluorescence were also observed for immobilized fluorophore labeled acetylcholine esterase upon the addition of acetyl acholine.

Synthesis and characterization of psyllium-NVP based drug delivery system through radiation crosslinking polymerization

NASA Astrophysics Data System (ADS)

Singh, Baljit; Kumar, S.

2008-08-01

In order to develop the hydrogels meant for the drug delivery, we have prepared psyllium- N-vinylpyrrolidone (NVP) based hydrogels by radiation induced crosslinking. Polymers were characterized with SEMs, FTIR and swelling studies. Swelling of the hydrogels was studied as a function of monomer concentration, total radiation dose, temperature, pH and [NaCl] of the swelling medium. The swelling kinetics of the hydrogels and release dynamics of anticancer model drug (5-fluorouracil) from the hydrogels have been carried out for the evaluation of swelling and drug release mechanism. It has been observed that diffusion exponent ' n' have 0.8, 0.9, 0.8 and gel characteristics constant ' k' have 9.22 × 10 -3, 2.06 × 10 -3, 11.72 × 10 -3 values for the release of drug from the drug loaded hydrogels in distilled water, pH 2.2 buffer and pH 7.4 buffer, respectively. The present study shows that the release of drug from the hydrogels occurred through Non-Fickian diffusion mechanism.

Development of a P((MAA-co-NVP)-g-EG) Hydrogel Platform for Oral Protein Delivery: Effects of Hydrogel Composition on Environmental Response and Protein Partitioning.

PubMed

Steichen, Stephanie; O'Connor, Colleen; Peppas, Nicholas A

2017-01-01

Hydrogels based upon terpolymers of methacrylic acid, N-vinyl pyrrolidone, and poly(ethylene glycol) are developed and characterized for their ability to respond to changes in environmental pH and to partition protein therapeutics of varying molecular weights and isoelectric points. P((MAA-co-NVP)-g-EG) hydrogels are synthesized with PEG-based cross-linking agents of varying length and incorporation densities. The composition is confirmed using FT-IR spectroscopy and shows peak shifts indicating hydrogen bonding. Scanning electron microscopy reveals microparticles with an irregular, planar morphology. The pH-responsive behavior of the hydrogels is confirmed under equilibrium and dynamic conditions, with the hydrogel collapsed at acidic pH and swollen at neutral pH. The ability of the hydrogels to partition model protein therapeutics at varying pH and ionic strength is evaluated using three model proteins: insulin, porcine growth hormone, and ovalbumin. Finally, the microparticles are evaluated for adverse interactions with two model intestinal cell lines and show minimal cytotoxicity at concentrations below 5 mg mL -1 . © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Switchable on/off drug release from gold nanoparticles-grafted dual light- and temperature-responsive hydrogel for controlled drug delivery.

PubMed

Amoli-Diva, Mitra; Sadighi-Bonabi, Rasoul; Pourghazi, Kamyar

2017-07-01

A switchable dual light- and temperature-responsive drug carrier using gold nanoparticles (Au NPs)-grafted poly(dimethylacrylamide-co-acrylamide)/poly acrylic acid [P(DMA-co-AAm)/PAAc] hydrogel was prepared by free radical polymerization procedure using N,N-methylenebisacrylamide as cross-linker and ammonium persulfate as initiator. Initial P(DMA-co-AAm) hydrogel and uniformly-distributed stable Au NPs, prepared by reduction of hydrogen tetrachloroaureate (III) hydrate in the presence of trisodium citrate, were synthesized separately. Then, the prepared P(DMA-co-AAm) and Au NPs were added to an acrylic acid solution along with the cross-linker and initiator to prepare PAAc hydrogel within the mixture. This improves the swelling ratio and stabilizes Au NPs in networks. Furthermore, a cross-linked P(DMA-co-AAm-co-AAc) random hydrogel was also prepared with the same monomer compositions as the above hydrogel for comparison of their properties. Then, swelling, thermal sensitivity and thermal and optical switching properties of the prepared hydrogels were investigated in two acidic (pH=1.2) and neutral (pH=7.4) buffered solutions to simulate stomach and intestine body conditions. Finally, loading and cumulative release (%) of ofloxacin antibiotic as model drug were considered in both thermal and optical switching conditions. Based on these results, pulsatile release vehicle was obtained which have the "on" state at higher temperatures and the "off" state at lower temperatures. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation and characterization of pH-sensitive methyl methacrylate-g-starch/hydroxypropylated starch hydrogels: in vitro and in vivo study on release of esomeprazole magnesium.

PubMed

Kumar, Pankaj; Ganure, Ashok Laxmanrao; Subudhi, Bharat Bhushan; Shukla, Shubhanjali

2015-06-01

In the present study, novel hydrogels were prepared through graft copolymerization of methyl methacrylate onto starch and hydroxypropylated starch for intestinal drug delivery. The successful grafting has been confirmed by FTIR, NMR spectroscopy, and elemental analysis. Morphological examination of copolymeric hydrogels by scanning electron microscopy (SEM) confirms the macroporous nature of the copolymers. The high decomposition temperature was observed in thermograms indicating the thermal stability of the hydrogels. To attain a hydrogel with maximum percent graft yield, the impact of reaction variables like concentration of ceric ammonium nitrate as initiator and methyl methacrylate as monomer were consistently optimized. X-ray powder diffraction and differential scanning calorimetric analysis supported the successful entrapment of the drug moiety (esomeprazole magnesium; proton pump inhibitor) within the hydrogel network. Drug encapsulation efficiency of optimized hydrogels was found to be >78%. Furthermore, swelling capacity of copolymeric hydrogels exhibited a pH-responsive behavior which makes the synthesized hydrogels potential candidates for controlled delivery of medicinal agents. In vitro drug release was found to be sustained up to 14 h with 80-90% drug release in pH 6.8 solution; however, the cumulative release was 40-45% in pH 1.2. The gastrointestinal transit behavior of optimized hydrogel was determined by gamma scintigraphy, using (99m)Tc as marker. The amount of radioactive tracer released from the labeled hydrogel was minimal when the hydrogel was in the stomach, whereas it increased as hydrogel reached in intestine. Well-correlated results of in vitro and in vivo analysis proved their controlled release behavior with preferential delivery into alkaline pH environment.

Optical fiber Fabry-Perot interferometer with pH sensitive hydrogel film for hazardous gases sensing

NASA Astrophysics Data System (ADS)

Zheng, Yangzi; Chen, Li Han; Chan, Chi Chiu; Dong, Xinyong; Yang, Jingyi; Tou, Zhi Qiang; So, Ping Lam

2015-09-01

An optical fiber Fabry-Perot interferometer (FPI) coated with polyvinyl alcohol/poly-acrylic acid (PVA/PAA) hydrogel film for toxic gases measurement has been developed. Splicing a short section of hollow core fiber between two single mode fibers forms the FPI. Dip-coated pH-sensitive PVA/PAA hydrogel film on the fiber end performs as a receptor for binding of volatile acids or ammonia, which makes the sensing film swelling or shrinking and results in the dip wavelength shift of the FPI. By demodulating the evolution of reflection spectrum for various concentrations of volatile acids, a sensitivity of 20.8 nm/ppm is achieved with uniform linearity.

Angiogenic potential of gellan-gum-based hydrogels for application in nucleus pulposus regeneration: in vivo study.

PubMed

Silva-Correia, Joana; Miranda-Gonçalves, Vera; Salgado, António J; Sousa, Nuno; Oliveira, Joaquim M; Reis, Rui M; Reis, Rui L

2012-06-01

Hydrogels for nucleus pulposus (NP) regeneration should be able to comprise a nonangiogenic or even antiangiogenic feature. Gellan gum (GG)-based hydrogels have been reported to possess adequate properties for being used as NP substitutes in acellular and cellular strategies, due to its ability to support cell encapsulation, adequate mechanical properties, and noncytotoxicity. In this study, the angiogenic response of GG-based hydrogels was investigated by performing the chorioallantoic membrane assay. The convergence of macroscopic blood vessels toward the GG, ionic-crosslinked methacrylated GG (iGG-MA), and photo-crosslinked methacrylated GG (phGG-MA) hydrogel discs was quantified. Gelatin sponge (GSp) and filter paper (FP) alone and with vascular endothelial growth factor were used as controls of angiogenesis. The images obtained were digitally processed and analyzed by three independent observers. The macroscopic blood vessel quantification demonstrated that the GG-based hydrogels are not angiogenic as compared with FP controls. No statistical differences between the GG-based hydrogels tested in respect to its angiogenic ability were observed. Hematoxylin and eosin staining and SNA-lectin immunohistochemistry assay indicated that the iGG-MA and phGG-MA hydrogels do not allow the ingrowth of chick endothelial cells, following 4 days of implantation. On the contrary, GG, GSp, and FP controls allowed cell infiltration. The histological data also indicated that the GG-based hydrogels do not elicit any acute inflammatory response. The results showed that the GG, iGG-MA, and phGG-MA hydrogels present different permeability to cells but functioned as a physical barrier for vascular invasion. These hydrogels present promising and tunable properties for being used as NP substitutes in the treatment of degenerative intervertebral disc.

pH-sensitive wax emulsion copolymerization with acrylamide hydrogel using gamma irradiation for dye removal

NASA Astrophysics Data System (ADS)

Ghobashy, Mohamed Mohamady; Elhady, Mohamed., A.

2017-05-01

Emulsion polymerization is an efficient method for the production of new wax-hydrogel matrices of cetyl alcohol: stearic acid wax and acrylamide hydrogel using triethylamine (TEA) as an emulsifier. A cross-linking reaction occurred when a mixture of wax-hydrogel solution was irradiated with gamma rays at a dose of 20 kGy. The gelation percentage of the matrices (CtOH-StA/PAAm) was 86%, which indicates that a sufficiently high conversion occurred in these new wax-hydrogel matrices. The ability of PAAm and CtOH-StA/PAAm as an adsorbent for dye removal was investigated. The removal of three reactive dyes, namely Remazol Red (RR), Amido Black (AB), and Toluidine Blue (TB), from aqueous solutions depends on the pH of the dye solution. Removal efficiency was investigated by UV spectrophotometry, and the results showed the affinity of the wax hydrogel to adsorb TB was 98% after 320 min. Fourier transform infrared-attenuated total reflectance spectra confirmed the cross-linking process involved between the chains of wax and hydrogel; furthermore, scanning electron microscopy images showed that the wax and hydrogel were completely miscible to form a single matrix. Swelling measurements showed the high affinity of adsorbed dyes from aqueous solutions at different pH values to the wax-hydrogel network; the highest swelling values of 13.05 and 8.24 (g/g) were observed at pH 10 and 6, respectively

Hydrogel-coated fiber Bragg grating sensor for pH monitoring

NASA Astrophysics Data System (ADS)

Pabbisetti, Vayu Nandana Kishore; Madhuvarasu, Sai Shankar

2016-06-01

We present a fiber-optic wavelength-modulated sensor for pH applications. Fiber Bragg grating (FBG) is functionalized with a stimulus-responsive hydrogel that induces a strain on FBG due to mechanical expansion of the gel in response to ambient pH changes. The gel is synthesized from the blends of poly (vinyl alcohol)/poly (acrylic acid). The induced strain results in a shift of FBG reflected peak that is monitored by an interrogator. The sensor system shows good linearity in the acidic pH range of 3 to 7 with a sensitivity of 12.16 pm/pH. In addition, it shows good repeatability and oscillator behavior, which proves it to be fit for pH sensing applications.

Double-pass Mach-Zehnder fiber interferometer pH sensor.

PubMed

Tou, Zhi Qiang; Chan, Chi Chiu; Hong, Jesmond; Png, Shermaine; Eddie, Khay Ming Tan; Tan, Terence Aik Huang

2014-04-01

A biocompatible fiber-optic pH sensor based on a unique double-pass Mach-Zehnder interferometer is proposed. pH responsive poly(2-hydroxyethyl methacrylate-co-2-(dimethylamino)ethyl methacrylate) hydrogel coating on the fiber swells/deswells in response to local pH, leading to refractive index changes that manifest as shifting of interference dips in the optical spectrum. The pH sensor is tested in spiked phosphate buffer saline and demonstrates high sensitivity of 1.71  nm/pH, pH 0.004 limit of detection with good responsiveness, repeatability, and stability. The proposed sensor has been successfully applied in monitoring the media pH in cell culture experiments to investigate the relationship between pH and cancer cell growth.

Improved fiber-optic chemical sensor for penicillin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Healy, B.G.; Walt, D.R.

An optical penicillin biosensor is described, based on the enzyme penicillinase. The sensor is fabricated by selective photodeposition of analyte-sensitive polymer matrices on optical imaging fibers. The penicillin-sensitive matrices are fabricated by immobilizing the enzyme as micrometer-sized particles in a polymer hydrogel with a covalently bound pH indicator. An array of penicillin-sensitive and pH-sensitive matrices are fabricated on the same fiber. This array allows for the simultaneous, independent measurement of pH and penicillin. Independent measurement of the two analytes allows penicillin to be quantitated in the presence of a concurrent pH change. An analysis was conducted of enzyme kinetic parametersmore » in order to model the penicillin response of the sensor at all pH values. This analysis accounts for the varying activity of the immobilized penicillinase at different pH values. The sensor detects penicillin in the range 0.25-10.0 mM in the pH range 6.2-7.5. The sensor was used to quantify penicillin concentration produced during a Penicillium chrysogenum fermentation. 27 refs., 7 figs., 1 tab.« less

MRI-detectable pH nanosensors incorporated into hydrogels for in vivo sensing of transplanted-cell viability

NASA Astrophysics Data System (ADS)

Chan, Kannie W. Y.; Liu, Guanshu; Song, Xiaolei; Kim, Heechul; Yu, Tao; Arifin, Dian R.; Gilad, Assaf A.; Hanes, Justin; Walczak, Piotr; van Zijl, Peter C. M.; Bulte, Jeff W. M.; McMahon, Michael T.

2013-03-01

Biocompatible nanomaterials and hydrogels have become an important tool for improving cell-based therapies by promoting cell survival and protecting cell transplants from immune rejection. Although their potential benefit has been widely evaluated, at present it is not possible to determine, in vivo, if and how long cells remain viable following their administration without the use of a reporter gene. Here, we report a pH-nanosensor-based magnetic resonance imaging (MRI) technique that can monitor cell death in vivo non-invasively. We demonstrate that specific MRI parameters that change on cell death of microencapsulated hepatocytes are associated with the measured bioluminescence imaging radiance. Moreover, the readout from this pH-sensitive nanosensor can be directly co-registered with high-resolution anatomical images. All of the components of these nanosensors are clinical grade and hence this approach should be a translatable and universal modification of hydrogels.

Hydrogels Based on Ag+ -Modulated Assembly of 5'-Adenosine Monophosphate for Enriching Biomolecules.

PubMed

Hu, Yuanyuan; Xie, Dong; Wu, Yang; Lin, Nangui; Song, Aixin; Hao, Jingcheng

2017-11-07

Supramolecular hydrogels obtained by combining 5'-adenosine monophosphate (AMP) with Ag + were fabricated in this work. Their gelation capability was enhanced by increasing the concentration of Ag + or decreasing the pH. The gels are very sensitive to light, which endows them with potential applications as visible-light photosensitive materials. Coordination between the nucleobase of AMP and Ag + , as well as π-π stacking of nucleobases, are considered to be the main driving forces for self-assembly. The hydrogels successfully achieved the encapsulation and enrichment of biomolecules. Hydrogen bonding between the amino group of guest molecules and silver nanoparticles along the nanofibers drives the enrichment and is considered to be a crucial interaction. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stimuli-sensitive hydrogels: an excellent carrier for drug and cell delivery.

PubMed

Garg, Tarun; Singh, Simranjit; Goyal, Amit Kumar

2013-01-01

The stimuli-sensitive hydrogel is an injectable formulation that is used to deliver drugs, cells, and genes into the body. Hydrogels are available in various physical forms such as solid molded, pressed powder matrix, microparticle, coating, or membrane forms. The network structure of hydrogels can be macroporous, microporous, or nonporous. Different categories of biomaterials, such as natural, synthetic, and combinations (e.g., semisynthetic such as natural-natural, natural-synthetic, and synthetic-synthetic polymers), are commonly used in hydrogel preparation. Classification of hydrogels mainly depends upon physical stimuli (temperature, electric fields, solvent composition, light, pressure, sound, and magnetic fields) and chemical or biochemical stimuli (pH, ions, and specific molecular recognition events). Several approaches for the synthesis of hydrogels have been reported, including emulsification, micromolding, photolithography, isostatic ultra high pressure, and microfluidic techniques. Hydrogels provide structural integrity and cellular organization, serve as tissue barriers, act as bioadhesive and drug depots, deliver bioactive agents and cells, and possess unique swelling properties and structures. This review provides a detailed account of the need for development of hydrogels, along with the materials used and techniques adopted to manufacture scaffolds for tissue engineering and for prolonged drug, cell, and gene delivery.

An injectable and biodegradable hydrogel based on poly(α,β-aspartic acid) derivatives for localized drug delivery.

PubMed

Lu, Caicai; Wang, Xiaojuan; Wu, Guolin; Wang, Jingjing; Wang, Yinong; Gao, Hui; Ma, Jianbiao

2014-03-01

An injectable hydrogel via hydrazone cross-linking was prepared under mild conditions without addition of cross-linker or catalyst. Hydrazine and aldehyde modified poly(aspartic acid)s were used as two gel precursors. Both of them are water-soluble and biodegradable polymers with a protein-like structure, and obtained by aminolysis reaction of polysuccinimide. The latter can be prepared by thermal polycondensation of aspartic acid. Hydrogels were prepared in PBS solution and characterized by different methods including gel content and swelling, Fourier transformed-infrared spectroscopy, and in vitro degradation experiment. A scanning electron microscope viewed the interior morphology of the obtained hydrogels, which showed porous three-dimensional structures. Different porous sizes were present, which could be well controlled by the degree of aldehyde substitution in precursor poly(aspartic acid) derivatives. The doxorubicin-loaded hydrogels were prepared and showed a pH-sensitive release profile. The release rate can be accelerated by decreasing the environmental pH from a physiological to a weak acidic condition. Moreover, the cell adhesion and growth behaviors on the hydrogel were studied and the polymeric hydrogel showed good biocompatibility. Copyright © 2013 Wiley Periodicals, Inc.

Mussel-inspired tough hydrogels with self-repairing and tissue adhesion

NASA Astrophysics Data System (ADS)

Gao, Zijian; Duan, Lijie; Yang, Yongqi; Hu, Wei; Gao, Guanghui

2018-01-01

The mussel-inspired polymeric hydrogels have been attractively explored owing to their self-repairing or adhesive property when the catechol groups of dopamine could chelate metal ions. However, it was a challenge for self-repairing hydrogels owning high mechanical properties. Herein, a synergistic strategy was proposed by combining catechol-Fe3+ complexes and hydrophobic association. The resulting hydrogels exhibited seamless self-repairing behavior, tissue adhesion and high mechanical property. Moreover, the pH-dependent stoichiometry of catechol-Fe3+ and temperature-sensitive hydrophobic association endue hydrogels with pH/thermo responsive characteristics. Subsequently, the self-repairing rate and mechanical property of hydrogels were investigated at different pH and temperature. This bio-inspired strategy would build an avenue for designing and constructing a new generation of self-repairing, tissue-adhesive and tough hydrogel.

Phenol red-silk tyrosine cross-linked hydrogels.

PubMed

Sundarakrishnan, Aswin; Herrero Acero, Enrique; Coburn, Jeannine; Chwalek, Karolina; Partlow, Benjamin; Kaplan, David L

2016-09-15

Phenol red is a cytocompatible pH sensing dye that is commonly added to cell culture media, but removed from some media formulations due to its structural mimicry of estrogen. Phenol red free media is also used during live cell imaging, to avoid absorbance and fluorescence quenching of fluorophores. To overcome these complications, we developed cytocompatible and degradable phenol red-silk tyrosine cross-linked hydrogels using horseradish peroxidase (HRP) enzyme and hydrogen peroxide (H2O2). Phenol red added to silk during tyrosine crosslinking accelerated di-tyrosine formation in a concentration-dependent reaction. Phenol red diffusion studies and UV-Vis spectra of phenol red-silk tyrosine hydrogels at different pHs showed altered absorption bands, confirming entrapment of dye within the hydrogel network. LC-MS of HRP-reacted phenol red and N-acetyl-l-tyrosine reaction products confirmed covalent bonds between the phenolic hydroxyl group of phenol red and tyrosine on the silk. At lower phenol red concentrations, leak-proof hydrogels which did not release phenol red were fabricated and found to be cytocompatible based on live-dead staining and alamar blue assessments of encapsulated fibroblasts. Due to the spectral overlap between phenol red absorbance at 415nm and di-tyrosine fluorescence at 417nm, phenol red-silk hydrogels provide both absorbance and fluorescence-based pH sensing. With an average pKa of 6.8 and good cytocompatibiltiy, phenol red-silk hydrogels are useful for pH sensing in phenol red free systems, cellular microenvironments and bioreactors. Phenol red entrapped within hydrogels facilitates pH sensing in phenol red free environments. Leak-proof phenol red based pH sensors require covalent binding techniques, but are complicated due to the lack of amino or carboxyl groups on phenol red. Currently, there is no simple, reliable technique to covalently link phenol red to hydrogel matrices, for real-time pH sensing in cell culture environments. Herein, we take advantage of phenolic groups for covalent linkage of phenol red to silk tyrosine in the presence of HRP and H2O2. The novelty of the current system stems from its simplicity and the use of silk protein to create a cytocompatible, degradable sensor capable of real-time pH sensing in cell culture microenvironments. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

pH-Responsive Hydrogel With an Anti-Glycation Agent for Modulating Experimental Periodontitis.

PubMed

Yu, Min-Chen; Chang, Chih-Yeun; Chao, Yi-Chi; Jheng, Yi-Han; Yang, Connie; Lee, Ning; Yu, Shan-Huey; Yu, Xin-Hong; Liu, Dean-Mo; Chang, Po-Chun

2016-06-01

Stimulus-responsive devices have emerged as a novel approach for local drug delivery. This study investigates the feasibility of a novel chitosan-based, pH-responsive hydrogel loaded with N-phenacylthiazolium bromide (PTB), which cleaves the crosslinks of advanced glycation end products on the extracellular matrix. A chitosan-based hydrogel loaded with PTB was fabricated, and the in vitro release profile was evaluated within pH 5.5 to 7.4. BALB/cJ mice and Sprague-Dawley rats were used to evaluate the effects during the induction and recovery phases of periodontitis, respectively, and animals in each phase were divided into four groups: 1) no periodontitis induction; 2) ligature-induced experimental periodontitis (group PR); 3) experimental periodontitis plus hydrogel without PTB (group PH); and 4) experimental periodontitis plus hydrogel with PTB (group PP). The therapeutic effects were evaluated by microcomputed tomographic imaging of periodontal bone level (PBL) loss and histomorphometry for inflammatory cell infiltration and collagen density. PTB was released faster at pH 5.5 to 6.5 and consistently slower at pH 7.4. In the induction phase, PBL and inflammatory cell infiltration were significantly reduced in group PP relative to group PR, and the loss of collagen matrix was significantly reduced relative to that observed in group PH. In the recovery phase, PBL and inflammatory cell infiltration were significantly reduced, and significantly greater collagen deposition was noted in group PP relative to groups PR and PH at 4 and 14 days after silk removal. Chitosan-based, pH-responsive hydrogels loaded with PTB can retard the initiation of and facilitate the recovery from experimental periodontitis.

Synthesis and characterization of a thermo-sensitive poly( N-methyl acryloylglycine methyl ester) used as a drug release carrier

NASA Astrophysics Data System (ADS)

Deng, Kui-Lin; Zhong, Hai-Bin; Jiao, Yi-Suo; Fan, Ting; Qiao, Xiao; Zhang, Peng-Fei; Ren, Xiao-Bo

2010-06-01

In this article, poly( N-methyl acryloylglycine methyl ester) (PNMAME) was prepared as a novel thermosensitive material with a lower critical solution temperature (LCST) at around 49.5°C. The chemical structures of the monomer NMAME and PNMAME were characterized by 1H NMR and IR measurements. The LCST was investigated systematically as a function of PNMAME concentration, inorganic salt solution and pH value. The results indicated that LCST of PNMAME was obviously dependent on PNMAME concentration and pH. The LCST was increased with a decrease in pH value and PNMAME concentration. To obtain a thermo-sensitive hydrogel with the phase transition temperature close to human body temperature, the copolymerization was conducted between NMAME and N-acryloylglycine ethyl ester (NAGEE). The release behavior of caffeine was evaluated at different temperatures and contents of cross-linkers ( N, N-methylenebis(acrylamide) (NMBA)). The increase of cross-linker content led to a decrease in the release rate of caffeine due to higher crossing density in the hydrogel network. In addition, a faster release of caffeine from the hydrogel with 3% NMBA at 37°C was found in contrast to that at 18°C.

Nanofiber-structured hydrogel yarns with pH-response capacity and cardiomyocyte-drivability for bio-microactuator application.

PubMed

Wu, Shaohua; Duan, Bin; Qin, Xiaohong; Butcher, Jonathan T

2017-09-15

Polymeric hydrogels have great potential in soft biological micro-actuator applications. However, inappropriate micro-architecture, non-anisotropy, weak biomechanics, and inferior response behaviors limit their development. In this study, we designed and manufactured novel polyacrylonitrile (PAN)-based hydrogel yarns composed with uniaxially aligned nanofibers. The nanofibrous hydrogel yarns possessed anisotropic architecture and robust mechanical properties with flexibility, and could be assembled into defined scaffold structures by subsequent processes. The as-prepared hydrogel yarns showed excellent pH response behaviors, with around 100% maximum length and 900% maximum diameter changes, and the pH response was completed within several seconds. Moreover, the hydrogel yarns displayed unique cell-responsive abilities to promote the cell adhesion, proliferation, and smooth muscle differentiation of human adipose derived mesenchymal stem cells (HADMSC). Chicken cardiomyocytes were further seeded onto our nanofibrous hydrogel yarns to engineer living cell-based microactuators. Our results demonstrated that the uniaxially aligned nanofibrous networks within the hydrogel yarns were the key characteristics leading to the anisotropic organization of cardiac cells, and improved sarcomere organization, mimicking the cardiomyocyte bundles in the native myocardium. The construct is capable of sustaining spontaneous cardiomyocyte pumping behaviors for 7days. Our PAN-based nanofibrous hydrogel yarns are attractive for creating linear microactuators with pH-response capacity and biological microactuators with cardiomyocyte-drivability. A mechanically robust polyacrylonitrile-based nanofibrous hydrogel yarn is fabricated by using a modified electrospinning setup in combination with chemical modification processes. The as-prepared hydrogel yarn possesses a uniaxially aligned nanofiber microarchitecture and supports a rapid, pH-dependent expansion/contraction response within a few seconds. Embryonic cardiomyocytes-seeded hydrogel yarn improves the sarcomere organization and mimics the cardiomyocyte bundles in the native myocardium, which sustains spontaneous cardiomyocyte pumping behaviors. The nanofibrous hydrogel yarn has several advantages over traditional bulk hydrogel scaffolds in terms of robust biomechanics, anisotropic aligned architecture, and superior pH response behaviors. Our nanofibrous hydrogel yarn holds the potential to be developed into novel linear and biological microactuators for various biomedical applications. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

An injectable particle-hydrogel hybrid system for glucose-regulatory insulin delivery.

PubMed

Zhao, Fuli; Wu, Di; Yao, Dan; Guo, Ruiwei; Wang, Weiwei; Dong, Anjie; Kong, Deling; Zhang, Jianhua

2017-12-01

Long-term and daily subcutaneous injections of insulin for the treatment of insulin-dependent diabetic patients often lead to poor patient compliance and undesired complications. Phenylboronic acid (PBA)-based polymeric hydrogels have been widely considered as one of the most promising insulin delivery system to replace the frequent insulin injections. However, their applications are limited by clinically irrelevant glucose-responsive range, slow response rate, low tissue-adhesiveness and poor biodegradability, undesirable leakage at normoglycemic state. Herein, we report a novel implantable insulin hydrogel for glucose-regulated delivery of insulin based on a unique particle-hydrogel hybrid platform featuring fast glucose responsiveness at physiological pH, shear-thinning behavior for injection, tissue-adhesive function for long-lasting adherence, and full biodegradability for safe use. The system was thoroughly characterized both in vitro and in vivo and was demonstrated to hold these unique functions. Using streptozotocin-induced diabetic mice as a model, it was shown that a single subcutaneous injection of the insulin-loaded particle-hydrogel formulation led to quasi-steady-state blood glucose levels within the normal range for about two weeks. In addition, the preparation of the formulation only involved simple mixing and self-assembling processes, and thus it had great scalability and reproducibility for practical use. The highly feasible preparation, excellent performance, inherent biocompatibility and biodegradability make this novel composite hydrogel promising platform for diabetes therapy. Phenylboronic acid (PBA)-based polymeric hydrogels have been widely considered as one of the most promising insulin delivery system to replace the frequent insulin injections. However, these hydrogels, mostly based on a variety of PBA-containing acrylamide monomers, are still far from clinical reality. Building upon a unique particle-hydrogel hybrid platform, herein we report a novel implantable insulin storage and delivery system with multifunctionalities including fast glucose-sensitiveness at physiological pH, shear-thinning behavior for injection, tissue-adhesive function for long-lasting adherence, biodegradable materials for safe use and well-controlled insulin release. These unique functions were demonstrated through research both in vitro and in vivo. In addition, the preparation of the formulation was simple, and thus it had great scalability and reproducibility for practical use. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Bacterial cellulose based hydrogel (BC-g-AA) and preliminary result of swelling behavior

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hakam, Adil; Lazim, Azwan Mat; Abdul Rahman, I. Irman

2013-11-27

In this study, hydrogel based on Bacterial cellulose (BC) or local known as Nata de Coco, which grafted with monomer: Acrylic acid (AA) is synthesis by using gamma radiation technique. These hydrogel (BC-g-AA) has unique characteristic whereby responsive to pH buffer solution.

Dual-pH/Magnetic-Field-Controlled Drug Delivery Systems Based on Fe3 O4 @SiO2 -Incorporated Salecan Graft Copolymer Composite Hydrogels.

PubMed

Hu, Xinyu; Wang, Yongmei; Zhang, Liangliang; Xu, Man; Zhang, Jianfa; Dong, Wei

2017-10-09

Salecan is a water-soluble extracellular β-glucan and has excellent physicochemical and biological properties for hydrogel preparation. In this study, a new pH/magnetic field dual-responsive hydrogel was prepared by the graft copolymerization of salecan with 4-pentenoic acid (PA) and N-hydroxyethylacrylamide (HEAA) in the presence of Fe 3 O 4 @SiO 2 nanoparticles for doxorubicin hydrochloride (DOX) release. Integration of Fe 3 O 4 @SiO 2 nanoparticles in salecan-g-poly(PA-co-HEAA) copolymers afforded magnetic sensitivity to the original material. DOX-loaded hydrogels exhibited a clear capacity for pH/magnetic field dual-responsive controlled drug release. Lowering the pH to acidic conditions or introducing an external magnetic field caused an enhancement in DOX release. This salecan-g-poly(PA-co-HEAA)/Fe 3 O 4 @SiO 2 composite hydrogel is a promising drug carrier for magnetically targeted drug delivery with enhanced DOX cytotoxicity against A549 cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mussel-inspired fabrication of konjac glucomannan/microcrystalline cellulose intelligent hydrogel with pH-responsive sustained release behavior.

PubMed

Wang, Lin; Du, Yu; Yuan, Yi; Mu, Ruo-Jun; Gong, Jingni; Ni, Yongsheng; Pang, Jie; Wu, Chunhua

2018-07-01

Intelligent hydrogels are attractive biomaterials for various applications, however, fabricating a hydrogel with both adequate self-healing ability and mechanical properties remains a challenge. Herein, a series of novel intelligent konjac glucomannan (KGM)/microcrystalline cellulose (MCC) hydrogels were prepared vis the mussel-inspired chemistry. MCC was firstly functionalized by the oxidative polymerization of dopamine, and the intelligent hydrogels were obtained by mixing aqueous solutions of KGM and functionalized MCC (PDMCC). By introducing PDMCC, a more compact interconnected porous structure formed for the resulting hydrogels. The self-healing ability and mechanical properties of intelligent hydrogels were dependence on the PDMCC content. Compared with KGM hydrogels, KGM/PDMCC hydrogels exhibited a more distinct pH sensitivity and a lower initial burst release, which was attributed to the compact structure and strong intermolecular hydrogen bond interaction between PDMCC and KGM. These results suggest that the KGM/PDMCC intelligent hydrogels may be promising carriers for controlled drug delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

Hydrogels of polyvinylpyrrolidone (PVP) and poly(acrylic acid) (PAA) synthesized by radiation-induced crosslinking of homopolymers

NASA Astrophysics Data System (ADS)

Kadłubowski, Sławomir; Henke, Artur; Ulański, Piotr; Rosiak, Janusz M.

2010-03-01

pH-sensitive PVP-PAA hydrogels have been prepared by electron-beam-induced irradiation at pH close to pKa of carboxylic groups. Protonation of these groups promoted the formation of hydrogen bonds between the PAA and PVP segments within the crosslinked structure and caused interpolymer complex formation. To demonstrate possible future application of such gels, we tested them as simple chemical detectors. When loaded with glucose oxidase, the PAA-PVP gel's turbidity and shrinkage was triggered by the presence of glucose due to a drop in pH caused by the enzymatic reaction.

pH responsive N-succinyl chitosan/Poly (acrylamide-co-acrylic acid) hydrogels and in vitro release of 5-fluorouracil.

PubMed

Bashir, Shahid; Teo, Yin Yin; Naeem, Sumaira; Ramesh, S; Ramesh, K

2017-01-01

There has been significant progress in the last few decades in addressing the biomedical applications of polymer hydrogels. Particularly, stimuli responsive hydrogels have been inspected as elegant drug delivery systems capable to deliver at the appropriate site of action within the specific time. The present work describes the synthesis of pH responsive semi-interpenetrating network (semi-IPN) hydrogels of N-succinyl-chitosan (NSC) via Schiff base mechanism using glutaraldehyde as a crosslinking agent and Poly (acrylamide-co-acrylic acid)(Poly (AAm-co-AA)) was embedded within the N-succinyl chitosan network. The physico-chemical interactions were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and field emission scanning electron microscope (FESEM). The synthesized hydrogels constitute porous structure. The swelling ability was analyzed in physiological mediums of pH 7.4 and pH 1.2 at 37°C. Swelling properties of formulations with various amounts of NSC/ Poly (AAm-co-AA) and crosslinking agent at pH 7.4 and pH 1.2 were investigated. Hydrogels showed higher swelling ratios at pH 7.4 while lower at pH 1.2. Swelling kinetics and diffusion parameters were also determined. Drug loading, encapsulation efficiency, and in vitro release of 5-fluorouracil (5-FU) from the synthesized hydrogels were observed. In vitro release profile revealed the significant influence of pH, amount of NSC, Poly (AAm-co-AA), and crosslinking agent on the release of 5-FU. Accordingly, rapid and large release of drug was observed at pH 7.4 than at pH 1.2. The maximum encapsulation efficiency and release of 5-FU from SP2 were found to be 72.45% and 85.99%, respectively. Kinetics of drug release suggested controlled release mechanism of 5-FU is according to trend of non-Fickian. From the above results, it can be concluded that the synthesized hydrogels have capability to adapt their potential exploitation as targeted oral drug delivery carriers.

pH responsive N-succinyl chitosan/Poly (acrylamide-co-acrylic acid) hydrogels and in vitro release of 5-fluorouracil

PubMed Central

Bashir, Shahid; Teo, Yin Yin; Naeem, Sumaira; Ramesh, S.; Ramesh, K.

2017-01-01

There has been significant progress in the last few decades in addressing the biomedical applications of polymer hydrogels. Particularly, stimuli responsive hydrogels have been inspected as elegant drug delivery systems capable to deliver at the appropriate site of action within the specific time. The present work describes the synthesis of pH responsive semi-interpenetrating network (semi-IPN) hydrogels of N-succinyl-chitosan (NSC) via Schiff base mechanism using glutaraldehyde as a crosslinking agent and Poly (acrylamide-co-acrylic acid)(Poly (AAm-co-AA)) was embedded within the N-succinyl chitosan network. The physico-chemical interactions were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and field emission scanning electron microscope (FESEM). The synthesized hydrogels constitute porous structure. The swelling ability was analyzed in physiological mediums of pH 7.4 and pH 1.2 at 37°C. Swelling properties of formulations with various amounts of NSC/ Poly (AAm-co-AA) and crosslinking agent at pH 7.4 and pH 1.2 were investigated. Hydrogels showed higher swelling ratios at pH 7.4 while lower at pH 1.2. Swelling kinetics and diffusion parameters were also determined. Drug loading, encapsulation efficiency, and in vitro release of 5-fluorouracil (5-FU) from the synthesized hydrogels were observed. In vitro release profile revealed the significant influence of pH, amount of NSC, Poly (AAm-co-AA), and crosslinking agent on the release of 5-FU. Accordingly, rapid and large release of drug was observed at pH 7.4 than at pH 1.2. The maximum encapsulation efficiency and release of 5-FU from SP2 were found to be 72.45% and 85.99%, respectively. Kinetics of drug release suggested controlled release mechanism of 5-FU is according to trend of non-Fickian. From the above results, it can be concluded that the synthesized hydrogels have capability to adapt their potential exploitation as targeted oral drug delivery carriers. PMID:28678803

Thermo-and pH-sensitive hydrogel membranes composed of poly(N-isopropylacrylamide)-hyaluronan for biomedical applications: Influence of hyaluronan incorporation on the membrane properties.

PubMed

Kamoun, Elbadawy A; Fahmy, Alaa; Taha, Tarek H; El-Fakharany, Esmail M; Makram, Mohamed; Soliman, Hesham M A; Shehata, Hassan

2018-01-01

Interpenetrating hydrogel membranes consisting of pH-sensitive hyaluronan (HA) and thermo-sensitive poly(N-isopropylacrylamide) (PNIPAAM) were synthesized using redox polymerization, followed by N,N-methylenebisacrylamide (BIS) and epichlorohydrin (EPI) were added as chemical crosslinkers. The interaction between membrane compositions has been characterized by FTIR spectroscopy and discussed intensively. The result indicates that HA incorporation in membranes increase the gel fraction, swelling uptake, and the flexibility/elasticity of crosslinked membranes, however it reduced oppositely the mechanical elongation of membranes. PNIPAAm-HA hydrogels responded to both temperature and pH changes and the stimuli-responsiveness was reversible. However, in vitro bioevaluation results revealed that the released ampicillin during the burst release time was sharply influenced and increased with increasing HA contents in membranes; afterwards it became sustainable. Whereas, high HA contents in hydrogels unexpectedly impacted negatively on the cells viability, owing to the viscosity of cell culture media changed. A big resistance was observed against microbial growth of Staphylococcus aureus, Salmonella typhi, and Candida albicans in case of pure PNIPAAm hydrogel membranes without HA or ampicillin. However, HA incorporation or the loaded ampicillin in membranes showed unexpected easily microbial growth. The fast release performance with dual pH-thermo-sensitive hydrogels were suggested as promising materials for quick drug carrier in the biomedical field. Copyright © 2017 Elsevier B.V. All rights reserved.

Non-monotonic swelling of surface grafted hydrogels induced by pH and/or salt concentration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Longo, Gabriel S.; Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208; Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois 60208

2014-09-28

We use a molecular theory to study the thermodynamics of a weak-polyacid hydrogel film that is chemically grafted to a solid surface. We investigate the response of the material to changes in the pH and salt concentration of the buffer solution. Our results show that the pH-triggered swelling of the hydrogel film has a non-monotonic dependence on the acidity of the bath solution. At most salt concentrations, the thickness of the hydrogel film presents a maximum when the pH of the solution is increased from acidic values. The quantitative details of such swelling behavior, which is not observed when themore » film is physically deposited on the surface, depend on the molecular architecture of the polymer network. This swelling-deswelling transition is the consequence of the complex interplay between the chemical free energy (acid-base equilibrium), the electrostatic repulsions between charged monomers, which are both modulated by the absorption of ions, and the ability of the polymer network to regulate charge and control its volume (molecular organization). In the absence of such competition, for example, for high salt concentrations, the film swells monotonically with increasing pH. A deswelling-swelling transition is similarly predicted as a function of the salt concentration at intermediate pH values. This reentrant behavior, which is due to the coupling between charge regulation and the two opposing effects triggered by salt concentration (screening electrostatic interactions and charging/discharging the acid groups), is similar to that found in end-grafted weak polyelectrolyte layers. Understanding how to control the response of the material to different stimuli, in terms of its molecular structure and local chemical composition, can help the targeted design of applications with extended functionality. We describe the response of the material to an applied pressure and an electric potential. We present profiles that outline the local chemical composition of the hydrogel, which can be useful information when designing applications that pursue or require the absorption of biomolecules or pH-sensitive molecules within different regions of the film.« less

Influence of polymer network parameters of tragacanth gum-based pH responsive hydrogels on drug delivery.

PubMed

Singh, Baljit; Sharma, Vikrant

2014-01-30

The present article deals with design of tragacanth gum-based pH responsive hydrogel drug delivery systems. The characterization of hydrogels has been carried out by SEMs, EDAX, FTIR, (13)C NMR, XRD, TGA/DTA/DTG and swelling studies. The correlation between reaction conditions and structural parameters of polymer networks such as polymer volume fraction in the swollen state (ϕ), Flory-Huggins interaction parameter (χ), molecular weight of the polymer chain between two neighboring cross links (M¯c), crosslink density (ρ) and mesh size (ξ) has been determined. The different kinetic models such as zero order, first order, Higuchi square root law, Korsmeyer-Peppas model and Hixson-Crowell cube root model were applied and it has been observed that release profile of amoxicillin best followed the first order model for the release of drug from the polymer matrix. The swelling of the hydrogels and release of drug from the drug loaded hydrogels occurred through non-Fickian diffusion mechanism in pH 7.4 solution. Copyright © 2013 Elsevier Ltd. All rights reserved.

Characterization and swelling-deswelling properties of wheat straw cellulose based semi-IPNs hydrogel.

PubMed

Liu, Jia; Li, Qian; Su, Yuan; Yue, Qinyan; Gao, Baoyu

2014-07-17

A novel wheat straw cellulose-g-poly(potassium acrylate)/polyvinyl alcohol (WSC-g-PKA/PVA) semi-interpenetrating polymer networks (semi-IPNs) hydrogel was prepared by polymerizing wheat straw and an aqueous solution of acrylic acid (AA), and further semi-interpenetrating with PVA occurred during the chemosynthesis. The swelling and deswelling properties of WSC-g-PKA/PVA semi-IPNs hydrogel and WSC-g-PKA hydrogel were studied and compared in various pH solutions, salt solutions, temperatures, particle sizes and ionic strength. The results indicated that both hydrogels had the largest swelling capacity at pH=6, and the effect of ions on the swelling of hydrogels was in the order: Na(+)>K(+)>Mg(2+)>Ca(2+). The Schott's pseudo second order model can be effectively used to evaluate swelling kinetics of hydrogels. Moreover, the semi-IPNs hydrogel had improved swelling-deswelling properties compared with that of WSC-g-PKA hydrogel. Copyright © 2014 Elsevier Ltd. All rights reserved.

pH and Glucose Dual-Responsive Injectable Hydrogels with Insulin and Fibroblasts as Bioactive Dressings for Diabetic Wound Healing.

PubMed

Zhao, Lingling; Niu, Lijing; Liang, Hongze; Tan, Hui; Liu, Chaozong; Zhu, Feiyan

2017-11-01

pH and glucose dual-responsive injectable hydrogels were prepared through the cross-linking of Schiff's base and phenylboronate ester using phenylboronic-modified chitosan, poly(vinyl alcohol) and benzaldehyde-capped poly(ethylene glycol). Protein drugs and live cells could be incorporated into the hydrogels during the in situ cross-linking, displaying sustained and pH/glucose-triggered drug release from the hydrogels and cell viability and proliferation in the three-dimensional hydrogel matrix as well. Hence, the hydrogels with insulin and fibroblasts were considered as bioactive dressings for diabetic wound healing. A streptozotocin-induced diabetic rat model was used to evaluate the efficacy of hydrogel dressings in wound repair. The results revealed that the incorporation of insulin and L929 in the hydrogels could promote neovascularization and collagen deposition and enhance the wound-healing process of diabetic wounds. Thus, the drug- and cell-loaded hydrogels have promising potential in wound healing as a medicated system for various therapeutic proteins and live cells.

A novel pH-responsive hydrogel-based on calcium alginate engineered by the previous formation of polyelectrolyte complexes (PECs) intended to vaginal administration.

PubMed

Ferreira, Natália Noronha; Perez, Taciane Alvarenga; Pedreiro, Liliane Neves; Prezotti, Fabíola Garavello; Boni, Fernanda Isadora; Cardoso, Valéria Maria de Oliveira; Venâncio, Tiago; Gremião, Maria Palmira Daflon

2017-10-01

This work aimed to develop a calcium alginate hydrogel as a pH responsive delivery system for polymyxin B (PMX) sustained-release through the vaginal route. Two samples of sodium alginate from different suppliers were characterized. The molecular weight and M/G ratio determined were, approximately, 107 KDa and 1.93 for alginate_S and 32 KDa and 1.36 for alginate_V. Polymer rheological investigations were further performed through the preparation of hydrogels. Alginate_V was selected for subsequent incorporation of PMX due to the acquisition of pseudoplastic viscous system able to acquiring a differential structure in simulated vaginal microenvironment (pH 4.5). The PMX-loaded hydrogel (hydrogel_PMX) was engineered based on polyelectrolyte complexes (PECs) formation between alginate and PMX followed by crosslinking with calcium chloride. This system exhibited a morphology with variable pore sizes, ranging from 100 to 200 μm and adequate syringeability. The hydrogel liquid uptake ability in an acid environment was minimized by the previous PECs formation. In vitro tests evidenced the hydrogels mucoadhesiveness. PMX release was pH-dependent and the system was able to sustain the release up to 6 days. A burst release was observed at pH 7.4 and drug release was driven by an anomalous transport, as determined by the Korsmeyer-Peppas model. At pH 4.5, drug release correlated with Weibull model and drug transport was driven by Fickian diffusion. The calcium alginate hydrogels engineered by the previous formation of PECs showed to be a promising platform for sustained release of cationic drugs through vaginal administration.

Rheological behavior and Ibuprofen delivery applications of pH responsive composite alginate hydrogels.

PubMed

Jabeen, Suraya; Maswal, Masrat; Chat, Oyais Ahmad; Rather, Ghulam Mohammad; Dar, Aijaz Ahmad

2016-03-01

Synthesis and structural characterization of hydrogels composed of sodium alginate, polyethylene oxide and acrylic acid with cyclodextrin as the hydrocolloid prepared at different pH values is presented. The hydrogels synthesized show significant variations in rheological properties, drug encapsulation capability and release kinetics. The hydrogels prepared at lower pH (pH 1) are more elastic, have high tensile strength and remain almost unaffected by varying temperature or frequency. Further, their Ibuprofen encapsulation capacity is low and releases it slowly. The hydrogel prepared at neutral pH (pH 7) is viscoelastic, thermo-reversible and also exhibits sol-gel transition on applying frequency and changing temperature. It shows highest Ibuprofen encapsulation capacity and also optimum drug release kinetics. The hydrogel prepared at higher pH (pH 12) is more viscous, has low tensile strength, is unstable to change in temperature and has fast drug release rate. The study highlights the pH responsiveness of three composite alginate hydrogels prepared under different conditions to be employed in drug delivery applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis and evaluation on pH- and temperature-responsive chitosan-p(MAA-co-NIPAM) hydrogels.

PubMed

Rasib, S Z M; Ahmad, Z; Khan, A; Akil, H M; Othman, M B H; Hamid, Z A A; Ullah, F

2018-03-01

In this study, chitosan-poly(methacrylic acid-co-N-isopropylacrylamide) [chitosan-p(MAA-co-NIPAM)] hydrogels were synthesized by emulsion polymerization. In order to be used as a carrier for drug delivery systems, the hydrogels had to be biocompatible, biodegradable and multi-responsive. The polymerization was performed by copolymerize MAA and NIPAM with chitosan polymer to produce a chitosan-based hydrogel. Due to instability during synthesis and complexity of components to produce the hydrogel, further study at different times of reaction is important to observe the synthesis process, the effect of end product on swelling behaviour and the most important is to find the best way to control the hydrogel synthesis in order to have an optimal swelling behaviour for drug release application. Studied by using Fourier transform infra-red (FTIR) spectroscopy found that, the synthesized was successfully produced stable chitosan-based hydrogel with PNIPAM continuously covered the outer surface of hydrogel which influenced much on the stability during synthesis. The chitosan and PMAA increased the zeta potential of the hydrogel and the chitosan capable to control shrinkage above human body temperature. The chitosan-p(MAA-co-NIPAM) hydrogels also responses to pH and temperature thus improved the ability to performance as a drug carrier. Copyright © 2017 Elsevier B.V. All rights reserved.

Self-Assembled Hydrogels from Poly[N-(2-hydroxypropyl)methacrylamide] Grafted with β-Sheet Peptides

PubMed Central

Radu-Wu, Larisa C.; Yang, Jiyuan; Wu, Kuangshi; Kopeček, Jindřich

2009-01-01

A new hybrid hydrogel based on poly[N-(2-hydroxypropyl)methacrylamide] grafted with a β-sheet peptide, Beta11, was designed. Circular dichroism spectroscopy indicated that the folding ability of β-sheet peptide was retained in the hybrid system, whereas the sensitivity of the peptide towards temperature and pH variations was hindered. The polymer backbone also prevented the twisting of the fibrils that resulted from the antiparallel arrangement of the β-strands, as proved by Fourier transform infrared spectroscopy. Thioflavin T binding experiments and transmission electron microscopy showed fibril formation with minimal lateral aggregation. As a consequence, the graft copolymer self-assembled into a hydrogel in aqueous environment. This process was mediated by association of β-sheet domains. Scanning electron microscopy revealed a particular morphology of the network, characterized by long-range order and uniformly aligned lamellae. Microrheology results confirmed that concentration-dependent gelation occurred. PMID:19591463

Design of poly(mPEGMA-co-MAA) hydrogel-based mPEG-b-PCL nanoparticles for oral meloxicam delivery.

PubMed

Shi, Yongli; Liu, Zhaomin; Yang, Yaxing; Xu, Xiaojie; Li, Yan; Li, Tong

2017-07-01

To enhance the therapeutic effects of meloxicam (MLX), we developed an oral MLX-loaded poly(ethylene glycol)-b-poly(ε-caprolactone) nanoparticles@hydrogel (MLX-NPs@hydrogel) preparation. The MLX-NPs were fabricated via a solvent evaporation method, and their morphologies were observed by a JEM-1011 transmission electron microscope (TEM). The poly(mPEGMA-co-MAA) hydrogels were synthesized, and studies on their pH sensibilities were carried out in pH1.2, 6.8, and 7.4 buffers. The final MLX-NPs@hydrogel preparation was obtained by immersing the hydrogels in the MLX-NPs suspensions (pH7.4) for 48h. The thermodynamic properties and cytotoxicity of the MLX-NPs@hydrogel preparation were also studied. TEM images illustrated that mPEG-b-PCL NPs had a uniform size distribution. The poly(mPEGMA-co-MAA) hydrogels showed an excellent pH-sensibility. Thermal gravity analysis (TGA) data suggested that the protection of hydrogels improved the stability of mPEG-b-PCL NPs. The release studies revealed that MLX-NPs@hydrogel could deliver the MLX-NPs into alkalescent environment (e.g. intestinal tract). Then, the medicated NPs released MLX at a sustained release profile. Such preparation could overcome the drawbacks of oral MLX, and enhance its therapeutic effects. Therefore, the NPs@hydrogel was a promising sustained-controlled release matrix. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation and characterization of pH sensitive crosslinked Linseed polysaccharides-co-acrylic acid/methacrylic acid hydrogels for controlled delivery of ketoprofen.

PubMed

Shabir, Farya; Erum, Alia; Tulain, Ume Ruqia; Hussain, Muhammad Ajaz; Ahmad, Mahmood; Akhter, Faiza

2017-01-01

Some pH responsive polymeric matrix of Linseed ( Linum usitatissimum ), L. hydrogel (LSH) was prepared by free radical polymerization using potassium persulfate (KPS) as an initiator, N,N -methylene bisacrylamide (MBA) as a crosslinker, acrylic acid (AA) and methacrylic acid (MAA) as monomers; while ketoprofen was used as a model drug. Different formulations of LSH-co-AA and LSH-co-MAA were formulated by varying the concentration of crosslinker and monomers. Structures obtained were thoroughly characterized using Fourier transforms infrared (FTIR) spectroscopy, XRD analysis and Scanning electron microscopy. Sol-gel fractions, porosity of the materials and ketoprofen loading capacity were also measured. Swelling and in vitro drug release studies were conducted at simulated gastric fluids, i.e., pH 1.2 and 7.4. FTIR evaluation confirmed successful grafting of AA and MAA to LSH backbone. XRD studies showed retention of crystalline structure of ketoprofen in LSH-co-AA and its amorphous dispersion in LSH-co-MAA. Gel content was increased by increasing MBA and monomer content; whereas porosity of hydrogel was increased by increasing monomer concentration and decreased by increasing MBA content. Swelling of copolymer hydrogels was high at pH 7.4 and low at pH 1.2. Ketoprofen release showed an increasing trend by increasing monomer content; however it was decreased with increasing MBA content. Sustained release of ketoprofen was noted from copolymers and release followed Korsmeyer-Peppas model.

Biomimetic hydrogels for biosensor implant biocompatibility: electrochemical characterization using micro-disc electrode arrays (MDEAs).

PubMed

Justin, Gusphyl; Finley, Stephen; Abdur Rahman, Abdur Rub; Guiseppi-Elie, Anthony

2009-02-01

Our interest is in the development of engineered microdevices for continuous remote monitoring of intramuscular lactate, glucose, pH and temperature during post-traumatic hemorrhaging. Two important design considerations in the development of such devices for in vivo diagnostics are discussed; the utility of micro-disc electrode arrays (MDEAs) for electrochemical biosensing and the application of biomimetic, bioactive poly(HEMA)-based hydrogel composites for implant biocompatibility. A poly(HEMA)-based hydrogel membrane containing polyethylene glycol (PEG) was UV cross-linked with tetraethyleneglycol diacrylate following application to MDEAs (50 mum discs) and to 250 mum diameter gold electrodes within 8-well culture ware. Cyclic voltammetry (CV) of the MDEAs revealed a reduction in the apparent diffusion coefficient of ferrocenemonocarboxylic acid (FcCO(2)H), from 6.68 x 10(-5) to 6.74 x 10(-6) cm(2)/s for the uncoated and 6 mum thick hydrogel coated devices, respectively. Single frequency (4 kHz) temporal impedance measurements of the hydrogels in the 8-well culture ware showed a reversible 5% change in the absolute impedance of the hydrogels when exposed to a pH change between 6.1 to 7.2 and a 20% drop between pH 6.1 and 8.8.

Flavonoid-based pH-responsive hydrogels as carrier of unstable drugs in oxidative conditions.

PubMed

Spizzirri, Umile Gianfranco; Cirillo, Giuseppe; Curcio, Manuela; Picci, Nevio; Iemma, Francesca

2015-05-01

In this study, pH-responsive hydrogels, synthesized by the coupling reaction of polyacrylic acid and catechin, are proposed as carriers of oxidable drugs toward the GI tract. The presence of polyphenolic moieties in the network gives the polymers properties suitable for the release of unstable drugs in oxidative conditions. The characterization of the hydrogels is obtained by means of morphological and physico-chemical analyses, antioxidant assays and evaluation of the swelling behavior in media simulating the gastric (pH 1.0) and the intestinal (pH 7.4) tracts. The hydrogels are tested as pH-responsive carriers in in vitro release studies of folic acid and thiamine, two model drugs easily degraded by oxidative conditions simulated by UV irradiation and t-butyl hydroperoxide treatment, respectively. Results show that catechin-based carriers are able to control the release of drugs at different pH values, giving a remarkable improvement in the stability of the therapeutics.

pH induced contrast in viscoelasticity imaging of biopolymers

PubMed Central

Yapp, R D; Insana, M F

2009-01-01

Understanding contrast mechanisms and identifying discriminating features is at the heart of diagnostic imaging development. This report focuses on how pH influences the viscoelastic properties of biopolymers to better understand the effects of extracellular pH on breast tumour elasticity imaging. Extracellular pH is known to decrease as much as 1 pH unit in breast tumours, thus creating a dangerous environment that increases cellular mutatation rates and therapeutic resistance. We used a gelatin hydrogel phantom to isolate the effects of pH on a polymer network with similarities to the extracellular matrix in breast stroma. Using compressive unconfined creep and stress relaxation measurements, we systematically measured the viscoelastic features sensitive to pH by way of time domain models and complex modulus analysis. These results are used to determine the sensitivity of quasi-static ultrasonic elasticity imaging to pH. We found a strong elastic response of the polymer network to pH, such that the matrix stiffness decreases as pH was reduced, however the viscous response of the medium to pH was negligible. While physiological features of breast stroma such as proteoglycans and vascular networks are not included in our hydrogel model, observations in this study provide insight into viscoelastic features specific to pH changes in the collagenous stromal network. These observations suggest that the large contrast common in breast tumours with desmoplasia may be reduced under acidic conditions, and that viscoelastic features are unlikely to improve discriminability. PMID:19174599

Investigation of copper (Cu2+) adsorption performances and gamma radiation dose effect of polymeric hydrogel

NASA Astrophysics Data System (ADS)

Hassan, Safia; Yasin, Tariq; Imran, Zahid; Batool, Syeda Sitwat

2018-02-01

In present study, series of gamma irradiated poly(acrylic acid)/Penytriethoxytrisilane (PTES) based hydrogels were synthesized. The hydrogels were used for the adsorption of Cu2+ from the aqueous solution. Batch adsorption experiments were performed by varying contact time (0-10 hours), pH value (2-6), hydrogels weight (15-155 mg) and initial Cu2+ concentration (0.003-90 mg/L). The results indicated that lowering the gamma irradiation dose (30-15 kGy) and PTES amount (1.65-0.83 μmol) into hydrogel polymeric networks, improved the initial rate of adsorption and final adsorption capacity of hydrogel for Cu2+. AA40/15 had 143.4mg/g Cu2+ adsorption capacity higher than AA80/30 which is 106.0mg/g. Hydrogels exhibited maximum o adsorption capacity for Cu2+ within a wide pH range. All adsorption data was described by the pseudo—first order and second order kinetic model equations and isotherm data by Langmuir model. FTIR spectra analysis before and after adsorption of Cu2+ on the AA hydrogels gave detail analysis of adsorption mechanism. The behavior of adsorption expressed that the enhanced adsorption capacity was due to the porous structure and e presence of functional groups onto surface of adsorbate. It is expected this polymeric hydrogel has potential to work as alternative biomedical sorbents and environmental use as pH altered.

Controlled drug release from hydrogels for contact lenses: Drug partitioning and diffusion.

PubMed

Pimenta, A F R; Ascenso, J; Fernandes, J C S; Colaço, R; Serro, A P; Saramago, B

2016-12-30

Optimization of drug delivery from drug loaded contact lenses assumes understanding the drug transport mechanisms through hydrogels which relies on the knowledge of drug partition and diffusion coefficients. We chose, as model systems, two materials used in contact lens, a poly-hydroxyethylmethacrylate (pHEMA) based hydrogel and a silicone based hydrogel, and three drugs with different sizes and charges: chlorhexidine, levofloxacin and diclofenac. Equilibrium partition coefficients were determined at different ionic strength and pH, using water (pH 5.6) and PBS (pH 7.4). The measured partition coefficients were related with the polymer volume fraction in the hydrogel, through the introduction of an enhancement factor following the approach developed by the group of C. J. Radke (Kotsmar et al., 2012; Liu et al., 2013). This factor may be decomposed in the product of three other factors E HS , E el and E ad which account for, respectively, hard-sphere size exclusion, electrostatic interactions, and specific solute adsorption. While E HS and E el are close to 1, E ad >1 in all cases suggesting strong specific interactions between the drugs and the hydrogels. Adsorption was maximal for chlorhexidine on the silicone based hydrogel, in water, due to strong hydrogen bonding. The effective diffusion coefficients, D e , were determined from the drug release profiles. Estimations of diffusion coefficients of the non-adsorbed solutes D=D e ×E ad allowed comparison with theories for solute diffusion in the absence of specific interaction with the polymeric membrane. Copyright © 2016 Elsevier B.V. All rights reserved.

The binary complex of poly(PEGMA-co-MAA) hydrogel and PLGA nanoparticles as a novel oral drug delivery system for ibuprofen delivery.

PubMed

Shang, Qing; Huang, Sijin; Zhang, Aixin; Feng, Jia; Yang, Song

2017-11-01

To improve the bioavailability of ibuprofen (IBU), we developed a novel binary complex of poly(PEGMA-co-MAA) hydrogel and IBU-loaded PLGA nanoparticles (IBU-PLGA NPs@hydrogels) as an oral intestinal targeting drug delivery system (OIDDS). The IBU-loaded PLGA NPs and pH-sensitive hydrogels were obtained via the solvent evaporation method and radical polymerization, respectively. The final OIDDS was obtained by immersing the hydrogel chips in the IBU-loaded PLGA NPs solutions (pH 7.4) for 3 d. The size distribution and morphology of cargo-free NPs were studied by laser granularity analyzer and transmission electron microscope (TEM). The inner structures of the pH-sensitive hydrogel chips were observed with an S-4800 scanning electron microscope (SEM). The distribution states of IBU in the OIDDS were also studied with X-ray diffraction (XRD) and differential scanning calorimetry (DSC). TEM photographs illustrated that the PLGA NPs had a round shape with an average diameter about 100 nm. Fourier transform infrared spectrum (FTIR) confirmed the synthesis of poly(PEGMA-co-MAA) hydrogel. The SEM picture showed that the final hydrogel had 3D net-work structures. Moreover, the poly(PEGMA-co-MAA) hydrogel showed an excellent pH-sensitivity. The XRD and DSC curves suggested that IBU distributed in the OIDDS with an amorphous state. The cumulated release profiles indicated that the final OIDDS could release IBU in alkaline environment (e.g. intestinal tract) at a sustained manner. Therefore, the novel OIDDS could improve the oral bioavailability of IBU, and had a potential application in drug delivery.

Synthesis and characterization of zinc chloride containing poly(acrylic acid) hydrogel by gamma irradiation

NASA Astrophysics Data System (ADS)

Park, Jong-Seok; Kuang, Jia; Gwon, Hui-Jeong; Lim, Youn-Mook; Jeong, Sung-In; Shin, Young-Min; Seob Khil, Myung; Nho, Young-Chang

2013-07-01

In this study, the characterization of zinc chloride incorporated into a poly(acrylic acid) (PAAc) hydrogel prepared by gamma-ray irradiation was investigated. Zinc chloride powder with different concentrations was dissolved in the PAAc solution, and it was crosslinked with gamma-ray irradiation. The effects of various parameters such as zinc ion concentration and irradiation doses on characteristics of the hydrogel formed were investigated in detail for obtaining an antibacterial wound dressing. In addition, the gel content, pH-sensitive (pH 4 or 7) swelling ratio, and UV-vis absorption spectra of the zinc particles in the hydrogels were characterized. Moreover, antibacterial properties of these new materials against Staphylococcus aureus and Escherichia coli strains were observed on solid growth media. The antibacterial tests indicated that the zinc chloride containing PAAc hydrogels have good antibacterial activity.

Stimulus-responsive hydrogels: Theory, modern advances, and applications

PubMed Central

Koetting, Michael C.; Peters, Jonathan T.; Steichen, Stephanie D.; Peppas, Nicholas A.

2016-01-01

Over the past century, hydrogels have emerged as effective materials for an immense variety of applications. The unique network structure of hydrogels enables very high levels of hydrophilicity and biocompatibility, while at the same time exhibiting the soft physical properties associated with living tissue, making them ideal biomaterials. Stimulus-responsive hydrogels have been especially impactful, allowing for unprecedented levels of control over material properties in response to external cues. This enhanced control has enabled groundbreaking advances in healthcare, allowing for more effective treatment of a vast array of diseases and improved approaches for tissue engineering and wound healing. In this extensive review, we identify and discuss the multitude of response modalities that have been developed, including temperature, pH, chemical, light, electro, and shear-sensitive hydrogels. We discuss the theoretical analysis of hydrogel properties and the mechanisms used to create these responses, highlighting both the pioneering and most recent work in all of these fields. Finally, we review the many current and proposed applications of these hydrogels in medicine and industry. PMID:27134415

Synthesis and Characterization of pH and Thermo Dual-Responsive Hydrogels with a Semi-IPN Structure Based on N-Isopropylacrylamide and Itaconamic Acid.

PubMed

Rwei, Syang-Peng; Tuan, Huynh Nguyen Anh; Chiang, Whe-Yi; Way, Tun-Fun

2018-04-28

A series of semi-interpenetrating polymer network (semi-IPN) hydrogels were synthesized and investigated in this study. Linear copolymer poly( N -isopropylacrylamide-co-itaconamic acid) p(NIPAM-co-IAM), which is formed by copolymerization of N -isopropylacrylamide (NIPAM) and itaconamic acid (IAM, 4-amino-2-ethylene-4-oxobutanoic acid), was introduced into a solution of NIPAM to form a series of pH and thermo dual-responsive p(NIPAM-co-IAM)/pNIPAM semi-IPN hydrogels by free radical polymerization. The structural, morphological, chemical, and physical properties of the linear copolymer and semi-IPN hydrogels were investigated. The semi-IPN hydrogel showed high thermal stability according to thermal gravimetric analyzer (TGA). Scanning electronic microscopy (SEM) images showed that the pore size was in the range of 119~297 µm and could be controlled by the addition ratio of the linear copolymer in the semi-IPN structure. The addition of linear copolymer increased the fracture strain from 57.5 ± 2.9% to 91.1 ± 4.9% depending on the added amount, while the compressive modulus decreased as the addition increased. Moreover, the pH and thermo dual-responsive properties were investigated using differential scanning calorimetry (DSC) and monitoring the swelling behavior of the hydrogels. In deionized (DI) water, the equilibrium swelling ratio of the hydrogels decreased as the temperature increased from 20 °C to 50 °C, while it varied in various pH buffer solutions. In addition, the swelling and deswelling rates of the hydrogels also significantly increased. The results indicate that the novel pH-thermo dual-responsive semi-IPN hydrogels were synthesized successfully and may be a potential material for biomedical, drug delivery, or absorption application.

Poly(ethylene glycol) (PEG)-lactic acid nanocarrier-based degradable hydrogels for restoring the vaginal microenvironment

PubMed Central

Rajan, Sujata Sundara; Turovskiy, Yevgeniy; Singh, Yashveer; Chikindas, Michael L.; Sinko, Patrick J.

2014-01-01

Women with bacterial vaginosis (BV) display reduced vaginal acidity, which make them susceptible to associated infections such as HIV. In the current study, poly(ethylene glycol) (PEG) nanocarrier-based degradable hydrogels were developed for the controlled release of lactic acid in the vagina of BV-infected women. PEG-lactic acid (PEG-LA) nanocarriers were prepared by covalently attaching lactic acid to 8-arm PEG-SH via cleavable thioester bonds. PEG-LA nanocarriers with 4 copies of lactic acid per molecule provided controlled release of lactic acid with a maximum release of 23% and 47% bound lactic acid in phosphate buffered saline (PBS, pH 7.4) and acetate buffer (AB, pH 4.3), respectively. The PEG nanocarrier-based hydrogels were formed by cross-linking the PEG-LA nanocarriers with 4-arm PEG-NHS via degradable thioester bonds. The nanocarrier-based hydrogels formed within 20 min under ambient conditions and exhibited an elastic modulus that was 100-fold higher than the viscous modulus. The nanocarrier-based degradable hydrogels provided controlled release of lactic acid for several hours; however, a maximum release of only 10%–14% bound lactic acid was observed possibly due to steric hindrance of the polymer chains in the cross-linked hydrogel. In contrast, hydrogels with passively entrapped lactic acid showed burst release with complete release within 30 min. Lactic acid showed antimicrobial activity against the primary BV pathogen Gardnerella vaginalis with a minimum inhibitory concentration (MIC) of 3.6 mg/ml. In addition, the hydrogels with passively entrapped lactic acid showed retained antimicrobial activity with complete inhibition G. vaginalis growth within 48 h. The results of the current study collectively demonstrate the potential of PEG nanocarrier-based hydrogels for vaginal administration of lactic acid for preventing and treating BV. PMID:25223229

Two-dimensional inverse opal hydrogel for pH sensing.

PubMed

Xue, Fei; Meng, Zihui; Qi, Fenglian; Xue, Min; Wang, Fengyan; Chen, Wei; Yan, Zequn

2014-12-07

A novel hydrogel film with a highly ordered macropore monolayer on its surface was prepared by templated photo-polymerization of hydrogel monomers on a two-dimensional (2D) polystyrene colloidal array. The 2D inverse opal hydrogel has prominent advantages over traditional three-dimensional (3D) inverse opal hydrogels. First, the formation of the 2D array template through a self-assembly method is considerably faster and simpler. Second, the stable ordering structure of the 2D array template makes it easier to introduce the polymerization solution into the template. Third, a simple measurement, a Debye diffraction ring, is utilized to characterize the neighboring pore spacing of the 2D inverse opal hydrogel. Acrylic acid was copolymerized into the hydrogel; thus, the hydrogel responded to pH through volume change, which resulted from the formation of the Donnan potential. The 2D inverse opal hydrogel showed that the neighboring pore spacing increased by about 150 nm and diffracted color red-shifted from blue to red as the pH increased from pH 2 to 7. In addition, the pH response kinetics and ionic strength effect of this 2D mesoporous polymer film were also investigated.

Facile preparation and characterization of pH sensitive Mt/CMC nanocomposite hydrogel beads for propranolol controlled release.

PubMed

Farhadnejad, Hassan; Mortazavi, Seyed Alireza; Erfan, Mohammad; Darbasizadeh, Behzad; Motasadizadeh, Hamidreza; Fatahi, Yousef

2018-05-01

The main aim of the present study was to design pH-sensitive nanocomposite hydrogel beads, based on carboxymethyl cellulose (CMC) and montmorillonite (Mt)-propranolol (PPN) nanohybrid, and evaluate whether the prepared nanocomposite beads could potentially be used as oral drug delivery systems. PPN-as a model drug-was intercalated into the interlayer space of Mt clay mineral via the ion exchange procedure. The resultant nanohybrid (Mt-PPN) was applied to fabricate nanocomposite hydrogel beads by association with carboxymethyl cellulose. The characterization of test samples was performed using different techniques: X-Ray Diffraction (XRD), IR spectroscopy (FT-IR), thermal gravity analysis (TGA), and scanning electron microscopy (SEM). The drug encapsulation efficiency was evaluated by UV-vis spectroscopy, and was found to be high for Mt/CMC beads. In vitro drug release test was performed in the simulated gastrointestinal conditions to evaluate the efficiency of Mt-PPN/CMC nanocomposite beads as a controlled-release drug carrier. The drug release profiles indicated that the Mt-PPN/CMC nanocomposite beads had high stability against stomach acid and a sustained- and controlled-release profile for PPN under the simulated intestinal conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

Combining inkjet printing and sol-gel chemistry for making pH-sensitive surfaces.

PubMed

Orsi, Gianni; De Maria, Carmelo; Montemurro, Francesca; Chauhan, Veeren M; Aylott, Jonathan W; Vozzi, Giovanni

2015-01-01

Today biomedical sciences are experiencing the importance of imaging biological parameters with luminescence methods. Studying 2D pH distribution with those methods allows building knowledge about complex cellular processes. Immobilizing pH sensitive nanoparticles inside hydrogel matrixes, in order to guarantee a proper SNR, could easily make stable and biocompatible 2D sensors. Inkjet printing is also well known as tool for printing images onto porous surfaces. Recently it has been used as a free-form fabrication method for building three-dimensional parts, and now is being explored as a way of printing electrical and optical devices. Inkjet printing was used either as a rapid prototyping method for custom biosensors. Sol-gel method is naturally bound with inkjet, because the picoliter-sized ink droplets evaporate quickly, thus allowing quick sol-gel transitions on the printed surface. In this work will be shown how to merge those technologies, in order to make a nanoparticles doped printable hydrogel, which could be used for making 2D/3D smart scaffolds able to monitor cell activities. An automated image analysis system was developed in order to quickly have the pH measurements from pH nanosensors fluorescence images.

Ultra-bright red-emitting photostable perylene bisimide dyes: new indicators for ratiometric sensing of high pH or carbon dioxide.

PubMed

Pfeifer, David; Klimant, Ingo; Borisov, Sergey M

2018-05-08

New pH sensitive perylene bisimide indicator dyes were synthesised and used for fabrication of optical sensors. The highly photostable dyes show absorption/emission bands in the red/near-infrared (NIR) region of the electromagnetic spectrum, high molar absorption coefficients (up to 100 000 M-1 cm-1) and fluorescence quantum yields close to unity. The absorption and emission spectra show strong bathochromic shift upon deprotonation of imidazole nitrogen which makes the dyes promising as ratiometric fluorescent indicators. Physical entrapment of the indicators into polyurethane hydrogel enables pH determination in alkaline pH. It is also shown that plastic carbon dioxide solid state sensor can be manufactured via immobilization of the pH indicator in a hydrophilic polymer, along with a quaternary ammonium base. The influence of plasticizer, different lipophilic bases and humidity on the sensitivity of the sensor material were systematically investigated. The disubstituted perylene, particularly, features two deprotonation equilibria enabling sensing over a very broad range from 0.5 to 1000 hPa pCO2. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Time-dependent gel to gel transformation of a peptide based supramolecular gelator.

PubMed

Baral, Abhishek; Basak, Shibaji; Basu, Kingshuk; Dehsorkhi, Ashkan; Hamley, Ian W; Banerjee, Arindam

2015-06-28

A dipeptide with a long fatty acid chain at its N-terminus gives hydrogels in phosphate buffer in the pH range 7.0-8.5. The hydrogel with a gelator concentration of 0.45% (w/v) at pH 7.46 (physiological pH) provides a very good platform to study dynamic changes within a supramolecular framework as it exhibits remarkable change in its appearance with time. Interestingly, the first formed transparent hydrogel gradually transforms into a turbid gel within 2 days. These two forms of the hydrogel have been thoroughly investigated by using small angle X-ray scattering (SAXS), powder X-ray diffraction (PXRD), field emission scanning electron microscopic (FE-SEM) and high-resolution transmission electron microscopic (HR-TEM) imaging, FT-IR and rheometric analyses. The SAXS and low angle PXRD studies substantiate different packing arrangements for the gelator molecules for these two different gel states (the freshly prepared and the aged hydrogel). Moreover, rheological studies of these two gels reveal that the aged gel is stiffer than the freshly prepared gel.

Reversible Modulation of DNA-Based Hydrogel Shapes by Internal Stress Interactions.

PubMed

Hu, Yuwei; Kahn, Jason S; Guo, Weiwei; Huang, Fujian; Fadeev, Michael; Harries, Daniel; Willner, Itamar

2016-12-14

We present the assembly of asymmetric two-layer hybrid DNA-based hydrogels revealing stimuli-triggered reversibly modulated shape transitions. Asymmetric, linear hydrogels that include layer-selective switchable stimuli-responsive elements that control the hydrogel stiffness are designed. Trigger-induced stress in one of the layers results in the bending of the linear hybrid structure, thereby minimizing the elastic free energy of the systems. The removal of the stress by a counter-trigger restores the original linear bilayer hydrogel. The stiffness of the DNA hydrogel layers is controlled by thermal, pH (i-motif), K + ion/crown ether (G-quadruplexes), chemical (pH-doped polyaniline), or biocatalytic (glucose oxidase/urease) triggers. A theoretical model relating the experimental bending radius of curvatures of the hydrogels with the Young's moduli and geometrical parameters of the hydrogels is provided. Promising applications of shape-regulated stimuli-responsive asymmetric hydrogels include their use as valves, actuators, sensors, and drug delivery devices.

Application of Fiber Optic ATR-FTIR Methods for In Situ Characterization of Protein Delivery Systems in Real Time

PubMed Central

McFearin, Cathryn L.; Sankaranarayanan, Jagadis; Almutairi, Adah

2011-01-01

Real Time Characterization of Protein Delivery Systems A fiber optic coupled ATR-FTIR spectroscopy technique was applied to the study of two different therapeutic delivery systems, acid degradable hydrogels and nanoparticles. Real time exponential release of a model protein, human serum albumin (HSA), was observed from two different polymeric hydrogels formulated with a pH sensitive crosslinker. Spectroscopic examination of nanoparticles formulated with an acid degradable polymer shell and encapsulated HSA exhibited vibrational signatures characteristic of both particle and payload when exposed to lowered pH conditions demonstrating the ability of this methodology to simultaneously measure phenomena arising from a system with a mixture of components. In addition, thorough characterization of these pH sensitive delivery vehicles without encapsulated protein was also accomplished in order to separate the effects of the payload during degradation. By providing in situ, real time detection in combination with the ability to specifically identify different components in a mixture without involved sample preparation and minimal sample disturbance, the versatility and suitability of this type of experiment for research in the pharmaceutical field is demonstrated. PMID:21476582

Modeling and simulation of a chemically stimulated hydrogel bilayer bending actuator

NASA Astrophysics Data System (ADS)

Sobczyk, Martin; Wallmersperger, Thomas

2017-04-01

Stimuli-sensitive hydrogels are polymeric materials, which are able to reversibly swell in water in response to evironmental changes. Relevant stimuli include variations of pH, temperature, concentration of specific ions etc. Stacked layers composed of multiple thin hydrogels - also referred to as hydrogel-layer composites - combine the distinct sensing properties of different hydrogels. This approach enables the development of sophisticated microfluidic devices such as bisensitive valves or fluid-sensitive deflectors. In order to numerically simulate the swelling of a polyelectrolyte hydrogel in response to an ion concentration change the multifield theory is adopted. The set of partial differential equations - including the description of the chemical, the electrical and the mechanical field - are solved using the Finite Element Method. Simulations are carried out on a two-dimensional domain in order to capture interactions between the different fields. In the present work, the ion transport is governed by diffusive and migrative fluxes. The distribution of ions in the gel and the solution bath result in an osmotic pressure difference, which is responsible for the mechanical deformation of the hydrogel-layer composite. The realized numerical investigation gives an insight into the evolution of the displacement field, the distribution of ions and the electric potential within the bulk material and the interface between gel and solution bath. The predicted behavior of the relevant field variables is in excellent agreement with results available in the literature.

Development, Fabrication, and Characterization of Hydrogel Based Piezoresistive Pressure Sensors with Perforated Diaphragms

PubMed Central

Orthner, M.P.; Buetefisch, Sebastian; Magda, J.; Rieth, L.W.; Solzbacher, F.

2010-01-01

Hydrogels have been demonstrated to swell in response to a number of external stimuli including pH, CO2, glucose, and ionic strength making them useful for detection of metabolic analytes. To measure hydrogel swelling pressure, we have fabricated and tested novel perforated diaphragm piezoresistive pressure sensor arrays that couple the pressure sensing diaphragm with a perforated semi-permeable membrane. The 2×2 arrays measure approximately 3 × 5 mm2 and consist of four square sensing diaphragms with widths of 1.0, 1.25, and 1.5 mm used to measure full scale pressures of 50, 25, and 5 kPa, respectively. An optimized geometry of micro pores was etched in silicon diaphragm to allow analyte diffusion into the sensor cavity where the hydrogel material is located. The 14-step front side wafer process was carried out by a commercial foundry service (MSF, Frankfurt (Oder), Germany) and diaphragm pores were created using combination of potassium hydroxide (KOH) etching and deep reactive ion etching (DRIE). Sensor characterization was performed (without the use of hydrogels) using a custom bulge testing apparatus that simultaneously measured deflection, pressure, and electrical output. Test results are used to quantify the sensor sensitivity and demonstrate proof-of-concept. Simulations showed that the sensitivity was slightly improved for the perforated diaphragm designs while empirical electrical characterization showed that the perforated diaphragm sensors were slightly less sensitive than solid diaphragm sensors. This discrepancy is believed to be due to the influence of compressive stress found within passivation layers and poor etching uniformity. The new perforated diaphragm sensors were fully functional with sensitivities ranging from 23 to 252 μV/V-kPa (FSO= 5 to 80mV), and show a higher nonlinearity at elevated pressures than identical sensors with solid diaphragms. Sensors (1.5×1.5 mm2) with perforated diaphragms (pores=40 μm) have a nonlinearity of approximately 10% while for the identical solid diaphragm sensor it was roughly 3 % over the entire 200 kPa range. This is the first time piezoresistive pressure sensors with integrated diffusion pores for detection of hydrogel swelling pressure have been fabricated and tested. PMID:20657810

SERS-Fluorescence Dual-Mode pH-Sensing Method Based on Janus Microparticles.

PubMed

Yue, Shuai; Sun, Xiaoting; Wang, Ning; Wang, Yaning; Wang, Yue; Xu, Zhangrun; Chen, Mingli; Wang, Jianhua

2017-11-15

A surface-enhanced Raman scattering (SERS)-fluorescence dual-mode pH-sensing method based on Janus microgels was developed, which combined the advantages of high specificity offered by SERS and fast imaging afforded by fluorescence. Dual-mode probes, pH-dependent 4-mercaptobenzoic acid, and carbon dots were individually encapsulated in the independent hemispheres of Janus microparticles fabricated via a centrifugal microfluidic chip. On the basis of the obvious volumetric change of hydrogels in different pHs, the Janus microparticles were successfully applied for sensitive and reliable pH measurement from 1.0 to 8.0, and the two hemispheres showed no obvious interference. The proposed method addressed the limitation that sole use of the SERS-based pH sensing usually failed in strong acidic media. The gastric juice pH and extracellular pH change were measured separately in vitro using the Janus microparticles, which confirmed the validity of microgels for pH sensing. The microparticles exhibited good stability, reversibility, biocompatibility, and ideal semipermeability for avoiding protein contamination, and they have the potential to be implantable sensors to continuously monitor pH in vivo.

Bioengineering vascularized tissue constructs using an injectable cell-laden enzymatically crosslinked collagen hydrogel derived from dermal extracellular matrix.

PubMed

Kuo, Kuan-Chih; Lin, Ruei-Zeng; Tien, Han-Wen; Wu, Pei-Yun; Li, Yen-Cheng; Melero-Martin, Juan M; Chen, Ying-Chieh

2015-11-01

Tissue engineering promises to restore or replace diseased or damaged tissue by creating functional and transplantable artificial tissues. The development of artificial tissues with large dimensions that exceed the diffusion limitation will require nutrients and oxygen to be delivered via perfusion instead of diffusion alone over a short time period. One approach to perfusion is to vascularize engineered tissues, creating a de novo three-dimensional (3D) microvascular network within the tissue construct. This significantly shortens the time of in vivo anastomosis, perfusion and graft integration with the host. In this study, we aimed to develop injectable allogeneic collagen-phenolic hydroxyl (collagen-Ph) hydrogels that are capable of controlling a wide range of physicochemical properties, including stiffness, water absorption and degradability. We tested whether collagen-Ph hydrogels could support the formation of vascularized engineered tissue graft by human blood-derived endothelial colony-forming cells (ECFCs) and bone marrow-derived mesenchymal stem cells (MSC) in vivo. First, we studied the growth of adherent ECFCs and MSCs on or in the hydrogels. To examine the potential formation of functional vascular networks in vivo, a liquid pre-polymer solution of collagen-Ph containing human ECFCs and MSCs, horseradish peroxidase and hydrogen peroxide was injected into the subcutaneous space or abdominal muscle defect of an immunodeficient mouse before gelation, to form a 3D cell-laden polymerized construct. These results showed that extensive human ECFC-lined vascular networks can be generated within 7 days, the engineered vascular density inside collagen-Ph hydrogel constructs can be manipulated through refinable mechanical properties and proteolytic degradability, and these networks can form functional anastomoses with the existing vasculature to further support the survival of host muscle tissues. Finally, optimized conditions of the cell-laden collagen-Ph hydrogel resulted in not only improving the long-term differentiation of transplanted MSCs into mineralized osteoblasts, but the collagen-Ph hydrogel also improved an increased of adipocytes within the vascularized bioengineered tissue in a mouse after 1 month of implantation. We reported a method for preparing autologous extracellular matrix scaffolds, murine collagen-Ph hydrogels, and demonstrated its suitability for use in supporting human progenitor cell-based formation of 3D vascular networks in vitro and in vivo. Results showed extensive human vascular networks can be generated within 7 days, engineered vascular density inside collagen-Ph constructs can be manipulated through refinable mechanical properties and proteolytic degradability, and these networks can form functional anastomoses with existing vasculature to further support the survival of host muscle tissues. Moreover, optimized conditions of cell-laden collagen-Ph hydrogel resulted in not only improving the long-term differentiation of transplanted MSCs into mineralized osteoblasts, but the collagen-Ph hydrogel also improved an increased of adipocytes within the vascularized bioengineered tissue in a mouse. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Electrochemical immunoassay for tumor markers based on hydrogels.

PubMed

Yin, Shuang; Ma, Zhanfang

2018-05-08

Hydrogel-based electrochemical immunoassays exhibit a large surface-to-volume ratio, excellent biocompatibility, unique stimuli-responsive behavior, high permeability and hydrophilicity and, thus, have shown great potential in the sensitive and accurate detection of tumor markers. Electrochemical immunosensing techniques for tumor markers based on hydrogels have greatly progressed in recent years. Areas covered: In this review, the authors describe the recent advances of hydrogel-based electrochemical immunosensing interface of tumor markers based on the different functions of hydrogels including conductive, catalytic, redox, stimuli-responsive and antifouling hydrogels. Expert commentary: Hydrogels have been successfully employed in electrochemical immunoassay of tumor markers, which is accountable to their unique properties. For further exploitation of hydrogel-based electrochemical biosensors, more variety of hydrogels need be fabricated with improved functionality.

Electrosynthesis of magnetoresponsive microrobot for targeted drug delivery using calcium alginate.

PubMed

Chengzhi Hu; Riederer, Katharina; Klemmer, Michael; Pane, Salvador; Nelson, Bradley J

2016-08-01

Targeted drug delivery systems deliver drugs precisely to a specific targeted site inside the body, and can also release the drugs with controlled kinetics to prolong the efficacy of single dose administration. The advantageous properties of hydrogels make them attractive for use in the area of drug delivery. Calcium alginate is a pH sensitive hydrogel stable in acidic media and soluble in basic media. This enables the hydrogel to absorb and release aqueous solutions at certain ranges of pH values. By absorbing an aqueous solution containing a drug, an active drug release can be triggered at a specified range of pH value. In this paper, we combined calcium alginate with cobalt nickel (CoNi) in a cylindrical hybrid micro robot by electrodeposition. The designed microrobot can be wirelessly actuated with an external magnetic manipulation system and, hence, targeted to a specific location in the human body. At this specific location, characterized by its pH range, the absorbed drug will be released. Here, the fabrication steps of the specified microrobot are characterized, namely the production of a template on a silicon chip and the subsequent template-assisted electrodeposition of CoNi and alginate. Additionally, the dynamics of drug release of calcium alginate is studied.

A Supramolecular Hydrogel Based on Polyglycerol Dendrimer-Specific Amino Group Recognition.

PubMed

Cho, Ik Sung; Ooya, Tooru

2018-05-24

Dendrimer-based supramolecular hydrogels have gained attention in biomedical fields. While biocompatible dendrimers were used to prepare hydrogels via physical and/or chemical crosslinking, smart functions such as pH and molecular control remain undeveloped. Here, we present polyglycerol dendrimer-based supramolecular hydrogel formation induced by a specific interaction between the polyglycerol dendrimer and an amino group of glycol chitosan. Gelation was achieved by mixing the two aqueous solutions. Hydrogel formation was controlled by varying the polyglycerol dendrimer generation. The hydrogel showed pH-dependent swelling; strongly acidic conditions induced degradation via dissociation of the specific interaction. It also showed unique L-arginine-responsive degradation capability due to competitive exchange of the amino groups of glycol chitosan and L-arginine. These polyglycerol dendrimer-based supramolecular characteristics allow multimodal application in smart biomaterials. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Peptide hydrogelation triggered by enzymatic induced pH switch

NASA Astrophysics Data System (ADS)

Cheng, Wei; Li, Ying

2016-07-01

It remains challenging to develop methods that can precisely control the self-assembling kinetics and thermodynamics of peptide hydrogelators to achieve hydrogels with optimal properties. Here we report the hydrogelation of peptide hydrogelators by an enzymatically induced pH switch, which involves the combination of glucose oxidase and catalase with D-glucose as the substrate, in which both the gelation kinetics and thermodynamics can be controlled by the concentrations of D-glucose. This novel hydrogelation method could result in hydrogels with higher mechanical stability and lower hydrogelation concentrations. We further illustrate the application of this hydrogelation method to differentiate different D-glucose levels.

Retention and release of oil-in-water emulsions from filled hydrogel beads composed of calcium alginate: impact of emulsifier type and pH.

PubMed

Zeeb, Benjamin; Saberi, Amir Hossein; Weiss, Jochen; McClements, David Julian

2015-03-21

Delivery systems based on filled hydrogel particles (microgels) can be fabricated from natural food-grade lipids and biopolymers. The potential for controlling release characteristics by modulating the electrostatic interactions between emulsifier-coated lipid droplets and the biopolymer matrix within hydrogel particles was investigated. A multistage procedure was used to fabricate calcium alginate beads filled with lipid droplets stabilized by non-ionic, cationic, anionic, or zwitterionic emulsifiers. Oil-in-water emulsions stabilized by Tween 60, DTAB, SDS, or whey protein were prepared by microfluidization, mixed with various alginate solutions, and then microgels were formed by simple extrusion into calcium solutions. The microgels were placed into a series of buffer solutions with different pH values (2 to 11). Lipid droplets remained encapsulated under acidic and neutral conditions, but were released under highly basic conditions (pH 11) due to hydrogel swelling when the alginate concentration was sufficiently high. Lipid droplet release increased with decreasing alginate concentration, which could be attributed to an increase in the pore size of the hydrogel matrix. These results have important implications for the design of delivery systems to entrap and control the release of lipophilic bioactive components within filled hydrogel particles.

Designing a biocompatible hydrogel for the delivery of mesalamine.

PubMed

Neufeld, Lena; Bianco-Peled, Havazelet

2015-08-01

A new design for nanocomposite hydrogels based on cross-linked chitosan for the delivery of mesalamine is presented. To enhance drug loading in chitosan, the mineral montmorillonite was incorporated into the matrix. The exfoliated silica montmorillonite nanosheets form interactions with both chitosan and mesalamine, which affect the hydrogel's drug release mechanism and swelling properties. The impact of montmorillonite and glutaraldehyde concentrations on the hydrogel properties was investigated. In vitro drug-release studies detected slower release over short times when montmorillonite was introduced into the matrix. This study is the first to evaluate the influence of pH during mixing and on mixing duration. It was shown that lowering the pH during mixing delayed the release since the positively charged drug was better introduced between the montmorillonite layers, as confirmed by differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FTIR) analysis. All hydrogels showed prolonged sustained release of mesalamine over 24h in simulated colonic fluid (pH 7.4). When modeled, the mesalamine release profile suggests a complex release mechanism, involving adsorption of the drug to the montmorillonite and its diffusion. The results imply that chitosan-montmorillonite hydrogels can serve as potential drug carriers for controlled-release applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Aromatic organic contaminant removal from an aqueous environment by p(4-VP)-based materials.

PubMed

Sahiner, Nurettin; Ozay, Ozgur; Aktas, Nahit

2011-10-01

p(4-vinylpyridine) (p(4-VP)) hydrogels were prepared in bulk (macro, 5 × 6 mm) and in nanosizes (370 nm) dimensions. The prepared hydrogels were used to remove organic aromatic contaminates such as 4-nitrophenol (4-NP), 2-nitrophenol (2-NP), phenol (Ph) and nitrobenzene (NB) from an aqueous environment. Important parameters affecting the absorption phenomena, such as the initial concentration of the organic species and the absorbent, absorption rate, absorption capacity, pH and the temperature of the medium, were evaluated for both hydrogel sizes. The absorption capacity of bulk and microgels were found to be 4-NP>2-NP>Ph>NB. Furthermore, p(4-VP) microgels were embedded in poly(acrylamide) (p(AAm)) bulk hydrogel as a microgel-hydrogel interpenetrating polymer network and proved to be very practical in overcoming the difficulty of using the microgels in real applications. Moreover, it was demonstrated that separately prepared magnetic ferrite particles inserted inside p(4-VP) microgels during synthesis allowed for trouble-free removal of p(4-VP)-magnetic composite microgels from the aqueous environment by an externally applied magnetic field upon completion of their task. Copyright © 2011 Elsevier Ltd. All rights reserved.

Biological performance of cell-encapsulated methacrylated gellan gum-based hydrogels for nucleus pulposus regeneration.

PubMed

Tsaryk, Roman; Silva-Correia, Joana; Oliveira, Joaquim Miguel; Unger, Ronald E; Landes, Constantin; Brochhausen, Christoph; Ghanaati, Shahram; Reis, Rui L; Kirkpatrick, C James

2017-03-01

Limitations of current treatments for intervertebral disc (IVD) degeneration have promoted interest in the development of tissue-engineering approaches. Injectable hydrogels loaded with cells can be used as a substitute material for the inner IVD part, the nucleus pulposus (NP), and provide an opportunity for minimally invasive treatment of IVD degeneration. The NP is populated by chondrocyte-like cells; therefore, chondrocytes and mesenchymal stem cells (MSCs), stimulated to differentiate along the chondrogenic lineage, could be used to promote NP regeneration. In this study, the in vitro and in vivo response of human bone marrow-derived MSCs and nasal chondrocytes (NCs) to modified gellan gum-based hydrogels was investigated. Both ionic- (iGG-MA) and photo-crosslinked (phGG-MA) methacrylated gellan gum hydrogels show no cytotoxicity in extraction assays with MSCs and NCs. Furthermore, the materials do not induce pro-inflammatory responses in endothelial cells. Moreover, MSCs and NCs can be encapsulated into the hydrogels and remain viable for at least 2 weeks, although apoptosis is observed in phGG-MA. Importantly, encapsulated MSCs and NCs show signs of in vivo chondrogenesis in a subcutaneous implantation of iGG-MA. Altogether, the data endorse the potential use of modified gellan gum-based hydrogel as a suitable material in NP tissue engineering. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Radiation synthesis of poly[(dimethylaminoethyl methacrylate)-co-(ethyleneglycol dimethacrylate)] hydrogels and its application as a carrier for anticancer delivery

NASA Astrophysics Data System (ADS)

Mazied, Nabila A.; Ismail, Sahar A.; Abou Taleb, Manal F.

2009-11-01

The use of hydrogels as carriers for anticancer delivery has been a subject of significant recent research. In our recent work, we have shown that diffusion-controlled delivery of flutamide from hydrogels containing poly (dimethylaminoethyl methacrylate (DMAEMA)/ethyleneglycol dimethacrylate (EGDMA)) can be possible and controlled by the three-dimensional structure. Hydrogels based essentially on dimethylaminoethyl methacrylate and different ratios of ethyleneglycol dimethacrylate monomers were synthesized using gamma radiation copolymerization. The influence of copolymer composition and pH value of the surrounding medium on swelling behavior into the glassy polymer were discussed. The results showed that the ratio of EGDMA in the comonomer feeding solution has a great effect on the gel fraction and water content in the final hydrogel. In this regard, it was observed that the increase of EGDMA ratio decreased these properties. The ability of the prepared copolymer to be used as drug carrier for anticancer drug-delivery system was estimated using flutamide as a model drug. In vitro drug-release studies in different buffer solutions show that the basic parameters affecting the drug release behavior of hydrogel are the pH of the solution and DMAEMA content of hydrogel.

Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation.

PubMed

Yan, Hong Ji; Casalini, Tommaso; Hulsart-Billström, Gry; Wang, Shujiang; Oommen, Oommen P; Salvalaglio, Matteo; Larsson, Sune; Hilborn, Jöns; Varghese, Oommen P

2018-04-01

Synthetic scaffolds that possess an intrinsic capability to protect and sequester sensitive growth factors is a primary requisite for developing successful tissue engineering strategies. Growth factors such as recombinant human bone morphogenetic protein-2 (rhBMP-2) is highly susceptible to premature degradation and to provide a meaningful clinical outcome require high doses that can cause serious side effects. We discovered a unique strategy to stabilize and sequester rhBMP-2 by enhancing its molecular interactions with hyaluronic acid (HA), an extracellular matrix (ECM) component. We found that by tuning the initial protonation state of carboxylic acid residues of HA in a covalently crosslinked hydrogel modulate BMP-2 release at physiological pH by minimizing the electrostatic repulsion and maximizing the Van der Waals interactions. At neutral pH, BMP-2 release is primarily governed by Fickian diffusion, whereas at acidic pH both diffusion and electrostatic interactions between HA and BMP-2 become important as confirmed by molecular dynamics simulations. Our results were also validated in an in vivo rat ectopic model with rhBMP-2 loaded hydrogels, which demonstrated superior bone formation with acidic hydrogel as compared to the neutral counterpart. We believe this study provides new insight on growth factor stabilization and highlights the therapeutic potential of engineered matrices for rhBMP-2 delivery and may help to curtail the adverse side effects associated with the high dose of the growth factor. Copyright © 2018 Elsevier Ltd. All rights reserved.

Development and characterization of novel alginate-based hydrogels as vehicles for bone substitutes.

PubMed

Morais, D S; Rodrigues, M A; Silva, T I; Lopes, M A; Santos, M; Santos, J D; Botelho, C M

2013-06-05

In this work three different hydrogels were developed to associate, as vehicles, with the synthetic bone substitute GR-HAP. One based on an alginate matrix (Alg); a second on a mixture of alginate and chitosan (Alg/Ch); and a third on alginate and hyaluronate (Alg/HA), using Ca(2+) ions as cross-linking agents. The hydrogels, as well as the respective injectable bone substitutes (IBSs), were fully characterized from the physical-chemical point of view. Weight change studies proved that all hydrogels were able to swell and degrade within 72 h at pH 7.4 and 4.0, being Alg/HA the hydrogel with the highest degradation rate (80%). Rheology studies demonstrated that all hydrogels are non-Newtonian viscoelastic fluids, and injectability tests showed that IBSs presented low maximum extrusion forces, as well as quite stable average forces. In conclusion, the studied hydrogels present the necessary features to be successfully used as vehicles of GR-HAP, particularly the hydrogel Alg/HA. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sustained Release of Naproxen in a New Kind Delivery System of Carbon Nanotubes Hydrogel

PubMed Central

Peng, Xiahui; Zhuang, Qiang; Peng, Dongming; Dong, Qiuli; Tan, Lini; Jiao, Feipeng; Liu, Linqi; Liu, jingyu; Zhao, Chenxi; Wang, Xiaomei

2013-01-01

In this paper, carbon nanotubes (CNTs) were added into chitosan (CS) hydrogels in the form of chitosan modified CNTs (CS-CNTs) composites to prepare carbon nanotubes hydrogels (CNTs-GEL). The products, named CS-MWCNTs, were characterized by scanning electron microscope (SEM) and Fourier transform infrared (FTIR) spectroscopy. Swelling properties and effect of pH on controlled release performance of the two kinds of hydrogels, CNTs- GEL and pure chitosan hydrogels without CNTs (GEL), were investigated respectively. The results showed that CNTs-GEL possess better controlled release performance than GEL. The releasing equilibrium time of CNTs-GEL was longer than that of GEL in both pH = w7.4 and pH=1.2 conditions, although the release ratios of the model drug are similar in the same pH buffer solutions. It is found that release kinetics is better fitted Ritger-Peppas empirical model indicating a fick-diffusion process in pH = 1.2, while in pH = 7.4 it was non-fick diffusion involving surface diffusion and corrosion diffusion processes. PMID:24523738

Rheological and mechanical properties of acellular and cell-laden methacrylated gellan gum hydrogels.

PubMed

Silva-Correia, Joana; Gloria, Antonio; Oliveira, Mariana B; Mano, João F; Oliveira, Joaquim M; Ambrosio, Luigi; Reis, Rui L

2013-12-01

Tissue engineered hydrogels hold great potential as nucleus pulposus substitutes (NP), as they promote intervertebral disc (IVD) regeneration and re-establish its original function. But, the key to their success in future clinical applications greatly depends on its ability to replicate the native 3D micro-environment and circumvent their limitation in terms of mechanical performance. In the present study, we investigated the rheological/mechanical properties of both ionic- (iGG-MA) and photo-crosslinked methacrylated gellan gum (phGG-MA) hydrogels. Steady shear analysis, injectability and confined compression stress-relaxation tests were carried out. The injectability of the reactive solutions employed for the preparation of iGG-MA and phGG-MA hydrogels was first studied, then the zero-strain compressive modulus and permeability of the acellular hydrogels were evaluated. In addition, human intervertebral disc (hIVD) cells encapsulated in both iGG-MA and phGG-MA hydrogels were cultured in vitro, and its mechanical properties also investigated under dynamic mechanical analysis at 37°C and pH 7.4. After 21 days of culturing, hIVD cells were alive (Calcein AM) and the E' of ionic-crosslinked hydrogels and photo-crosslinked was higher than that observed for acellular hydrogels. Our study suggests that methacrylated gellan gum hydrogels present promising mechanical and biological performance as hIVD cells were producing extracellular matrix. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

Chitosan/chondroitin sulfate hydrogels prepared in [Hmim][HSO4] ionic liquid.

PubMed

Nunes, Cátia S; Rufato, Kessily B; Souza, Paulo R; de Almeida, Elizângela A M S; da Silva, Michael J V; Scariot, Débora B; Nakamura, Celso V; Rosa, Fernanda A; Martins, Alessandro F; Muniz, Edvani C

2017-08-15

[Hmim][HSO 4 ] ionic liquid (IL) and bio-renewable sources as chitosan (CHT) and chondroitin sulfate (CS) were used to yield hydrogel-based materials (CHT/CS). The use of IL to solubilize both polysaccharides was considered an innovative way based on "green chemistry" principle, aiming the production of CHT/CS blended systems. CHT/CS hydrogels were carried out in homogeneous medium from short dissolution times. The hydrogels were characterized and achieved with excellent stabilities (in the 1.2-10pH range), larger swelling capacities, as well as devoid of cytotoxicity towards the normal VERO and diseased HT29 cells. The CHT/CS hydrogels carried out in [Hmim][HSO 4 ] could be applied in many technological purposes, like medical, pharmaceutical, and environmental fields. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vitro BMP-2 peptide release from thiolated chitosan based hydrogel.

PubMed

Liu, Xujie; Yu, Bo; Huang, Qianli; Liu, Rui; Feng, Qingling; Cai, Qiang; Mi, Shengli

2016-12-01

Thiolated chitosan based thermo-sensitive hydrogel is a water soluble system and the existing thiol groups are beneficial for the delivery of cysteine-rich peptides. In the present study, a kind of thiolated chitosan, i.e. chitosan-4-thio-butylamidine (CS-TBA) conjugate was characterized and used to prepare CS-TBA/hydroxyapatite (HA)/beta-glycerophosphate disodium (β-GP) thermo-sensitive hydrogel. The cysteine terminated peptide 24 (P24) containing residues 73-92 of the knuckle epitope of BMP-2 (N→C: KIPKASSVPTELSAISTLYLSGGC) was synthesized and characterized. The release behavior of P24 from CS-TBA based hydrogel was investigated in vitro. The thiol groups in CS-TBA may react with thiol groups in P24, thus decreases the P24 release rate and maintains the peptide release for a longer time compared with unmodified chitosan based hydrogel. Moreover, the bioactivity of P24 is preserved during release process. These results indicate that P24 loaded CS-TBA based thermosensitive hydrogel is a potential material for minimally invasive surgery of bone repair. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation, properties and biological application of pH-sensitive poly(ethylene oxide) (PEO) hydrogels grafted with acrylic acid(AAc) using gamma-ray irradiation

NASA Astrophysics Data System (ADS)

Nho, Young Chang; Mook Lim, Youn; Moo Lee, Young

2004-09-01

pH-sensitive hydrogels were studied as a drug carrier for the protection of insulin from the acidic environment of the stomach before releasing it in the small intestine. In this study, hydrogels based on poly(ethylene oxide) (PEO) networks grafted with acrylic acid (AAc) were prepared via a two-step process. PEO hydrogels were prepared by γ-ray irradiation, and then grafting by AAc monomer onto the PEO hydrogels with the subsequent irradiation (radiation dose: 5-20 kGy, dose rate: 2.15 kGy/h). These grafted hydrogels showed a pH-sensitive swelling behavior. The grafted hydrogels were used as a carrier for the drug delivery systems for the controlled release of insulin. The in vitro drug release behaviors of these hydrogels were examined by quantification analysis with a UV/VIS spectrophotometer. Insulin was loaded into freeze-dried hydrogels (7 mm×3 mm×2.5 mm) and administrated orally to healthy and diabetic Wistar rats. The oral administration of insulin-loaded hydrogels to Wistar rats decreased the blood glucose levels obviously for at least 4 h due to the absorption of insulin in the gastrointestinal tract.

Triply responsive films in bioelectrocatalysis with a binary architecture: combined layer-by-layer assembly and hydrogel polymerization.

PubMed

Yao, Huiqin; Hu, Naifei

2011-05-26

In this work, triply responsive films with a specific binary architecture combining layer-by-layer assembly (LbL) and hydrogel polymerization were successfully prepared. First, concanavalin A (Con A) and dextran (Dex) were assembled into {Con A/Dex}(5) LbL layers on electrode surface by the lectin-sugar biospecific interaction between them. The poly(N,N-diethylacrylamide) (PDEA) hydrogels with entrapped horseradish peroxidase (HRP) were then synthesized by polymerization on the surface of LbL inner layers, forming {Con A/Dex}(5)-(PDEA-HRP) films. The films demonstrated reversible pH-, thermo-, and salt-responsive on-off behavior toward electroactive probe Fe(CN)(6)(3-) in its cyclic voltammetric responses. This multiple stimuli-responsive films could be further used to realize triply switchable electrochemical reduction of H(2)O(2) catalyzed by HRP immobilized in the films and mediated by Fe(CN)(6)(3-) in solution. The responsive mechanism of the films was explored and discussed. The pH-sensitive property of the system was attributed to the electrostatic interaction between the {Con A/Dex}(5) inner layers and the probe at different pH, and the thermo- and salt-responsive behaviors should be ascribed to the structure change of PDEA hydrogels for the PDEA-HRP outermost layers under different conditions. The concept of binary architecture was also used to fabricate {Con A/Dex}(5)-(PDEA-GOD) films on electrodes, where GOD = glucose oxidase, which was applied to realize the triply switchable bioelectrocatalysis of glucose by GOD in the films with ferrocenedicarboxylic acid as the mediator in solution. This film system with the unique binary architecture may establish a foundation for fabricating a novel type of multicontrollable biosensors based on bioelectrocatalysis with immobilized enzymes.

Converting drugs into gelators: supramolecular hydrogels from N-acetyl-L-cysteine and coinage-metal salts.

PubMed

Casuso, Pablo; Carrasco, Pedro; Loinaz, Iraida; Grande, Hans J; Odriozola, Ibon

2010-12-07

Here we present the concept of metallophilic hydrogels, supramolecular systems in which the gelator species are metal-thiolates that self-assemble through metallophilic attractions. The principle is applied for a small drug, the mucolytic agent N-acetyl-l-cysteine (NAC), which readily forms hydrogels in the presence of Au(iii), Ag(i) and Cu(ii) salts. The resulting transparent hydrogels present pH induced sol/gel transition. Scanning electron microscopy (SEM) measurements reveal a microporous structure in form of flakes for the three of them. The low pH at which these hydrogels are formed (pH < 4) limits their direct use as drug-delivery systems, but still this system constitutes a novel method for easy and fast conversion of small drugs into potent hydrogelators. Future developments will help to fully develop the idea in order to create a new class of supramolecular drug-delivery systems.

Electroactive hydrogel comprising poly(methyl 2-acetamido acrylate) for an artificial actuator

NASA Astrophysics Data System (ADS)

Ha, Eun-Ju; Kim, Bong-Soo; Park, Chun-ho; Lee, Jang-Oo; Paik, Hyun-jong

2013-08-01

A poly(methyl 2-acetamidoacrylic acrylate) (MAA) hydrogel was developed for use in an artificial actuator. The equilibrium swelling ratio of the MAA hydrogel was observed at different pH values with different concentrations of cross-linking agent; the hydrogel containing 2% cross-linking agent exhibited the maximum equilibrium swelling ratio at pH 10. The bending behavior of the MAA hydrogel under an electric field was measured in aqueous NaCl. The actuation response of the MAA hydrogel occurred via reversible bending behavior at 6 V. It was found that the MAA hydrogel features stable bending behavior over consecutive cycles in aqueous NaCl at different voltages depending on the cross-linking agent. Hence, the MAA hydrogel can be utilized as an artificial actuator using electrical stimulus.

Synthesis, characterization, and evaluation of poly(aminoethyl) modified chitosan and its hydrogel used as antibacterial wound dressing.

PubMed

Zhang, Yubei; Dang, Qifeng; Liu, Chengsheng; Yan, Jingquan; Cha, Dongsu; Liang, Shengnan; Li, Xiaoli; Fan, Bing

2017-09-01

This study aims to develop new antibacterial hydrogel wound dressings composed of poly(aminoethyl) modified chitosan (PAEMCS). FTIR, 1 H NMR, and elemental analysis demonstrated that PAEMCS was successfully synthesized via grafting poly(aminoethyl) groups onto hydroxyl groups on chitin first, and removing acetyl groups from the grafted polymer afterward. XRD and TGA implied its well-defined crystallinity and thermostability. Furthermore, a series of hydrogels were fabricated under the participation of dipotassium hydrogen phosphate (DHP). The gelation tests suggested that the higher concentration of PAEMCS or DHP was beneficial to the formation of hydrogels. The pH values of hydrogels at 37°C were all in the range of 7.12-7.50. The rheological tests indicated that PAEMCS-based hydrogels were of lower DHP addition and higher elasticity than CS-based hydrogels to achieve the same gelation temperature under the same polymer's concentration. Additionally, the swelling, anti-bacteria, and cytotoxicity experiments showed that PAEMCS-based hydrogels possessed excellent hygroscopicity, high antibacterial activity against E. coli, S. aureus, or S. epidermidis, and good cytocompatibility toward L929 cells or HUVECs, respectively. All the results implied that PAEMCS-based hydrogels not only maintained inherent multiple properties of chitosan but also possessed excellent antibacterial activity, and might be promising antibacterial hydrogel dressings used in wound therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Polysaccharide-based hydrogels with tunable composition as 3D cell culture systems.

PubMed

Gentilini, Roberta; Munarin, Fabiola; Bloise, Nora; Secchi, Eleonora; Visai, Livia; Tanzi, Maria Cristina; Petrini, Paola

2018-04-01

To date, cell cultures have been created either on 2-dimensional (2D) polystyrene surfaces or in 3-dimensional (3D) systems, which do not offer a controlled chemical composition, and which lack the soft environment encountered in vivo and the chemical stimuli that promote cell proliferation and allow complex cellular behavior. In this study, pectin-based hydrogels were developed and are proposed as versatile cell culture systems. Pectin-based hydrogels were produced by internally crosslinking pectin with calcium carbonate at different initial pH, aiming to control crosslinking kinetics and degree. Additionally, glucose and glutamine were added as additives, and their effects on the viscoelastic properties of the hydrogels and on cell viability were investigated. Pectin hydrogels showed in high cell viability and shear-thinning behavior. Independently of hydrogel composition, an initial swelling was observed, followed by a low percentage of weight variation and a steady-state stage. The addition of glucose and glutamine to pectin-based hydrogels rendered higher cell viability up to 90%-98% after 1 hour of incubation, and these hydrogels were maintained for up to 7 days of culture, yet no effect on viscoelastic properties was detected. Pectin-based hydrogels that offer tunable composition were developed successfully. They are envisioned as synthetic extracellular matrix (ECM) either to study complex cellular behaviors or to be applied as tissue engineering substitutes.

Biologically Inspired Electronic, Photovoltaic and Microfluidic Devices Based on Aqueous Soft Matter

NASA Astrophysics Data System (ADS)

Koo, Hyung Jun

Hydrogels are a water-based soft material where three dimensional networks of hydrophilic polymer retain large amounts of water. We developed hydrogel based devices with new functionalities inspired by materials, structures and processes in nature. The advantages, such as softness, biocompatibility and high ionic conductivity, could enable hydrogels to be novel materials for biomimetic devices operated by ionic current. Moreover, microfluidic patterns are easily embedded in moldable hydrogels and allow for unique convective/diffusive transport mechanism in porous gel to be used for uniform delivery of reagent solution. We first developed and characterized a device with unidirectional ionic current flow across a SiO2/Gel junction, which showed highly efficient rectification of the ionic current by non-linear conductivity of SiO2 films. Addition of polyelectrolytes and salt to the gel layer significantly improved the performance of the new diode device because of the enhanced gel conductance. A soft matter based diode composed of hydrogel and liquid metal (eutectic gallium indium, EGaIn) was also presented. The ability to control the thickness, and thus resistivity, of an insulating oxide skin on the metal enables the current rectification. The effect of ionic conductivity and pH on the formation of the insulating oxide was investigated in a simple model system with liquid metal/electrolyte solution or hydrogel/Pt interfaces. Finally, we present a diode composed entirely of soft materials by replacing the platinum electrode with a second liquid metal electrode. A new type of hydrogel-based photovoltaic systems (HGPVs) was constructed. Two photosensitive ionized molecules embedded in aqueous gel served as photoactive species. The HGPVs showed performance comparable with or higher than those of some other biomimetic or ionic photovoltaic systems reported recently. We suggest a provisional mechanism of the device operation, based on a synergetic effect of the two dye molecules. To reduce the fabrication cost without efficiency loss, we found an inexpensive replacement of the expensive Pt counter-electrode with copper coated with carbon materials. Biologically derived photoactive molecules, such as Chlorophyll and Photosystem II, were successfully operated in the aqueous gel of such HGPVs. As a proof of demonstration of biomimetic structures, a light driven biomimetic reactor was developed by using hydrogel media with embedded photocatalytic TiO2 nanoparticles. Uniform supply of the reactants and extraction of the products was accomplished via a microfluidic channel network, broadly similar to the vein structure of live leaves. The dyes were transported in the gel between the microchannels and degraded by photocatalytic oxidation by the illuminated TiO2 particles. Quantitative analysis of the photocatalytic degradation rate of the injected dyes revealed that the microvascular reactor has high quantum efficiency per catalyst mass. Numerical modeling was performed to explore how a soluble reagent could be supplied rapidly and efficiently through microfluidic channel networks embedded in hydrogels. The computational model takes into account the fluid transport in porous media and the solute convection and diffusion, to simulate the solute distribution and outflux with time in microfluidic hydrogel media. The effect of the channel dimensions and shapes on mass transport rapidity and efficiency was quantitatively evaluated. Experimental data proved the validity of the time dependent concentration profile calculated by the simulation. Lastly, a microfluidic hydrogel solar cell with biomimetic regeneration functionality was demonstrated as a result of the above experimental and modeling studies. A new concept of open and replenishable photovoltaics was constructed on the basis of dye-sensitized solar cells. Photovoltaic reagents, dyes and redox electrolytes, were uniformly delivered via microfluidic networks embedded in a hydrogel, resulting in increase of photocurrent generation. The regeneration process was established, based on the pH dependence of adsorption/desorption kinetics of the dye molecules on a TiO2 photoanode. Complete and reliable recovery of the photocurrent after an accelerated photodegradation in the biomimetic photovoltaics was demonstrated.

Rapid antibiotic susceptibility testing in a microfluidic pH sensor.

PubMed

Tang, Yanyan; Zhen, Li; Liu, Jingqing; Wu, Jianmin

2013-03-05

For appropriate selection of antibiotics in the treatment of pathogen infection, rapid antibiotic susceptibility testing (AST) is urgently needed in clinical practice. This study reports the utilization of a microfluidic pH sensor for monitoring bacterial growth rate in culture media spiked with different kinds of antibiotics. The microfluidic pH sensor was fabricated by integration of pH-sensitive chitosan hydrogel with poly(dimethylsiloxane) (PDMS) microfluidic channels. For facilitating the reflectometric interference spectroscopic measurements, the chitosan hydrogel was coated on an electrochemically etched porous silicon chip, which was used as the substrate of the microfluidic channel. Real-time observation of the pH change in the microchannel can be realized by Fourier transform reflectometric interference spectroscopy (FT-RIFS), in which the effective optical thickness (EOT) was selected as the optical signal for indicating the reversible swelling process of chitosan hydrogel stimulated by pH change. With this microfluidic pH sensor, we demonstrate that confinement of bacterial cells in a nanoliter size channel allows rapid accumulation of metabolic products and eliminates the need for long-time preincubation, thus reducing the whole detection time. On the basis of this technology, the whole bacterial growth curve can be obtained in less than 2 h, and consequently rapid AST can be realized. Compared with conventional methods, the AST data acquired from the bacterial growth curve can provide more detailed information for studying the antimicrobial behavior of antibiotics during different stages. Furthermore, the new technology also provides a convenient method for rapid minimal inhibition concentration (MIC) determination of individual antibiotics or the combinations of antibiotics against human pathogens that will find application in clinical and point-of-care medicine.

Bioresorbable polypeptide-based comb-polymers efficiently improves the stability and pharmacokinetics of proteins in vivo.

PubMed

Turabee, Md Hasan; Thambi, Thavasyappan; Lym, Jae Seung; Lee, Doo Sung

2017-03-28

Stimuli-responsive polypeptides are a promising class of biomaterials due to their tunable physicochemical and biological properties. Herein, a series of novel pH- and thermo-responsive block copolymers based on polypeptides were synthesized by ring-opening polymerization of γ-benzyl-l-glutamate-N-carboxyanhydride in the presence of poly(ethylene glycol)-diamine macroinitiator followed by aminolysis. The resulting polypeptide-based triblock copolymer, poly[(2-(dibutylamino)ethyl-l-glutamate)-co-(γ-benzyl-l-glutamate)]-poly(ethylene glycol)-b-poly[(2-(dibutylamino)ethyl-l-glutamate)-co-(γ-benzyl-l-glutamate)] (PNLG-co-PBLG-b-PEG-b-PBLG-co-PNLG), exists as a low viscous sol at low pH and temperature (≤pH 6.4, 25 °C) but it transforms to a soft gel under physiological conditions (pH 7.4 and 37 °C). The physical properties of the polypeptide gel can be tuned by controlling the ratio between hydrophobic PBLG and pH-sensitive PNLG blocks. The polypeptide-based copolymer did not show any noticeable cytotoxicity to fibroblast cells in vitro. It was found that subcutaneous injection of the polypeptide copolymer solution into the dorsal region of Sprague-Dawley (SD) rats formed a gel instantly without major inflammation. The gels were completely biodegraded in six weeks and found to be bioresorbable. Human growth hormone (hGH)-loaded polypeptide-based biodegradable copolymer sols readily formed a viscoelastic gel that inhibited an initial burst and prolonged the hGH release for one week. Overall, due to their bioresorbable and sustained release protein characteristics, polypeptide hydrogels may serve as viable platforms for therapeutic protein delivery and the surface tunable properties of polypeptide hydrogels can be exploited for other potential therapeutic proteins.

Sodium alginate/graphene oxide hydrogel beads as permeable reactive barrier material for the remediation of ciprofloxacin-contaminated groundwater.

PubMed

Zhao, Pingping; Yu, Fei; Wang, Ruoyu; Ma, Yao; Wu, Yanqing

2018-06-01

The wide occurrence of antibiotics in groundwater has raised serious concerns due to their impacts on humans and the ecosystem. Most of the research in groundwater remediation focuses on the exploitation of nano-materials. However, nano-materials have several disadvantages such as high production cost, rapid reduction in permeability, disposal problems, and high sensitivity to environmental conditions. To solve these issues, novel sodium alginate/graphene oxide hydrogel beads (GSA) were synthesised and their effectiveness as permeable reactive barrier (PRB) backfill material in the remediation of ciprofloxacin (CPX)-contaminated groundwater was tested. The adsorption of CPX onto GSA followed the pseudo-second-order kinetic model. The isotherm data followed the Freundlich model. The maximum adsorption capacity was 100 mg g -1 at pH 7.0. The adsorption process was sensitive to contact time, initial CPX concentration and ionic strength. However, it was not pH sensitive. Hydrophobic interaction, electrostatic interaction, ion exchange, H-bonding, and pore filling were proposed to be the main adsorption mechanisms. The effects of flow rate, influent CPX concentration, and ionic strength on the performance of PRB were confirmed through flow-through column experiments and by using a chemical non-equilibrium two-site model. Accordingly, a proper PRB was designed based on hydrogeological conditions. Finally, the lifetime and cost of the PRBs were calculated. The results obtained provided concrete evidence that GSA is a promising adsorbent material for PRBs applications in the remediation of CPX-contaminated groundwater. Copyright © 2018 Elsevier Ltd. All rights reserved.

Swelling of Superabsorbent Poly(Sodium-Acrylate Acrylamide) Hydrogels and Influence of Chemical Structure on Internally Cured Mortar

NASA Astrophysics Data System (ADS)

Krafcik, Matthew J.; Erk, Kendra A.

Superabsorbent hydrogel particles show promise as internal curing agents for high performance concrete (HPC). These gels can absorb and release large volumes of water and offer a solution to the problem of self-dessication in HPC. However, the gels are sensitive to ions naturally present in concrete. This research connects swelling behavior with gel-ion interactions to optimize hydrogel performance for internal curing, reducing the chance of early-age cracking and increasing the durability of HPC. Four different hydrogels of poly(sodium-acrylate acrylamide) are synthesized and characterized with swelling tests in different salt solutions. Depending on solution pH, ionic character, and gel composition, diffrerent swelling behaviors are observed. As weight percent of acrylic acid increases, gels demonstrate higher swelling ratios in reverse osmosis water, but showed substantially decreased swelling when aqueous cations are present. Additionally, in multivalent cation solutions, overshoot peaks are present, whereby the gels have a peak swelling ratio but then deswell. Multivalent cations interact with deprotonated carboxylic acid groups, constricting the gel and expelling water. Mortar containing hydrogels showed reduced autogenous shrinkage and increased relative humidity.

Synthesis, Characterization, and Acute Oral Toxicity Evaluation of pH-Sensitive Hydrogel Based on MPEG, Poly(ε-caprolactone), and Itaconic Acid

PubMed Central

Tan, Liwei; Song, Jia; Luo, Feng

2013-01-01

A kind of chemically cross-linked pH-sensitive hydrogels based on methoxyl poly(ethylene glycol)-poly(caprolactone)-acryloyl chloride (MPEG-PCL-AC, PECA), poly(ethylene glycol) methyl ether methacrylate (MPEGMA, MEG), N,N-methylenebisacrylamide (BIS), and itaconic acid (IA) were prepared without using any organic solvent by heat-initiated free radical method. The obtained macromonomers and hydrogels were characterized by 1H NMR and FT-IR, respectively. Morphology study of hydrogels was also investigated in this paper, and it showed that the hydrogels had good pH-sensitivity. The acute toxicity test and histopathological study were conducted in BALB/c mice. The results indicated that the maximum tolerance dose of the hydrogel was higher than 10000 mg/kg body weight. No morality or signs of toxicity were observed during the whole 7-day observation period. Compared to the control groups, there were no important adverse effects in the variables of hematology routine test and serum chemistry analysis both in male or female treatment group. Histopathological study also did not show any significant lesions, including heart, liver, lung, spleen, kidney, stomach, intestine, and testis. All the results demonstrated that this hydrogel was nontoxic after gavage. Thus, the hydrogel might be the biocompatible potential candidate for oral drug delivery system. PMID:24364030

Diffusion of water-soluble sorptive drugs in HEMA/MAA hydrogels.

PubMed

Liu, D E; Dursch, T J; Taylor, N O; Chan, S Y; Bregante, D T; Radke, C J

2016-10-10

We measure and, for the first time, theoretically predict four prototypical aqueous-drug diffusion coefficients in five soft-contact-lens material hydrogels where solute-specific adsorption is pronounced. Two-photon fluorescence confocal microscopy and UV/Vis-absorption spectrophotometry assess transient solute concentration profiles and concentration histories, respectively. Diffusion coefficients are obtained for acetazolamide, riboflavin, sodium fluorescein, and theophylline in 2-hydroxyethyl methacrylate/methacrylic acid (HEMA/MAA) copolymer hydrogels as functions of composition, equilibrium water content (30-90%), and aqueous pH (2 and 7.4). At pH2, MAA chains are nonionic, whereas at pH7.4, MAA chains are anionic (pKa≈5.2). All studied prototypical drugs specifically interact with HEMA and nonionic MAA (at pH2) moieties. Conversely, none of the prototypical drugs adsorb specifically to anionic MAA (at pH7.4) chains. As expected, diffusivities of adsorbing solutes are significantly diminished by specific interactions with hydrogel strands. Despite similar solute size, relative diffusion coefficients in the hydrogels span several orders of magnitude because of varying degrees of solute interactions with hydrogel-polymer chains. To provide a theoretical framework for the new diffusion data, we apply an effective-medium model extended for solute-specific interactions with hydrogel copolymer strands. Sorptive-diffusion kinetics is successfully described by local equilibrium and Henry's law. All necessary parameters are determined independently. Predicted diffusivities are in good agreement with experiment. Copyright © 2016 Elsevier B.V. All rights reserved.

Dextran hydrogels by crosslinking with amino acid diamines and their viscoelastic properties.

PubMed

O'Connor, Naphtali A; Jitianu, Mihaela; Nunez, Greisly; Picard, Quentin; Wong, Madeline; Akpatsu, David; Negrin, Adam; Gharbaran, Rajendra; Lugo, Daniel; Shaker, Sundus; Jitianu, Andrei; Redenti, Stephen

2018-05-01

Amine functionalized polysaccharide hydrogels such as those based on chitosan are widely examined as biomaterials. Here we set out to develop a facile procedure for developing such hydrogels by crosslinking dextran with amino acid diamines. The dextran-amino acid gels were formed by the addition of the amino acid diamines to a dextran and epichlorohydrin solution once it became homogeneous. This was demonstrated with three amino acid diamines, lysine, lysine methyl ester, and cystine dimethyl ester. Hydrogel networks with albumin entrapped were also demonstrated. These hydrogels were characterized by FTIR, SEM, rotational rheometry, swelling studies and cell biocompatibility analysis. These hydrogels showed the unexpected pH-responsive behavior of greater swelling at more basic pH, similar to that of an anionic hydrogel. This is uncharacteristic for amine functionalized gels as they typically exhibit cationic hydrogel behavior. All hydrogels showed similar biocompatibility to that of dextran crosslinked without amino acids. Copyright © 2018 Elsevier B.V. All rights reserved.

Self-assembling N-(9-Fluorenylmethoxycarbonyl)-l-Phenylalanine hydrogel as novel drug carrier.

PubMed

Snigdha, Kirti; Singh, Brijesh K; Mehta, Abijeet Singh; Tewari, R P; Dutta, P K

2016-12-01

Supramolecular hydrogel as a novel drug carrier was prepared from N-(9-Fluorenylmethoxycarbonyl) (Fmoc) modified l-phenylalanine. Its different properties like stability at different pH, temperature and rheology were evaluated in reference to salicylic acid (SA) as a model drug, entrapped in the supramolecular hydrogel network. The release behaviour of SA drug in supramolecular hydrogel was investigated by UV-vis spectroscopy. The influence of hydrogelator, pH values of the accepting media, temperature and concentration of SA drug on the release behaviour was investigated under static conditions. The results indicated that the release rate of SA in the supramolecular hydrogels was slightly retarded with an increase of the hydrogelator concentration. Also, the release rates of SA increased with an increase of temperature and its concentration. Furthermore, the release behaviour of SA was found to be different at various pH values in buffers. The study of the release kinetics indicated that the release behaviour of SA from the carrier was in accord with the Peppas model and the diffusion controlled mechanism involved in the Fickian model. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of a Hierarchical Network of Hyaluronic Acid/Gelatin Composite for use as a Smart Injectable Biomaterial

PubMed Central

Heris, Hossein K.; Rahmat, Meysam

2015-01-01

Hybrid HA/Ge hydrogel particles are embedded in a secondary HA network to improve their structural integrity. The internal microstructure of the particles is imaged through TEM. CSLM is used to identify the location of the Ge molecules in the microgels. Through indentation tests, the Young’s modulus of the individual particles is found to be 22 ± 2.5 kPa. The overall shear modulus of the composite is 75 ± 15 Pa at 1 Hz. The mechanical properties of the substrate are found to be viable for cell adhesion. The particles’ diameter at pH = 8 is twice that at pH = 5. The pH sensitivity is found to be appropriate for smart drug delivery. Based on their mechanical and structural properties, HA–Ge hierarchical materials may be well suited for use as injectable biomaterials for tissue reconstruction. PMID:22147507

Mussel-inspired histidine-based transient network metal coordination hydrogels

PubMed Central

Fullenkamp, Dominic E.; He, Lihong; Barrett, Devin G.; Burghardt, Wesley R.; Messersmith, Phillip B.

2013-01-01

Transient network hydrogels cross-linked through histidine-divalent cation coordination bonds were studied by conventional rheologic methods using histidine-modified star poly(ethylene glycol) (PEG) polymers. These materials were inspired by the mussel, which is thought to use histidine-metal coordination bonds to impart self-healing properties in the mussel byssal thread. Hydrogel viscoelastic mechanical properties were studied as a function of metal, pH, concentration, and ionic strength. The equilibrium metal-binding constants were determined by dilute solution potentiometric titration of monofunctional histidine-modified methoxy-PEG and were found to be consistent with binding constants of small molecule analogs previously studied. pH-dependent speciation curves were then calculated using the equilibrium constants determined by potentiometric titration, providing insight into the pH dependence of histidine-metal ion coordination and guiding the design of metal coordination hydrogels. Gel relaxation dynamics were found to be uncorrelated with the equilibrium constants measured, but were correlated to the expected coordination bond dissociation rate constants. PMID:23441102

Reusable self-healing hydrogels realized via in situ polymerization.

PubMed

Vivek, Balachandran; Prasad, Edamana

2015-04-09

In this work, a self-healing hydrogel has been prepared using in situ polymerization of acrylic acid and acrylamide in the presence of glycogen. The hydrogel was characterized using NMR, SEM, FT-IR, rheology, and dynamic light scattering (DLS) studies. The developed hydrogel exhibits self-healing properties at neutral pH, high swelling ability, high elasticity, and excellent mechanical strength. The hydrogel exhibits modulus values (G', G″) as high as 10(6) Pa and shows an exceptionally high degree of swelling ratio (∼3.5 × 10(3)). Further, the polymer based hydrogel adsorbs toxic metal ions (Cd(2+), Pb(2+), and Hg(2+)) and organic dyes (methylene blue and methyl orange) from contaminated water with remarkable efficiency (90-98%). The mechanistic analysis indicated the presence of pseudo-second-order reaction kinetics. The reusability of the hydrogel has been demonstrated by repeating the adsorption-desorption process over five cycles with identical results in the adsorption efficiency.

A study in the adsorption of Fe(2+) and NO(3)(-) on pine needles based hydrogels.

PubMed

Chauhan, Ghanshyam S; Chauhan, Sandeep; Kumar, Sunil; Kumari, Anita

2008-09-01

Novel supports for use as cation and anion adsorbents were prepared from lignocellulosics using pine needles and their carboxymethylated forms by network/hydrogel formation with acrylamide and N,N-methylene bisacrylamide. The hydrogels thus prepared were further functionalized by partial alkaline hydrolysis with 0.5 N NaOH and were characterized by FTIR, SEM and nitrogen analysis. Adsorption of Fe(2+) on these hydrogels was carried as a function of time, temperature, pH and ionic strength. The hydrogel having the maximum adsorption capacity was loaded with Fe(2+) at the conditions those afforded maximum uptake and was used as novel anionic adsorbent for NO(3)(-). The water uptake capacities and biodegradability of the hydrogels before and after the ion loading was studied to evaluate the possible end-uses of these hydrogels as alternate materials in the removal of ionic species from water.

Adsorption of ammonium and phosphate by feather protein based semi-interpenetrating polymer networks hydrogel as a controlled-release fertilizer.

PubMed

Su, Yuan; Liu, Jia; Yue, Qinyan; Li, Qian; Gao, Baoyu

2014-01-01

A new feather protein-grafted poly(potassium acrylate)/polyvinyl alcohol (FP-g-PKA/PVA) semi-interpenetrating polymer networks (semi-IPNs) hydrogel was produced through graft copolymerization with FP as a basic macromolecular skeletal material, acrylic acid as a monomer and PVA as a semi-IPNs polymer. The adsorption of ammonium and phosphate ions from aqueous solution using the new hydrogel as N and P controlled-release fertilizer with water-retention capacity was studied. The effects of pH value, concentration, contact time and ion strength on NH4+ and PO3-4 removal by FP-g-PKA/PVA semi-IPNs hydrogel were investigated using batch adsorption experiments. The results indicated that the hydrogel had high adsorption capacities and fast adsorption rates for NH4+ and PO3-4 in wide pH levels ranging from 4.0 to 9.0. Kinetic analysis presented that both NH4+ and PO3-4 removal were closely fitted with the pseudo-second-order model. Furthermore, the adsorption isotherms of hydrogel were best represented by the Freundlich model. The adsorption-desorption experimental results showed the sustainable stability of FP-g-PKA/PVA semi-IPNs hydrogel for NH4+ and PO3-4 removal. Overall, FP-g-PKA/PVA could be considered as an efficient material for the removal and recovery of nitrogen and phosphorus with the agronomic reuse as a fertilizer.

Fluorescent materials for pH sensing and imaging based on novel 1,4-diketopyrrolo-[3,4-c]pyrrole dyes†Electronic supplementary information (ESI) available: NMR and MS spectra, further sensor characteristics and sensor long-time performance. See DOI: 10.1039/c3tc31130aClick here for additional data file.

PubMed

Aigner, Daniel; Ungerböck, Birgit; Mayr, Torsten; Saf, Robert; Klimant, Ingo; Borisov, Sergey M

2013-09-28

New optical pH-sensors relying on 1,4-diketopyrrolo-[3,4- c ]pyrroles (DPPs) as fluorescent pH-indicators are presented. Different polymer hydrogels are useful as immobilization matrices, achieving excellent sensitivity and good brightness in the resulting sensor. The operational pH can be tuned over a wide range (pH 5-12) by selecting the fine structure of the indicator and the matrix. A ratiometric sensor in the form of nanoparticles is also presented. It is suitable for RGB camera readout, and its practical applicability for fluorescence imaging in microfluidic systems is demonstrated. The indicators are synthesized starting from the commercially available DPP pigments by a straightforward concept employing chlorosulfonation and subsequent reaction with amines. Their sensitivity derives from two distinct mechanisms. At high pH (>9), they exhibit a remarkable alteration of both absorption and fluorescence spectra due to deprotonation of the lactam nitrogen atoms. If a phenolic group is introduced, highly effective fluorescence quenching at near-neutral pH occurs due to photoinduced electron transfer (PET) involving the phenolate form.

pH sensitive thiolated cationic hydrogel for oral insulin delivery.

PubMed

Sonia, T A; Sharma, Chandra P

2014-04-01

The objective of this work is to study the efficacy of pH sensitive thiolated Polydimethylaminoethylmethacrylate for oral delivery of insulin. Synthesis of pH sensitive thiolated Polydimethylaminoethylmethacrylate (PDCPA) was carried out by crosslinking Polymethacrylic acid with thiolated Polydimethylaminoethylmethacrylate (PDCys) via carbodiimide chemistry. Prior to in vivo experiment, various physicochemical and biological characterisation were carried out to evaluate the efficacy of PDCPA. Modification was confirmed by IR and NMR spectroscopy. The particle size was found to be 284 nm with a zeta potential of 37.3+/-1.58 mV. Texture analyser measurements showed that PDCPA is more mucoadhesive than the parent polymer. Transepithelial electrical measurements showed a reduction of greater than 50% on incubation with PDCPA particles. Permeation studies showed that PDCPA is more permeable than the parent polymer. On in vivo evaluation on male diabetic rats, insulin loaded PDCPA exhibited a blood glucose reduction of 19%.

Glucose-responsive hydrogel electrode for biocompatible glucose transistor

NASA Astrophysics Data System (ADS)

Kajisa, Taira; Sakata, Toshiya

2017-12-01

In this paper, we propose a highly sensitive and biocompatible glucose sensor using a semiconductor-based field effect transistor (FET) with a functionalized hydrogel. The principle of the FET device contributes to the easy detection of ionic charges with high sensitivity, and the hydrogel coated on the electrode enables the specific detection of glucose with biocompatibility. The copolymerized hydrogel on the Au gate electrode of the FET device is optimized by controlling the mixture ratio of biocompatible 2-hydroxyethylmethacrylate (HEMA) as the main monomer and vinylphenylboronic acid (VPBA) as a glucose-responsive monomer. The gate surface potential of the hydrogel FETs shifts in the negative direction with increasing glucose concentration from 10 μM to 40 mM, which results from the increase in the negative charges on the basis of the diol-binding of PBA derivatives with glucose molecules in the hydrogel. Moreover, the hydrogel coated on the gate suppresses the signal noise caused by the nonspecific adsorption of proteins such as albumin. The hydrogel FET can serve as a highly sensitive and biocompatible glucose sensor in in vivo or ex vivo applications such as eye contact lenses and sheets adhering to the skin.

Thermo-sensitive injectable glycol chitosan-based hydrogel for treatment of degenerative disc disease.

PubMed

Li, Zhengzheng; Shim, Hyeeun; Cho, Myeong Ok; Cho, Ik Sung; Lee, Jin Hyun; Kang, Sun-Woong; Kwon, Bosun; Huh, Kang Moo

2018-03-15

The use of injectable hydrogel formulations have been suggested as a promising strategy for the treatment of degenerative disc disease to both restore the biomechanical function and reduce low back pain. In this work, a new thermo-sensitive injectable hydrogels with tunable thermo-sensitivity and enhanced stability were developed with N-hexanoylation of glycol chitosan (GC) for treatment of degenerative disc disease, and their physico-chemical and biological properties were evaluated. The sol-gel transition temperature of the hydrogels was controlled in a range of 23-56 °С, depending on the degree of hexanoylation and the polymer concentration. In vitro and in vivo tests showed no cytotoxicity and no adverse effects in a rat model. The hydrogel filling of the defective IVD site in an ex vivo porcine model maintained its stability for longer than 28 days. These results suggest that the hydrogel can be used as an alternative material for treatment of disc herniation. Copyright © 2018 Elsevier Ltd. All rights reserved.

1,3,5-Triazine-2,4,6-tribenzaldehyde derivative as a new crosslinking agent for synthesis of pH-thermo dual responsive chitosan hydrogels and their nanocomposites: Swelling properties and drug release behavior.

PubMed

Karimi, Ali Reza; Tarighatjoo, Mahsa; Nikravesh, Golara

2017-12-01

In this work, 1,3,5-triazine-2,4,6-tribenzaldehyde was synthesized and chosen as the cross-linking agent for preparation of novel thermo- and pH-responsive hydrogels based on chitosan. The cross-linking proceeds through formation of imine bond by reaction of amino groups of chitosan with aldehyde groups of the cross-linker. The various amounts (6, 10, 14% w/w) of the cross-linker were used with respect to chitosan to produce three 1,3,5-triazine-2,4,6-tribenzaldehyde cross-linked chitosans. Then, their hydrogel nanocomposites were prepared by crosslinking of chitosan with 1,3,5-triazine-2,4,6-tribenzaldehyde in the presence of 0.1% and 0.3% (w/w) multi-walled carbon nanotubes (MWCNTs). The structure and properties of the hydrogels and their nanocomposites were characterized by FT-IR, 1 H NMR and scanning electron microscopy (SEM). The swelling behavior of prepared hydrogels and their nanocomposites at different pHs and temperatures was investigated. The results showed that they exhibit a pH and temperature-responsive swelling ratio. The swelling behavior of the prepared chitosan hydrogels was strongly dependent on the amounts of cross-linker and MWCNTs. In vitro controlled release behavior of metronidazole model drug was studied with prepared hydrogels and nanocomposite hydrogels. The pH, temperature and wt% of MWCNTs were found to strongly influence the drug release behavior of the hydrogels. Copyright © 2017 Elsevier B.V. All rights reserved.

Soft matter strategies for controlling food texture: formation of hydrogel particles by biopolymer complex coacervation

NASA Astrophysics Data System (ADS)

Wu, Bi-cheng; Degner, Brian; McClements, David Julian

2014-11-01

Soft matter physics principles can be used to address important problems in the food industry. Starch granules are widely used in foods to create desirable textural attributes, but high levels of digestible starch may pose a risk of diabetes. Consequently, there is a need to find healthier replacements for starch granules. The objective of this research was to create hydrogel particles from protein and dietary fiber with similar dimensions and functional attributes as starch granules. Hydrogel particles were formed by mixing gelatin (0.5 wt%) with pectin (0 to 0.2 wt%) at pH values above the isoelectric point of the gelatin (pH 9, 30 °C). When the pH was adjusted to pH 5, the biopolymer mixture spontaneously formed micron-sized particles due to electrostatic attraction of cationic gelatin with anionic pectin through complex coacervation. Differential interference contrast (DIC) microscopy showed that the hydrogel particles were translucent and spheroid, and that their dimensions were determined by pectin concentration. At 0.01 wt% pectin, hydrogel particles with similar dimensions to swollen starch granules (D3,2 ≈ 23 µm) were formed. The resulting hydrogel suspensions had similar appearances to starch pastes and could be made to have similar textural attributes (yield stress and shear viscosity) by adjusting the effective hydrogel particle concentration. These hydrogel particles may therefore be used to improve the texture of reduced-calorie foods and thereby help tackle obesity and diabetes.

Highly Stretchable and Transparent Thermistor Based on Self-Healing Double Network Hydrogel.

PubMed

Wu, Jin; Han, Songjia; Yang, Tengzhou; Li, Zhong; Wu, Zixuan; Gui, Xuchun; Tao, Kai; Miao, Jianmin; Norford, Leslie K; Liu, Chuan; Huo, Fengwei

2018-06-06

An ultrastretchable thermistor that combines intrinsic stretchability, thermal sensitivity, transparency, and self-healing capability is fabricated. It is found the polyacrylamide/carrageenan double network (DN) hydrogel is highly sensitive to temperature and therefore can be exploited as a novel channel material for a thermistor. This thermistor can be stretched from 0 to 330% strain with the sensitivity as high as 2.6%/°C at extreme 200% strain. Noticeably, the mechanical, electrical, and thermal sensing properties of the DN hydrogel can be self-healed, analogous to the self-healing capability of human skin. The large mechanical deformations, such as flexion and twist with large angles, do not affect the thermal sensitivity. Good flexibility enables the thermistor to be attached on nonplanar curvilinear surfaces for practical temperature detection. Remarkably, the thermal sensitivity can be improved by introducing mechanical strain, making the sensitivity programmable. This thermistor with tunable sensitivity is advantageous over traditional rigid thermistors that lack flexibility in adjusting their sensitivity. In addition to superior sensitivity and stretchability compared with traditional thermistors, this DN hydrogel-based thermistor provides additional advantages of good transparency and self-healing ability, enabling it to be potentially integrated in soft robots to grasp real world information for guiding their actions.

Novel amelogenin-releasing hydrogel for remineralization of enamel artificial caries

PubMed Central

Fan, Yuwei; Wen, Zezhang T; Liao, Sumei; Lallier, Thomas; Hagan, Joseph L; Twomley, Jefferson T; Zhang, Jian-Feng; Sun, Zhi; Xu, Xiaoming

2013-01-01

Recently, the use of recombinant full-length amelogenin protein in combination with fluoride has shown promising results in the formation of densely packed enamel-like structures. In this study, amelogenin (rP172)-releasing hydrogels containing calcium, phosphate, and fluoride were investigated for remineralization efficacy using in vitro early enamel caries models. The hydrogels were applied to artificial caries lesions on extracted human third molars, and the remineralization efficacy was tested in different models: static gel remineralization in the presence of artificial saliva, pH cyclic treatment at pH 5.4 acetic buffer and pH 7.3 gel remineralization, and treatment with multispecies oral biofilms grown in a continuous flowing constant-depth film fermenter. The surface microhardness of remineralized enamel increased significantly when amelogenin was released from hydrogel. No cytotoxicity was observed when periodontal ligament cells were cultured with the mineralized hydrogels. PMID:23338820

Novel thermal-sensitive hydrogel enhances both humoral and cell-mediated immune responses by intranasal vaccine delivery.

PubMed

Wu, Youbin; Wu, Shipo; Hou, Lihua; Wei, Wei; Zhou, Meng; Su, Zhiguo; Wu, Jie; Chen, Wei; Ma, Guanghui

2012-08-01

A novel thermal sensitive hydrogel was formulated with N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC) and α, β-glycerophosphate (α, β-GP). A serial of hydrogels containing different amount of GP and HTCC with diverse quarternize degree (QD, 41%, 59%, 79.5%, and 99%) were prepared and characterized by rheological method. The hydrogel was subsequently evaluated for intranasal vaccine delivery with adenovirus based Zaire Ebola virus glycoprotein antigen (Ad-GPZ). Results showed that moderate quarternized HTCC (60% and 79.5%) hydrogel/antigen formulations induced highest IgG, IgG1, and IgG2a antibody titers in serum, as well as mucosal IgA responses in lung wash, which may attributed to the prolonged antigen residence time due to the thermal-sensitivity of this hydrogel. Furthermore, CD8(+) splenocytes for IFN-γ positive cell assay and the release profile of Th1/Th2 type cytokines (IFN-γ, IL-2, IL-10, and IL-4) showed that hydrogel/Ad-GPZ generated an overwhelmingly enhanced Th1 biased cellular immune response. In addition, this hydrogel displayed low toxicity to nasal tissue and epithelial cells even by frequently intranasal dosing of hydrogel. All these results strongly supported this hydrogel as a safe and effective delivery system for nasal immunization. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Hydrogel based QCM aptasensor for detection of avian influenza virus.

PubMed

Wang, Ronghui; Li, Yanbin

2013-04-15

The objective of this study was to develop a quartz crystal microbalance (QCM) aptasensor based on ssDNA crosslinked polymeric hydrogel for rapid, sensitive and specific detection of avian influenza virus (AIV) H5N1. A selected aptamer with high affinity and specificity against AIV H5N1 surface protein was used, and hybridization between the aptamer and ssDNA formed the crosslinker in the polymer hydrogel. The aptamer hydrogel was immobilized on the gold surface of QCM sensor using a self-assembled monolayer method. The hydrogel remained in the state of shrink if no H5N1 virus was present in the sample because of the crosslinking between the aptamer and ssDNA in the polymer network. When it exposed to target virus, the binding reaction between the aptamer and H5N1 virus caused the dissolution of the linkage between the aptamer and ssDNA, resulting in the abrupt swelling of the hydrogel. The swollen hydrogel was monitored by the QCM sensor in terms of decreased frequency. Three polymeric hydrogels with different ratio (100:1 hydrogel I, 10:1 hydrogel II, 1:1 hydrogel III) of acrylamide and the aptamer monomer were synthesized, respectively, and then were used as the QCM sensor coating material. The results showed that the developed hydrogel QCM aptasensor was capable of detecting target H5N1 virus, and among the three developed aptamer hydrogels, hydrogel III coated QCM aptasensor achieved the highest sensitivity with the detection limit of 0.0128 HAU (HA unit). The total detection time from sampling to detection was only 30 min. In comparison with the anti-H5 antibody coated QCM immunosensor, the hydrogel QCM aptasensor lowered the detection limit and reduced the detection time. Copyright © 2012 Elsevier B.V. All rights reserved.

Light-addressable electrodeposition of cell-encapsulated alginate hydrogels for a cellular microarray using a digital micromirror device

PubMed Central

Huang, Shih-Hao; Hsueh, Hui-Jung; Jiang, Yeu-Long

2011-01-01

This paper describes a light-addressable electrolytic system used to perform an electrodeposition of calcium alginate hydrogels using a digital micromirror device (DMD). In this system, a patterned light illumination is projected onto a photoconductive substrate serving as a photo-anode to electrolytically produce protons, which can lead to a decreased pH gradient. The low pH generated at the anode can locally release calcium ions from insoluble calcium carbonate (CaCO3) to cause gelation of calcium alginate through sol-gel transition. By controlling the illumination pattern on the DMD, a light-addressable electrodeposition of calcium alginate hydrogels with different shapes and sizes, as well as multiplexed micropatterning was performed. The effects of the concentration of the alginate and CaCO3 solutions on the dimensional resolution of alginate hydrogel formation were experimentally examined. A 3 × 3 array of cell-encapsulated alginate hydrogels was also successfully demonstrated through light-addressable electrodeposition. Our proposed method provides a programmable method for the spatiotemporally controllable assembly of cell populations into cellular microarrays and could have a wide range of biological applications in cell-based biosensing, toxicology, and drug discovery. PMID:22685500

Light-addressable electrodeposition of cell-encapsulated alginate hydrogels for a cellular microarray using a digital micromirror device.

PubMed

Huang, Shih-Hao; Hsueh, Hui-Jung; Jiang, Yeu-Long

2011-09-01

This paper describes a light-addressable electrolytic system used to perform an electrodeposition of calcium alginate hydrogels using a digital micromirror device (DMD). In this system, a patterned light illumination is projected onto a photoconductive substrate serving as a photo-anode to electrolytically produce protons, which can lead to a decreased pH gradient. The low pH generated at the anode can locally release calcium ions from insoluble calcium carbonate (CaCO(3)) to cause gelation of calcium alginate through sol-gel transition. By controlling the illumination pattern on the DMD, a light-addressable electrodeposition of calcium alginate hydrogels with different shapes and sizes, as well as multiplexed micropatterning was performed. The effects of the concentration of the alginate and CaCO(3) solutions on the dimensional resolution of alginate hydrogel formation were experimentally examined. A 3 × 3 array of cell-encapsulated alginate hydrogels was also successfully demonstrated through light-addressable electrodeposition. Our proposed method provides a programmable method for the spatiotemporally controllable assembly of cell populations into cellular microarrays and could have a wide range of biological applications in cell-based biosensing, toxicology, and drug discovery.

Three-dimensional culture and differentiation of human osteogenic cells in an injectable hydroxypropylmethylcellulose hydrogel.

PubMed

Trojani, Christophe; Weiss, Pierre; Michiels, Jean-François; Vinatier, Claire; Guicheux, Jérôme; Daculsi, Guy; Gaudray, Patrick; Carle, Georges F; Rochet, Nathalie

2005-09-01

The present work evaluates a newly developed silated hydroxypropylmethylcellulose (Si-HPMC)-based hydrogel as a scaffold for 3D culture of osteogenic cells. The pH variation at room temperature catalyzes the reticulation and self-hardening of the viscous polymer solution into a gelatine state. We designed reticulation time, final consistency and pH in order to obtain an easy handling matrice, suitable for in vitro culture and in vivo injection. Three human osteogenic cell lines and normal human osteogenic (HOST) cells were cultured in 3D inside this Si-HPMC hydrogel. We show here that osteosarcoma cells proliferate as clonogenic spheroids and that HOST colonies survive for at least 3 weeks. Mineralization assay and gene expression analysis of osteoblastic markers and cytokines, indicate that all the cells cultured in 3D into this hydrogel, exhibited a more mature differentiation status than cells cultured in monolayer on plastic. This study demonstrates that this Si-HPMC hydrogel is well suited to support osteoblastic survival, proliferation and differentiation when used as a new scaffold for 3D culture and represents also a potential basis for an innovative bone repair material.

Biodegradability and swelling capacity of kaolin based chitosan-g-PHEMA nanocomposite hydrogel.

PubMed

Pradhan, Arun Kumar; Rana, Pradeep Kumar; Sahoo, Prafulla Kumar

2015-03-01

Chitosan, a natural biopolymer, obtained by alkaline deacetylation of chitin, exhibits excellent biological properties such as biodegradability, immunological and antibacterial activity. Recently, there has been a growing interest in the chemical modification of chitosan in order to widen its applications. The chemical modification of chitosan has been achieved via grafting of monomer, 2-hydroxyethyl methacrylate (HEMA) in the presence of the initiator, ammonium persulfate (APS) and kaolin was added to improve the mechanical strength of the newly developed nanocomposites hydrogel. The so prepared grafted nanocomposites hydrogel was characterized by FTIR, XRD, SEM, TEM and TGA. The equilibrium water content (EWC) of the samples were measured at different pH ranges 6.5-8.0 and found optimum at pH 7.5 for biomedical applications. Further, the biodegradability of the samples was studied at different time intervals from 15 days to 1 year but, the kaolin based nanohydrogels exhibited good biodegradability. Copyright © 2015 Elsevier B.V. All rights reserved.

A pH-Sensing Optode for Mapping Spatiotemporal Gradients in 3D Paper-Based Cell Cultures.

PubMed

Kenney, Rachael M; Boyce, Matthew W; Whitman, Nathan A; Kromhout, Brenden P; Lockett, Matthew R

2018-02-06

Paper-based cultures are an emerging platform for preparing 3D tissue-like structures. Chemical gradients can be imposed upon these cultures, generating microenvironments similar to those found in poorly vascularized tumors. There is increasing evidence that the tumor microenvironment is responsible for promoting drug resistance and increased invasiveness. Acidosis, or the acidification of the extracellular space, is particularly important in promoting these aggressive cancer phenotypes. To better understand how cells respond to acidosis there is a need for 3D culture platforms that not only model relevant disease states but also contain sensors capable of quantifying small molecules in the extracellular environment. In this work, we describe pH-sensing optodes that are capable of generating high spatial and temporal resolution maps of pH gradients in paper-based cultures. This sensor was fabricated by suspending microparticles containing pH-sensitive (fluorescein) and pH-insensitive (diphenylanthracene) dyes in a polyurethane hydrogel, which was then coated onto a transparent film. The pH-sensing films have a fast response time, are reversible, stable in long-term culture environments, have minimal photobleaching, and are not cytotoxic. These films have a pK a of 7.61 ± 0.04 and are sensitive in the pH range corresponding to normal and tumorigenic tissues. With these optodes, we measured the spatiotemporal evolution of pH gradients in paper-based tumor models.

Quaternized Cellulose Hydrogels as Sorbent Materials and Pickering Emulsion Stabilizing Agents

PubMed Central

Udoetok, Inimfon A.; Wilson, Lee D.; Headley, John V.

2016-01-01

Quaternized (QC) and cross-linked/quaternized (CQC) cellulose hydrogels were prepared by cross-linking native cellulose with epichlorohydrin (ECH), with subsequent grafting of glycidyl trimethyl ammonium chloride (GTMAC). Materials characterization via carbon, hydrogen and nitrogen (CHN) analysis, thermogravimetric analysis (TGA), and Fourier transform infrared (FTIR)/13C solid state NMR spectroscopy provided supportive evidence of the hydrogel synthesis. Enhanced thermal stability of the hydrogels was observed relative to native cellulose. Colloidal stability of octanol and water mixtures revealed that QC induces greater stabilization over CQC, as evidenced by the formation of a hexane–water Pickering emulsion system. Equilibrium sorption studies with naphthenates from oil sands process water (OSPW) and 2-naphthoxy acetic acid (NAA) in aqueous solution revealed that CQC possess higher affinity relative to QC with the naphthenates. According to the Langmuir isotherm model, the sorption capacity of CQC for OSPW naphthenates was 33.0 mg/g and NAA was 69.5 mg/g. CQC displays similar affinity for the various OSPW naphthenate component species in aqueous solution. Kinetic uptake of NAA at variable temperature, pH and adsorbent dosage showed that increased temperature favoured the uptake process at 303 K, where Qm = 76.7 mg/g. Solution conditions at pH 3 or 9 had a minor effect on the sorption process, while equilibrium was achieved in a shorter time at lower dosage (ca. three-fold lower) of hydrogel (100 mg vs. 30 mg). The estimated activation parameters are based on temperature dependent rate constants, k1, which reveal contributions from enthalpy-driven electrostatic interactions. The kinetic results indicate an ion-based associative sorption mechanism. This study contributes to a greater understanding of the adsorption and physicochemical properties of cellulose-based hydrogels. PMID:28773767

Chitosan-based thermosensitive hydrogel as a promising ocular drug delivery system: preparation, characterization, and in vivo evaluation.

PubMed

Chen, Xingwei; Li, Xinru; Zhou, Yanxia; Wang, Xiaoning; Zhang, Yanhui; Fan, Yating; Huang, Yanqing; Liu, Yan

2012-11-01

The purpose of this study was to evaluate the feasibility of in situ thermosensitive hydrogel based on chitosan in combination with disodium α-d-Glucose 1-phosphate (DGP) for ocular drug delivery system. Aqueous solution of chitosan/DGP underwent sol-gel transition as temperature increased which was flowing sol at room temperature and then turned into non-flowing hydrogel at physiological temperature. The properties of gels were characterized regarding gelation time, gelation temperature, and morphology. The sol-to-gel phase transition behaviors were affected by the concentrations of chitosan, DGP and the model drug levocetirizine dihydrochloride (LD). The developed hydrogel presented a characteristic of a rapid release at the initial period followed by a sustained release and remarkably enhanced the cornea penetration of LD. The results of ocular irritation demonstrated the excellent ocular tolerance of the hydrogel. The ocular residence time for the hydrogel was significantly prolonged compared with eye drops. The drug-loaded hydrogel produced more effective anti-allergic conjunctivitis effects compared with LD aqueous solution. These results showed that the chitosan/DGP thermosensitive hydrogel could be used as an ideal ocular drug delivery system in terms of the suitable sol-gel transition temperature, mild pH environment in the hydrogel as well as the organic solvent free.

Gellan gum-based hydrogels for intervertebral disc tissue-engineering applications.

PubMed

Silva-Correia, J; Oliveira, J M; Caridade, S G; Oliveira, J T; Sousa, R A; Mano, J F; Reis, R L

2011-06-01

Intervertebral disc (IVD) degeneration is a challenging clinical problem that urgently demands viable nucleus pulposus (NP) implant materials. The best suited biomaterial for NP regeneration has yet to be identified, but it is believed that biodegradable hydrogel-based materials are promising candidates. In this work, we have developed ionic- and photo-crosslinked methacrylated gellan gum (GG-MA) hydrogels to be used in acellular and cellular tissue-engineering strategies for the regeneration of IVDs. The physicochemical properties of the developed hydrogels were investigated by Fourier-transform infrared spectroscopy, (1) H nuclear magnetic resonance and differential scanning calorimetry. The swelling ability and degradation rate of hydrogels were also analysed in phosphate-buffered saline solution at physiological pH for a period of 30 days. Additionally, the morphology and mechanical properties of the hydrogels were assessed under a scanning electron microscope and dynamic compression, respectively. An in vitro study was carried out to screen possible cytotoxicity of the gellan gum-based hydrogels by culturing rat lung fibroblasts (L929 cells) with hydrogel leachables up to 7 days. The results demonstrated that gellan gum was successfully methacrylated. We observed that the produced GG-MA hydrogels possess improved mechanical properties and lower water uptake ability and degradation rate as compared to gellan gum. This work also revealed that GG-MA hydrogels are non-cytotoxic in vitro, thus being promising biomaterials to be used in IVD tissue-engineering strategies. Copyright © 2010 John Wiley & Sons, Ltd.

Responsive Hydrogel-based Photonic Nanochains for Microenvironment Sensing and Imaging in Real Time and High Resolution.

PubMed

Luo, Wei; Cui, Qian; Fang, Kai; Chen, Ke; Ma, Huiru; Guan, Jianguo

2018-01-17

Microenvironment sensing and imaging are of importance in microscale zones like microreactors, microfluidic systems, and biological cells. But they are so far implemented only based on chemical colors from dyes or quantum dots, which suffered either from photobleaching, quenching, or photoblinking behaviors, or from limited color gamut. In contrast, structural colors from hydrogel-based photonic crystals (PCs) may be stable and tunable in the whole visible spectrum by diffraction peak shift, facilitating the visual detection with high accuracy. However, the current hydrogel-based PCs are all inappropriate for microscale detection due to the bulk size. Here we demonstrate the smallest hydrogel-based PCs, responsive hydrogel-based photonic nanochains with high-resolution and real-time response, by developing a general hydrogen bond-guided template polymerization method. A variety of mechanically separated stimuli-responsive hydrogel-based photonic nanochains have been obtained in a large scale including those responding to pH, solvent, and temperature. Each of them has a submicrometer diameter and is composed of individual one-dimensional periodic structure of magnetic particles locked by a tens-of-nanometer-thick peapod-like responsive hydrogel shell. Taking the pH-responsive hydrogel-based photonic nanochains, for example, pH-induced hydrogel volume change notably alters the nanochain length, resulting in a significant variation of the structural color. The submicrometer size endows the nanochains with improved resolution and response time by 2-3 orders of magnitude than the previous counterparts. Our results for the first time validate the feasibility of using structural colors for microenvironment sensing and imaging and may further promote the applications of responsive PCs, such as in displays and printing.

A pH- and temperature-responsive bioresorbable injectable hydrogel based on polypeptide block copolymers for the sustained delivery of proteins in vivo.

PubMed

Turabee, Md Hasan; Thambi, Thavasyappan; Duong, Huu Thuy Trang; Jeong, Ji Hoon; Lee, Doo Sung

2018-02-27

Sustained delivery of protein therapeutics is limited owing to the fragile nature of proteins. Despite its great potential, delivery of proteins without any loss of bioactivity remains a challenge in the use of protein therapeutics in the clinic. To surmount this shortcoming, we report a pH- and temperature-responsive in situ-forming injectable hydrogel based on comb-type polypeptide block copolymers for the controlled delivery of proteins. Polypeptide block copolymers, composed of hydrophilic polyethylene glycol (PEG), temperature-responsive poly(γ-benzyl-l-glutamate) (PBLG), and pH-responsive oligo(sulfamethazine) (OSM), exhibit pH- and temperature-induced sol-to-gel transition behavior in aqueous solutions. Polypeptide block copolymers were synthesized by combining N-carboxyanhydride-based ring-opening polymerization and post-functionalization of the chain-end using N-hydroxy succinimide ester activated OSM. The physical properties of polypeptide-based hydrogels were tuned by varying the composition of temperature- and pH-responsive PBLG and OSM in block copolymers. Polypeptide block copolymers were non-toxic to human embryonic kidney cells at high concentrations (2000 μg mL -1 ). Subcutaneous administration of polypeptide block copolymer sols formed viscoelastic gel instantly at the back of Sprague-Dawley (SD) rats. The in vivo gels exhibited sustained degradation and were found to be bioresorbable in 6 weeks without any noticeable inflammation at the injection site. Anionic characteristics of hydrogels allow efficient loading of a cationic model protein, lysozyme, through electrostatic interaction. Lysozyme-loaded polypeptide block copolymer sols readily formed a viscoelastic gel in vivo and sustained lysozyme release for at least a week. Overall, the results demonstrate an elegant approach to control the release of certain charged proteins and open a myriad of therapeutic possibilities in protein therapeutics.

Kinetically Controlled Lifetimes in Redox-Responsive Transient Supramolecular Hydrogels.

PubMed

Wojciechowski, Jonathan P; Martin, Adam D; Thordarson, Pall

2018-02-28

It remains challenging to program soft materials to show dynamic, tunable time-dependent properties. In this work, we report a strategy to design transient supramolecular hydrogels based on kinetic control of competing reactions. Specifically, the pH-triggered self-assembly of a redox-active supramolecular gelator, N,N'-dibenzoyl-l-cystine (DBC) in the presence of a reducing agent, which acts to disassemble the system. The lifetimes of the transient hydrogels can be tuned simply by pH or reducing agent concentration. We find through kinetic analysis that gel formation hinders the ability of the reducing agent and enables longer transient hydrogel lifetimes than would be predicted. The transient hydrogels undergo clean cycles, with no kinetically trapped aggregates observed. As a result, multiple transient hydrogel cycles are demonstrated and can be predicted. This work contributes to our understanding of designing transient assemblies with tunable temporal control.

Hydrogel based sensor arrays (2 × 2) with perforated piezoresistive diaphragms for metabolic monitoring (in vitro)

PubMed Central

Orthner, M.P.; Lin, G.; Avula, M.; Buetefisch, S.; Magda, J.; Rieth, L.W.; Solzbacher, F.

2010-01-01

This report details the first experimental results from novel hydrogel sensor array (2 × 2) which incorporates analyte diffusion pores into a piezoresistive diaphragm for the detection of hydrogel swelling pressures and hence chemical concentrations. The sensor assembly was comprised of three components, the active four sensors, HPMA/DMA/TEGDMA (hydroxypropyl methacrylate (HPMA), N,N-dimethylaminoethyl methacrylate (DMA) and crosslinker tetra-ethyleneglycol dimethacrylate (TEGDMA)) hydrogel, and backing plate. Each of the individual sensors of the array can be used with various hydrogels used to measure the presence of a number of stimuli including pH, ionic strength, and glucose concentrations. Ideally, in the future, these sensors will be used for continuous metabolic monitoring applications and implanted subcutaneously. In this paper and to properly characterize the sensor assembly, hydrogels sensitive to changes ionic strength were synthesized using hydroxypropyl methacrylate (HPMA), N,N-dimethylaminoethyl methacrylate (DMA) and crosslinker tetra-ethyleneglycol dimethacrylate (TEGDMA) and inserted into the sensor assembly. This hydrogel quickly and reversibly swells when placed environments of physiological buffer solutions (PBS) with ionic strengths ranging from 0.025 to 0.15 M, making it ideal for proof-of-concept testing and initial characterization. The assembly was wire bonded to a printed circuit board and coated with 3 ± 0.5 μm of Parylene-C using chemical vapor deposition (CVD) to protect the sensor and electrical connections during ionic strength wet testing. Two versions of sensors were fabricated for comparison, the first incorporated diffusion pores into the diaphragm, and the second used a solid diaphragm with perforated backing plate. This new design (perforated diaphragm) was shown to have slightly higher sensitivity than solid diaphragm sensors with separate diffuse backing plates when coupled with the hydrogel. The sensitivities for the 1 mm × 1 mm, 1.25 mm × 1.25 mm, 1.5 mm × 1.5 mm perforated diaphragm sensors were 53.3 ± 6.5, 171.7 ± 8.8, and 271.47 ± 27.53 mV/V-M, respectively. These results show that perforations in the diaphragm can be used not only to allow the diffusion of analyte into the cavity but to increase mechanical stress in the piezoresistive diaphragm, thereby increasing sensor output signal. The time constants for swelling (τswelling) and contracting (τcontracting) were calculated by fitting the sensor output half cycles to an exponential growth function. We found that the sensors' response was initially retarded during the preliminary hydrogel conditioning period then improved after 3–5 cycles with values of approximately 9 and 7 min for τswelling and τcontracting. For all sensors tested τswelling > τcontracting. This may be due to the increased loading on the hydrogel from the diaphragm during the swelling process. During contraction the diaphragm aids the hydrogel by reversibly applying mechanical pressure and therefore reducing τcontracting. Long term stability testing showed the sensors remained functional for upwards of 2 weeks in the test phosphate buffer solution (PBS). PMID:23750073

Hydrogel based sensor arrays (2 × 2) with perforated piezoresistive diaphragms for metabolic monitoring (in vitro).

PubMed

Orthner, M P; Lin, G; Avula, M; Buetefisch, S; Magda, J; Rieth, L W; Solzbacher, F

2010-03-19

This report details the first experimental results from novel hydrogel sensor array (2 × 2) which incorporates analyte diffusion pores into a piezoresistive diaphragm for the detection of hydrogel swelling pressures and hence chemical concentrations. The sensor assembly was comprised of three components, the active four sensors, HPMA/DMA/TEGDMA (hydroxypropyl methacrylate (HPMA), N,N-dimethylaminoethyl methacrylate (DMA) and crosslinker tetra-ethyleneglycol dimethacrylate (TEGDMA)) hydrogel, and backing plate. Each of the individual sensors of the array can be used with various hydrogels used to measure the presence of a number of stimuli including pH, ionic strength, and glucose concentrations. Ideally, in the future, these sensors will be used for continuous metabolic monitoring applications and implanted subcutaneously. In this paper and to properly characterize the sensor assembly, hydrogels sensitive to changes ionic strength were synthesized using hydroxypropyl methacrylate (HPMA), N,N-dimethylaminoethyl methacrylate (DMA) and crosslinker tetra-ethyleneglycol dimethacrylate (TEGDMA) and inserted into the sensor assembly. This hydrogel quickly and reversibly swells when placed environments of physiological buffer solutions (PBS) with ionic strengths ranging from 0.025 to 0.15 M, making it ideal for proof-of-concept testing and initial characterization. The assembly was wire bonded to a printed circuit board and coated with 3 ± 0.5 μm of Parylene-C using chemical vapor deposition (CVD) to protect the sensor and electrical connections during ionic strength wet testing. Two versions of sensors were fabricated for comparison, the first incorporated diffusion pores into the diaphragm, and the second used a solid diaphragm with perforated backing plate. This new design (perforated diaphragm) was shown to have slightly higher sensitivity than solid diaphragm sensors with separate diffuse backing plates when coupled with the hydrogel. The sensitivities for the 1 mm × 1 mm, 1.25 mm × 1.25 mm, 1.5 mm × 1.5 mm perforated diaphragm sensors were 53.3 ± 6.5, 171.7 ± 8.8, and 271.47 ± 27.53 mV/V-M, respectively. These results show that perforations in the diaphragm can be used not only to allow the diffusion of analyte into the cavity but to increase mechanical stress in the piezoresistive diaphragm, thereby increasing sensor output signal. The time constants for swelling ( τ swelling ) and contracting ( τ contracting ) were calculated by fitting the sensor output half cycles to an exponential growth function. We found that the sensors' response was initially retarded during the preliminary hydrogel conditioning period then improved after 3-5 cycles with values of approximately 9 and 7 min for τ swelling and τ contracting . For all sensors tested τ swelling > τ contracting . This may be due to the increased loading on the hydrogel from the diaphragm during the swelling process. During contraction the diaphragm aids the hydrogel by reversibly applying mechanical pressure and therefore reducing τ contracting . Long term stability testing showed the sensors remained functional for upwards of 2 weeks in the test phosphate buffer solution (PBS).

Comparison effects and dielectric properties of different dose methylene-blue-doped hydrogels.

PubMed

Yalçın, O; Coşkun, R; Okutan, M; Öztürk, M

2013-08-01

The dielectric properties of methylene blue (MB)-doped hydrogels were investigated by impedance spectroscopy. The real part (ε') and the imaginary part (ε") of the complex dielectric constant and the energy loss tangent/dissipation factor (tan δ) were measured in the frequency range of 10 Hz to 100 MHz at room temperature for pH 5.5 value. Frequency variations of the resistance, the reactance, and the impedance of the samples have also been investigated. The dielectric permittivity of the MB-doped hydrogels is sensitive to ionic conduction and electrode polarization in low frequency. Furthermore, the dielectric behavior in high-frequency parts was attributed to the Brownian motion of the hydrogen bonds. The ionic conduction for MB-doped samples was prevented for Cole-Cole plots, while the Cole-Cole plots for pure sample show equivalent electrical circuit. The alternative current (ac) conductivity increases with the increasing MB concentration and the frequency.

Physics of soft hyaluronic acid-collagen type II double network gels

NASA Astrophysics Data System (ADS)

Morozova, Svetlana; Muthukumar, Murugappan

2015-03-01

Many biological hydrogels are made up of multiple interpenetrating, charged components. We study the swelling, elastic diffusion, mechanical, and optical behaviors of 100 mol% ionizable hyaluronic acid (HA) and collagen type II fiber networks. Dilute, 0.05-0.5 wt% hyaluronic acid networks are extremely sensitive to solution salt concentration, but are stable at pH above 2. When swelled in 0.1M NaCl, single-network hyaluronic acid gels follow scaling laws relevant to high salt semidilute solutions; the elastic shear modulus G' and diffusion constant D scale with the volume fraction ϕ as G' ~ϕ 9 / 4 and D ~ϕ 3 / 4 , respectively. With the addition of a collagen fiber network, we find that the hyaluronic acid network swells to suspend the rigid collagen fibers, providing extra strength to the hydrogel. Results on swelling equilibria, elasticity, and collective diffusion on these double network hydrogels will be presented.

Electrically responsive materials based on polycarbazole/sodium alginate hydrogel blend for soft and flexible actuator application.

PubMed

Sangwan, Watchara; Petcharoen, Karat; Paradee, Nophawan; Lerdwijitjarud, Wanchai; Sirivat, Anuvat

2016-10-20

The electromechanical properties, namely the storage modulus sensitivity and bending, of sodium alginate (SA) hydrogels and polycarbazole/sodium alginate (PCB/SA) hydrogel blends under applied electric field was investigated. The electromechanical properties of the pristine SA were studied under effects of crosslinking types and SA molecular weights, whereas the PCB/SA hydrogel blends were studied under the effect of PCB concentrations. The storage modulus sensitivity and bending of the pristine SA as crosslinked by the ionic crosslinking agent were found to be higher than those of the covalent crosslinking. The storage modulus sensitivity and deflection of the SA increased monotonically with increasing molecular weight. The highest electromechanical response of the PCB/SA hydrogel blends was obtained from the blend with 0.10% v/v PCB as it provided surprisingly the highest ever storage modulus sensitivity, (G'-G'0)/G'0 where G'0 and G' are the storage modulus without and with applied electric field, respectively, at 18.5 under applied electric field strength of 800V/mm. Copyright © 2016 Elsevier Ltd. All rights reserved.

Wood mimetic hydrogel beads for enzyme immobilization.

PubMed

Park, Saerom; Kim, Sung Hee; Won, Keehoon; Choi, Joon Weon; Kim, Yong Hwan; Kim, Hyung Joo; Yang, Yung-Hun; Lee, Sang Hyun

2015-01-22

Wood component-based composite hydrogels have potential applications in biomedical fields owing to their low cost, biodegradability, and biocompatibility. The controllable properties of wood mimetic composites containing three major wood components are useful for enzyme immobilization. Here, lipase from Candida rugosa was entrapped in wood mimetic beads containing cellulose, xylan, and lignin by dissolving wood components with lipase in [Emim][Ac], followed by reconstitution. Lipase entrapped in cellulose/xylan/lignin beads in a 5:3:2 ratio showed the highest activity; this ratio is very similar to that in natural wood. The lipase entrapped in various wood mimetic beads showed increased thermal and pH stability. The half-life times of lipase entrapped in cellulose/alkali lignin hydrogel were 31- and 82-times higher than those of free lipase during incubation under denaturing conditions of high temperature and low pH, respectively. Owing to their biocompatibility, biodegradability, and controllable properties, wood mimetic hydrogel beads can be used to immobilize various enzymes for applications in the biomedical, bioelectronic, and biocatalytic fields. Copyright © 2014 Elsevier Ltd. All rights reserved.

Folic acid conjugated cross-linked acrylic polymer (FA-CLAP) hydrogel for site specific delivery of hydrophobic drugs to cancer cells.

PubMed

Pillai, Jisha Jayadevan; Thulasidasan, Arun Kumar Theralikattu; Anto, Ruby John; Chithralekha, Devika Nandan; Narayanan, Ashwanikumar; Kumar, Gopalakrishnapillai Sankaramangalam Vinod

2014-07-15

The hydrogel based system is found to be rarely reported for the delivery of hydrophobic drug due to the incompatibility of hydrophilicity of the polymer network and the hydrophobicity of drug. This problem can be solved by preparing semi-interpenetrating network of cross-linked polymer for tuning the hydrophilicity so as to entrap the hydrophobic drugs. The current study is to develop a folic acid conjugated cross-linked pH sensitive, biocompatible polymeric hydrogel to achieve a site specific drug delivery. For that, we have synthesized a folic acid conjugated PEG cross-linked acrylic polymer (FA-CLAP) hydrogel and investigated its loading and release of curcumin. The formed polymer hydrogel was then conjugated with folic acid for the site specific delivery of curcumin to cancer cells and then further characterized and conducted the cell uptake and cytotoxicity studies on human cervical cancer cell lines (HeLa). In this study, we synthesized folic acid conjugated cross-linked acrylic hydrogel for the delivery of hydrophobic drugs to the cancer site. Poly (ethyleneglycol) (PEG) diacrylate cross-linked acrylic polymer (PAA) was prepared via inverse emulsion polymerization technique and later conjugated it with folic acid (FA-CLAP). Hydrophobic drug curcumin is entrapped into it and investigated the entrapment efficiency. Characterization of synthesized hydogel was done by using Fourier Transform-Infrared spectroscopy (FT-IR), Transmission Electron Microscopy (TEM), Differential Scanning Calorimetry (DSC). Polymerization and folate conjugation was confirmed by FT-IR spectroscopy. The release kinetics of drug from the entrapped form was studied which showed initial burst release followed by sustained release due to swelling and increased cross-linking. In vitro cytotoxicity and cell uptake studies were conducted in human cervical cancer (HeLa) cell lines. Results showed that curcumin entrapped folate conjugated cross-linked acrylic polymer (FA-CLAP) hydrogel showed higher cellular uptake than the non folate conjugated form. So this can be suggested as a better delivery system for site specific release of hydrophobic cancer drugs.

Synthesis of a chitosan-based photo-sensitive hydrogel and its biocompatibility and biodegradability.

PubMed

He, Ming; Han, Baoqin; Jiang, Zhiwen; Yang, Yan; Peng, Yanfei; Liu, Wanshun

2017-06-15

Hydroxyethyl chitosan (HECTS) is one of the most important water soluble derivatives of chitosan. In this study, photo-sensitive azidehydroxyethyl chitosan (AZ-HECTS) was synthesized with grafting degree 3.4%, and its water solution resulted in an insoluble hydrogel by 254nm UV irradiation for 90s. AZ-HECTS hydrogels, with water absorption 86.21%, had little impact on growth of mouse fibroblast (L929) and presented good cell biocompatibility. Obvious sudden degradation stage, slow degradation stage and no apparent toxicity was observed after AZ-HECTS hydrogels implanted into rats, and tissue inflammation was slighter, which indicated favorable biological safety. Furthermore, AZ-HECTS hydrogels was loaded with heparin, and released 50% of heparin accumulated 14d. AZ-HECTS-heparin hydrogels showed inhibitory effects on L929, and pro-growth functions within vascular endothelial cells seeded on the hydrogels, meanwhile a positive influence on vascular endothelial growth factor expression. In conclusion, AZ-HECTS hydrogels possessed favorable biocompatibility and biodegradability and had good potential as drug carrier. Copyright © 2017 Elsevier Ltd. All rights reserved.

A programmable soft chemo-mechanical actuator exploiting a catalyzed photochemical water-oxidation reaction.

PubMed

Yuan, P; McCracken, J M; Gross, D E; Braun, P V; Moore, J S; Nuzzo, R G

2017-10-18

We describe a composite hydrogel containing an embedding coupled chemistry for light-sensitized catalytic reactions that enables chemo-mechanical actuation of poly(acrylic acid)-based gels. In these materials, a photosensitizer and catalyst-ruthenium trisbipyridine and iridium dioxide nanoparticles, respectively-are incorporated into the hydrogel where together, with visible light irradiation, they undergo a catalytic water-oxidation reaction that lowers the pH and induces a dissipative/chemically-driven strain change in the gel. To demonstrate the capacity for 3D chemo-mechanical actuation, a layer of non-pH responsive poly(2-hydroxyethyl methacrylate) is added to the photo-active composite gel to create a model bimorph actuator. Triggering and terminating the water-oxidation reaction leads to a programmatic expansion and contraction of the active layer, which induces different modes of biomimetic curling motions in the bimorph actuator in light and dark environments. The efficiency of this system is fundamentally limited by the system-level design, which provides no capacity to sustain a local pH gradient against diffusive mixing. Even so, if the initial pH of the background solution is reestablished either actively or passively between each reaction cycle, it is possible to realize multiple cycles of reversible actuation. We describe a thermodynamic analysis of this system which identifies specific features mediating efficiency losses and conceptual requirements for mesoscopic design rules for optimization of this system and for advancing soft actuation systems in general.

Construction and characterization of a pure protein hydrogel for drug delivery application.

PubMed

Xu, Xu; Xu, ZhaoKang; Yang, XiaoFeng; He, YanHao; Lin, Rong

2017-02-01

Injectable hydrogels have a variety of applications, including regenerative medicine, tissue engineering and controlled drug delivery. In this paper, we reported on a pure protein hydrogel based on tetrameric recombinant proteins for the potential drug delivery application. This protein hydrogel was formed instantly by simply mixing two recombinant proteins (ULD-TIP1 and ULD-GGGWRESAI) through the specific protein-peptide interaction. The protein hydrogel was characterized by rheology and scanning electron microscopy (SEM). In vitro cytotoxicity test indicated that the developed protein hydrogel had no apparent cytotoxicity against L-929 cells and HCEC cells after 48h incubation. The formed protein hydrogels was gradually degraded after incubation in phosphate buffered solution (PBS, pH=7.4) for a period of 144h study, as indicated by in vitro degradation test. Encapsulation of model drug (sodium diclofenac; DIC) were achieved by simple mixing of drugs with hydrogelator and the entrapped drugs was almost completely released from hydrogels within 24h via a diffusion manner. As a conclusion, the simple and mild preparation procedure and good biocompatibility of protein hydrogel would render its good promising candidate for drug delivery applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Versatile Dual Photoresponsive System for Precise Control of Chemical Reactions.

PubMed

Xu, Can; Bing, Wei; Wang, Faming; Ren, Jinsong; Qu, Xiaogang

2017-08-22

A versatile method for photoregulation of chemical reactions was developed through a combination of near-infrared (NIR) and ultraviolet (UV) light sensitive materials. This regulatory effect was achieved through photoresponsive modulation of reaction temperature and pH values, two prominent factors influencing reaction kinetics. Photothermal nanomaterial graphene oxide (GO) and photobase reagent malachite green carbinol base (MGCB) were selected for temperature and pH regulation, respectively. Using nanocatalyst- and enzyme-mediated chemical reactions as model systems, we demonstrated the feasibility and high efficiency of this method. In addition, a photoresponsive, multifunctional "Band-aid"-like hydrogel platform was presented for programmable wound healing. Overall, this simple, efficient, and reversible system was found to be effective for controlling a wide variety of chemical reactions. Our work may provide a method for remote and sustainable control over chemical reactions for industrial and biomedical applications.

Synthesis of Acylated Xylan-Based Magnetic Fe3O4 Hydrogels and Their Application for H2O2 Detection

PubMed Central

Dai, Qing-Qing; Ren, Jun-Li; Peng, Feng; Chen, Xiao-Feng; Gao, Cun-Dian; Sun, Run-Cang

2016-01-01

Acylated xylan-based magnetic Fe3O4 nanocomposite hydrogels (ACX-MNP-gels) were prepared by fabricating Fe3O4 nanoctahedra in situ within a hydrogel matrix which was synthesized by the copolymerization of acylated xylan (ACX) with acrylamide and N-isopropylacrylamide under ultraviolet irradiation. The size of the Fe3O4 fabricated within the hydrogel matrix could be adjusted through controlling the crosslinking concentrations (C). The magnetic hydrogels showed desirable magnetic and mechanical properties, which were confirmed by XRD, Raman spectroscopy, physical property measurement system, SEM, TGA, and compression test. Moreover, the catalytic performance of the magnetic hydrogels was explored. The magnetic hydrogels (C = 7.5 wt %) presented excellent catalytic activity and provided a sensitive response to H2O2 detection even at a concentration level of 5 × 10−6 mol·L−1. This approach to preparing magnetic hydrogels loaded with Fe3O4 nanoparticles endows xylan-based hydrogels with new promising applications in biotechnology and environmental chemistry. PMID:28773811

Ultrasensitive Wearable Soft Strain Sensors of Conductive, Self-healing, and Elastic Hydrogels with Synergistic "Soft and Hard" Hybrid Networks.

PubMed

Liu, Yan-Jun; Cao, Wen-Tao; Ma, Ming-Guo; Wan, Pengbo

2017-08-02

Robust, stretchable, and strain-sensitive hydrogels have recently attracted immense research interest because of their potential application in wearable strain sensors. The integration of the synergistic characteristics of decent mechanical properties, reliable self-healing capability, and high sensing sensitivity for fabricating conductive, elastic, self-healing, and strain-sensitive hydrogels is still a great challenge. Inspired by the mechanically excellent and self-healing biological soft tissues with hierarchical network structures, herein, functional network hydrogels are fabricated by the interconnection between a "soft" homogeneous polymer network and a "hard" dynamic ferric (Fe 3+ ) cross-linked cellulose nanocrystals (CNCs-Fe 3+ ) network. Under stress, the dynamic CNCs-Fe 3+ coordination bonds act as sacrificial bonds to efficiently dissipate energy, while the homogeneous polymer network leads to a smooth stress-transfer, which enables the hydrogels to achieve unusual mechanical properties, such as excellent mechanical strength, robust toughness, and stretchability, as well as good self-recovery property. The hydrogels demonstrate autonomously self-healing capability in only 5 min without the need of any stimuli or healing agents, ascribing to the reorganization of CNCs and Fe 3+ via ionic coordination. Furthermore, the resulted hydrogels display tunable electromechanical behavior with sensitive, stable, and repeatable variations in resistance upon mechanical deformations. Based on the tunable electromechanical behavior, the hydrogels can act as a wearable strain sensor to monitor finger joint motions, breathing, and even the slight blood pulse. This strategy of building synergistic "soft and hard" structures is successful to integrate the decent mechanical properties, reliable self-healing capability, and high sensing sensitivity together for assembling a high-performance, flexible, and wearable strain sensor.

2D ratiometric fluorescent pH sensor for tracking of cells proliferation and metabolism.

PubMed

Ma, Jun; Ding, Changqin; Zhou, Jie; Tian, Yang

2015-08-15

Extracellular pH plays a vital role no matter in physiological or pathological studies. In this work, a hydrogel, CD@Nile-FITC@Gel (Gel sensor), entrapping the ratiometric fluorescent probe CD@Nile-FITC was developed. The Gel sensor was successfully used for real-time extracellular pH monitoring. In the case of CD@Nile-FITC, pH-sensitive fluorescent dye fluorescein isothiocyanate (FITC) was chosen as the response signal for H(+) and Nile blue chloride (Nile) as the reference signal. The developed fluorescent probe exhibited high selectivity for pH over other metal ions and amino acids. Meanwhile, the carbon-dots-based inorganic-organic probe demonstrated excellent photostability against long-term light illumination. In order to study the extracellular pH change in processes of cell proliferation and metabolism, CD@Nile-FITC probe was entrapped in sodium alginate gel and consequently formed CD@Nile-FITC@Gel. The MTT assay showed low cytotoxicity of the Gel and the pH titration indicated that it could monitor the pH fluctuations linearly and rapidly within the pH range of 6.0-9.0, which is valuable for physiological pH determination. As expected, the real-time bioimaging of the probe was successfully achieved. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of β-cyclodextrin-based hydrogel microparticles for solubility enhancement of rosuvastatin: an in vitro and in vivo evaluation

PubMed Central

Sarfraz, Rai Muhammad; Ahmad, Mahmood; Mahmood, Asif; Akram, Muhammad Rouf; Abrar, Asad

2017-01-01

The aim of this study was to enhance the solubility of rosuvastatin (RST) calcium by developing β-cyclodextrin-g-poly(2-acrylamido-2-methylpropane sulfonic acid [AMPS]) hydrogel microparticles through aqueous free-radical polymerization technique. Prepared hydrogel microparticles were characterized for percent entrapment efficiency, solubility studies, Fourier transform infrared spectroscopy, differential scanning calorimetry, thermal gravimetric analysis, powder X-ray diffraction, scanning electron microscopy, zeta size and potential, swelling and release studies. Formulations (HS1–HS9) have shown entrapment efficiency between 83.50%±0.30% and 88.50%±0.25%, and optimum release was offered by formulation HS7 at both pH levels, ie, 1.2 (89%) and 7.4 (92%). The majority of microparticles had a particle size of less than 500 µm and zeta potential of −37 mV. Similarly, optimum solubility, ie, 10.66-fold, was determined at pH 6.8 as compared to pure RST calcium, ie, 7.30-fold. In vivo studies on fabricated hydrogel microparticulate system in comparison to pure drug were carried out, and better results regarding pharmacokinetic parameters were seen in the case of hydrogel microparticles. A potential approach for solubility enhancement of RST calcium and other hydrophobic moieties was successfully developed. PMID:29123380

Revisiting structure-property relationship of pH-responsive polymers for drug delivery applications.

PubMed

Bazban-Shotorbani, Salime; Hasani-Sadrabadi, Mohammad Mahdi; Karkhaneh, Akbar; Serpooshan, Vahid; Jacob, Karl I; Moshaverinia, Alireza; Mahmoudi, Morteza

2017-05-10

pH-responsive polymers contain ionic functional groups as pendants in their structure. The total number of charged groups on polymer chains determines the overall response of the system to changes in the external pH. This article reviews various pH-responsive polymers classified as polyacids (e.g., carboxylic acid based polymers, sulfonamides, anionic polysaccharides, and anionic polypeptides) and polybases (e.g., polyamines, pyridine and imidazole containing polymers, cationic polysaccharides, and cationic polypeptides). We correlate the pH variations in the body at the organ level (e.g., gastrointestinal tract and vaginal environment), tissue level (e.g., cancerous and inflamed tissues), and cellular level (e.g., sub-cellular organelles), with the intrinsic properties of pH-responsive polymers. This knowledge could help to select more effective ('smart') polymeric systems based on the biological target. Considering the pH differences in the body, various drug delivery systems can be designed by utilizing smart biopolymeric compounds with the required pH-sensitivity. We also review the pharmaceutical application of pH-responsive polymeric carriers including hydrogels, polymer-drug conjugates, micelles, dendrimers, and polymersomes. © 2016.

In vivo eye surface residence determination by high-resolution scintigraphy of a novel ion-sensitive hydrogel based on gellan gum and kappa-carrageenan.

PubMed

Fernández-Ferreiro, Anxo; Silva-Rodríguez, Jesús; Otero-Espinar, Francisco Javier; González-Barcia, Miguel; Lamas, María Jesús; Ruibal, Alvaro; Luaces-Rodríguez, Andrea; Vieites-Prado, Alba; Lema, Isabel; Herranz, Michel; Gómez-Lado, Noemí; Blanco-Mendez, José; Gil-Martínez, María; Pardo, María; Moscoso, Alexis; Cortes, Julia; Sánchez-Martínez, María; Pardo-Montero, Juan; Aguiar, Pablo

2017-05-01

In last years, sensitive hydrogels have become a breakthrough in ophthalmic pharmaceutical technology aimed at developing new strategies to increase the residence time of active substances. In a previous paper, we qualitatively demonstrated the capacity of a new ion sensitive hydrogel to increase the residence time. Nevertheless, the clearance of the gel from the ocular surface was not quantifiable with the used methodology. The aim of the present work was to use a well-established approach based on scintigraphy to quantitatively estimate the residence time of the previously proposed hydrogel. The rat corneal residence time of a topic ophthalmic formulation containing gellan gum and kappa carragenan (0.82% w/v) labeled with 99m Tc-DTPA radiotracer was evaluated and compared with the residence of an aqueous solution. Ophthalmic safety studies such as eye irritation or passage through the cornea were also carried out. After 1.5h of contact, 77% of the hydrogel remained in the ocular surface, presenting kinetics of disappearance one-phase decay and a half time of 262min. We conclude that the novel ophthalmic hydrogel developed with kappa carrageenan and gellan gum remains for long periods of time on the corneal surface, presenting a drop that fits an exponential decay. Copyright © 2017 Elsevier B.V. All rights reserved.

Biodegradable Cellulose-based Hydrogels: Design and Applications

PubMed Central

Sannino, Alessandro; Demitri, Christian; Madaghiele, Marta

2009-01-01

Hydrogels are macromolecular networks able to absorb and release water solutions in a reversible manner, in response to specific environmental stimuli. Such stimuli-sensitive behaviour makes hydrogels appealing for the design of ‘smart’ devices, applicable in a variety of technological fields. In particular, in cases where either ecological or biocompatibility issues are concerned, the biodegradability of the hydrogel network, together with the control of the degradation rate, may provide additional value to the developed device. This review surveys the design and the applications of cellulose-based hydrogels, which are extensively investigated due to the large availability of cellulose in nature, the intrinsic degradability of cellulose and the smart behaviour displayed by some cellulose derivatives.

Mathematical Models for Controlled Drug Release Through pH-Responsive Polymeric Hydrogels.

PubMed

Manga, Ramya D; Jha, Prateek K

2017-02-01

Hydrogels consisting of weakly charged acidic/basic groups are ideal candidates for carriers in oral delivery, as they swell in response to pH changes in the gastrointestinal tract, resulting in drug entrapment at low pH conditions of the stomach and drug release at high pH conditions of the intestine. We have developed 1-dimensional mathematical models to study the drug release behavior through pH-responsive hydrogels. Models are developed for 3 different cases that vary in the level of rigor, which together can be applied to predict both in vitro (drug release from carrier) and in vivo (drug concentration in the plasma) behavior of hydrogel-drug formulations. A detailed study of the effect of hydrogel and drug characteristics and physiological conditions is performed to gain a fundamental insight into the drug release behavior, which may be useful in the design of pH-responsive drug carriers. Finally, we describe a successful application of these models to predict both in vitro and in vivo behavior of docetaxel-loaded micelle in a pH-responsive hydrogel, as reported in a recent experimental study. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Distributed sensor for water and pH measurements using fiber optics and swellable polymeric systems

NASA Astrophysics Data System (ADS)

Michie, W. C.; Culshaw, B.; McKenzie, I.; Konstantakis, M.; Graham, N. B.; Moran, C.; Santos, F.; Bergqvist, E.; Carlstrom, B.

1995-01-01

We report on the design, construction and test of a generic form of sensor for making distributed measurements of a range of chemical parameters. The technique combines optical time-domain reflectometry with chemically sensitive water-swellable polymers (hydrogels). Initial experiments have concentrated on demonstrating a distributed water detector; however, gels have been developed that enable this sensor to be

The structural, morphological and thermal properties of grafted pH-sensitive interpenetrating highly porous polymeric composites of sodium alginate/acrylic acid copolymers for controlled delivery of diclofenac potassium.

PubMed

Jalil, Aamir; Khan, Samiullah; Naeem, Fahad; Haider, Malik Suleman; Sarwar, Shoaib; Riaz, Amna; Ranjha, Nazar Muhammad

2017-01-01

In present investigation new formulations of Sodium Alginate/Acrylic acid hydrogels with high porous structure were synthesized by free radical polymerization technique for the controlled drug delivery of analgesic agent to colon. Many structural parameters like molecular weight between crosslinks ( M c ), crosslink density ( M r ), volume interaction parameter ( v 2, s ), Flory Huggins water interaction parameter and diffusion coefficient ( Q ) were calculated. Water uptake studies was conducted in different USP phosphate buffer solutions. All samples showed higher swelling ratio with increasing pH values because of ionization of carboxylic groups at higher pH values. Porosity and gel fraction of all the samples were calculated. New selected samples were loaded with the model drug (diclofenac potassium).The amount of drug loaded and released was determined and it was found that all the samples showed higher release of drug at higher pH values. Release of diclofenac potassium was found to be dependent on the ratio of sodium alginate/acrylic acid, EGDMA and pH of the medium. Experimental data was fitted to various model equations and corresponding parameters were calculated to study the release mechanism. The Structural, Morphological and Thermal Properties of interpenetrating hydrogels were studied by FTIR, XRD, DSC, and SEM.

Magnetic hyaluronate hydrogels: preparation and characterization

NASA Astrophysics Data System (ADS)

Tóth, Ildikó Y.; Veress, Gábor; Szekeres, Márta; Illés, Erzsébet; Tombácz, Etelka

2015-04-01

A novel soft way of hyaluronate (HyA) based magnetic hydrogel preparation was revealed. Magnetite nanoparticles (MNPs) were prepared by co-precipitation. Since the naked MNPs cannot be dispersed homogenously in HyA-gel, their surface was modified with natural and biocompatible chondroitin-sulfate-A (CSA) to obtain CSA-coated MNPs (CSA@MNPs). The aggregation state of MNPs and that loaded with increasing amount of CSA up to 1 mmol/g was measured by dynamic light scattering at pH~6. Only CSA@MNP with ≥0.2 mmol/g CSA content was suitable for magnetic HyA-gel preparation. Rheological studies showed that the presence of CSA@MNP with up to 2 g/L did not affect the hydrogel's rheological behavior significantly. The results suggest that the HyA-based magnetic hydrogels may be promising formulations for future biomedical applications, e.g. as intra-articular injections in the treatment of osteoarthritis.

Thin Hydrogel Films for Optical Biosensor Applications

PubMed Central

Mateescu, Anca; Wang, Yi; Dostalek, Jakub; Jonas, Ulrich

2012-01-01

Hydrogel materials consisting of water-swollen polymer networks exhibit a large number of specific properties highly attractive for a variety of optical biosensor applications. This properties profile embraces the aqueous swelling medium as the basis of biocompatibility, non-fouling behavior, and being not cell toxic, while providing high optical quality and transparency. The present review focuses on some of the most interesting aspects of surface-attached hydrogel films as active binding matrices in optical biosensors based on surface plasmon resonance and optical waveguide mode spectroscopy. In particular, the chemical nature, specific properties, and applications of such hydrogel surface architectures for highly sensitive affinity biosensors based on evanescent wave optics are discussed. The specific class of responsive hydrogel systems, which can change their physical state in response to externally applied stimuli, have found large interest as sophisticated materials that provide a complex behavior to hydrogel-based sensing devices. PMID:24957962

Application of a Dense Gas Technique for Sterilizing Soft Biomaterials

PubMed Central

Karajanagi, Sandeep S.; Yoganathan, Roshan; Mammucari, Raffaella; Park, Hyoungshin; Cox, Julian; Zeitels, Steven M.; Langer, Robert; Foster, Neil R.

2017-01-01

Sterilization of soft biomaterials such as hydrogels is challenging because existing methods such as gamma irradiation, steam sterilization, or ethylene oxide sterilization, while effective at achieving high sterility assurance levels (SAL), may compromise their physicochemical properties and biocompatibility. New methods that effectively sterilize soft biomaterials without compromising their properties are therefore required. In this report, a dense-carbon dioxide (CO2)-based technique was used to sterilize soft polyethylene glycol (PEG)-based hydrogels while retaining their structure and physicochemical properties. Conventional sterilization methods such as gamma irradiation and steam sterilization severely compromised the structure of the hydrogels. PEG hydrogels with high water content and low elastic shear modulus (a measure of stiffness) were deliberately inoculated with bacteria and spores and then subjected to dense CO2. The dense CO2-based methods effectively sterilized the hydrogels achieving a SAL of 10−7 without compromising the viscoelastic properties, pH, water-content, and structure of the gels. Furthermore, dense CO2-treated gels were biocompatible and non-toxic when implanted subcutaneously in ferrets. The application of novel dense CO2-based methods to sterilize soft biomaterials has implications in developing safe sterilization methods for soft biomedical implants such as dermal fillers and viscosupplements. PMID:21337339

Skin-Inspired Multifunctional Autonomic-Intrinsic Conductive Self-Healing Hydrogels with Pressure Sensitivity, Stretchability, and 3D Printability.

PubMed

Darabi, Mohammad Ali; Khosrozadeh, Ali; Mbeleck, Rene; Liu, Yuqing; Chang, Qiang; Jiang, Junzi; Cai, Jun; Wang, Quan; Luo, Gaoxing; Xing, Malcolm

2017-08-01

The advent of conductive self-healing (CSH) hydrogels, a class of novel materials mimicking human skin, may change the trajectory of the industrial process because of their potential applications in soft robots, biomimetic prostheses, and health-monitoring systems. Here, the development of a mechanically and electrically self-healing hydrogel based on physically and chemically cross-linked networks is reported. The autonomous intrinsic self-healing of the hydrogel is attained through dynamic ionic interactions between carboxylic groups of poly(acrylic acid) and ferric ions. A covalent cross-linking is used to support the mechanical structure of the hydrogel. Establishing a fair balance between the chemical and physical cross-linking networks together with the conductive nanostructure of polypyrrole networks leads to a double network hydrogel with bulk conductivity, mechanical and electrical self-healing properties (100% mechanical recovery in 2 min), ultrastretchability (1500%), and pressure sensitivity. The practical potential of CSH hydrogels is further revealed by their application in human motion detection and their 3D-printing performance. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel Hydrogels from Renewable Resources

NASA Astrophysics Data System (ADS)

Karaaslan, Muzafer Ahmet

2011-12-01

The cell wall of most plant biomass from forest and agricultural resources consists of three major polymers, cellulose, hemicellulose and lignin. Of these, hemicelluloses have gained increasing attention as sustainable raw materials. In the first part of this study, novel pH-sensitive semi-IPN hydrogels based on hemicelluloses and chitosan were prepared using glutaraldehyde as the crosslinking agent. The hemicellulose isolated from aspen was analyzed for sugar content by HPLC, and its molecular weight distribution was determined by high performance size exclusion chromatography. Results revealed that hemicellulose had a broad molecular weight distribution with a fair amount of polymeric units, together with xylose, arabinose and glucose. The effect of hemicellulose content on mechanical properties and swelling behavior of hydrogels were investigated. The semi-IPNs hydrogel structure was confirmed by FT-IR, X-ray study and ninhydrin assay method. X-ray analysis showed that higher hemicellulose contents yielded higher crystallinity. Mechanical properties were mainly dependent on the crosslink density and average molecular weight between crosslinks. Swelling ratios increased with increasing hemicellulose content and were high at low pH values due to repulsion between similarly charged groups. In vitro release study of a model drug showed that these semi-IPN hydrogels could be used for controlled drug delivery into gastric fluid. The aim of the second part of this study was to control the crosslink density and the mechanical properties of hemicellulose/chitosan semi-IPN hydrogels by changing the crosslinking sequence. It has been hypothesized that by performing the crosslinking step before introducing hemicellulose, covalent crosslinking of chitosan would not be hindered and therefore more and/or shorter crosslinks could be formed. Furthermore, additional secondary interactions and crystalline domains introduced through hemicellulose could be favorable in terms of mechanical stability of semi-IPN hydrogels. In this last section of this study, the natural affinity of hemicellulose to cellulose was utilized to coat cellulose whiskers with chemically modified hemicellulose isolated from wood fiber. Surface modified cellulose nanowhiskers were used to prepare nanocomposite hydrogels using free radical polymerization of 2-hydroxyethyl methacrylate (HEMA), a biocompatible monomer. The effect of morphology and concentration of the incorporated nanocrystals on the hydrogel network was related to the mechanical properties, viscoelastic behavior and swelling of the hydrogels.

Antagonistic Enzymes in a Biocatalytic pH Feedback System Program Autonomous DNA Hydrogel Life Cycles.

PubMed

Heinen, Laura; Heuser, Thomas; Steinschulte, Alexander; Walther, Andreas

2017-08-09

Enzymes regulate complex functions and active behavior in natural systems and have shown increasing prospect for developing self-regulating soft matter systems. Striving for advanced autonomous hydrogel materials with fully programmable, self-regulated life cycles, we combine two enzymes with an antagonistic pH-modulating effect in a feedback-controlled biocatalytic reaction network (BRN) and couple it to pH-responsive DNA hydrogels to realize hydrogel systems with distinct preprogrammable lag times and lifetimes in closed systems. The BRN enables precise and orthogonal internal temporal control of the "ON" and "OFF" switching times of the temporary gel state by modulation of programmable, nonlinear pH changes. The time scales are tunable by variation of the enzyme concentrations and additional buffer substances. The resulting material system operates in full autonomy after injection of the chemical fuels driving the BRN. The concept may open new applications inherent to DNA hydrogels, for instance, autonomous shape memory behavior for soft robotics. We further foresee general applicability to achieve autonomous life cycles in other pH switchable systems.

Preparation of the chitosan/poly(glutamic acid)/alginate polyelectrolyte complexing hydrogel and study on its drug releasing property.

PubMed

Chen, Yu; Yan, Xiaoting; Zhao, Jian; Feng, Huaiyu; Li, Puwang; Tong, Zongrui; Yang, Ziming; Li, Sidong; Yang, Jueying; Jin, Shaohua

2018-07-01

In the current study, a novel semi-dissolution/acidification/sol-gel transition (SD-A-SGT) method was explored for the preparation of polyelectrolyte complexing (PEC) composite hydrogels with natural polymers only. A chitosan (CS) powder was uniformly dispersed in a solution of poly(glutamic acid) (PGA) and alginate (SA) to form a semi-dissolved slurry mixture that was then exposed to an gaseous acidic atmosphere. CS was gradually dissolved and interacted with PGA and SA to form a CS/PGA/SA PEC composite hydrogel with a homogeneous structure. The SD-A-SGT procedure was able to overcome the shortcomings of direct mixing method via the PEC interaction. The effects of the hydrogel composition on its structure and properties were investigated by FTIR, XRD, rheology study, XPS, SEM, and swelling kinetics. The drug delivery performance of the CS/PGA/SA hydrogel was explored using piroxicam (PXC) as a model drug. PXC was in situ embedded in the hydrogel by the SD-A-SGT method. The hydrogel exhibited pH responsive drug release behaviors that were affected by the hydrogel composition. In all, the SD-A-SGT method for preparing PEC composite hydrogels has a great application potential in constructing the CS based hydrogels as medical materials. Copyright © 2018 Elsevier Ltd. All rights reserved.

Tumor Growth Suppression Induced by Biomimetic Silk Fibroin Hydrogels

NASA Astrophysics Data System (ADS)

Yan, Le-Ping; Silva-Correia, Joana; Ribeiro, Viviana P.; Miranda-Gonçalves, Vera; Correia, Cristina; da Silva Morais, Alain; Sousa, Rui A.; Reis, Rui M.; Oliveira, Ana L.; Oliveira, Joaquim M.; Reis, Rui L.

2016-08-01

Protein-based hydrogels with distinct conformations which enable encapsulation or differentiation of cells are of great interest in 3D cancer research models. Conformational changes may cause macroscopic shifts in the hydrogels, allowing for its use as biosensors and drug carriers. In depth knowledge on how 3D conformational changes in proteins may affect cell fate and tumor formation is required. Thus, this study reports an enzymatically crosslinked silk fibroin (SF) hydrogel system that can undergo intrinsic conformation changes from random coil to β-sheet conformation. In random coil status, the SF hydrogels are transparent, elastic, and present ionic strength and pH stimuli-responses. The random coil hydrogels become β-sheet conformation after 10 days in vitro incubation and 14 days in vivo subcutaneous implantation in rat. When encapsulated with ATDC-5 cells, the random coil SF hydrogel promotes cell survival up to 7 days, whereas the subsequent β-sheet transition induces cell apoptosis in vitro. HeLa cells are further incorporated in SF hydrogels and the constructs are investigated in vitro and in an in vivo chick chorioallantoic membrane model for tumor formation. In vivo, Angiogenesis and tumor formation are suppressed in SF hydrogels. Therefore, these hydrogels provide new insights for cancer research and uses of biomaterials.

Wound healing applications of sericin/chitosan-capped silver nanoparticles incorporated hydrogel.

PubMed

Verma, Jyoti; Kanoujia, Jovita; Parashar, Poonam; Tripathi, Chandra Bhusan; Saraf, Shubhini A

2017-02-01

Microbial contamination in wounds leading to severe sepsis can be treated by silver-based antiseptics. However, frequent application of silver-based antiseptics, staining of skin, burning, and irritation at application site resulted to poor patient compliances. Thus, we formulated sericin- and chitosan-capped silver nanoparticle (S/C-SNP)-loaded hydrogel for accelerated wound healing and antimicrobial properties. The wound healing property of sericin, antibacterial nature of chitosan and silver, and mucoadhesive property of carbopol were utilized in development of novel wound dressing hydrogel to investigate the combined effect of these materials for effective treatment of wounds. The chemical reduction method was successfully employed for the synthesis of SNPs using sericin and chitosan as a capping/reducing agent. The SNPs were characterized by ultraviolet-spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). The optimized SNPs were further used for preparation of carbopol hydrogel (0.5, 0.75, and 1.0 % w/v). The prepared hydrogels were characterized for pH, viscosity, and texture analysis. The antimicrobial activity and wound healing activity of the optimized hydrogel (S/C-SNPs G-1) demonstrated higher bactericidal activity and wound closure, as supported by results of histopathology. Hydrogel containing capped SNPs has application in wound healing treatment.

Enzyme-Regulated Fast Self-Healing of a Pillararene-Based Hydrogel.

PubMed

Zhang, Xin; Xu, Jiayun; Lang, Chao; Qiao, Shanpeng; An, Guo; Fan, Xiaotong; Zhao, Linlu; Hou, Chunxi; Liu, Junqiu

2017-06-12

Self-healing, one of the exciting properties of materials, is frequently used to repair the damage of biological and artificial systems. Here we have used enzymatic catalysis approaches to develop a fast self-healing hydrogel, which has been constructed by dynamic aldimine cross-linking of pillar[5]arene-derivant and dialdehyde-functionalized PEG followed by encapsulation of glucose oxidase (GOx) and catalase (CAT). In specific, the two hydroxyl groups at terminal of PEG 4000 are functionalized with benzaldehydes that can interact with amino-containing pillar[5]arene-derivant through dynamic aldimine cross-links, resulting in reversible dynamic hydrogels. Modulus analysis indicated that storage modulus (G') and loss modulus (G″) of the hydrogel increased obviously as the concentration of dialdehyde-functionalized PEG 4000 (DF-PEG 4000 ) increased or the pH values decreased. Once glucose oxidase (GOx) and catalase (CAT) are located, the hydrogel could be fast repaired, with self-healing efficiency up to 100%. Notably tensile test showed that the repair process of pillararene-based hydrogel can finish in several minutes upon enzyme catalysis, while it needed more than 24 h to achieve this recovery without enzymes. This enzyme-regulated self-healing hydrogel would hold promise for delivering drugs and for soft tissue regeneration in the future.

Water-soluble drug partitioning and adsorption in HEMA/MAA hydrogels.

PubMed

Dursch, Thomas J; Taylor, Nicole O; Liu, David E; Wu, Rong Y; Prausnitz, John M; Radke, Clayton J

2014-01-01

Two-photon confocal microscopy and back extraction with UV/Vis-absorption spectrophotometry quantify equilibrium partition coefficients, k, for six prototypical drugs in five soft-contact-lens-material hydrogels over a range of water contents from 40 to 92%. Partition coefficients were obtained for acetazolamide, caffeine, hydrocortisone, Oregon Green 488, sodium fluorescein, and theophylline in 2-hydroxyethyl methacrylate/methacrylic acid (HEMA/MAA, pKa≈5.2) copolymer hydrogels as functions of composition, aqueous pH (2 and 7.4), and salinity. At pH 2, the hydrogels are nonionic, whereas at pH 7.4, hydrogels are anionic due to MAA ionization. Solute adsorption on and nonspecific electrostatic interaction with the polymer matrix are pronounced. To express deviation from ideal partitioning, we define an enhancement or exclusion factor, E ≡ k/φ1, where φ1 is hydrogel water volume fraction. All solutes exhibit E > 1 in 100 wt % HEMA hydrogels owing to strong specific adsorption to HEMA strands. For all solutes, E significantly decreases upon incorporation of anionic MAA into the hydrogel due to lack of adsorption onto charged MAA moieties. For dianionic sodium fluorescein and Oregon Green 488, and partially ionized monoanionic acetazolamide at pH 7.4, however, the decrease in E is more severe than that for similar-sized nonionic solutes. Conversely, at pH 2, E generally increases with addition of the nonionic MAA copolymer due to strong preferential adsorption to the uncharged carboxylic-acid group of MAA. For all cases, we quantitatively predict enhancement factors for the six drugs using only independently obtained parameters. In dilute solution for solute i, Ei is conveniently expressed as a product of individual enhancement factors for size exclusion (Ei(ex)), electrostatic interaction (Ei(el)), and specific adsorption (Ei(ad)):Ei≡Ei(ex)Ei(el)Ei(ad). To obtain the individual enhancement factors, we employ an extended Ogston mesh-size distribution for Ei(ex); Donnan equilibrium for Ei(el); and Henry's law characterizing specific adsorption to the polymer chains for Ei(ad). Predicted enhancement factors are in excellent agreement with experiment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bioengineering vascularized tissue constructs using an injectable cell-laden enzymatically crosslinked collagen hydrogel derived from dermal extracellular matrix

PubMed Central

Kuo, Kuan-Chih; Lin, Ruei-Zeng; Tien, Han-Wen; Wu, Pei-Yun; Li, Yen-Cheng; Melero-Martin, Juan M.; Chen, Ying-Chieh

2015-01-01

Tissue engineering promises to restore or replace diseased or damaged tissue by creating functional and transplantable artificial tissues. The development of artificial tissues with large dimensions that exceed the diffusion limitation will require nutrients and oxygen to be delivered via perfusion instead of diffusion alone over a short time period. One approach to perfusion is to vascularize engineered tissues, creating a de novo three-dimensional (3D) microvascular network within the tissue construct. This significantly shortens the time of in vivo anastomosis, perfusion and graft integration with the host. In this study, we aimed to develop injectable allogeneic collagen-phenolic hydroxyl (collagen-Ph) hydrogels that are capable of controlling a wide range of physicochemical properties, including stiffness, water absorption and degradability. We tested whether collagen-Ph hydrogels could support the formation of vascularized engineered tissue graft by human blood-derived endothelial colony-forming cells (ECFCs) and bone marrow-derived mesenchymal stem cells (MSC) in vivo. First, we studied the growth of adherent ECFCs and MSCs on or in the hydrogels. To examine the potential formation of functional vascular networks in vivo, a liquid pre-polymer solution of collagen-Ph containing human ECFCs and MSCs, horseradish peroxidase and hydrogen peroxide was injected into the subcutaneous space or abdominal muscle defect of an immunodeficient mouse before gelation, to form a 3D cell-laden polymerized construct. These results showed that extensive human ECFC-lined vascular networks can be generated within 7 days, the engineered vascular density inside collagen-Ph hydrogel constructs can be manipulated through refinable mechanical properties and proteolytic degradability, and these networks can form functional anastomoses with the existing vasculature to further support the survival of host muscle tissues. Finally, optimized conditions of the cell-laden collagen-Ph hydrogel resulted in not only improving the long-term differentiation of transplanted MSCs into mineralized osteoblasts, but the collagen-Ph hydrogel also improved an increased of adipocytes within the vascularized bioengineered tissue in a mouse after 1 month of implantation. PMID:26348142

Kinetic research on dechlorinating dichlorobenzene in aqueous system by nano-scale nickel/iron loaded with CMC/NFC hydrogel.

PubMed

Wan, Xiao-Fang; Guo, Congbao; Liu, Yu; Chai, Xin-Sheng; Li, Youming; Chen, Guangxue

2018-03-01

In this study, we reported on the nano-scale nickel/iron particles loaded in carboxymethyl/nanofibrillated cellulose (CMC/NFC) hydrogel for the dechlorination of o-dichlorobenzene (DCB) in aqueous solution. The biodegradable hydrogel may provide an ideal supporting material for fastening the bimetallic nano-scale particles, which was examined and characterized by TEM, SEM-EDX, FT-IR and BET. The performance of the selected bimetallic particles was evaluated by conducting the dechlorination of DCB in the solution under different reaction conditions (e.g., pH, dosage of nickel/iron nanoparticles and temperature). The results showed that about 70% of DCB could be dechlorinated at 20 °C in 8 h, which indicated that the immobilized reactive material had a high reduction activity when Ni/Fe loading dosage in the hydrogel (18 wt%) was considered. Moreover, the reduction behavior agreed to the pseudo-first order reaction, in which the dechlorination rate was irrelative to the pH aqueous solution. A kinetic model for predicting the concentration of DCB during the reduction reaction was established based on the experimental data. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hydrogel microparticles for biosensing

PubMed Central

Le Goff, Gaelle C.; Srinivas, Rathi L.; Hill, W. Adam; Doyle, Patrick S.

2015-01-01

Due to their hydrophilic, biocompatible, and highly tunable nature, hydrogel materials have attracted strong interest in the recent years for numerous biotechnological applications. In particular, their solution-like environment and non-fouling nature in complex biological samples render hydrogels as ideal substrates for biosensing applications. Hydrogel coatings, and later, gel dot surface microarrays, were successfully used in sensitive nucleic acid assays and immunoassays. More recently, new microfabrication techniques for synthesizing encoded particles from hydrogel materials have enabled the development of hydrogel-based suspension arrays. Lithography processes and droplet-based microfluidic techniques enable generation of libraries of particles with unique spectral or graphical codes, for multiplexed sensing in biological samples. In this review, we discuss the key questions arising when designing hydrogel particles dedicated to biosensing. How can the hydrogel material be engineered in order to tune its properties and immobilize bioprobes inside? What are the strategies to fabricate and encode gel particles, and how can particles be processed and decoded after the assay? Finally, we review the bioassays reported so far in the literature that have used hydrogel particle arrays and give an outlook of further developments of the field. PMID:26594056

Nanomaterials for the cleaning and pH adjustment of vegetable-tanned leather

NASA Astrophysics Data System (ADS)

Baglioni, Michele; Bartoletti, Angelica; Bozec, Laurent; Chelazzi, David; Giorgi, Rodorico; Odlyha, Marianne; Pianorsi, Diletta; Poggi, Giovanna; Baglioni, Piero

2016-02-01

Leather artifacts in historical collections and archives are often contaminated by physical changes such as soiling, which alter their appearance and readability, and by chemical changes which occur on aging and give rise to excessive proportion of acids that promote hydrolysis of collagen, eventually leading to gelatinization and loss of mechanical properties. However, both cleaning and pH adjustment of vegetable-tanned leather pose a great challenge for conservators, owing to the sensitivity of these materials to the action of solvents, especially water-based formulations and alkaline chemicals. In this study, the cleaning of historical leather samples was optimized by confining an oil-in-water nanostructured fluid in a highly retentive chemical hydrogel, which allows the controlled release of the cleaning fluid on sensitive surfaces. The chemical gel exhibits optimal viscoelasticity, which facilitates its removal after the application without leaving residues on the object. Nanoparticles of calcium hydroxide and lactate, dispersed in 2-propanol, were used to adjust the pH up to the natural value of leather, preventing too high alkalinity which causes swelling of fibers and denaturation of the collagen. The treated samples were characterized using scanning electron microscopy, controlled environment dynamic mechanical analysis, and infrared spectroscopy. The analytical assessment validated the use of tools derived from colloid and materials science for the preservation of collagen-based artifacts.

Dual Cross-Linked Biofunctional and Self-Healing Networks to Generate User-Defined Modular Gradient Hydrogel Constructs.

PubMed

Wei, Zhao; Lewis, Daniel M; Xu, Yu; Gerecht, Sharon

2017-08-01

Gradient hydrogels have been developed to mimic the spatiotemporal differences of multiple gradient cues in tissues. Current approaches used to generate such hydrogels are restricted to a single gradient shape and distribution. Here, a hydrogel is designed that includes two chemical cross-linking networks, biofunctional, and self-healing networks, enabling the customizable formation of modular gradient hydrogel construct with various gradient distributions and flexible shapes. The biofunctional networks are formed via Michael addition between the acrylates of oxidized acrylated hyaluronic acid (OAHA) and the dithiol of matrix metalloproteinase (MMP)-sensitive cross-linker and RGD peptides. The self-healing networks are formed via dynamic Schiff base reaction between N-carboxyethyl chitosan (CEC) and OAHA, which drives the modular gradient units to self-heal into an integral modular gradient hydrogel. The CEC-OAHA-MMP hydrogel exhibits excellent flowability at 37 °C under shear stress, enabling its injection to generate gradient distributions and shapes. Furthermore, encapsulated sarcoma cells respond to the gradient cues of RGD peptides and MMP-sensitive cross-linkers in the hydrogel. With these superior properties, the dual cross-linked CEC-OAHA-MMP hydrogel holds significant potential for generating customizable gradient hydrogel constructs, to study and guide cellular responses to their microenvironment such as in tumor mimicking, tissue engineering, and stem cell differentiation and morphogenesis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

ADVANCED MOLECULAR DESIGN OF BIOPOLYMERS FOR TRANSMUCOSAL AND INTRACELLULAR DELIVERY OF CHEMOTHERAPEUTIC AGENTS AND BIOLOGICAL THERAPEUTICS

PubMed Central

Liechty, William B.; Caldorera-Moore, Mary; Phillips, Margaret A.; Schoener, Cody; Peppas, Nicholas A.

2011-01-01

Hydrogels have been instrumental in the development of polymeric systems for controlled release of therapeutic agents. These materials are attractive for transmucosal and intracellular drug delivery because of their facile synthesis, inherent biocompatibility, tunable physicochemical properties, and capacity to respond to various physiological stimuli. In this contribution, we outline a multifaceted hydrogel-based approach for expanding the range of therapeutics in oral formulations from classical small-molecule drugs to include proteins, chemotherapeutics, and nucleic acids. Through judicious materials selection and careful design of copolymer composition and molecular architecture, we can engineer systems capable of responding to distinct physiological cues, with tunable physicochemical properties that are optimized to load, protect, and deliver valuable macromolecular payloads to their intended site of action. These hydrogel carriers, including complexation hydrogels, tethered hydrogels, interpenetrating networks, nanoscale hydrogels, and hydrogels with decorated structures are investigated for their ability respond to changes in pH, to load and release insulin and fluorescein, and remain non-toxic to Caco-2 cells. Our results suggest these novel hydrogel networks have great potential for controlled delivery of proteins, chemotherapeutics, and nucleic acids. PMID:21699934

Programmable and Bidirectional Bending of Soft Actuators Based on Janus Structure with Sticky Tough PAA-Clay Hydrogel.

PubMed

Zhao, Lei; Huang, Jiahe; Zhang, Yuancheng; Wang, Tao; Sun, Weixiang; Tong, Zhen

2017-04-05

Facile preparation, rapid actuating, and versatile actions are great challenges in exploring new kinds of hydrogel actuators. In this paper, we presented a facile sticking method to prepare Janus bilayer and multilayer hydrogel actuators that benefited from a special tough and adhesive PAA-clay hydrogel. Combining physical and chemical cross-linking reagents, we endowed the PAA gel with both toughness and adhesion. This PAA gel was reinforced by further cross-linking with Fe 3+ . These two hydrogels with different cross-linking densities exhibited different swelling capabilities and moduli in the media manipulated by pH and ionic strength, thus acting as promising candidates for soft actuators. On the basis of these gels, we designed hydrogel actuators of rapid response in several minutes and precisely controlled actuating direction by sticking two hydrogel layers together. Elaborate soft actuators such as bidirectional bending flytrap, gel hand with grasp, open, and gesturing actions as well as word-writing actuator were prepared. This method could be generalized by using other stimuli-responsive hydrogels combined with the adhesive PAA gel, which would open a new way to programmable and versatile soft actuators.

Bromelain Loading and Release from a Hydrogel Formulated Using Alginate and Arabic Gum.

PubMed

Ataide, Janaína Artem; Cefali, Letícia Caramori; Rebelo, Marcia de Araujo; Spir, Lívia Genovez; Tambourgi, Elias Basile; Jozala, Angela Faustino; Chaud, Marco Vinícius; Silveira, Edgar; Gu, Xiaochen; Gava Mazzola, Priscila

2017-07-01

An ideal wound dressing ensures a moist environment around the wound area and absorbs exudates from the wound surface. Topical application of bromelain to incised wounds has been shown to reprogram the wound microenvironment to promote effective tissue repair. Combining the characteristics of hydrogels and bromelain is therefore of great interest. Herein, we describe the development of a hydrogel, formulated using alginate and Arabic gum, for bromelain loading and release. The hydrogel formulation was evaluated using response surface methodology, considering the pH value and the concentration of alginate and Arabic gum. Bromelain loading and release were evaluated based on passive diffusion. Differential scanning calorimetry and Fourier transform infrared spectroscopy were performed to confirm bromelain immobilization in the hydrogel. The final hydrogel formulation had a swelling ratio of 227 % and incorporated 19 % of bromelain from a bromelain solution. Bromelain immobilization in the hydrogel was the result of hydrogen bond formation and was optimal at 4 °C after 4 h of contact. This evidence suggests that bromelain entrapment into a hydrogel is a promising strategy for the development of wound dressings that support the debridement of burns and wounds. Georg Thieme Verlag KG Stuttgart · New York.

Hydrogel Actuation by Electric Field Driven Effects

NASA Astrophysics Data System (ADS)

Morales, Daniel Humphrey

Hydrogels are networks of crosslinked, hydrophilic polymers capable of absorbing and releasing large amounts of water while maintaining their structural integrity. Polyelectrolyte hydrogels are a subset of hydrogels that contain ionizable moieties, which render the network sensitive to the pH and the ionic strength of the media and provide mobile counterions, which impart conductivity. These networks are part of a class of "smart" material systems that can sense and adjust their shape in response to the external environment. Hence, the ability to program and modulate hydrogel shape change has great potential for novel biomaterial and soft robotics applications. We utilized electric field driven effects to manipulate the interaction of ions within polyelectrolyte hydrogels in order to induce controlled deformation and patterning. Additionally, electric fields can be used to promote the interactions of separate gel networks, as modular components, and particle assemblies within gel networks to develop new types of soft composite systems. First, we present and analyze a walking gel actuator comprised of cationic and anionic gel legs attached by electric field-promoted polyion complexation. We characterize the electro-osmotic response of the hydrogels as a function of charge density and external salt concentration. The gel walkers achieve unidirectional motion on flat elastomer substrates and exemplify a simple way to move and manipulate soft matter devices in aqueous solutions. An 'ionoprinting' technique is presented with the capability to topographically structure and actuate hydrated gels in two and three dimensions by locally patterning ions induced by electric fields. The bound charges change the local mechanical properties of the gel to induce relief patterns and evoke localized stress, causing rapid folding in air. The ionically patterned hydrogels exhibit programmable temporal and spatial shape transitions which can be tuned by the duration and/or strength of the applied electric field. We extend the use of ionoprinting to develop multi-responsive bilayer gel systems capable of more complex shape transformation. The localized crosslinked regions determine the bending axis as the gel responds to the external environment. The bending can be tuned to reverse direction isothermally by changing the solvent quality or by changing the temperature at a fixed concentration. The multi-responsive behavior is caused by the volume transitions of a non-ionic, thermos-sensitive hydrogel coupled with a superabsorbent ionic hydrogel. Lastly, electric field driven microparticle assembly, using dielectrophoretic (DEP) forces, organized colloidal microparticles within a hydrogel matrix. The use of DEP forces enables rapid, efficient and precise control over the colloidal distribution. The resulting supracolloidal endoskeleton structures impart directional bending as the hydrogel shrinks. We compare the ordered particles structures to random particle distributions in affecting the hydrogel sheet bending response. This study demonstrates a universal technique for imparting directional properties in hydrogels towards new generations of hybrid soft materials.

Rapid enrichment of rare-earth metals by carboxymethyl cellulose-based open-cellular hydrogel adsorbent from HIPEs template.

PubMed

Zhu, Yongfeng; Wang, Wenbo; Zheng, Yian; Wang, Feng; Wang, Aiqin

2016-04-20

A series of monolithic open-cellular hydrogel adsorbents based on carboxymethylcellulose (CMC) were prepared through high internal phase emulsions (HIPEs) and used to enrich the rare-earth metals La(3+) and Ce(3+). The changes of pore structure, and the effects of pH, contact time, initial concentration on the adsorption performance were systematically studied. The results show that the as-prepared monolithic hydrogel adsorbents possess good open-cellular framework structure and have fast adsorption kinetics and high adsorption capacity for La(3+) and Ce(3+). The involved adsorption system can reach equilibrium within 30min and the maximal adsorption capacity is determined to be 384.62mg/g for La(3+) and 333.33mg/g for Ce(3+). Moreover, these porous hydrogel adsorbents show an excellent adsorptive reusability for La(3+) and Ce(3+) through five adsorption-desorption cycles. Such a pore hierarchy structure makes this monolithic open-cellular hydrogel adsorbent be an effective adsorbent for effective enrichment of La(3+) and Ce(3+) from aqueous solution. Copyright © 2015 Elsevier Ltd. All rights reserved.

A dipeptide-based superhydrogel: Removal of toxic dyes and heavy metal ions from waste water.

PubMed

Nandi, Nibedita; Baral, Abhishek; Basu, Kingshuk; Roy, Subhasish; Banerjee, Arindam

2017-01-01

A short peptide-based molecule has been found to form a strong hydrogel at phosphate buffer solution of pH 7.46. The hydrogel has been characterized thoroughly using various techniques including field emission scanning electron microscopy (FE-SEM), wide angle powder X-ray diffraction (PXRD), and rheological analysis. It has been observed from FE-SEM images that entangled nanofiber network is responsible for gelation. Rheological investigation demonstrates that the self-assembly of this synthetic dipeptide results in the formation of mechanically strong hydrogel with storage modulus (G') around 10 4 Pa. This gel has been used for removing both cationic and anionic toxic organic dyes (Brilliant Blue, Congo red, Malachite Green, Rhodamine B) and metal ions (Co 2+ and Ni 2+ ) from waste water. Moreover, only a small amount of the gelator is required (less than 1 mg/mL) for preparation of this superhydrogel and even this hydrogel can be reused three times for dye/metal ion absorption. This signifies the importance of the hydrogel towards waste water management. © 2016 Wiley Periodicals, Inc.

Carbon Nanotubes Reinforced Maleic Anhydride-Modified Xylan-g-Poly(N-isopropylacrylamide) Hydrogel with Multifunctional Properties

PubMed Central

Liu, Xinxin; Song, Tao; Chang, Minmin; Meng, Ling; Wang, Xiaohui; Sun, Runcang; Ren, Junli

2018-01-01

Introducing multifunctional groups and inorganic material imparts xylan-based hydrogels with excellent properties, such as responsiveness to pH, temperature, light, and external magnetic field. In this work, a composite hydrogel was synthesized by introducing acid treated carbon nanotubes (AT-CNTs) into the maleic anhydride modified xylan grafted with poly(N-isopropylacrylamide) (MAX-g-PNIPAM) hydrogels network. It was found that the addition of AT-CNTs affected the MAX-g-PNIPAM hydrogel structure, the swelling ratio and mechanical properties, and imparted the hydrogel with new properties of electrical conductivity and near infrared region (NIR) photothermal conversion. AT-CNTs could reinforce the mechanical properties of MAX-g-PNIPAM hydrogels, being up to 83 kPa for the compressive strength when the amount was 11 wt %, which was eight times than that of PNIPAM hydrogel and four times than that of MAX-g-PNIPAM hydrogel. The electroconductibility was enhanced by the increase of AT-CNTs amounts. Meanwhile, the composite hydrogel also exhibited multiple shape memory and NIR photothermal conversion properties, and water temperature was increased from 26 °C to 56 °C within 8 min under the NIR irradiation. Thus, the AT-CNTs reinforced MAX-g-PNIPAM hydrogel possessed promising multifunctional properties, which offered many potential applications in the fields of biosensors, thermal-arrest technology, and drug-controlled release. PMID:29495611

Carbon Nanotubes Reinforced Maleic Anhydride-Modified Xylan-g-Poly(N-isopropylacrylamide) Hydrogel with Multifunctional Properties.

PubMed

Liu, Xinxin; Song, Tao; Chang, Minmin; Meng, Ling; Wang, Xiaohui; Sun, Runcang; Ren, Junli

2018-02-28

Introducing multifunctional groups and inorganic material imparts xylan-based hydrogels with excellent properties, such as responsiveness to pH, temperature, light, and external magnetic field. In this work, a composite hydrogel was synthesized by introducing acid treated carbon nanotubes (AT-CNTs) into the maleic anhydride modified xylan grafted with poly(N-isopropylacrylamide) (MAX-g-PNIPAM) hydrogels network. It was found that the addition of AT-CNTs affected the MAX-g-PNIPAM hydrogel structure, the swelling ratio and mechanical properties, and imparted the hydrogel with new properties of electrical conductivity and near infrared region (NIR) photothermal conversion. AT-CNTs could reinforce the mechanical properties of MAX-g-PNIPAM hydrogels, being up to 83 kPa for the compressive strength when the amount was 11 wt %, which was eight times than that of PNIPAM hydrogel and four times than that of MAX-g-PNIPAM hydrogel. The electroconductibility was enhanced by the increase of AT-CNTs amounts. Meanwhile, the composite hydrogel also exhibited multiple shape memory and NIR photothermal conversion properties, and water temperature was increased from 26 °C to 56 °C within 8 min under the NIR irradiation. Thus, the AT-CNTs reinforced MAX-g-PNIPAM hydrogel possessed promising multifunctional properties, which offered many potential applications in the fields of biosensors, thermal-arrest technology, and drug-controlled release.

Functional Self-Assembling Peptide Nanofiber Hydrogels Designed for Nerve Degeneration.

PubMed

Sun, Yuqiao; Li, Wen; Wu, Xiaoli; Zhang, Na; Zhang, Yongnu; Ouyang, Songying; Song, Xiyong; Fang, Xinyu; Seeram, Ramakrishna; Xue, Wei; He, Liumin; Wu, Wutian

2016-01-27

Self-assembling peptide (SAP) RADA16-I (Ac-(RADA)4-CONH2) has been suffering from a main drawback associated with low pH, which damages cells and host tissues upon direct exposure. In this study, we presented a strategy to prepare nanofiber hydrogels from two designer SAPs at neutral pH. RADA16-I was appended with functional motifs containing cell adhesion peptide RGD and neurite outgrowth peptide IKVAV. The two SAPs were specially designed to have opposite net charges at neutral pH, the combination of which created a nanofiber hydrogel (-IKVAV/-RGD) characterized by significantly higher G' than G″ in a viscoelasticity examination. Circular dichroism, Fourier transform infrared spectroscopy, and Raman measurements were performed to investigate the secondary structure of the designer SAPs, indicating that both the hydrophobic/hydrophilic properties and electrostatic interactions of the functional motifs play an important role in the self-assembling behavior of the designer SAPs. The neural progenitor cells (NPCs)/stem cells (NSCs) fully embedded in the 3D-IKVAV/-RGD nanofiber hydrogel survived, whereas those embedded within the RADA 16-I hydrogel hardly survived. Moreover, the -IKVAV/-RGD nanofiber hydrogel supported NPC/NSC neuron and astrocyte differentiation in a 3D environment without adding extra growth factors. Studies of three nerve injury models, including sciatic nerve defect, intracerebral hemorrhage, and spinal cord transection, indicated that the designer -IKVAV/-RGD nanofiber hydrogel provided a more permissive environment for nerve regeneration than the RADA 16-I hydrogel. Therefore, we reported a new mechanism that might be beneficial for the synthesis of SAPs for in vitro 3D cell culture and nerve regeneration.

Design and synthesis of an amphiphilic graft hydrogel having a hydrophobic domain formed by multiple interactions.

PubMed

Nitta, Kyohei; Kimoto, Atsushi; Watanabe, Junji

2016-11-01

A novel hydrogel having hydrophobic oligo segments and hydrophilic poly(acrylamidoglycolic acid) (PAGA) as pH responsive polymer segments was designed and synthesized to be used as a soft biomaterial. Poly(trimethylene carbonate) (PTMC) as the side chain, for which the degrees of polymerization were 9, 19, and 49, and the composition ratios were 1, 5, and 10mol%, was used as the oligo segment in the hydrogel. The swelling ratio of the hydrogel was investigated under various changes in conditions such as pH, temperature, and hydrogen bonding upon urea addition. Under pH2-11 conditions, the graft gel reversibly swelled and shrank due to the effect of PAGA main chain. The interior morphology and skin layer of the hydrogel was observed by a scanning electron microscope. The hydrogel composed of PAGA as the hydrophilic polymer backbone had a sponge-like structure, with a pore size of approximately 100μm. On the other hand, upon increasing the ratio of trimethylene carbonate (TMC) units in the hydrogel, the pores became smaller or disappeared. Moreover, thickness of the skin layer significantly increased with the swelling ratio depended on the incorporation ratios of the PTMC macromonomer. Molecular incorporation in the hydrogel was evaluated using a dye as a model drug molecule. These features would play an important role in drug loading. Increasing the ratio of TMC units favored the adsorption of the dye and activation of the incorporation behavior. Copyright © 2016 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahmud, Maznah; Radiation Processing Technology Division, Malaysian Nuclear Agency, 43000 Kajang, Selangor; Daik, Rusli

Poly(vinylpyrrolidone) (PVP)-crosslinked chitosan hydrogels were prepared by gamma radiation at various doses; 1, 3 5, 7, 10, 15, 20, 25 and 30kGy. Gamma radiation was used as a crosslinking tool which requires no chemical initiator, no heating process and need no purification step on the end products obtained. The hydrogel formulations were composed of 6% chitosan with average molecular weight (Mw) = 48 800 g/mol and 14% PVP with Mw = 10 000 g/mol in 2% lactic acid. Physical properties of hydrogels such as gel fraction and swelling property at pH 5.5 and pH 7.0 as well as syneresis activitymore » were determined. It was found that different radiation dose induces different effect on hydrogels’ network formed. Morphological study of hydrogels has been carried out by scanning electron microscope (SEM). From these preliminary evaluations, it can be concluded that gamma radiation is an effective tool for network development of hydrogels and it also induces enhancement on characteristics of hydrogels synthesized.« less

Preparation of CMC-g-P(SPMA) super adsorbent hydrogels: Exploring their capacity for MB removal from waste water.

PubMed

Salama, Ahmed

2018-01-01

A novel superadsorbent anionic hydrogel was synthesized by grafting of poly (3-sulfopropyl methacrylate), P(SPMA), onto carboxymethyl cellulose (CMC). CMC-g-P(SPMA) superadsorbent hydrogel was applied as an efficient and sustainable adsorbent to remove methylene blue (MB) from waste water. Batch adsorption experiments showed that the solution pH had an obvious effect on the adsorption capacity with an optimal sorption pH at 6. The CMC-g-P(SPMA) hydrogel had rapid adsorption kinetics for MB and the adsorption equilibrium reached within 40min. The adsorption kinetics were more accurately described by pseudo second-order model and the Langmuir-fitted adsorption isotherms revealed a maximum capacity of 1675mg/g. The current anionic hydrogel is reusable as the adsorption capacity remained at 89% level after five adsorption-desorption cycles. CMC-g-P(SPMA) hydrogel was presented as a sustainable promising adsorbent with high adsorption capacity and good regenerability for effective cationic dyes removal. Copyright © 2017 Elsevier B.V. All rights reserved.

Cell-specific and pH-sensitive nanostructure hydrogel based on chitosan as a photosensitizer carrier for selective photodynamic therapy.

PubMed

Belali, Simin; Karimi, Ali Reza; Hadizadeh, Mahnaz

2018-04-15

The major problems of porphyrins as promising materials for photodynamic therapy (PDT) are their low solubility, subsequently aggregation in biological environments, and a lack of tumor selectivity. With this in mind, a chitosan-based hydrogel conjugated with tetrakis(4-aminophenyl)porphyrin (NH 2 -TPP) and 2,4,6-tris(p-formylphenoxy)-1,3,5-triazine (TRIPOD) via Schiff base linkage, functionalized with folate was designed and synthesized as a pH-sensitive, self-healable and injectable targeted PS delivery system. This new hydrogel was characterized by FT-IR, 1 H NMR, SEM, UV-vis, fluorescence spectroscopy and zeta potential. Formation of imine bonds with the aldehyde group of TRIPOD and amine group of NH 2 -TPP and chitosan, as a dynamic connection, was approved by rheological analysis. Spectroscopic characterizations revealed that aggregation of porphyrin in aqueous media was eliminated due to diminished π stacking interaction of porphyrin in 3D cross-linked hydrogel structure. Hydrogel 3D microporous structure efficiently transfers the excitation energy to the porphyrin unit, yielding improvement singlet oxygen releases. Cytotoxicity and phototoxicity analysis of the CS/NH 2 -TPP/FA hydrogels indicating an excellent capability to kill cancer cells selectively and prevent damage to normal cells. This work presents a new and efficient model for the preparation of highly efficient and targeting photosensitizer delivery system. Copyright © 2018. Published by Elsevier B.V.

Establishing contact between cell-laden hydrogels and metallic implants with a biomimetic adhesive for cell therapy supported implants.

PubMed

Barthes, Julien; Mutschler, Angela; Dollinger, Camille; Gaudinat, Guillaume; Lavalle, Philippe; Le Houerou, Vincent; Brian McGuinness, Garrett; Engin Vrana, Nihal

2017-12-15

For in-dwelling implants, controlling the biological interface is a crucial parameter to promote tissue integration and prevent implant failure. For this purpose, one possibility is to facilitate the establishment of the interface with cell-laden hydrogels fixed to the implant. However, for proper functioning, the stability of the hydrogel on the implant should be ensured. Modification of implant surfaces with an adhesive represents a promising strategy to promote the adhesion of a cell-laden hydrogel on an implant. Herein, we developed a peptidic adhesive based on mussel foot protein (L-DOPA-L-lysine) 2 -L-DOPA that can be applied directly on the surface of an implant. At physiological pH, unoxidized (L-DOPA-L-lysine) 2 -L-DOPA was supposed to strongly adhere to metallic surfaces but it only formed a very thin coating (less than 1 nm). Once oxidized at physiological pH, (L-DOPA-L-lysine) 2 -L-DOPA forms an adhesive coating about 20 nm thick. In oxidized conditions, L-lysine can adhere to metallic substrates via electrostatic interaction. Oxidized L-DOPA allows the formation of a coating through self-polymerization and can react with amines so that this adhesive can be used to fix extra-cellular matrix based materials on implant surfaces through the reaction of quinones with amino groups. Hence, a stable interface between a soft gelatin hydrogel and metallic surfaces was achieved and the strength of adhesion was investigated. We have shown that the adhesive is non-cytotoxic to encapsulated cells and enabled the adhesion of gelatin soft hydrogels for 21 days on metallic substrates in liquid conditions. The adhesion properties of this anchoring peptide was quantified by a 180° peeling test with a more than 60% increase in peel strength in the presence of the adhesive. We demonstrated that by using a biomimetic adhesive, for the application of cell-laden hydrogels to metallic implant surfaces, the hydrogel/implant interface can be ensured without relying on the properties of the deposited biomaterials.

An ultrasensitive method of real time pH monitoring with complementary metal oxide semiconductor image sensor.

PubMed

Devadhasan, Jasmine Pramila; Kim, Sanghyo

2015-02-09

CMOS sensors are becoming a powerful tool in the biological and chemical field. In this work, we introduce a new approach on quantifying various pH solutions with a CMOS image sensor. The CMOS image sensor based pH measurement produces high-accuracy analysis, making it a truly portable and user friendly system. pH indicator blended hydrogel matrix was fabricated as a thin film to the accurate color development. A distinct color change of red, green and blue (RGB) develops in the hydrogel film by applying various pH solutions (pH 1-14). The semi-quantitative pH evolution was acquired by visual read out. Further, CMOS image sensor absorbs the RGB color intensity of the film and hue value converted into digital numbers with the aid of an analog-to-digital converter (ADC) to determine the pH ranges of solutions. Chromaticity diagram and Euclidean distance represent the RGB color space and differentiation of pH ranges, respectively. This technique is applicable to sense the various toxic chemicals and chemical vapors by situ sensing. Ultimately, the entire approach can be integrated into smartphone and operable with the user friendly manner. Copyright © 2014 Elsevier B.V. All rights reserved.

Reversible Polymer Hydrogels

DTIC Science & Technology

2008-12-01

glucosamine hydrochloride was dissolved in 100 mL of de- ionized water and placed in an ice bath at >5oC and purged with N2 gas for 20 minutes; 3.25...Temperature sensitive hydrogels based on N-isopropyl acrylamide (NIPA) and acryloyl glucosamine (AG) were synthesized using ammonium persulfate (APS) as...hydrogels by copolymerization of poly (N-isopropylacrylamide) (NIPA), and acryloyl glucosamine (AG) a derivative of chi- tosan, a biopolymer from

Lysozyme adsorption in pH-responsive hydrogel thin-films: the non-trivial role of acid-base equilibrium.

PubMed

Narambuena, Claudio F; Longo, Gabriel S; Szleifer, Igal

2015-09-07

We develop and apply a molecular theory to study the adsorption of lysozyme on weak polyacid hydrogel films. The theory explicitly accounts for the conformation of the network, the structure of the proteins, the size and shape of all the molecular species, their interactions as well as the chemical equilibrium of each titratable unit of both the protein and the polymer network. The driving forces for adsorption are the electrostatic attractions between the negatively charged network and the positively charged protein. The adsorption is a non-monotonic function of the solution pH, with a maximum in the region between pH 8 and 9 depending on the salt concentration of the solution. The non-monotonic adsorption is the result of increasing negative charge of the network with pH, while the positive charge of the protein decreases. At low pH the network is roughly electroneutral, while at sufficiently high pH the protein is negatively charged. Upon adsorption, the acid-base equilibrium of the different amino acids of the protein shifts in a nontrivial fashion that depends critically on the particular kind of residue and solution composition. Thus, the proteins regulate their charge and enhance adsorption under a wide range of conditions. In particular, adsorption is predicted above the protein isoelectric point where both the solution lysozyme and the polymer network are negatively charged. This behavior occurs because the pH in the interior of the gel is significantly lower than that in the bulk solution and it is also regulated by the adsorption of the protein in order to optimize protein-gel interactions. Under high pH conditions we predict that the protein changes its charge from negative in the solution to positive within the gel. The change occurs within a few nanometers at the interface of the hydrogel film. Our predictions show the non-trivial interplay between acid-base equilibrium, physical interactions and molecular organization under nanoconfined conditions, which leads to non-trivial adsorption behavior that is qualitatively different from what would be predicted from the state of the proteins in the bulk solution.

Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery

NASA Astrophysics Data System (ADS)

Hou, Lin; Shi, Yuyang; Jiang, Guixiang; Liu, Wei; Han, Huili; Feng, Qianhua; Ren, Junxiao; Yuan, Yujie; Wang, Yongchao; Shi, Jinjin; Zhang, Zhenzhong

2016-08-01

A safe and efficient nanocomposite hydrogel for colon cancer drug delivery was synthesized using pH-sensitive and biocompatible graphene oxide (GO) containing azoaromatic crosslinks as well as poly (vinyl alcohol) (PVA) (GO-N=N-GO/PVA composite hydrogels). Curcumin (CUR), an anti-cancer drug, was encapsulated successfully into the hydrogel through a freezing and thawing process. Fourier transform infrared spectroscopy, scanning electron microscopy and Raman spectroscopy were performed to confirm the formation and morphological properties of the nanocomposite hydrogel. The hydrogels exhibited good swelling properties in a pH-sensitive manner. Drug release studies under conditions mimicking stomach to colon transit have shown that the drug was protected from being released completely into the physiological environment of the stomach and small intestine. In vivo imaging analysis, pharmacokinetics and a distribution of the gastrointestinal tract experiment were systematically studied and evaluated as colon-specific drug delivery systems. All the results demonstrated that GO-N=N-GO/PVA composite hydrogels could protect CUR well while passing through the stomach and small intestine to the proximal colon, and enhance the colon-targeting ability and residence time in the colon site. Therefore, CUR loaded GO-N=N-GO/PVA composite hydrogels might potentially provide a theoretical basis for the treatment of colon cancer with high efficiency and low toxicity.

Peptide hydrogelation and cell encapsulation for 3D culture of MCF-7 breast cancer cells.

PubMed

Huang, Hongzhou; Ding, Ying; Sun, Xiuzhi S; Nguyen, Thu A

2013-01-01

Three-dimensional (3D) cell culture plays an invaluable role in tumor biology by providing in vivo like microenviroment and responses to therapeutic agents. Among many established 3D scaffolds, hydrogels demonstrate a distinct property as matrics for 3D cell culture. Most of the existing pre-gel solutions are limited under physiological conditions such as undesirable pH or temperature. Here, we report a peptide hydrogel that shows superior physiological properties as an in vitro matrix for 3D cell culture. The 3D matrix can be accomplished by mixing a self-assembling peptide directly with a cell culture medium without any pH or temperature adjustment. Results of dynamic rheological studies showed that this hydrogel can be delivered multiple times via pipetting without permanently destroying the hydrogel architecture, indicating the deformability and remodeling ability of the hydrogel. Human epithelial cancer cells, MCF-7, are encapsulated homogeneously in the hydrogel matrix during hydrogelation. Compared with two-dimensional (2D) monolayer culture, cells residing in the hydrogel matrix grow as tumor-like clusters in 3D formation. Relevant parameters related to cell morphology, survival, proliferation, and apoptosis were analyzed using MCF-7 cells in 3D hydrogels. Interestingly, treatment of cisplatin, an anti-cancer drug, can cause a significant decrease of cell viability of MCF-7 clusters in hydrogels. The responses to cisplatin were dose- and time-dependent, indicating the potential usage of hydrogels for drug testing. Results of confocal microscopy and Western blotting showed that cells isolated from hydrogels are suitable for downstream proteomic analysis. The results provided evidence that this peptide hydrogel is a promising 3D cell culture material for drug testing.

Peptide Hydrogelation and Cell Encapsulation for 3D Culture of MCF-7 Breast Cancer Cells

PubMed Central

Sun, Xiuzhi S.; Nguyen, Thu A.

2013-01-01

Three-dimensional (3D) cell culture plays an invaluable role in tumor biology by providing in vivo like microenviroment and responses to therapeutic agents. Among many established 3D scaffolds, hydrogels demonstrate a distinct property as matrics for 3D cell culture. Most of the existing pre-gel solutions are limited under physiological conditions such as undesirable pH or temperature. Here, we report a peptide hydrogel that shows superior physiological properties as an in vitro matrix for 3D cell culture. The 3D matrix can be accomplished by mixing a self-assembling peptide directly with a cell culture medium without any pH or temperature adjustment. Results of dynamic rheological studies showed that this hydrogel can be delivered multiple times via pipetting without permanently destroying the hydrogel architecture, indicating the deformability and remodeling ability of the hydrogel. Human epithelial cancer cells, MCF-7, are encapsulated homogeneously in the hydrogel matrix during hydrogelation. Compared with two-dimensional (2D) monolayer culture, cells residing in the hydrogel matrix grow as tumor-like clusters in 3D formation. Relevant parameters related to cell morphology, survival, proliferation, and apoptosis were analyzed using MCF-7 cells in 3D hydrogels. Interestingly, treatment of cisplatin, an anti-cancer drug, can cause a significant decrease of cell viability of MCF-7 clusters in hydrogels. The responses to cisplatin were dose- and time-dependent, indicating the potential usage of hydrogels for drug testing. Results of confocal microscopy and Western blotting showed that cells isolated from hydrogels are suitable for downstream proteomic analysis. The results provided evidence that this peptide hydrogel is a promising 3D cell culture material for drug testing. PMID:23527204

The structural, morphological and thermal properties of grafted pH-sensitive interpenetrating highly porous polymeric composites of sodium alginate/acrylic acid copolymers for controlled delivery of diclofenac potassium

PubMed Central

Jalil, Aamir; Khan, Samiullah; Naeem, Fahad; Haider, Malik Suleman; Sarwar, Shoaib; Riaz, Amna; Ranjha, Nazar Muhammad

2017-01-01

Abstract In present investigation new formulations of Sodium Alginate/Acrylic acid hydrogels with high porous structure were synthesized by free radical polymerization technique for the controlled drug delivery of analgesic agent to colon. Many structural parameters like molecular weight between crosslinks (M c), crosslink density (M r), volume interaction parameter (v 2,s), Flory Huggins water interaction parameter and diffusion coefficient (Q) were calculated. Water uptake studies was conducted in different USP phosphate buffer solutions. All samples showed higher swelling ratio with increasing pH values because of ionization of carboxylic groups at higher pH values. Porosity and gel fraction of all the samples were calculated. New selected samples were loaded with the model drug (diclofenac potassium).The amount of drug loaded and released was determined and it was found that all the samples showed higher release of drug at higher pH values. Release of diclofenac potassium was found to be dependent on the ratio of sodium alginate/acrylic acid, EGDMA and pH of the medium. Experimental data was fitted to various model equations and corresponding parameters were calculated to study the release mechanism. The Structural, Morphological and Thermal Properties of interpenetrating hydrogels were studied by FTIR, XRD, DSC, and SEM. PMID:29491802

Mechanically Robust 3D Nanostructure Chitosan-Based Hydrogels with Autonomic Self-Healing Properties.

PubMed

Karimi, Ali Reza; Khodadadi, Azam

2016-10-12

Fabrication of hydrogels based on chitosan (CS) with superb self-healing behavior and high mechanical and electrical properties has become a challenging and fascinating topic. Most of the conventional hydrogels lack these properties at the same time. Our objectives in this research were to synthesize, characterize, and evaluate the general properties of chitosan covalently cross-linked with zinc phthalocyanine tetra-aldehyde (ZnPcTa) framework. Our hope was to access an unprecedented self-healable three-dimensional (3D) nanostructure that would harvest the superior mechanical and electrical properties associated with chitosan. The properties of cross-linker such as the structure, steric effect, and rigidity of the molecule played important roles in determining the microstructure and properties of the resulting hydrogels. The tetra-functionalized phthalocyanines favor a dynamic Schiff-base linkage with chitosan to form a 3D porous nanostructure. Based on this strategy, the self-healing ability, as demonstrated by rheological recovery and macroscopic and microscopic observations, is introduced through dynamic covalent Schiff-base linkage between NH 2 groups in CS and benzaldehyde groups at cross-linker ends. The hydrogel was characterized using FT-IR, NMR, UV/vis, and rheological measurements. In addition, cryogenic scanning electron microscopy (cryo-SEM) was employed as a technique to visualize the internal morphology of the hydrogels. Study of the surface morphology of the hydrogel showed a 3D porous nanostructure with uniform morphology. Furthermore, incorporating the conductive nanofillers, such as carbon nanotubes (CNTs), into the structure can modulate the mechanical and electrical properties of the obtained hydrogels. Interestingly, these hydrogel nanocomposites proved to have very good film-forming properties, high modulus and strength, acceptable electrical conductivity, and excellent self-healing properties at neutral pH. Such properties can be finely tuned through variation of the cross-linker and CNT concentration, and as a result these structures are promising candidates for potential applications in various fields of research.

Facile synthesis of degradable and electrically conductive polysaccharide hydrogels.

PubMed

Guo, Baolin; Finne-Wistrand, Anna; Albertsson, Ann-Christine

2011-07-11

Degradable and electrically conductive polysaccharide hydrogels (DECPHs) have been synthesized by functionalizing polysaccharide with conductive aniline oligomers. DECPHs based on chitosan (CS), aniline tetramer (AT), and glutaraldehyde were obtained by a facile one-pot reaction by using the amine group of CS and AT under mild conditions, which avoids the multistep reactions and tedious purification involved in the synthesis of degradable conductive hydrogels in our previous work. Interestingly, these one-pot hydrogels possess good film-forming properties, electrical conductivity, and a pH-sensitive swelling behavior. The chemical structure and morphology before and after swelling of the hydrogels were verified by FT-IR, NMR, and SEM. The conductivity of the hydrogels was tuned by adjusting the content of AT. The swelling ratio of the hydrogels was altered by the content of tetraaniline and cross-linker. The hydrogels underwent slow degradation in a buffer solution. The hydrogels obtained by this facile approach provide new possibilities in biomedical applications, for example, biodegradable conductive hydrogels, films, and scaffolds for cardiovascular tissue engineering and controlled drug delivery.

Shape-Memory Hydrogels: Evolution of Structural Principles To Enable Shape Switching of Hydrophilic Polymer Networks.

PubMed

Löwenberg, Candy; Balk, Maria; Wischke, Christian; Behl, Marc; Lendlein, Andreas

2017-04-18

The ability of hydrophilic chain segments in polymer networks to strongly interact with water allows the volumetric expansion of the material and formation of a hydrogel. When polymer chain segments undergo reversible hydration depending on environmental conditions, smart hydrogels can be realized, which are able to shrink/swell and thus alter their volume on demand. In contrast, implementing the capacity of hydrogels to switch their shape rather than volume demands more sophisticated chemical approaches and structural concepts. In this Account, the principles of hydrogel network design, incorporation of molecular switches, and hydrogel microstructures are summarized that enable a spatially directed actuation of hydrogels by a shape-memory effect (SME) without major volume alteration. The SME involves an elastic deformation (programming) of samples, which are temporarily fixed by reversible covalent or physical cross-links resulting in a temporary shape. The material can reverse to the original shape when these molecular switches are affected by application of a suitable stimulus. Hydrophobic shape-memory polymers (SMPs), which are established with complex functions including multiple or reversible shape-switching, may provide inspiration for the molecular architecture of shape-memory hydrogels (SMHs), but cannot be identically copied in the world of hydrophilic soft materials. For instance, fixation of the temporary shape requires cross-links to be formed also in an aqueous environment, which may not be realized, for example, by crystalline domains from the hydrophilic main chains as these may dissolve in presence of water. Accordingly, dual-shape hydrogels have evolved, where, for example, hydrophobic crystallizable side chains have been linked into hydrophilic polymer networks to act as temperature-sensitive temporary cross-links. By incorporating a second type of such side chains, triple-shape hydrogels can be realized. Considering the typically given light permeability of hydrogels and the fully hydrated state with easy permeation by small molecules, other types of stimuli like light, pH, or ions can be employed that may not be easily used in hydrophobic SMPs. In some cases, those molecular switches can respond to more than one stimulus, thus increasing the number of opportunities to induce actuation of these synthetic hydrogels. Beyond this, biopolymer-based hydrogels can be equipped with a shape switching function when facilitating, for example, triple helix formation in proteins or ionic interactions in polysaccharides. Eventually, microstructured SMHs such as hybrid or porous structures can combine the shape-switching function with an improved performance by helping to overcome frequent shortcomings of hydrogels such as low mechanical strength or volume change upon temporary cross-link cleavage. Specifically, shape switching without major volume alteration is possible in porous SMHs by decoupling small volume changes of pore walls on the microscale and the macroscopic sample size. Furthermore, oligomeric rather than short aliphatic side chains as molecular switches allow stabilization of the sample volumes. Based on those structural principles and switching functionalities, SMHs have already entered into applications as soft actuators and are considered, for example, for cell manipulation in biomedicine. In the context of those applications, switching kinetics, switching forces, and reversibility of switching are aspects to be further explored.

Design of a single-step immunoassay principle based on the combination of an enzyme-labeled antibody release coating and a hydrogel copolymerized with a fluorescent enzyme substrate in a microfluidic capillary device.

PubMed

Wakayama, Hideki; Henares, Terence G; Jigawa, Kaede; Funano, Shun-ichi; Sueyoshi, Kenji; Endo, Tatsuro; Hisamoto, Hideaki

2013-11-21

A combination of an enzyme-labeled antibody release coating and a novel fluorescent enzyme substrate-copolymerized hydrogel in a microchannel for a single-step, no-wash microfluidic immunoassay is demonstrated. This hydrogel discriminates the free enzyme-conjugated antibody from an antigen-enzyme-conjugated antibody immunocomplex based on the difference in molecular size. A selective and sensitive immunoassay, with 10-1000 ng mL(-1) linear range, is reported.

Effect of pH on chitosan hydrogel polymer network structure.

PubMed

Xu, Hongcheng; Matysiak, Silvina

2017-06-29

Chitosan is a molecule that can form water-filled 3D polymer networks with a wide range of applications. A new coarse-grained model for chitosan hydrogel was developed to explore its pH-dependent self-assembly behavior and mechanical properties. Our results indicate that the underlying polymer physical crosslinking pattern induced by solution pH has a significant effect on hydrogel elastic moduli. With this model, we obtain pH-dependent structural and mechanical property changes in agreement with experimental observations, and provide a molecular mechanism behind the changes in polymer crosslinking patterns.

Isosteric Substitution of 4H-1,2,4-Triazole by 1H-1,2,3-Triazole in Isophthalic Derivative Enabled Hydrogel Formation for Controlled Drug Delivery.

PubMed

Häring, Marleen; Rodríguez-López, Julio; Grijalvo, Santiago; Tautz, Markus; Eritja, Ramón; Martín, Víctor S; Díaz Díaz, David

2018-02-20

In this work, we demonstrated that the simple substitution of the 1,2,4-triazole moiety in 5-(4H-1,2,4-triazol-4-yl)isophthalic acid (5-TIA) by the 1H-1,2,3-triazol-5-yl unit enables the preparation of a hydrogelator (click-TIA). In sharp contrast to 5-TIA, its isostere click-TIA undergoes self-assembly in water upon sonication, leading to the formation of stable supramolecular viscoelastic hydrogels with a critical gelation concentration of 6 g/L. Hydrogels made of click-TIA as well as hybrid hydrogels made of the mixture click-TIA + 5-TIA (molar ratio 1:0.2) were used to compare different properties of the materials (i.e., rheological properties, thermal properties, mechanical stability, morphology). In terms of toxicity, neither click-TIA nor 5-TIA showed cytotoxic effects on cellular viability of HeLa cells up to 2.3 × 10 -3 g/L when compared to untreated cells incubated with DMSO. Furthermore, the hydrogels were used for the encapsulation and in vitro controlled release of oxytetracycline that followed first-order kinetics. For the hydrogel made of click-TIA, a maximum drug release of ∼60% was reached after ∼8 h within a pH range between 6.5 and 10. However, the release rate was reduced to approximately half of its value at pH values between 1.2 and 5.0, whereas the use of hybrid hydrogels made of click-TIA + 5-TIA allowed to reduce the original rate at pH ≤ 6.5.

Therapeutic applications of hydrogels in oral drug delivery

PubMed Central

Sharpe, Lindsey A; Daily, Adam M; Horava, Sarena D; Peppas, Nicholas A

2015-01-01

Introduction Oral delivery of therapeutics, particularly protein-based pharmaceutics, is of great interest for safe and controlled drug delivery for patients. Hydrogels offer excellent potential as oral therapeutic systems due to inherent biocompatibility, diversity of both natural and synthetic material options and tunable properties. In particular, stimuli-responsive hydrogels exploit physiological changes along the intestinal tract to achieve site-specific, controlled release of protein, peptide and chemotherapeutic molecules for both local and systemic treatment applications. Areas covered This review provides a wide perspective on the therapeutic use of hydrogels in oral delivery systems. General features and advantages of hydrogels are addressed, with more considerable focus on stimuli-responsive systems that respond to pH or enzymatic changes in the gastrointestinal environment to achieve controlled drug release. Specific examples of therapeutics are given. Last, in vitro and in vivo methods to evaluate hydrogel performance are discussed. Expert opinion Hydrogels are excellent candidates for oral drug delivery, due to the number of adaptable parameters that enable controlled delivery of diverse therapeutic molecules. However, further work is required to more accurately simulate physiological conditions and enhance performance, which is important to achieve improved bioavailability and increase commercial interest. PMID:24848309

Characterization of Particle Translocation through Mucin Hydrogels

PubMed Central

Lieleg, Oliver; Vladescu, Ioana; Ribbeck, Katharina

2010-01-01

Abstract Biological functional entities surround themselves with selective barriers that control the passage of certain classes of macromolecules while rejecting others. A prominent example of such a selective permeability barrier is given by mucus. Mucus is a biopolymer-based hydrogel that lines all wet epithelial surfaces of the human body. It regulates the uptake of nutrients from our gastrointestinal system, adjusts itself with the menstrual cycle to control the passage of sperm, and shields the underlying cells from pathogens such as bacteria and viruses. In the case of drug delivery, the mucus barrier needs to be overcome for successful medical treatment. Despite its importance for both physiology and medical applications, the underlying principles which regulate the permeability of mucus remain enigmatic. Here, we analyze the mobility of microscopic particles in reconstituted mucin hydrogels. We show that electrostatic interactions between diffusing particles and mucin polymers regulate the permeability properties of reconstituted mucin hydrogels. As a consequence, various parameters such as particle surface charge and mucin density, and buffer conditions such as pH and ionic strength, can modulate the microscopic barrier function of the mucin hydrogel. Our findings suggest that the permeability of a biopolymer-based hydrogel such as native mucus can be tuned to a wide range of settings in different compartments of our bodies. PMID:20441741

A novel vehicle for local protein delivery to the inner ear: injectable and biodegradable thermosensitive hydrogel loaded with PLGA nanoparticles.

PubMed

Dai, Juan; Long, Wei; Liang, Zhongping; Wen, Lu; Yang, Fan; Chen, Gang

2018-01-01

Delivery of biomacromolecular drugs into the inner ear is challenging, mainly because of their inherent instability as well as physiological and anatomical barriers. Therefore, protein-friendly, hydrogel-based delivery systems following local administration are being developed for inner ear therapy. Herein, biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing interferon α-2 b (IFN α-2 b) were loaded in chitosan/glycerophosphate (CS/GP)-based thermosensitive hydrogel for IFN delivery by intratympanic injection. The injectable hydrogel possessed a physiological pH and formed semi-solid gel at 37 °C, with good swelling and deswelling properties. The CS/GP hydrogel could slowly degrade as visualized by scanning electron microscopy (SEM). The presence of NPs in CS/GP gel largely influenced in vitro drug release. In the guinea pig cochlea, a 1.5- to 3-fold increase in the drug exposure time of NPs-CS/GP was found than those of the solution, NPs and IFN-loaded hydrogel. Most importantly, a prolonged residence time was attained without obvious histological changes in the inner ear. This biodegradable, injectable, and thermosensitive NPs-CS/GP system may allow longer delivery of protein drugs to the inner ear, thus may be a potential novel vehicle for inner ear therapy.

DNA Hydrogel with Tunable pH-Responsive Properties Produced by Rolling Circle Amplification.

PubMed

Xu, Wanlin; Huang, Yishun; Zhao, Haoran; Li, Pan; Liu, Guoyuan; Li, Jing; Zhu, Chengshen; Tian, Leilei

2017-12-22

Recently, smart DNA hydrogels, which are generally formed by the self-assembly of oligonucleotides or through the cross-linking of oligonucleotide-polymer hybrids, have attracted tremendous attention. However, the difficulties of fabricating DNA hydrogels limit their practical applications. We report herein a novel method for producing pH-responsive hydrogels by rolling circle amplification (RCA). In this method, pH-sensitive cross-linking sites were introduced into the polymeric DNA chains during DNA synthesis. As the DNA sequence can be precisely defined by its template, the properties of such hydrogels can be finely tuned in a very facile way through template design. We have investigated the process of hydrogel formation and pH-responsiveness to provide rationales for functional hydrogel design based on the RCA reaction. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A novel multi-responsive polyampholyte composite hydrogel with excellent mechanical strength and rapid shrinking rate.

PubMed

Xu, Kun; Tan, Ying; Chen, Qiang; An, Huiyong; Li, Wenbo; Dong, Lisong; Wang, Pixin

2010-05-15

Series of hydrophilic core-shell microgels with cross-linked poly(N-isopropylacrylamide) (PNIPAAm) as core and poly(vinyl amine) (PVAm) as shell are synthesized via surfactant-free emulsion polymerization. Then, the microgels are treated with a small amount of potassium persulfate (KPS) to generate free radicals on the amine nitrogens of PVAm, which subsequently initiate the graft copolymerization of acrylic acid (AA), acryloyloxyethyl trimethyl ammonium chloride (DAC), and acrylamide (AAm) onto microgels to prepare multi-responsive composite hydrogels. The composite hydrogels consist of cross-linked ungrafted polyampholyte chains as the first network and microgels with grafted polyampholyte chains as graft point and second network and show surprising mechanical strength and rapid response rate. The investigation shows the compress strength of composite hydrogels is up to 17-30 MPa, which is 60-100 times higher than that of the hydrogel matrix. The composite hydrogel shows reversible switch of transmittance when traveling the lowest critical temperature (LCST) of microgels. When the composite hydrogel swollen in pH 2.86 solution at ambient condition is immersed into the pH 7.00 solution at 45 °C, a rapid dynamic shrinking can be observed. And the character time (τ) of shrinking dynamic of composite hydrogel is 251.9 min, which is less than that of hydrogel matrix (τ=2273.7 min). Copyright © 2010 Elsevier Inc. All rights reserved.

Assessment of alginate hydrogel degradation in biological tissue using viscosity-sensitive fluorescent dyes

NASA Astrophysics Data System (ADS)

Shkand, Tatiana V.; Chizh, Mykola O.; Sleta, Iryna V.; Sandomirsky, Borys P.; Tatarets, Anatoliy L.; Patsenker, Leonid D.

2016-12-01

The main goal of this study is to investigate a combination of viscosity-sensitive and viscosity-insensitive fluorescent dyes to distinguish different rheological states of hydrogel based biostructural materials and carriers in biological tissues and to assess their corresponding location areas. The research is done in the example of alginate hydrogel stained with viscosity-sensitive dyes Seta-470 and Seta-560 as well as the viscosity-insensitive dye Seta-650. These dyes absorb/emit at 469/518, 565/591 and 651/670 nm, respectively. The rheological state of the alginate, the area of the fluorescence signal and the mass of the dense alginate versus the calcium gluconate concentration utilized for alginate gelation were studied in vitro. The most pronounced change in the fluorescence signal area was found at the same concentrations of calcium gluconate (below ~1%) as the change in the alginate plaque mass. The stained alginate was also implanted in situ in rat hip and myocardium and monitored using fluorescence imaging. In summary, our data indicate that the viscosity sensitive dye in combination with the viscosity-insensitive dye allow tracking the biodegradation of the alginate hydrogel and determining the rheological state of hydrogel in biological tissue, which both should have relevance for research and clinical applications. Using this method we estimated the half-life of the dense alginate hydrogel in a rat hip to be in the order of 4 d and about 6-8 d in rat myocardium. The half-life of the dense hydrogel in the myocardium was found to be long enough to prevent aneurysm rupture of the left ventricle wall, one of the more severe complications of the early post-infarction period.

Wood hemicellulose/chitosan-based semi-interpenetrating network hydrogels : mechanical swelling and controlled drug release properties

Treesearch

Ahmet M. Karaaslan; Mandla A. Tshabalala; Gisela Buschle-Diller

2010-01-01

The cell wall of most plant biomass from forest and agricultural resources consists of three major polymers, cellulose, hemicellulose, and lignin. Of these, hemicelluloses have gained increasing attention as sustainable raw materials. In this study, novel pH-sensitive semi-IPN hydrogels based on hemicelluloses and chitosan were prepared using glutaraldehyde as the...

Preparation and evaluation of thermosensitive liposomal hydrogel for enhanced transcorneal permeation of ofloxacin.

PubMed

Hosny, Khaled Mohamed

2009-01-01

Ofloxacin, available as ophthalmic solution, has two major problems: first, it needs frequent administration every 4 hours or even every 1 hour to treat severe eye infection; second, there is formation of white crystalline deposit on cornea due to its pH-dependent solubility, which is very low at pH of corneal fluid. In order to provide a solution to previous problems, ofloxacin in this study is prepared as topically effective in situ thermosensitive prolonged release liposomal hydrogel. Two preparation procedures were carried out, leading to the formation of multilamellar vesicles (MLVs) and reverse-phase evaporation vesicles (REVs) at pH 7.4. Effects of method of preparation, lipid content, and charge inducers on encapsulation efficiency were studied. For the preparation of in situ thermosensitive hydrogel, chitosan/beta-glycerophosphate system was synthesized and used as carrier for ofloxacin liposomes. The effect of addition of liposomes on gelation temperature, gelation time, and rheological behaviors of the hydrogel were evaluated. In vitro transcorneal permeation was also determined. MLVs entrapped greater amount of ofloxacin than REVs liposomes at pH 7.4; drug loading was increased by including charge-inducing agent and by increasing cholesterol content until a certain limit. The gelation time was decreased by the addition of liposomes into the hydrogel. The prepared liposomal hydrogel enhances the transcorneal permeation sevenfold more than the aqueous solution. These results suggested that the in situ thermosensitive ofloxacin liposomal hydrogel ensures steady and prolonged transcorneal permeation, which improves the ocular bioavailability, minimizes the need for frequent administration, and decreases the ocular side effect of ofloxacin.

A glucose-sensitive block glycopolymer hydrogel based on dynamic boronic ester bonds for insulin delivery.

PubMed

Cai, Baoqi; Luo, Yanping; Guo, Qianqian; Zhang, Xinge; Wu, Zhongming

2017-06-05

Hydrogels are good candidates to satisfy many needs for functional and tunable biomaterials. How to precisely control the gel structure and functions is crucial for the construction of sophisticated soft biomaterials comprising the hydrogels, which facilitates the impact of the surrounding environment on a unique biological function occurring. Here, glucose-responsive hydrogels comprised of 3-acrylamidophenyl boronic acid copolymerized with 2-lactobionamidoethyl methacrylate (p(APBA-b-LAMA)) were synthesized, and further evaluated as carriers for insulin delivery. The formation of (p(APBA-b-LAMA)) hydrogel was based on dynamic covalent bond using the association of boronic acid with diols. P(APBA-b-LAMA) hydrogel with the typical porous structure showed a rapid increase in equilibrium of swelling, which was up to 1856% after incubation with aqueous solution. Using insulin as a model protein therapeutic, p(APBA-b-LAMA) hydrogel exhibited high drug loading capability up to 15.6%, and also displayed glucose-dependent insulin release under physiological conditions. Additionally, the viability of NIH3T3 cells was more than 90% after treated with p(APBA-b-LAMA) hydrogel, indicating that the hydrogel had no cytotoxicity. Consequently, the novel p(APBA-b-LAMA) hydrogel has a practical application for diabetes treatment. Copyright © 2017. Published by Elsevier Ltd.

Biodegradable HEMA-based hydrogels with enhanced mechanical properties.

PubMed

Moghadam, Mohamadreza Nassajian; Pioletti, Dominique P

2016-08-01

Hydrogels are widely used in the biomedical field. Their main purposes are either to deliver biological active agents or to temporarily fill a defect until they degrade and are followed by new host tissue formation. However, for this latter application, biodegradable hydrogels are usually not capable to sustain any significant load. The development of biodegradable hydrogels presenting load-bearing capabilities would open new possibilities to utilize this class of material in the biomedical field. In this work, an original formulation of biodegradable photo-crosslinked hydrogels based on hydroxyethyl methacrylate (HEMA) is presented. The hydrogels consist of short-length poly(2-hydroxyethyl methacrylate) (PHEMA) chains in a star shape structure, obtained by introducing a tetra-functional chain transfer agent in the backbone of the hydrogels. They are cross-linked with a biodegradable N,O-dimethacryloyl hydroxylamine (DMHA) molecule sensitive to hydrolytic cleavage. We characterized the degradation properties of these hydrogels submitted to mechanical loadings. We showed that the developed hydrogels undergo long-term degradation and specially meet the two essential requirements of a biodegradable hydrogel suitable for load bearing applications: enhanced mechanical properties and low molecular weight degradation products. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1161-1169, 2016. © 2015 Wiley Periodicals, Inc.

25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine

PubMed Central

Annabi, Nasim; Tamayol, Ali; Uquillas, Jorge Alfredo; Akbari, Mohsen; Bertassoni, Luiz E.; Cha, Chaenyung; Camci-Unal, Gulden; Dokmeci, Mehmet R.

2014-01-01

Hydrogels are hydrophilic polymer-based materials with high water content and physical characteristics that resemble the native extracellular matrix. Because of their remarkable properties, hydrogel systems are used for a wide range of biomedical applications, such as three-dimensional (3D) matrices for tissue engineering, drug-delivery vehicles, composite biomaterials, and as injectable fillers in minimally invasive surgeries. In addition, the rational design of hydrogels with controlled physical and biological properties can be used to modulate cellular functionality and tissue morphogenesis. Here, the development of advanced hydrogels with tunable physiochemical properties is highlighted, with particular emphasis on elastomeric, light-sensitive, composite, and shape-memory hydrogels. Emerging technologies developed over the past decade to control hydrogel architecture are also discussed and a number of potential applications and challenges in the utilization of hydrogels in regenerative medicine are reviewed. It is anticipated that the continued development of sophisticated hydrogels will result in clinical applications that will improve patient care and quality of life. PMID:24741694

High-Performance Biomass-Based Flexible Solid-State Supercapacitor Constructed of Pressure-Sensitive Lignin-Based and Cellulose Hydrogels.

PubMed

Peng, Zhiyuan; Zou, Yubo; Xu, Shiqi; Zhong, Wenbin; Yang, Wantai

2018-06-19

Employing renewable, earth-abundant, environmentally friendly, low-cost natural materials to design flexible supercapacitors (FSCs) as energy storage devices in wearable/portable electronics represents the global perspective to build sustainable and green society. Chemically stable and flexible cellulose and electroactive lignin have been employed to construct a biomass-based FSC for the first time. The FSC was assembled using lignosulfonate/single-walled carbon nanotube HNO 3 (Lig/SWCNT HNO 3 ) pressure-sensitive hydrogels as electrodes and cellulose hydrogels as an electrolyte separator. The assembled biomass-based FSC shows high specific capacitance (292 F g -1 at a current density of 0.5 A g -1 ), excellent rate capability, and an outstanding energy density of 17.1 W h kg -1 at a power density of 324 W kg -1 . Remarkably, the FSC presents outstanding electrochemical stability even suffering 1000 bending cycles. Such excellent flexibility, stability, and electrochemical performance enable the designed biomass-based FSCs as prominent candidates in applications of wearable electronic devices.

Light-triggered methylcellulose gold nanoparticle hydrogels for leptin release to inhibit fat stores in adipocytes.

PubMed

Liao, Zi-Xian; Liu, Meng-Chia; Kempson, Ivan M; Fa, Yu-Chen; Huang, Kuo-Yen

2017-01-01

Leptin is released in response to increased triglyceride storage in adipocytes and impacts body weight, but has drawbacks such as poor therapeutic effect and side effects when delivered systemically. Leptin also modifies adipocyte sensitivity to insulin to inhibit lipid accumulation. Here, light-triggered degradation of hydrogels was used to improve accuracy and effectiveness for sustained and controllable release. In our approach, leptin was entrapped within methylcellulose (MC)-based hydrogels, with incorporation of gold nanoparticles (NP). The incorporation of gold NP into MC hydrogels led to a tunable light irradiation response that dictated the hydrogel release rate of leptin. This manuscript demonstrates feasibility in designing tunable thermosensitive hydrogels for loading multimodality therapeutic agents to enhance the bioactivity of leptin for obesity therapy.

Self-healing pH-sensitive poly[(methyl vinyl ether)-alt-(maleic acid)]-based supramolecular hydrogels formed by inclusion complexation between cyclodextrin and adamantane.

PubMed

Ma, Xiaoe; Zhou, Naizhen; Zhang, Tianzhu; Hu, Wanjun; Gu, Ning

2017-04-01

Self-healing materials are of interest for drug delivery, cell and gene therapy, tissue engineering, and other biomedical applications. In this work, on the base of biocompatible polymer poly(methyl vinyl ether-alt-maleic acid) (P(MVE-alt-MA)), host polymer β-cyclodextrin-grafted P(MVE-alt-MA) (P(MVE-alt-MA)-g-β-CD) and guest polymer adamantane-grafted P(MVE-alt-MA) (P(MVE-alt-MA)-g-Ad) were first prepared. Then through taking advantage of the traditional host-guest interaction of β-cyclodextrin and adamantane, a novel self-healing pH-sensitive physical P(MVE-alt-MA)-g-β-CD/P(MVE-alt-MA)-g-Ad supramolecular hydrogels were obtained after simply mixing the aqueous solution of host polymer and guest polymer. This kind of supramolecular hydrogels not only possess pH-sensitivity, but also possess the ability to repair themselves after being damaged. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel alginate hydrogel core-shell systems for combination delivery of ranitidine HCl and aceclofenac.

PubMed

Jana, Sougata; Samanta, Abhijit; Nayak, Amit Kumar; Sen, Kalyan Kumar; Jana, Subrata

2015-03-01

A novel hydrogel system was successfully developed based on core-shell approach for the delivery of ranitidine HCl and aceclofenac. Aceclofenac-loaded alginate microspheres coated with eudragit L-100 was used as core material and that of freeze-thaw cross-linked chitosan-PVA gels containing ranitidine HCl served as the shell-forming material. The alginate microspheres coated with eudragit L-100 showed drug encapsulation efficiency of 56.06±1.12 to 68.03±2.16% and had average particle sizes of 551.29±25.92 to 677.18±27.05 μm. The viscosity of chitosan-PVA gels ranged between 505.74±1.04 and 582.41±2.09 cps. The formulations were characterized by FTIR, SEM and polarized microscopy analyses. The release of ranitidine HCl was comparatively higher in acidic medium (pH 1.2) than in alkaline medium (pH 7.4). The release of aceclofenac became slower in alkaline medium (pH 7.4) and continued up to 3.5 h. Super case-II transport mechanism was assumed for the release of ranitidine HCl in both media; whereas non-Fickian (anomalous) diffusion mechanism predominated in the release of aceclofenc. Thus, hydrogel-based core-shell formulations were found suitable for simultaneous delivery of aceclofenac and ranitidine HCl which could minimize the chances of excessive gastric acid secretion through suitable ranitidine HCl release in gastric region. Copyright © 2014. Published by Elsevier B.V.

Organic hydrogels as potential sorbent materials for water purification

NASA Astrophysics Data System (ADS)

Linardatos, George; Bekiari, Vlasoula; Bokias, George

2014-05-01

Hydrogels are three-dimensional, hydrophilic, polymeric networks capable to adsorb large amounts of water or biological fluids. The networks are composed of homopolymers or copolymers and are insoluble due to the presence of chemical or physical cross-links. Depending on the nature of the structural units, swelling or shrinking of these gels can be activated by several external stimuli, such as solvent, heat, pH, electric stimuli. As a consequence, these materials are attractive for several applications in a variety of fields: drug delivery, muscle mimetic soft linear actuators, hosts of nanoparticles and semiconductors, regenerative medicine etc. Of special interest is the application of hydrogels for water purification, since they can effectively adsorb several water soluble pollutants such as metal ions, inorganic or organic anions, organic dyestaff, etc. In the present work, anionic hydrogels bearing negatively charged -COO- groups were prepared and investigated. These are based on the anionic monomer sodium acrylate (ANa) and the nonionic one N,N-dimethylacrylamide (DMAM). A series of copolymeric hydrogels (P(DMAM-co-ANax) were synthesized. The molar content x of ANa units (expressing the molar charged content of the hydrogel) varies from 0 (nonionic poly(N,N-dimethylacrylamide), PDMAM, hydrogel) up to 1 (fully charged poly(sodium acrylate), PANa, hydrogel). The hydrogels were used to extract organic or inorganic solutes from water. Cationic and anionic model dyes, as well as multivalent inorganic ions, have been studied. It is found that cationic dyes are strongly adsorbed and retained by the hydrogels, while adsorbance of anionic dyes was negligible. Both maximum adsorption and equilibrium binding constant depend on the chemical structure of the dye, the presence of functional chemical groups and the hydrophobic-hydrophilic balance. In the case of metal cations, adsorption depends mostly on the charge of the cation. In addition, crucial factors controlling the adsorption efficiency is the charge content of the hydrogel x, as well as the pH of the aqueous solution, since acrylic acid is a weak acid. ACKNOWLEDGMENTS. This research has been co-financed by the European Union (European Social Fund - ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program: Archimedes III. Investing in knowledge society through the European Social Fund; research project Archimedes III: "Synthesis and characterization of novel nanostructured materials and study of their use as water purification systems".

Photodimerisation of a coumarin-dipeptide gelator.

PubMed

Draper, Emily R; McDonald, Tom O; Adams, Dave J

2015-08-18

Here we report a coumarin based hydrogelator that can form bulk gels, or homogeneous thin gels via an electrochemical pH drop. The gel can then be strengthened by post-gelation photodimerisation of the coumarin groups by irradiating with UV light.

Fiber Optic Biosensors

DTIC Science & Technology

2006-12-01

CDM Camp Dresser & McKee Inc. CSU Colorado State University DCA dichloroethane DO dissolved oxygen DoD Department of Defense EA EA...Ph.D. (PI), Camp Dresser & McKee Inc. (CDM); John Eisenbeis, Ph.D., CDM; Kristy Warren, CDM; Dan Adams, CDM; Michael Allen, Bangor Naval Submarine Base...alcohol (PVA) using cyanuric chloride, and the resulting product was cross -linked with glutaraldehyde in presence of HCl to form a hydrogel that was

Composite chitosan hydrogels for extended release of hydrophobic drugs.

PubMed

Delmar, Keren; Bianco-Peled, Havazelet

2016-01-20

A composite chitosan hydrogel durable in physiological conditions intended for sustained release of hydrophobic drugs was investigated. The design is based on chitosan crosslinked with genipin with embedded biocompatible non-ionic microemulsion (ME). A prolonged release period of 48 h in water, and of 24h in phosphate buffer saline (PBS) of pH 7.4 was demonstrated for Nile red and curcumin. The differences in release patterns in water and PBS were attributed to distinct dissimilarities in the swelling behaviors; in water, the hydrogels swell enormously, while in PBS they expel water and shrink. The release mechanism dominating this system is complex due to intermolecular bonding between the oil droplets and the polymeric network, as confirmed by Fourier transform infrared spectroscopy (FTIR) experiments. This is the first time that oil in water microemulsions were introduced into a chitosan hydrogels for the creation of a hydrophobic drug delivery system. Copyright © 2015 Elsevier Ltd. All rights reserved.

Exploring pH-Sensitive Hydrogels Using an Ionic Soft Contact Lens: An Activity Using Common Household Materials

ERIC Educational Resources Information Center

Chen, Yueh-Huey; He, Yu-Chi; Yaung, Jing-Fun

2014-01-01

Hydrogels of the so-called smart polymers or environment-sensitive polymers are important modern biomaterials. Herein, we describe a hands-on activity to explore the pH-responsive characteristics of hydrogels using a commercially available ionic soft contact lens that is a hydrogel of poly(2-hydroxyethyl methacrylate-"co"-methacrylic…

Radiation synthesis of superabsorbent CMC based hydrogels for agriculture applications

NASA Astrophysics Data System (ADS)

Raafat, Amany I.; Eid, Mona; El-Arnaouty, Magda B.

2012-07-01

A series of superabsorbent hydrogel based on carboxymethylcellulose (CMC) and polyvinylpyrrolidone (PVP) crosslinked with gamma irradiation have been proposed for agriculture application. The effect of preparation conditions such as feed solution composition and absorbed irradiation dose on the gelation and swelling degree was evaluated. The structure and the morphology of the superabsorbent CMC/PVP hydrogel were characterized using Fourier transform infrared spectroscopy technique (FTIR), and scanning electron microscope (SEM). Effect of ionic strength and cationic and anionic kinds on the swelling behavior of the obtained hydrogel was investigated. Urea as an agrochemical model was loaded onto the obtained hydrogel to provide nitrogen (N) nutrients. The water retention capability and the urea release behavior of the CMC/PVP hydrogels were investigated. It was found that, the obtained CMC/PVP hydrogels have good swelling degree that greatly affected by its composition and absorbed dose. The swelling was also extremely sensitive to the ionic strength and cationic kind. Owing to its considerable slow urea release, good water retention capacity, being economical, and environment-friendly, it might be useful for its application in agriculture field.

Column study of Cr(VI) removal by cationic hydrogel for in-situ remediation of contaminated groundwater and soil

NASA Astrophysics Data System (ADS)

Tang, Samuel C. N.; Yin, Ke; Lo, Irene M. C.

2011-07-01

Column experiments were conducted for examining the effectiveness of the cationic hydrogel on Cr(VI) removal from groundwater and soil. For in-situ groundwater remediation, the effects of background anions, humic acid (HA) and pH were studied. Cr(VI) has a higher preference for being adsorbed onto the cationic hydrogel than sulphate, bicarbonate ions and HA. However, the adsorbed HA reduced the Cr(VI) removal capacity of the cationic hydrogel, especially after regeneration of the adsorbents, probably due to the blockage of adsorption sites. The Cr(VI) removal was slightly influenced by the groundwater pH that could be attributed to Cr(VI) speciation. The 6-cycle regeneration and reusability study shows that the effectiveness of the cationic hydrogel remained almost unchanged. On average, 93% of the adsorbed Cr(VI) was recovered in each cycle and concentrated Cr(VI) solution was obtained after regeneration. For in-situ soil remediation, the flushing water pH had an insignificant effect on the release of Cr(VI) from the soils. Multiple-pulse flushing increased the removal of Cr(VI) from the soils. In contrast, more flushing water and longer operation may be required to achieve the same removal level by continuous flushing.

Chitosan cross-linked with poly(ethylene glycol)dialdehyde via reductive amination as effective controlled release carriers for oral protein drug delivery.

PubMed

Jing, Zi-Wei; Ma, Zhi-Wei; Li, Chen; Jia, Yi-Yang; Luo, Min; Ma, Xi-Xi; Zhou, Si-Yuan; Zhang, Bang-Le

2017-02-15

The covalently cross-linked chitosan-poly(ethylene glycol) 1540 derivatives have been developed as a controlled release system with potential for the delivery of protein drug. The swelling characteristics of the hydrogels based on these derivatives as the function of different PEG content and the release profiles of a model protein (bovine serum albumin, BSA) from the hydrogels were evaluated in simulated gastric fluid with or without enzyme in order to simulate the gastrointestinal tract conditions. The derivatives cross-linked with difunctional PEG 1540 -dialdehyde via reductive amination can swell in alkaline pH and remain insoluble in acidic medium. The cumulative release amount of BSA was relatively low in the initial 2h and increased significantly at pH 7.4 with intestinal lysozyme for additional 12h. The results proved that the release-and-hold behavior of the cross-linked CS-PEG 1540 H-CS hydrogel provided a swell and intestinal enzyme controlled release carrier system, which is suitable for oral protein drug delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

In vitro dynamic swelling behaviors of radiation synthesized polyacrylamide with crosslinkers in the simulated physiological body fluids

NASA Astrophysics Data System (ADS)

Saraydın, Dursun; Işıkver, Yasemin; Karadağ, Erdener; Sahiner, Nurettin; Güven, Olgun

2002-03-01

Acrylamide hydrogels, containing different amounts and types of crosslinkers, were synthesized via γ-irradiation technique. Their swellings in simulated body fluids, such as physiological saline (0.89% NaCl) isoosmotic phosphate buffer at pH 7.4, gastric fluid at pH 1.1 (glycine-HCl), protein (aqueous solution of bovine serum albumin), urine (aqueous solution of urea), glucose and distilled water, were studied. Equilibrium swellings of the hydrogels were changed in the range 27-85 depending upon the fluids, type and amount of crosslinkers. The diffusion exponents were found over half for all hydrogels.

Structural characteristics of thermosensitive chitosan glutamate hydrogels in variety of physiological environments

NASA Astrophysics Data System (ADS)

Modrzejewska, Z.; Nawrotek, K.; Maniukiewicz, W.; Douglas, T.

2014-09-01

In this paper the properties of thermosensitive chitosan hydrogels prepared with the use of chitosan glutamate and β-glycerophosphate are presented. The study is focused on the determination of changes in the hydrogel structure in different environments: during conditioning in water and buffer at pH 7 and pH 2 respectively. The structure of gels was observed under the Scanning Electron Microscopy (SEM) and was investigated by infrared (IR) spectroscopy. The crystallinity of gel structure was determined by X-ray diffraction analysis (XRD). On the basis of structural changes during the conditioning in water a mechanism of their formation was proposed.

Ultrasonic-assisted synthesis of superabsorbent hydrogels based on sodium lignosulfonate and their adsorption properties for Ni2.

PubMed

Wang, Xiaohong; Wang, Yingying; He, Shufu; Hou, Haiqian; Hao, Chen

2018-01-01

Nowadays, the attention of both academic and industrial research is paid to the novel materials based on renewable organic resources. Sodium lignosulphonate (SLS) is selected in this study to synthesize novel superabsorbent hydrogels by ultrasonic polymerization. The structure, morphology and stability of SLS-based hydrogel were confirmed by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). Under the optimal condition, SLS-based hydrogel possesses the water absorbency of 1328g·g -1 in distilled water and 110g·g -1 in 0.9wt% NaCl solution. In addition, the prepared SLS-hydrogel as an adsorbent was applied to remove Ni 2+ from an aqueous solution in virtue of its low cost and favorable adsorption capacity. The various experimental conditions that influence the adsorption capacity were investigated such as temperature (20-60°C), pH (2.0-7.0), contact time (0-360min) and initial concentration of the Ni 2+ solution (100-600mg·L -1 ). Then the adsorption capability could reach 293mg·g -1 under optimal conditions. The results revealed that the adsorption behavior is spontaneous and endothermic. Furthermore, it was observed that the adsorption mechanism and adsorption equilibrium data obeyed pseudo-second-order kinetic and Freundlich models. Copyright © 2017 Elsevier B.V. All rights reserved.

Bioorthogonal in Situ Hydrogels Based on Polyether Polyols for New Biosensor Materials with High Sensitivity.

PubMed

Herrmann, Anna; Kaufmann, Lena; Dey, Pradip; Haag, Rainer; Schedler, Uwe

2018-04-04

Both noncovalent and covalent encapsulations of active biomolecules, for example, proteins and oligonucleotides, for a new biosensor matrix in an in situ bioorthogonal hydrogel formation via a strain-promoted azide-alkyne cycloaddition reaction were investigated. Unspecific interaction between the gel and the biomolecules as well as protein denaturation was prevented by the bioorthogonal gel components, which ensure a uniform aqueous environment in the hydrogel network. No leaching of the active biomolecules was observed. Additionally, a much higher and also adjustable loading of biomolecules in the hydrogel matrix was achieved compared to conventional biosensor surfaces, where the sensor molecules are immobilized on monolayers (2D surfaces) or brushlike structures (3D surfaces). Spotting experiments of the hydrogel confirm the possibility to use this new surface for microarray-based multiplex applications which require very high signal-to-noise ratios.

Chiral betulin-imino-chitosan hydrogels by dynamic covalent sonochemistry.

PubMed

Iftime, Manuela Maria; Marin, Luminita

2018-07-01

A series of chiral hydrogels was prepared from a homogeneous mixture of chitosan and betulinic aldehyde in different molar ratios, under the effect of ultrasound. The hydrogelation mechanism has been investigated by FTIR and CD spectroscopy, wide angle X-ray diffraction and polarized light microscopy. The morphology of hydrogels was examined by SEM. The swelling ability has been tested in three media of different pH. It was concluded that hydrogelation occurred by different pathways, closely related to the peculiarities of the chitosan-betulin systems. Circular dichroism measurements revealed chiroptical properties of the hydrogels, correlated to their content and crosslinking pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

Hydrogel research in Germany: the priority programme, Intelligent Hydrogels

NASA Astrophysics Data System (ADS)

Wallmersperger, Thomas; Sadowski, Gabriele

2009-03-01

The priority programme "Intelligent Hydrogels" was established by the German Research Foundation (DFG) in 2006 in order to strengthen the hydrogel-related research in Germany. The programme is being coordinated by Gabriele Sadowski, Technische Universität Dortmund. The aim of this priority programme is to develop new methods for the synthesis and characterization of smart hydrogels and to develop new modelling strategies in order to a) prepare the hydrogels for special applications and/or b) to develop and extend their capabilities for any desired use. In this programme, 73 scientists (36 professors and 37 scientific assistants/PhD students) from all over Germany are involved, working in 23 projects.

Magnetic- and pH-responsive κ-carrageenan/chitosan complexes for controlled release of methotrexate anticancer drug.

PubMed

Mahdavinia, Gholam Reza; Mosallanezhad, Amirabbas; Soleymani, Moslem; Sabzi, Mohammad

2017-04-01

The aim of the present work was to develop green carriers for methotrexate using κ-carrageenan/chitosan complexes. Magnetic Fe 3 O 4 nanoparticles were first synthesized in the presence of κ-carrageenan through in situ method. Then, the obtained magnetic κ-carrageenan was crosslinked using the polycation chitosan biopolymer. The physical and structural properties of hydrogels were investigated by FTIR, XRD, SEM, TEM, TGA, and VSM techniques. The pH-dependent swelling behavior of hydrogels was examined in various buffer solutions. All of the prepared hydrogels showed a high swelling capacity in basic solutions. The introduction of magnetite nanoparticles into κ-carrageenan/chitosan complexes had a significant effect on the swelling capacity of magnetic hydrogels, as the water absorbency of hydrogels decreased with increasing magnetite content. Methotrexate as an anticancer and model drug was loaded on hydrogels and the release profiles were investigated at pH=7.4 and 5.3. The methotrexate encapsulation efficiency was increased by increasing magnetite and chitosan contents. The results demonstrated that the release of methotrexate from magnetic hydrogels is pH-dependent with a high release content at pH=7.4. The release profiles were analyzed by Peppas's empirical model and the release of drug from hydrogels followed Fickian type of diffusion mechanism at both pHs. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis and characterization of a novel cationic hydrogel base on salecan-g-PMAPTAC.

PubMed

Wei, Wei; Qi, Xiaoliang; Li, Junjian; Zhong, Yin; Zuo, Gancheng; Pan, Xihao; Su, Ting; Zhang, Jianfa; Dong, Wei

2017-08-01

Salecan is a biological macromolecular and biocompatible polysaccharide that has been investigated for recent years. Herein, we report a novel cationic hydrogel fabricated by graft-polymerizing 3-(methacryloylamino)propyl-trimethylammonium chloride (MAPTAC) onto salecan chains. The obtained hydrogels were transparent, solid-elastic, macro-porous, ion-sensitive, and non-cytotoxic. The swelling ratios increased with salecan content, while mechanical strength does the opposite. Moreover, drug delivery test was studied as a potential application. Diclofenac sodium (DS) and insulin were selected as model drugs. Interestingly, in drug loading process, DS molecules exhibited highly affinity to these cationic hydrogels. Almost all the DS molecules in loading solution were absorbed and spread into the hydrogel. For drug release profiles, insulin-loaded hydrogel showed an initial rapid release and a sustained release. As a comparison, DS-loaded hydrogel exhibited a more sustained release profile. Results suggested salecan-g-PMAPTAC hydrogel could be a good candidate for anionic drug loading and delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

A study of chitosan hydrogel with embedded mesoporous silica nanoparticles loaded by ibuprofen as a dual stimuli-responsive drug release system for surface coating of titanium implants.

PubMed

Zhao, Pengkun; Liu, Hongyu; Deng, Hongbing; Xiao, Ling; Qin, Caiqin; Du, Yumin; Shi, Xiaowen

2014-11-01

In this study, the complex pH and electro responsive system made of chitosan hydrogel with embedded mesoporous silica nanoparticles (MSNs) was evaluated as a tunable drug release system. As a model drug, ibuprofen (IB) was used; its adsorption in MSNs was evidenced by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and thermogravimetric analysis (TG). In order to prepare the complex drug release system, the loaded particles IB-MSNs were dispersed in chitosan solution and then the complex IB-MSNs/chitosan film of 2mm thickness was deposited as a hydrogel on the titanium electrode. The codeposition of components was performed under a negative biasing of the titanium electrode at -0.75 mA/cm2 current density during 30 min. The IB release from the IB-MSNs/chitosan hydrogel film was studied as dependent on pH of the release media and electrical conditions applied to the titanium plate. When incubating the complex hydrogel film in buffers with different pH, the IB release followed a near zero-order profile, though its kinetics varied. Compared to the spontaneous IB release from the hydrogel in 0.9% NaCl solution (at 0 V), the application of negative biases to the coated titanium plate had profound effluences on the release behavior. The release was retarded when -1.0 V was applied, but a faster kinetics was observed at -5.0 V. These results imply that a rapid, mild and facile electrical process for covering titanium implants by complex IB-MSNs/chitosan hydrogel films can be used for controlled drug delivery applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Injectable MMP-sensitive alginate hydrogels as hMSC delivery systems.

PubMed

Fonseca, Keila B; Gomes, David B; Lee, Kangwon; Santos, Susana G; Sousa, Aureliana; Silva, Eduardo A; Mooney, David J; Granja, Pedro L; Barrias, Cristina C

2014-01-13

Hydrogels with the potential to provide minimally invasive cell delivery represent a powerful tool for tissue-regeneration therapies. In this context, entrapped cells should be able to escape the matrix becoming more available to actively participate in the healing process. Here, we analyzed the performance of proteolytically degradable alginate hydrogels as vehicles for human mesenchymal stem cells (hMSC) transplantation. Alginate was modified with the matrix metalloproteinase (MMP)-sensitive peptide Pro-Val-Gly-Leu-Iso-Gly (PVGLIG), which did not promote dendritic cell maturation in vitro, neither free nor conjugated to alginate chains, indicating low immunogenicity. hMSC were entrapped within MMP-sensitive and MMP-insensitive alginate hydrogels, both containing cell-adhesion RGD peptides. Softer (2 wt % alginate) and stiffer (4 wt % alginate) matrices were tested. When embedded in a Matrigel layer, hMSC-laden MMP-sensitive alginate hydrogels promoted more extensive outward cell migration and invasion into the tissue mimic. In vivo, after 4 weeks of subcutaneous implantation in a xenograft mouse model, hMSC-laden MMP-sensitive alginate hydrogels showed higher degradation and host tissue invasion than their MMP-insensitive equivalents. In both cases, softer matrices degraded faster than stiffer ones. The transplanted hMSC were able to produce their own collagenous extracellular matrix, and were located not only inside the hydrogels, but also outside, integrated in the host tissue. In summary, injectable MMP-sensitive alginate hydrogels can act as localized depots of cells and confer protection to transplanted cells while facilitating tissue regeneration.

Preparation of new GO-based slide ring hydrogel through a convenient one-pot approach as methylene blue absorbent.

PubMed

Soleimani, Khadijeh; Dadkhah Tehrani, Abbas; Adeli, Mohsen

2018-05-01

Slide ring hydrogels (SRHG) with supramolecular structures are a new class of hydrogels that contrary to the traditional hydrogels comprise dynamic cross-linking points. Herein, we reported on the fabrication of a new slide ring hydrogel through a very convenient one-pot approach. In this regard, isocyanate functionalized GO was synthesized and used as a stopper as well as cross-linker in the presence of a polypseudorotaxane of cyclodextrin threaded on poly(ethylene glycol) (PR). The surface of the resulting SRHG modified via graft polymerization with polyacrylamide (PAAm) and its application as a new type of absorbent for wastewater treatment was studied. Due to its porous structure and its high content of surface functional groups, the synthesized hydrogel was able to efficiently remove cationic dye methylene blue (MB) from wastewater in a short time. The maximum adsorption capacity of the resulting hydrogel was 92.3 mg/g which exhibited an almost 100% increment as compared to that of untreated GO. The adsorption mechanism of MB was also investigated. The kinetic data, obtained at the optimum pH 7, were fitted well with the pseudo-second-order model. Results from degradation and recycling experiments toward MB showed that the SRHG was stable and reusable. Copyright © 2018 Elsevier Ltd. All rights reserved.

Amphiphilic Polyurethane Hydrogels as Smart Carriers for Acidic Hydrophobic Drugs.

PubMed

Fonseca, Lucas P; Trinca, Rafael B; Isabel Felisberti, Maria

2018-05-14

Amphiphilic hydrogels are widely reported as systems with great potential for controlled drug release. Nevertheless, the majority of studies make use of functionalization or attachment of drugs to the polymer chains. In this study, we propose a strategy of combining amphiphilic polyurethanes with pH-responsive drugs to develop smart drug carriers. While the amphiphilic character of the polymer imparts an efficient load of hydrophobic and hydrophilic drugs, the drug's characteristics determine the selectivity of the medium delivery. Drug loading and release behavior as well as hydrolytic degradation of chemically crosslinked polyurethane hydrogels based on PEG and PCL-triol (PU (polyurethane) hydrogels) synthesized by an easy one-pot route were studied. PU hydrogels have been shown to successfully load the hydrophobic acidic drug sodium diclofenac, reaching a partition coefficient of 8 between the most hydrophobic PU and diclofenac/ethanol solutions. Moreover, an oral administration simulation was conducted by changing the environment from an acidic to a neutral medium. PU hydrogels release less than 5 % of the drug in an acidic medium; however, in a PBS pH 7.4 solution, diclofenac is delivered in a sustained fashion for up to 40 hours, achieving 80% of cumulative release. Copyright © 2018. Published by Elsevier B.V.

Thermodynamic Analysis of the Selectivity Enhancement Obtained by Using Smart Hydrogels That Are Zwitterionic When Detecting Glucose With Boronic Acid Moieties

PubMed Central

Horkay, F.; Cho, S. H.; Tathireddy, P.; Rieth, L.; Solzbacher, F.; Magda, J.

2011-01-01

Because the boronic acid moiety reversibly binds to sugar molecules and has low cytotoxicity, boronic acid-containing hydrogels are being used in a variety of implantable glucose sensors under development, including sensors based on optical, fluorescence, and swelling pressure measurements. However, some method of glucose selectivity enhancement is often necessary, because isolated boronic acid molecules have a binding constant with glucose that is some forty times smaller than their binding constant with fructose, the second most abundant sugar in the human body. In many cases, glucose selectivity enhancement is obtained by incorporating pendant tertiary amines into the hydrogel network, thereby giving rise to a hydrogel that is zwitterionic at physiological pH. However, the mechanism by which incorporation of tertiary amines confers selectivity enhancement is poorly understood. In order to clarify this mechanism, we use the osmotic deswelling technique to compare the thermodynamic interactions of glucose and fructose with a zwitterionic smart hydrogel containing boronic acid moieties. We also investigate the change in the structure of the hydrogel that occurs when it binds to glucose or to fructose using the technique of small angle neutron scattering. PMID:22190765

Nanomechanics of layer-by-layer polyelectrolyte complexes: a manifestation of ionic cross-links and fixed charges.

PubMed

Han, Biao; Chery, Daphney R; Yin, Jie; Lu, X Lucas; Lee, Daeyeon; Han, Lin

2016-01-28

This study investigates the roles of two distinct features of ionically cross-linked polyelectrolyte networks - ionic cross-links and fixed charges - in determining their nanomechanical properties. The layer-by-layer assembled poly(allylamine hydrochloride)/poly(acrylic acid) (PAH/PAA) network is used as the model material. The densities of ionic cross-links and fixed charges are modulated through solution pH and ionic strength (IS), and the swelling ratio, elastic and viscoelastic properties are quantified via an array of atomic force microscopy (AFM)-based nanomechanical tools. The roles of ionic cross-links are underscored by the distinctive elastic and viscoelastic nanomechanical characters observed here. First, as ionic cross-links are highly sensitive to solution conditions, the instantaneous modulus, E0, exhibits orders-of-magnitude changes upon pH- and IS-governed swelling, distinctive from the rubber elasticity prediction based on permanent covalent cross-links. Second, ionic cross-links can break and self-re-form, and this mechanism dominates force relaxation of PAH/PAA under a constant indentation depth. In most states, the degree of relaxation is >90%, independent of ionic cross-link density. The importance of fixed charges is highlighted by the unexpectedly more elastic nature of the network despite low ionic cross-link density at pH 2.0, IS 0.01 M. Here, the complex is a net charged, loosely cross-linked, where the degree of relaxation is attenuated to ≈50% due to increased elastic contribution arising from fixed charge-induced Donnan osmotic pressure. In addition, this study develops a new method for quantifying the thickness of highly swollen polymer hydrogel films. It also underscores important technical considerations when performing nanomechanical tests on highly rate-dependent polymer hydrogel networks. These results provide new insights into the nanomechanical characters of ionic polyelectrolyte complexes, and lay the ground for further investigation of their unique time-dependent properties.

Sensing Structures Inspired by Blind Cave Fish

NASA Astrophysics Data System (ADS)

McConney, Michael E.; Chen, Nannan; Lu, David; Anderson, Kyle D.; Hu, Huan; Liu, Chang; Tsukruk, Vladimir V.

2009-03-01

Blind cave fish, with degenerated non-functioning eyes, have evolved to ``see'' their hydrodynamic environment by using the flow receptors of the lateral line system. The hair-cell receptors are encapsulated in a hydrogel-like material, called a cupula, which increases the sensitivity of the hair-cell receptors by coupling their motion to the surrounding flowing media. We characterized the viscoelastic properties and of blind cave fish cupulae by using colloidal-probe spectroscopy in fluid. A photo-patternable hydrogel with similar properties was developed to mimic the fish receptor coupling structure. Flow-based measurements indicated that the hydrogels enhance drag through increased surface area, but also inherent material properties. These bio-inspired structures endowed micro-fabricated flow sensors with sensitivities rivaling that of fish.

The effect of pH on the rheology of mixed gels containing whey protein isolate and xanthan-curdlan hydrogel.

PubMed

Shiroodi, Setareh Ghorban; Lo, Y Martin

2015-11-01

The ultimate goal of this work was to examine the effect of xanthan-curdlan hydrogel complex (XCHC) on the rheology of whey protein isolate (WPI) within the pH range of 4-7 upon heating and cooling. Dynamic rheological properties of WPI and XCHC were studied individually and in combination, as a function of time or temperature. For pure WPI, gels were pH-dependent, and in all pH values except 7, gels formed upon first heating from 40 to 90 °C. At pH 7, WPI did not form gel upon first heating, and the storage modulus (G') started to increase during the holding time at 90 °C. The onset of gelation temperature of WPI was lower in acidic pH ranges compared to the neutral pH. In mixed gels, the presence of XCHC increased the G' of the gels. The rheological behaviour was pH-dependent and initially was controlled by XCHC; however, after the consolidation of WPI network, the behaviour was led by the whey protein isolate. Results showed that XCHC had a synergistic effect on enhancing the elastic modulus of the gels after the consolidation of WPI network. Based on the results of this study, it is possible to use these biopolymers in the formulation of frozen dairy-based products and enable food manufactures to improve the textural and physicochemical properties, and as a result the consumer acceptance of the food product.

Deformable and conformal silk hydrogel inverse opal

PubMed Central

Kim, Sookyoung; Kim, Sunghwan

2017-01-01

Photonic crystals (PhCs) efficiently manipulate photons at the nanoscale. Applying these crystals to biological tissue that has been subjected to large deformation and humid environments can lead to fascinating bioapplications such as in vivo biosensors and artificial ocular prostheses. These applications require that these PhCs have mechanical durability, deformability, and biocompatibility. Herein, we introduce a deformable and conformal silk hydrogel inverse opal (SHIO); the photonic lattice of this 3D PhC can be deformed by mechanical strain. This SHIO is prepared by the UV cross-linking of a liquid stilbene/silk solution, to give a transparent and elastic hydrogel. The pseudophotonic band gap (pseudo-PBG) of this material can be stably tuned by deformation of the photonic lattice (stretching, bending, and compressing). Proof-of-concept experiments demonstrate that the SHIO can be applied as an ocular prosthesis for better vision, such as that provided by the tapeta lucida of nocturnal or deep-sea animals. PMID:28559327

Temperature-responsive nanogel multilayers of poly(N-vinylcaprolactam) for topical drug delivery.

PubMed

Zavgorodnya, Oleksandra; Carmona-Moran, Carlos A; Kozlovskaya, Veronika; Liu, Fei; Wick, Timothy M; Kharlampieva, Eugenia

2017-11-15

We report nanothin temperature-responsive hydrogel films of poly(N-vinylcaprolactam) nanoparticles (νPVCL) with remarkably high loading capacity for topical drug delivery. Highly swollen (νPVCL) n multilayer hydrogels, where n denotes the number of nanoparticle layers, are produced by layer-by-layer hydrogen-bonded assembly of core-shell PVCL-co-acrylic acid nanoparticles with linear PVPON followed by cross-linking of the acrylic acid shell with either ethylene diamine (EDA) or adipic acid dihydrazide (AAD). We demonstrate that a (νPVCL) 5 film undergoes dramatic and reversible swelling up to 9 times its dry thickness at pH = 7.5, indicating 89v/v % of water inside the network. These hydrogels exhibit highly reversible ∼3-fold thickness changes with temperature variations from 25 to 50°C at pH = 5, the average pH of human skin. We also show that a (νPVCL) 30 hydrogel loaded with ∼120µgcm -2 sodium diclofenac, a non-steroidal anti-inflammatory drug used for osteoarthritis pain management, provides sustained permeation of this drug through an artificial skin membrane for up to 24h at 32°C (the average human skin surface temperature). The cumulative amount of diclofenac transported at 32°C from the (νPVCL) 30 hydrogel after 24h is 12 times higher than that from the (νPVCL) 30 hydrogel at 22°C. Finally, we demonstrate that the (νPVCL) hydrogels can be used for multiple drug delivery by inclusion of Nile red, fluorescein and DAPI dyes within the νPVCL nanoparticles prior to hydrogel assembly. Using confocal microscopy we observed the presence of separate dye-loaded νPVCL compartments within the hydrogel matrix with all three dyes confined to the nanogel particles without intermixing between the dyes. Our study provides opportunity for development of temperature-responsive multilayer hydrogel coatings made via the assembly of core-shell nanogel particles which can be used for skin-sensitive materials for topical drug delivery. Copyright © 2017 Elsevier Inc. All rights reserved.

[Thromboresistance of glucose-containing hydrogels].

PubMed

Valuev, I L; Valuev, L I; Vanchugova, L V; Obydennova, I V; Valueva, T A

2013-01-01

The thromboresistance of glucose-sensitive polymer hydrogels, modeling one of the functions of the pancreas, namely, the ability to secrete insulin in response to the introduction of glucose into the environment, has been studied. Hydrogels were synthesized by the copolymerization of hydroxyethyl methacrylate with N-acryloyl glucosamine in the presence of a cross-linking agent and subsequently treated with concanavalin A. Introduction of glucose residues into the hydrogel did not result in significant changes in either the number of trombocytes adhered to the hydrogel or the degree of denaturation of blood plasma proteins interacting with the hydrogel. Consequently, the biological activity of insulin did not change after release from the hydrogel. The use of glucose-sensitive hydrogels is supposed to contribute to the development of a novel strategy for the treatment of diabetes.

Hybrid hydrogels produced by ionizing radiation technique

NASA Astrophysics Data System (ADS)

Oliveira, M. J. A.; Amato, V. S.; Lugão, A. B.; Parra, D. F.

2012-09-01

The interest in biocompatible hydrogels with particular properties has increased considerably in recent years due to their versatile applications in biomedicine, biotechnology, pharmacy, agriculture and controlled release of drugs. The use of hydrogels matrices for particular drug-release applications has been investigated with the synthesis of modified polymeric hydrogel of PVAl and 0.5, 1.0, 1.5% nano-clay. They were processed using gamma radiation from Cobalt-60 source at 25 kGy dose. The characterization of the hydrogels was conducted and toxicity was evaluated. The dried hydrogel was analyzed for thermogravimetry analysis (TGA), infrared spectroscopy (FTIR) and swelling in solutions of different pH. The membranes have no toxicity. The nano-clay influences directly the equilibrium swelling.

Nanosensor aided photoacoustic measurement of pH in vivo

NASA Astrophysics Data System (ADS)

Ray, Aniruddha; Yoon, Hyung Ki; Kopelman, Raoul; Wang, Xueding

2013-03-01

pH plays a critical role in many aspects of cell and tissues physiology. Lower pH is also a typical characteristic of arthritic joints and tumor tissues. These pH anomalies are also exploited in different drug delivery mechanisms. Here we present, a new method of pH sensing in vivo using spectroscopic photoacoustic measurements facilitated by pH sensitive nanosensors. The nanosensors consist of Seminaphtharhodafluor (SNARF), a pH sensitive dye, encapsulated in a specially designed polyacrylamide hydrogel matrix with a hydrophobic core. The photoacoustic intensity ratio between the excitation wavelengths of 585nm and 565nm increases in the pH range from 6.0 to 8.0 and is used to determine the pH of the local environment. These nanosensors are biodegradable, biocompatible, have a long plasma lifetime and can be targeted to any type of cells or tissues by surface modification using proper targeting moieties. The encapsulation of the dye prevents the interaction of the dye with proteins in plasma and also reduces the dye degradation. The SNARF dye in its free form loses 90% of its absorbance in presence of albumin, a protein found in abundance in plasma, and this has severely limited its adaptation to in vivo environments. In comparison, the SNARF nanosensors lose only 16% of their absorbance in the same environment. We employ these nanosensors to demonstrate the feasibility of pH sensing in vivo through photoacoustic measurements on a rat joint model.

In vitro proliferation and osteogenic differentiation of human dental pulp stem cells in injectable thermo-sensitive chitosan/β-glycerophosphate/hydroxyapatite hydrogel.

PubMed

Chen, Yantian; Zhang, Fengli; Fu, Qiang; Liu, Yong; Wang, Zejian; Qi, Nianmin

2016-09-01

Injectable thermo-sensitive hydrogels have a potential application in bone tissue engineering for their sensitivities and minimal invasive properties. Human dental pulp stem cells have been considered a promising tool for tissue reconstruction. The objective of this study was to investigate the proliferation and osteogenic differentiation of dental pulp stem cells in injectable thermo-sensitive chitosan/β-glycerophosphate/hydroxyapatite hydrogel in vitro. The chitosan /β-glycerophosphate hydrogel and chitosan/β-glycerophosphate/hydroxyapatite hydrogel were prepared using the sol-gel method. The injectability of chitosan /β-glycerophosphate hydrogel and chitosan/β-glycerophosphate/hydroxyapatite hydrogel was measured using a commercial disposable syringe. Scanning electron microscopy was used to observe the inner structure of hydrogels. Then dental pulp stem cells were seeded in chitosan /β-glycerophosphate hydrogel and chitosan/β-glycerophosphate/hydroxyapatite hydrogel, respectively. The growth of dental pulp stem cells was periodically observed under an inverted microscope. The proliferation of dental pulp stem cells was detected by using an Alamar Blue kit, while cell apoptosis was determined by using a Live/Dead Viability/Cytotoxicity kit. The osteogenic differentiations of dental pulp stem cells in chitosan /β-glycerophosphate hydrogel and chitosan/β-glycerophosphate/hydroxyapatite hydrogel were evaluated by alkaline phosphatase activity assay and mRNA expression of osteogenesis gene for 21 days in osteogenic medium. The results indicated that there was no significant difference between chitosan /β-glycerophosphate hydrogel and chitosan/β-glycerophosphate/hydroxyapatite hydrogel in injectability. Cells within the chitosan/β-glycerophosphate/hydroxyapatite hydrogel displayed a typical adherent cell morphology and rapid proliferation with high cellular viability after 14 days of culture. Dental pulp stem cells seeded in chitosan/β-glycerophosphate/hydroxyapatite hydrogels had a higher alkaline phosphatase activity and better up-regulation of gene expression levels of Runx-2, Collagen I, alkaline phosphatase and osteocalcin than in chitosan /β-glycerophosphate hydrogels after osteogenic differentiation. These results demonstrated that the chitosan/β-glycerophosphate/hydroxyapatite hydrogel had excellent cellular compatibility and the superiority in promoting dental pulp stem cells osteogenic differentiation in vitro, showing that the combination of dental pulp stem cells and chitosan/β-glycerophosphate/hydroxyapatite hydrogel has the potential to be used for bone tissue engineering. © The Author(s) 2016.

Self-assembled three-dimensional reduced graphene oxide-based hydrogel for highly efficient and facile removal of pharmaceutical compounds from aqueous solution.

PubMed

Umbreen, Nadia; Sohni, Saima; Ahmad, Imtiaz; Khattak, Nimat Ullah; Gul, Kashif

2018-05-14

Herein, self-assembled three-dimensional reduced graphene oxide (RGO)-based hydrogels were synthesized and characterized in detail. A thorough investigation on the uptake of three widely used pharmaceutical drugs, viz. Naproxen (NPX), Ibuprofen (IBP) and Diclofenac (DFC) was carried out from aqueous solutions. To ensure the sustainability of developed hydrogel assembly, practically important parameters such as desorption, recyclability and applicability to real samples were also evaluated. Using the developed 3D hydrogels as adsorptive platforms, excellent decontamination for the above mentioned persistent pharmaceutical drugs was achieved in acidic pH with a removal efficiency in the range of 70-80%. These hydrogels showed fast adsorption kinetics and experimental findings were fitted to different kinetic models, such as pseudo-first order, pseudo-second order, intra-particle and the Elovich models in an attempt to better understand the adsorption kinetics. Furthermore, equilibrium adsorption data was fitted to the Langmuir and Freundlich models, where relatively higher R 2 values obtained in case of former one suggested that monolayer adsorption played an important part in drug uptake. Thermodynamic aspects were also studied and negative ΔG 0 values obtained indicated the spontaneous nature of adsorption process. The study was also extended to check practical utility of as-prepared hydrogels by spiking real aqueous samples with drug solution, where high % recoveries obtained for NPX, IBP and DFC were of particular importance with regard to prospective application in wastewater treatment systems. We advocate RGO-based hydrogels as environmentally benign, readily recoverable/recyclable material with excellent adsorption capacity for application in wastewater purification. Copyright © 2018 Elsevier Inc. All rights reserved.

A PEG-Based Hydrogel for Effective Wound Care Management

PubMed Central

Chen, Sen-Lu; Fu, Ru-Huei; Liao, Shih-Fei; Liu, Shih-Ping; Lin, Shinn-Zong; Wang, Yu-Chi

2018-01-01

It is extremely challenging to achieve strong adhesion in soft tissues while minimizing toxicity, tissue damage, and other side effects caused by wound sealing materials. In this study, flexible synthetic hydrogel sealants were prepared based on polyethylene glycol (PEG) materials. PEG is a synthetic material that is nontoxic and inert and, thus, suitable for use in medical products. We evaluated the in vitro biocompatibility tests of the dressings to assess cytotoxicity and irritation, sensitization, pyrogen toxicity, and systemic toxicity following the International Organization for Standardization 10993 standards and the in vivo effects of the hydrogel samples using Coloskin liquid bandages as control samples for potential in wound closure. PMID:29637814

Stable thermosensitive in situ gel-forming systems based on the lyophilizate of chitosan/α,β-glycerophosphate salts.

PubMed

Wu, Guanghao; Yuan, Yuan; He, Jintian; Li, Ying; Dai, Xiaojing; Zhao, Baohua

2016-09-10

In the present study, lyophilization was attempted to improve the long-term storage of CS/GP thermogelling systems for biopharmaceutical applications. After lyophilization, CS/α,β-GP lyophilizate could not be dissolved in water, but some metal salts, such as NaCl, CaCl2, and MgCl2 surprisingly facilitated its dissolution. X-ray powder diffraction analysis suggested that calcium ions might preferentially form salts with α,β-GP, inhibit the transfer of protons from CS to α,β-GP, and then inhibit the aggregation of CS molecules during lyophilization. Comparison of the freshly prepared CS/α,β-GP/salt solutions and the reconstituted solutions from lyophilizates showed that lyophilization clearly influenced the properties of reconstituted CS/α,β-GP/salt solutions such as gelation time, viscosity, and pH. Furthermore, the reconstituted CS/α,β-GP/CaCl2 solutions maintained thermogelling properties and formed hydrogels at 37°C within approximately 5min, but did not form hydrogels at 20°C and 4°C over 2 weeks. The model protein bovine serum albumin (BSA) was further incorporated into the CS/α,β-GP/CaCl2 system. In vitro release experiments showed the sustained release of BSA from CS/α,β-GP/CaCl2 hydrogels in a pH-sensitive manner, demonstrating that CS/α,β-GP/CaCl2 may be useful as an in situ gel-forming system. Copyright © 2016 Elsevier B.V. All rights reserved.

Three-Dimensional Printing of Complex Structures by Freeform Reversible Embedding of Suspended Hydrogels (FRESH)

NASA Astrophysics Data System (ADS)

Feinberg, Adam

We demonstrate the additive manufacturing of complex three-dimensional (3D) structures using soft protein and polysaccharide hydrogels that are challenging or impossible to create using traditional fabrication approaches. These structures are built by embedding the printed hydrogel within a secondary hydrogel that serves as a temporary, thermoreversible, and biocompatible support. This process, termed freeform reversible embedding of suspended hydrogels (FRESH), enables 3D printing of hydrated materials with an elastic modulus less than 500 kPa including alginate, collagen, hyaluronic acid and fibrin. A range of crosslinking mechanisms can be used depending on the polymer being printed, including ionic, enzymatic, pH, thermal and light based approaches. CAD models of 3D optical, computed tomography, and magnetic resonance imaging data can be 3D printed at a resolution of 100 μm and at low cost by leveraging open-source hardware and software tools. Proof-of-concept structures based on femurs, branched coronary arteries, trabeculated embryonic hearts, and human brains are mechanically robust and recreate complex 3D internal and external anatomical architectures. Recent advances have improved the resolution and broadened the range of materials that can be FRESH 3D printed. This work was supported in part by the NIH Director's New Innovator Award (DP2HL117750) and the NSF CAREER Award (1454248).

Modeling and simulation of deformation of hydrogels responding to electric stimulus.

PubMed

Li, Hua; Luo, Rongmo; Lam, K Y

2007-01-01

A model for simulation of pH-sensitive hydrogels is refined in this paper to extend its application to electric-sensitive hydrogels, termed the refined multi-effect-coupling electric-stimulus (rMECe) model. By reformulation of the fixed-charge density and consideration of finite deformation, the rMECe model is able to predict the responsive deformations of the hydrogels when they are immersed in a bath solution subject to externally applied electric field. The rMECe model consists of nonlinear partial differential governing equations with chemo-electro-mechanical coupling effects and the fixed-charge density with electric-field effect. By comparison between simulation and experiment extracted from literature, the model is verified to be accurate and stable. The rMECe model performs quantitatively for deformation analysis of the electric-sensitive hydrogels. The influences of several physical parameters, including the externally applied electric voltage, initial fixed-charge density, hydrogel strip thickness, ionic strength and valence of surrounding solution, are discussed in detail on the displacement and average curvature of the hydrogels.

Supramolecular Lego assembly towards three-dimensional multi-responsive hydrogels.

PubMed

Ma, Chunxin; Li, Tiefeng; Zhao, Qian; Yang, Xuxu; Wu, Jingjun; Luo, Yingwu; Xie, Tao

2014-08-27

Inspired by the assembly of Lego toys, hydrogel building blocks with heterogeneous responsiveness are assembled utilizing macroscopic supramolecular recognition as the adhesion force. The Lego hydrogel provides 3D transformation upon pH variation. After disassembly of the building blocks by changing the oxidation state, they can be re-assembled into a completely new shape. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electrochemical writing on edible polysaccharide films for intelligent food packaging.

PubMed

Wu, Si; Wang, Wenqi; Yan, Kun; Ding, Fuyuan; Shi, Xiaowen; Deng, Hongbing; Du, Yumin

2018-04-15

Polysaccharide films used as intelligent food packaging possess the advantages of renewability, safety and biodegradability. Printing on the polysaccharidic food packaging is challenging due to the high demand for edible-ink and the need for a suitable printing technique. In this work, we propose an electrochemical method for writing on polysaccharide film. Unlike conventional printing, this electrochemical writing process relies on the pH responsive color change of anthocyanin embedded in the chitosan/agarose hydrogel. By biasing a negative potential to a stainless wire (used as a pen) contacting the surface of the chitosan/agarose/ATH hydrogel, the locally generated pH change induced the color change of ATH and wrote programmed information on the hydrogel. We demonstrate the writing can be temporary in the hydrogel but stable when the hydrogel is dried. We further demonstrate that the written film is applicable for the detection of the spoilage of crucian fish. The reported electrochemical writing process provides a novel method for printing information on polysaccharide film and great potential for intelligent food packaging. Copyright © 2018 Elsevier Ltd. All rights reserved.

Design, characterisation and application of alginate-based encapsulated pig liver esterase.

PubMed

Pauly, Jan; Gröger, Harald; Patel, Anant V

2018-06-05

Encapsulation of hydrolases in biopolymer-based hydrogels often suffers from low activities and encapsulation efficiencies along with high leaching and unsatisfactory recycling properties. Exemplified for the encapsulation of pig liver esterase the coating of alginate and chitosan beads have been studied by creating various biopolymer hydrogel beads. Enzyme activity and encapsulation efficiency were notably enhanced by chitosan coating of alginate beads while leaching remained nearly unchanged. This was caused by the enzymatic reaction acidifying the matrix, which increased enzyme retention through enhanced electrostatic enzyme-alginate interaction but decreased activity through enzyme deactivation. A practical and ready-to-use method for visualising pH in beads during reaction by co-encapsulation of a conventional pH indicator was also found. Our method proves that pH control inside the beads can only be realised by buffering. The resulting beads provided a specific activity of 0.267 μmol ∙ min -1 ∙ mg -1 , effectiveness factor 0.88, encapsulation efficiency of 88%, 5% leaching and good recycling properties. This work will contribute towards better understanding and application of encapsulated hydrolases for enzymatic syntheses. Copyright © 2018 Elsevier B.V. All rights reserved.

A β-cyclodextrin, polyethyleneimine and silk fibroin hydrogel containing Centella asiatica extract and hydrocortisone acetate: releasing properties and in vivo efficacy for healing of pressure sores.

PubMed

Lee, M S; Seo, S R; Kim, J-C

2012-10-01

  Pressure sores are lesions caused by impaired blood flow. Conventional dressings can absorb exudates, but do not promote wound healing. A hydrogel composed of β-cyclodextrin (β-CD), polyethyleneimine (PEI) and silk fibroin (SF) was assessed for use in healing of pressure sores. The hydrogel was prepared by crosslinking β-CD-grafted PEI and SF using epichlorohydrin. The gel was then immersed in an aqueous solution of Centella asiatica extract (CAE) 0.7 mg/mL and/or hydrocortisone acetate (HCA) 0.5 mg/mL. The in vivo pressure sore-healing efficacy of the dry gel (with or without the drugs) was investigated in terms of the hyperplasia of epidermis and the number of neutrophils in the skin tissue. The specific loading of CAE was 0.0091 g/g of dry gel. The percentage of CAE released at 24 h at pH 3.0, 5.0 and 7.4 was approximately 63.9%, 55.0% and 44.4%, respectively. This pH-dependent release is possibly due to the degree of gel swelling, which decreased with increasing pH. The specific loading of HCA was 0.0050 g/g dry gel, and the percentage release of HCA at 24 h was around 20% at all three pH points. It is likely that HCA release is independent of pH. HCA is a hydrophobic compound, and therefore the release of HCA is affected by the partitioning of HCA between the β-CD cavity and the bulk water phase, but not by the degree of swelling of the hydrogel. The pressure sores treated with the hydrogel healed in 6 days, compared with 10 days for controls. In this study, a β-CD/PEI/SF hydrogel containing CAE and HCA reduced the healing time for pressure sores. © The Author(s). CED © 2012 British Association of Dermatologists.

Determination of the parameters controlling swelling of chemically cross-linked pH-sensitive poly(N-vinylimidazole) hydrogels.

PubMed

Molina, M Jesús; Gómez-Antón, M Rosa; Piérola, Inés F

2007-10-25

The number of variables controlling the behavior of ionic gels is large and very often some of them are unknown. The aim of this work is to interpret quantitatively the swelling behavior of pH sensitive gels, with the minimum number of simplifying assumptions. With this purpose, the equilibrium degree of swelling (S) and protonation (alpha) of chemically cross-linked poly(N-vinylimidazole) (PVI) immersed in aqueous salt solutions were measured as a function of the ionic strength (mu), in the whole range of pH. In acid solutions with pH in the range 0 to 4, imidazole moieties become protonated, and PVI behaves as a polyelectrolyte gel: S decreases upon increasing mu both for NaCl and for CaCl(2), with HCl as protonating acid. In aqueous solutions with larger pH, between 4 and 12, the hydrogel is practically neutral, and S increases as mu rises, showing a salting-in effect. From the quantitative analysis of these results, the following facts emerged. Protonation induces chain stiffness (as measured by the non-Gaussian factor) and worsening of the solvent quality of the aqueous media (as measured by the polymer-solvent interaction parameter). For alpha below 33%, swelling seems to be governed by the excess of mobile counterions inside the gel with respect to the bath, with a minor but still significantly negative contribution of the osmotic swelling pressure due to polymer-solvent mixing. Above 33% protonation, it is necessary to consider Manning counterion condensation to get parameters with physical meaning. The crossover between polyelectrolyte and salting-in effects corresponds to alpha and mu values with the same ionic and mixing contributions to the osmotic swelling pressure. The formation of ionic nonpermanent cross-links, with H(2)SO(4) as the protonating acid, was discarded.

Evaluation of Gentamicin and Lidocaine Release Profile from Gum Acacia-crosslinked-poly(2-hydroxyethylmethacrylate)-carbopol Based Hydrogels.

PubMed

Singh, Baljit; Dhiman, Abhishek

2017-01-01

No doubt, the prevention of infection is an indispensable aspect of the wound management, but, simultaneous wound pain relief is also required. Therefore, herein this article, incorporation of antibiotic agent 'gentamicin' and pain relieving agent 'lidocaine' into hydrogel wound dressings, prepared by using acacia gum, carbopol and poly(2-hydroxyethylmethacrylate) polymers, has been carried out. The hydrogels were evaluated as a drug carrier for model drugs gentamicin and lidocaine. Synthesis of hydrogel wound dressing was carried out by free radical polymerization technique. The drug loading was carried out by swelling equilibrium method and gel strength of hydrogels was measured by a texture analyzer. Porous microstructure of the hydrogel was observed in cryo-SEM images. The hydrogel showed mesh size 37.29 nm, cross-link density 2.19× 10-5 mol/cm3, molecular weight between two cross-links 60.25× 10-3 g/mol and gel strength 0.625±0.112 N in simulated wound fluid. It is concluded that the pH of swelling medium has influenced the network structure of hydrogel i.e., molecular weight of the polymer chain between two neighboring cross links, crosslink density and the corresponding mesh size. A good correlation was established between gel strength and network parameters. Cryo-SEM images showed porous morphology of hydrogels. These hydrogels were found to be biodegradable and antimicrobial in nature. Drug release occurred through Fickian diffusion mechanism and release profile was best fitted in first order model. Overall it is concluded that modification in GA has led to formation of a porous hydrogels for wound dressing applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A Review on Recent Advances in Stabilizing Peptides/Proteins upon Fabrication in Hydrogels from Biodegradable Polymers

PubMed Central

Raza, Faisal; Zafar, Hajra; Zhu, Ying; Ren, Yuan; -Ullah, Aftab; Khan, Asif Ullah; He, Xinyi; Han, Han; Aquib, Md; Boakye-Yiadom, Kofi Oti; Ge, Liang

2018-01-01

Hydrogels evolved as an outstanding carrier material for local and controlled drug delivery that tend to overcome the shortcomings of old conventional dosage forms for small drugs (NSAIDS) and large peptides and proteins. The aqueous swellable and crosslinked polymeric network structure of hydrogels is composed of various natural, synthetic and semisynthetic biodegradable polymers. Hydrogels have remarkable properties of functionality, reversibility, sterilizability, and biocompatibility. All these dynamic properties of hydrogels have increased the interest in their use as a carrier for peptides and proteins to be released slowly in a sustained manner. Peptide and proteins are remarkable therapeutic agents in today’s world that allow the treatment of severe, chronic and life-threatening diseases, such as diabetes, rheumatoid arthritis, hepatitis. Despite few limitations, hydrogels provide fine tuning of proteins and peptides delivery with enormous impact in clinical medicine. Novels drug delivery systems composed of smart peptides and molecules have the ability to drive self-assembly and form hydrogels at physiological pH. These hydrogels are significantly important for biological and medical fields. The primary objective of this article is to review current issues concerned with the therapeutic peptides and proteins and impact of remarkable properties of hydrogels on these therapeutic agents. Different routes for pharmaceutical peptides and proteins and superiority over other drugs candidates are presented. Recent advances based on various approaches like self-assembly of peptides and small molecules to form novel hydrogels are also discussed. The article will also review the literature concerning the classification of hydrogels on a different basis, polymers used, “release mechanisms” their physical and chemical characteristics and diverse applications. PMID:29346275

Subconjunctivally Implanted Hydrogels for Sustained Insulin Release to Reduce Retinal Cell Apoptosis in Diabetic Rats.

PubMed

Imai, Hisanori; Misra, Gauri P; Wu, Linfeng; Janagam, Dileep R; Gardner, Thomas W; Lowe, Tao L

2015-12-01

Diabetic retinopathy (DR) is a leading cause of blindness in diabetic patients that involves early-onset retinal cell loss. Here, we report our recent work using subconjunctivally implantable hydrogels for sustained insulin release to the retina to prevent retinal degeneration. The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide and a dextran macromer containing oligolactate-(2-hydroxyetheyl methacrylate) units. Insulin was loaded into the hydrogels during the synthesis. The ex vivo bioactivity of insulin released from the hydrogels was tested on fresh rat retinas using immunoprecipitation and immunoblotting to measure insulin receptor tyrosine and Akt phosphorylation. The biosafety and the effect on the blood glucose of the hydrogels were evaluated in rats 2 months after subconjunctival implantation. The release of insulin from the hydrogels was studied both in vitro in PBS (pH 7.4), and in vivo using confocal microscopy and RIA kit. The in vivo bioactivity of the released insulin was investigated in diabetic rats using DNA fragmentation method. The hydrogels could load insulin with approximately 98% encapsulation efficiency and continuously release FITC-insulin in PBS (pH = 7.4) at 37°C for at least 5 months depending on their composition. Insulin lispro released from the hydrogels was biologically active by increasing insulin receptor tyrosine and Akt serine phosphorylation of ex vivo retinas. In vivo studies showed normal retinal histology 2 months post subconjunctival implantation. Insulin released from subconjunctivally implanted hydrogels could be detected in the retina by using confocal microscopy and RIA kit for 1 week. The implanted hydrogels with insulin lispro did not change the blood glucose level of normal and diabetic rats, but significantly reduced the DNA fragmentation of diabetic retinas for 1 week. The developed hydrogels have great potential to sustain release of insulin to the retina via subconjunctival implantation to minimize DR without the risk of hypoglycemia.

Subconjunctivally Implanted Hydrogels for Sustained Insulin Release to Reduce Retinal Cell Apoptosis in Diabetic Rats

PubMed Central

Imai, Hisanori; Misra, Gauri P.; Wu, Linfeng; Janagam, Dileep R.; Gardner, Thomas W.; Lowe, Tao L.

2015-01-01

Purpose Diabetic retinopathy (DR) is a leading cause of blindness in diabetic patients that involves early-onset retinal cell loss. Here, we report our recent work using subconjunctivally implantable hydrogels for sustained insulin release to the retina to prevent retinal degeneration. Methods The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide and a dextran macromer containing oligolactate-(2-hydroxyetheyl methacrylate) units. Insulin was loaded into the hydrogels during the synthesis. The ex vivo bioactivity of insulin released from the hydrogels was tested on fresh rat retinas using immunoprecipitation and immunoblotting to measure insulin receptor tyrosine and Akt phosphorylation. The biosafety and the effect on the blood glucose of the hydrogels were evaluated in rats 2 months after subconjunctival implantation. The release of insulin from the hydrogels was studied both in vitro in PBS (pH 7.4), and in vivo using confocal microscopy and RIA kit. The in vivo bioactivity of the released insulin was investigated in diabetic rats using DNA fragmentation method. Results The hydrogels could load insulin with approximately 98% encapsulation efficiency and continuously release FITC-insulin in PBS (pH = 7.4) at 37°C for at least 5 months depending on their composition. Insulin lispro released from the hydrogels was biologically active by increasing insulin receptor tyrosine and Akt serine phosphorylation of ex vivo retinas. In vivo studies showed normal retinal histology 2 months post subconjunctival implantation. Insulin released from subconjunctivally implanted hydrogels could be detected in the retina by using confocal microscopy and RIA kit for 1 week. The implanted hydrogels with insulin lispro did not change the blood glucose level of normal and diabetic rats, but significantly reduced the DNA fragmentation of diabetic retinas for 1 week. Conclusions The developed hydrogels have great potential to sustain release of insulin to the retina via subconjunctival implantation to minimize DR without the risk of hypoglycemia. PMID:26658505

Polyelectrolyte polymer properties in relation to male contraceptive RISUG action.

PubMed

Roy, Sohini; Ghosh, Debidas; Guha, Sujoy K

2009-02-15

RISUG a polyelectrolytic hydrogel (styrene maleic anhydride and dimethyl sulfoxide) has proven to be efficacious as a contraceptive for a long term when injected into the lumen of vas deferens. Currently it is in advanced phase III clinical trials in India. Present investigation analyzes the swelling characteristics of RISUG hydrogel in different pH buffers and various biological fluids to understand its retention in the vas deferens as reported in previous studies. Significant variation in degree of swelling and equilibrium swelling ratio with transformation of Fickian to non-Fickian mode of diffusion was observed with increased pH. This might be due to ionization of carboxylic groups at high pH resulting in increased electrostatic repulsive force and high osmotic pressure inside the hydrogel network affecting its physical cross-linking and increases the free volume. Conversely, at low pH the dissociation of carboxylic group is limited making the hydrogel more stable. Interaction with various biomolecules present in various biological fluids was also studied. SEM, AFM and FTIR were used to analyze the topological and structural parameters of the polymer in different mediums. Loosening of structure and increasing porosity with significant adsorption of various biomolecules was observed. AFM revealed a significant change in overall roughness of polymer surface on interaction with different biological fluids. These observations suggest that the swelling and increased roughness will lead to increased resistance to sperm movement in the vas deferens.

Stimuli-Responsive DNA-Based Hydrogels: From Basic Principles to Applications.

PubMed

Kahn, Jason S; Hu, Yuwei; Willner, Itamar

2017-04-18

The base sequence of nucleic acids encodes structural and functional information into the DNA biopolymer. External stimuli such as metal ions, pH, light, or added nucleic acid fuel strands provide triggers to reversibly switch nucleic acid structures such as metal-ion-bridged duplexes, i-motifs, triplex nucleic acids, G-quadruplexes, or programmed double-stranded hybrids of oligonucleotides (DNA). The signal-triggered oligonucleotide structures have been broadly applied to develop switchable DNA nanostructures and DNA machines, and these stimuli-responsive assemblies provide functional scaffolds for the rapidly developing area of DNA nanotechnology. Stimuli-responsive hydrogels undergoing signal-triggered hydrogel-to-solution transitions or signal-controlled stiffness changes attract substantial interest as functional matrices for controlled drug delivery, materials exhibiting switchable mechanical properties, acting as valves or actuators, and "smart" materials for sensing and information processing. The integration of stimuli-responsive oligonucleotides with hydrogel-forming polymers provides versatile means to exploit the functional information encoded in the nucleic acid sequences to yield stimuli-responsive hydrogels exhibiting switchable physical, structural, and chemical properties. Stimuli-responsive DNA-based nucleic acid structures are integrated in acrylamide polymer chains and reversible, switchable hydrogel-to-solution transitions of the systems are demonstrated by applying external triggers, such as metal ions, pH-responsive strands, G-quadruplex, and appropriate counter triggers that bridge and dissociate the polymer chains. By combining stimuli-responsive nucleic acid bridges with thermosensitive poly(N-isopropylacrylamide) (pNIPAM) chains, systems undergoing reversible solution ↔ hydrogel ↔ solid transitions are demonstrated. Specifically, by bridging acrylamide polymer chains by two nucleic acid functionalities, where one type of bridging unit provides a stimuli-responsive element and the second unit acts as internal "bridging memory", shape-memory hydrogels undergoing reversible and switchable transitions between shaped hydrogels and shapeless quasi-liquid states are demonstrated. By using stimuli-responsive hydrogel cross-linking units that can assemble the bridging units by two different input signals, the orthogonally-triggered functions of the shape-memory were shown. Furthermore, a versatile approach to assemble stimuli-responsive DNA-based acrylamide hydrogel films on surfaces is presented. The method involves the activation of the hybridization chain-reaction (HCR) by a surface-confined promoter strand, in the presence of acrylamide chains modified with two DNA hairpin structures and appropriate stimuli-responsive tethers. The resulting hydrogel-modified surfaces revealed switchable stiffness properties and signal-triggered catalytic functions. By applying the method to assemble the hydrogel microparticles, substrate-loaded, stimuli-responsive microcapsules are prepared. The signal-triggered DNA-based hydrogel microcapsules are applied as drug carriers for controlled release. The different potential applications and future perspectives of stimuli responsive hydrogels are discussed. Specifically, the use of these smart materials and assemblies as carriers for controlled drug release and as shape-memory matrices for information storage and inscription and the use of surface-confined stimuli-responsive hydrogels, exhibiting switchable stiffness properties, for catalysis and controlled growth of cells are discussed.

Rheological investigation of high-acyl gellan gum hydrogel and its mixtures with simulated body fluids.

PubMed

Osmałek, Tomasz Zbigniew; Froelich, Anna; Jadach, Barbara; Krakowski, Marek

2018-05-01

Purpose Most of the studies concerning gellan have been focused on its application as a food ingredient, however, gellan is often considered as a candidate for the development of novel pharmaceutical formulations. Taking into account that gellan is ion-sensitive, it can be assumed that its initial mechanical properties can change upon contact with body secretions. Therefore, the aim of the work was to investigate the rheological properties of pure high-acyl gellan gum hydrogel (0.4%) and its mixtures with selected simulated body fluids. Methods The rheological investigations were performed on rotational rheometer and included oscillatory temperature, amplitude, and frequency sweeping. The results enabled estimation of the linear viscoelastic regime, calculation of the cross-over points, and percentage of structure recovery. Results In the case of pure hydrogel no evidence of thermosensitivity was observed in the range of 20-40°C. In pH = 1.2 (NaCl/HCl) the hydrogel structure was almost entirely destroyed. Mixing with phosphate buffer (pH = 4.5) resulted in higher gel strength than after dilution with deionized water. The opposite effect was observed in the case of pH = 7.4. The studies performed for the mixture of GG hydrogel and mucin indicated interaction between the components. The hydrogel elasticity increased in the presence of simulated tear, but decreased in simulated saliva and vaginal fluid. Conclusions In this study, it was shown that the stability of a three-dimensional gellan structure may be affected by pH and the presence of mucin which most probably competed with gellan gum in divalent cations binding. The observations presented in this study may be important in terms of potential application of gellan gum as a potential carrier in drug delivery systems.

New fluorescent perylene bisimide indicators--a platform for broadband pH optodes.

PubMed

Aigner, Daniel; Borisov, Sergey M; Klimant, Ingo

2011-06-01

Asymmetric perylene bisimide (PBI) dyes are prepared and are shown to be suitable for the preparation of fluorescence chemosensors for pH. They carry one amino-functional substituent which introduces pH sensitivity via photoinduced electron transfer (PET) while the other one increases solubility. The luminescence quantum yields for the new indicators exceed 75% in the protonated form. The new indicators are non-covalently entrapped in polyurethane hydrogel D4 and poly(hydroxyalkylmethacrylates). Several PET functions including aliphatic and aromatic amino groups were successfully used to tune the dynamic range of the sensor. Because of their virtually identical spectral properties, various PBIs with selected PET functions can easily be integrated into a single sensor with enlarged dynamic range (over 4 pH units). PBIs with two different substitution patterns in the bay position are investigated and possess variable spectral properties. Compared with their tetrachloro analogues, tetra-tert-butyl-substituted PBIs yield more long-wave excitable sensors which feature excellent photostability. Cross-sensitivity to ionic strength was found to be negligible. The practical applicability of the sensors may be compromised by the long response times (especially in case of tetra-tert-butyl-substituted PBIs).

Ciprofloxacin-lidocaine-based hydrogel: development, characterization, and in vivo evaluation in a second-degree burn model.

PubMed

Sanchez, María Florencia; Breda, Susana Andrea; Soria, Elio Andrés; Tártara, Luis Ignacio; Manzo, Rubén Hilario; Olivera, María Eugenia

2018-04-13

The purpose of this work was to develop an effective carbomer hydrogel to be used to treat second-degree burns that combined ciprofloxacin and lidocaine (CbCipLid hydrogel). Its antibiotic and anesthetic efficacy and the physical and chemical properties of the CbCipLid hydrogel (release rate and kinetics, rheology, appearance, and drug content) were evaluated both before and after a sterilization cycle and also after 6 months of storage. For the in vivo studies, second-degree burns were developed in a rat model. Animals were divided into three groups: CbCipLid hydrogel, silver sulfadiazine cream (reference), and carbomer hydrogel (as control). The treatments were applied daily for 21 days, and the healing was monitored by macroscopic observation and histologic evaluation. The anesthetic effect was evaluated through the corneal touch threshold in a rabbit eye model. The CbCipLid hydrogel obtained is transparent and allows the loading of ciprofloxacin above its solubility at a neutral pH, with a rheology which is convenient for topical administration. Its physical and chemical properties remained unchanged after sterilization and for at least six additional months. Both ciprofloxacin and lidocaine are reversibly released from the CbCipLid hydrogel with a kinetics fitting the Higuchi model. The presence of a biologic-like fluid increased the rate of drug delivery through an ionic exchange mechanism. Treatment with the CbCipLid hydrogel decreased the wound-healing period, compared with the reference, and was associated with a greater number of fibroblasts and a faster rate of epithelialization and dermis reconstruction. These differences were assigned to the moist environment provided by the hydrogel and also to the presence of a therapeutic concentration of ciprofloxacin. Moreover, CbCipLid hydrogel provides an immediate anesthetic effect, which is significantly more intense than that of the reference. Based on these results, it is believed that the CbCipLid hydrogel could be a potential candidate in the prophylaxis/treatment of second-degree burns.

Slow-release NPK fertilizer encapsulated by carboxymethyl cellulose-based nanocomposite with the function of water retention in soil.

PubMed

Olad, Ali; Zebhi, Hamid; Salari, Dariush; Mirmohseni, Abdolreza; Reyhani Tabar, Adel

2018-09-01

In this study, new slow release fertilizer encapsulated by superabsorbent nanocomposite was prepared by in-situ graft polymerization of sulfonated-carboxymethyl cellulose (SCMC) with acrylic acid (AA) in the presence of polyvinylpyrrolidone (PVP), silica nanoparticles and nitrogen (N), phosphorous (P), and potassium (K) (NPK) fertilizer compound. The prepared materials were characterized by FT-IR, XRD and scanning electron microscopy (SEM) techniques. The incorporation of NPK fertilizer into hydrogel nanocomposite network was verified by results of these analyses. Also, the swelling behavior in various pH and saline solutions as well as water retention capability of the prepared hydrogel nanocomposite was evaluated. The fertilizer release behavior of the NPK loaded hydrogel nanocomposite was in good agreement with the standard of Committee of European Normalization (CEN), indicating its excellent slow release property. These good characteristics revealed that the hydrogel nanocomposite fertilizer formulation can be practically used in agricultural and horticultural applications. Copyright © 2018 Elsevier B.V. All rights reserved.

Micro- and nano-hydroxyapatite as active reinforcement for soft biocomposites.

PubMed

Munarin, F; Petrini, P; Gentilini, R; Pillai, R S; Dirè, S; Tanzi, M C; Sglavo, V M

2015-01-01

Pectin-based biocomposite hydrogels were produced by internal gelation, using different hydroxyapatite (HA) powders from commercial source or synthesized by the wet chemical method. HA possesses the double functionality of cross-linking agent and inorganic reinforcement. The mineralogical composition, grain size, specific surface area and microstructure of the hydroxyapatite powders are shown to strongly influence the properties of the biocomposites. Specifically, the grain size and specific surface area of the HA powders are strictly correlated to the gelling time and rheological properties of the hydrogels at room temperature. Pectin pH is also significant for the formation of ionic cross-links and therefore for the hydrogels stability at higher temperatures. The obtained results point out that micrometric-size hydroxyapatite can be proposed for applications which require rapid gelling kinetics and improved mechanical properties; conversely the nanometric hydroxyapatite synthesized in the present work seems the best choice to obtain homogeneous hydrogels with more easily controlled gelling kinetics. Copyright © 2014 Elsevier B.V. All rights reserved.

Facile preparation of mussel-inspired polyurethane hydrogel and its rapid curing behavior.

PubMed

Sun, Peiyu; Wang, Jing; Yao, Xiong; Peng, Ying; Tu, Xiaoxiong; Du, Pengfei; Zheng, Zhen; Wang, Xinling

2014-08-13

A facile method was found to incorporate a mussel-inspired adhesive moiety into synthetic polymers, and mussel mimetic polyurethanes were developed as adhesive hydrogels. In these polymers, a urethane backbone was substituted for the polyamide chain of mussel adhesive proteins, and dopamine was appended to mimic the adhesive moiety of adhesive proteins. A series of mussel mimetic polyurethanes were created through a step-growth polymerization based on hexamethylene diisocyanate as a hard segment, PEG having different molecular weights as a soft segment, and lysine-dopamine as a chain extender. Upon a treatment with Fe(3+), the aqueous mussel mimetic polyurethane solutions can be triggered by pH adjustment to form adhesive hydrogels instantaneously; these materials can be used as injectable adhesive hydrogels. Upon a treatment with NaIO4, the mussel mimetic polyurethane solutions can be cured in a controllable period of time. The successful combination of the unique mussel-inspired adhesive moiety with a tunable polyurethane structure can result in a new kind of mussel-inspired adhesive polymers.

Poly(N-Isopropylacrylamide)-co-Acrylamide Hydrogels for the Controlled Release of Bromelain from Agroindustrial Residues of Ananas comosus.

PubMed

Croisfelt, Fernanda; Martins, Bianca C; Rescolino, Robson; Coelho, Diego F; Zanchetta, Beatriz; Mazzola, Priscila G; Goulart, Luis Ricardo; Pessoa, Adalberto; Tambourgi, Elias B; Silveira, Edgar

2015-12-01

This works reports the purification of bromelain extracted from Ananas comosus industrial residues by ethanol purification, its partial characterization from the crude extract as well as the ethanol purified enzyme, and its application onto poly(N-isopropylacrylamide)-co-acrylamide hydrogels. Bromelain was recovered within the 30-70 % ethanol fraction, which achieved a purification factor of 3.12-fold, and yielded more than 90 % of its initial activity. The resulting purified bromelain contained more than 360 U · mg(-1), with a maximum working temperature of 60 °C and pH of 8.0. Poly(N-isopropylacrylamide)-co-acrylamide hydrogels presented a swelling rate of 125 %, which was capable of loading 56 % of bromelain from the solution, and was able to release up to 91 % of the retained bromelain. Ethanol precipitation is suitable for bromelain recovery and application onto poly(N-isopropylacrylamide)-co-acrylamide hydrogels based on its processing time and the applied ethanol prices. Georg Thieme Verlag KG Stuttgart · New York.

Low cytotoxic tissue adhesive based on oxidized dextran and epsilon-poly-L-lysine.

PubMed

Hyon, Suong-Hyu; Nakajima, Naoki; Sugai, Hajime; Matsumura, Kazuaki

2014-08-01

A novel adhesive hydrogel consisting of dextran and epsilon-poly(L-lysine) (dextran-PL) with multiple biomedical applications was developed. Periodate oxidation in aqueous media almost stoichiometrically introduces aldehyde groups in dextran molecules, and aldehyde dextran can react with the primary amino groups in epsilon-PL (ɛ-PL) at neutral pH to form a hydrogel. The gelation time of the hydrogel can be easily controlled by the extent of oxidation in dextran and of the acylation in ɛ-PL by anhydrides. The shear adhesion strength of dextran-PL was 10 times higher than that of fibrin glue, when wet collagen sheets were selected as test specimens. The cytotoxicity of aldehyde dextran and ɛ-PL were 1000 times lower than that of glutaraldehyde and poly(allylamine). The considerably low cytotoxicity of aldehyde dextran could be ascribed to its low reactivity with amine species when compared with glutaraldehyde. In contrast, a high reactivity of amino groups in ɛ-PL was observed when compared with glycine, L-lysine, and gelatin, which could be explained by their poor dissociation at neutral pH, thus leading to low cytotoxicity. © 2013 Wiley Periodicals, Inc.

Synthesis and Characterization of Stimuli Responsive Block Copolymers, Self-Assembly Behavior and Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Determan, Michael Duane

The central theme of this thesis work is to develop new block copolymer materials for biomedical applications. While there are many reports of stimuli-responsive amphiphilic [19-21] and crosslinked hydrogel materials [22], the development of an in situ gel forming, pH responsive pentablock copolymer is a novel contribution to the field, Figure 1.1 is a sketch of an ABCBA pentablock copolymer. The A blocks are cationic tertiary amine methacrylates blocked to a central Pluronic F127 triblock copolymer. In addition to the prerequisite synthetic and macromolecular characterization of these new materials, the self-assembled supramolecular structures formed by the pentablock were experimentally evaluated.more » This synthesis and characterization process serves to elucidate the important structure property relationships of these novel materials, The pH and temperature responsive behavior of the pentablock copolymer were explored especially with consideration towards injectable drug delivery applications. Future synthesis work will focus on enhancing and tuning the cell specific targeting of DNA/pentablock copolymer polyplexes. The specific goals of this research are: (1) Develop a synthetic route for gel forming pentablock block copolymers with pH and temperature sensitive properties. Synthesis of these novel copolymers is accomplished with ATRP, yielding low polydispersity and control of the block copolymer architecture. Well defined macromolecular characteristics are required to tailor the phase behavior of these materials. (2) Characterize relationship between the size and shape of pentablock copolymer micelles and gel structure and the pH and temperature of the copolymer solutions with SAXS, SANS and CryoTEM. (3) Evaluate the temperature and pH induced phase separation and macroscopic self-assembly phenomenon of the pentablock copolymer. (4) Utilize the knowledge gained from first three goals to design and formulate drug delivery formulations based on the multi-responsive properties of the pentablock copolymer. Demonstrate potential biomedical applications of these materials with in vitro drug release studies from pentablock copolymer hydrogels. The intent of this work is to contribute to the knowledge necessary for further tailoring of these, and other functional block copolymer materials for biomedical applications.« less

Characterization of a fluorescent hydrogel synthesized using chitosan, polyvinyl alcohol and 9-anthraldehyde for the selective detection and discrimination of trace Fe3+ and Fe2+ in water for live-cell imaging.

PubMed

Maity, Santu; Parshi, Nira; Prodhan, Chandraday; Chaudhuri, Keya; Ganguly, Jhuma

2018-08-01

A three-dimensional fluorescent hydrogel based on chitosan, polyvinyl alcohol and 9-anthraldehyde (ChPA) has been successfully designed and synthesized for the selective detection and discrimination of Fe 3+ and Fe 2+ in aqueous environment. The unique characteristics of ChPA has been confirmed by the Fourier-transform infrared spectroscopy (FTIR), rheological measurement, scanning electron microscopy (SEM), thermogravimetry and differential thermogravimetry (TG-DTG), ultraviolet-visible spectroscopy (UV-vis), fluorescence studies, transmission electron microscopy (TEM), energy dispersive x-ray spectroscopy (EDX), x-ray diffraction (XRD) and dynamic light scattering (DLS). The emission intensity at 516 nm of the hydrogel has been enhanced remarkably with the addition of Fe 3+ due to the inhibition of the photoinduced electron transfer (PET) process. However, it gets strongly quenched in the case of Fe 2+ owing to chelation enhanced quenching (CHEQ). The probe (ChPA) causes no significant change in the fluorescence and becomes highly specific and sensitive towards Fe 3+ and Fe 2+ compared to other interfering heavy and transition metal ions (HTM). The detection limits of the sensor for the Fe 3+ and Fe 2+ are 0.124 nM and 0.138 nM, respectively. The probe is also promising as a selective sensor for the Fe 3+ and Fe 2+ in the fluorescence imaging of living cells. Thus, such a probe opens up new opportunities to improve the chitosan based fluorescent chemosensor having biocompatibility, biodegradability, sufficient thermal stability and stability in a wide pH range. Copyright © 2018 Elsevier Ltd. All rights reserved.

Targeted nanosensor aided three-dimensional pH mapping in tumor spheroids using two-photon microscopy

NASA Astrophysics Data System (ADS)

Ray, Aniruddha; Lee, Yong-Eun Koo; Elbez, Remy; Kopelman, Raoul

2012-03-01

Tumors are generally characterized by a pH lower than the surrounding tissues. The mapping of tumor pH is of great importance as it plays a critical role in drug delivery and its effectiveness. Here we present a pH mapping technique in tumor spheroids, using targeted, ratiometric, fluorescent, pH nano-sensor that is based on two-photon excitation. Spheroids are micro-tumors that are widely used as an in-vitro three dimensional tumor model to study the different properties of the tumor for the purpose of drug delivery, therapy etc. The nanosensor consists of 8-Hydroxypyrene- 1,3,6-trisulfonic acid (HPTS), a pH sensitive dye, encapsulated in polyacrylamide hydrogel nanoparticle matrix and F3 peptide, conjugated to the nanoparticle's surface. The nanosensor has an average size of 68nm and contains approximately 0.5% dye by weight. The fluorescence intensity ratio, at the two-photon excitation wavelengths of 900nm and 750nm, increases linearly in the pH range from 6.0 to 8.0 and is used to determine the pH of the local environment. Our study reveals the pH distribution inside human cervix cancer spheroids (of different sizes) during the various stages of their formation. This information can be used to develop more efficient drug delivery mechanisms. The two-photon excitation used for this purpose is especially useful as it drastically minimizes both photobleaching and autofluorescence, thus leading to an increase in the signal-to-noise ratio. It also enables deep tissue imaging due to higher photon penetration depth.

Highly photostable near-infrared fluorescent pH indicators and sensors based on BF2-chelated tetraarylazadipyrromethene dyes.

PubMed

Jokic, Tijana; Borisov, Sergey M; Saf, Robert; Nielsen, Daniel A; Kühl, Michael; Klimant, Ingo

2012-08-07

In this study, a series of new BF(2)-chelated tetraarylazadipyrromethane dyes are synthesized and are shown to be suitable for the preparation of on/off photoinduced electron transfer modulated fluorescent sensors. The new indicators are noncovalently entrapped in polyurethane hydrogel D4 and feature absorption maxima in the range 660-710 nm and fluorescence emission maxima at 680-740 nm. Indicators have high molar absorption coefficients of ~80,000 M(-1) cm(-1), good quantum yields (up to 20%), excellent photostability and low cross-sensitivity to the ionic strength. pK(a) values of indicators are determined from absorbance and fluorescence measurements and range from 7 to 11, depending on the substitution pattern of electron-donating and -withdrawing functionalities. Therefore, the new indicators are suitable for exploitation and adaptation in a diverse range of analytical applications. Apparent pK(a) values in sensor films derived from fluorescence data show 0.5-1 pH units lower values in comparison with those derived from the absorption data due to Förster resonance energy transfer from protonated to deprotonated form. A dual-lifetime referenced sensor is prepared, and application for monitoring of pH in corals is demonstrated.

Compositional tuning of epoxide-polyetheramine "click" reaction toward cytocompatible, cationic hydrogel particles with antimicrobial and DNA binding activities.

PubMed

Tang, Shuangcheng; Huang, Lu; Daniels-Mulholland, Robert J; Dlugosz, Elizabeth; Morin, Emily A; Lenaghan, Scott; He, Wei

2016-10-01

The "click" characteristics of nucleophilic opening of epoxide have recently been exploited for the development of a functional hydrogel particle system based on commercially available bisepoxide and triamine polyetheramine monomers. Key features of these particles include high cationic charges and responsiveness to temperature, pH, and oxidation. Despite these advantages, the cytocompatibility of these particles must be considered prior to use in biomedical applications. Here we demonstrate that, by introducing a diamine polyetheramine as a comonomer in the "click" reaction, and tuning its molar ratio with the triamine monomer, cationic nanoparticles with improved cytocompatibility can be prepared. The reduced cytotoxicity is primarily due to the hydrophilic backbone of the diamine comonomer, which has polyethylene glycol as a primary component. The resulting nanoparticles formed from the diamine comonomer exhibited a lower surface charge, while maintaining a comparable size. In addition, the responsiveness of the nanoparticles to temperature, pH, and oxidation was conserved, while achieving greater colloidal stability at basic pH. Results from this study further demonstrated that the nanoparticles were able to encapsulate Nile red, a model for hydrophobic drug molecules, were effective against the bacteria Staphylococcus aureus, and were capable of binding DNA through ionic complexation. Based on the results from this work, the use of diamine comonomers significantly reduces the cytotoxicity of similarly developed hydrogel nanoparticles, allowing for numerous biomedical applications, including nanocarriers for therapeutic agents with poor water solubility, treatment of bacterial infection, and non-viral vectors for gene therapy. In recent years significant attention has been placed on the development of nanocarriers for numerous biomedical applications. Of particular interest are cationic polymers, which contain high positive surface charges that allow binding of numerous therapeutic agents. Unfortunately, the advantages of cationic polymers for binding, are often negated by the tendency of these polymers to be cytotoxic. Previous studies have developed highly responsive cationic hydrogel nanoparticles, which meet several of the criteria for biomedical applications, but were acutely cytotoxic. In this work, cationic hydrogel nanoparticles, with significantly improved cytocompatibility, were synthesized using simple, green epoxy chemistry. In addition, the ability of these nanoparticles to maintain a small size (<500nm), bind DNA, encapsulate hydrophobic drugs, and kill bacteria was maintained. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Electromechanical response of silk fibroin hydrogel and conductive polycarbazole/silk fibroin hydrogel composites as actuator material.

PubMed

Srisawasdi, Thanida; Petcharoen, Karat; Sirivat, Anuvat; Jamieson, Alexander M

2015-11-01

Pure silk fibroin (SF) hydrogel and polycarbazole/silk fibroin (SF/PCZ) hydrogels were fabricated by solvent casting technique to evaluate electromechanical responses, dielectric properties, and cantilever deflection properties as functions of electric field strength, SF concentration, glutaraldehyde concentration, and PCZ concentration in the blends. Electromechanical properties were characterized in oscillatory shear mode at electric field strengths ranging from 0 to 600V/mm and at a temperature of 27°C. For both the pristine SF and SF/PCZ hydrogels, the storage modulus response (ΔG') and the storage modulus sensitivity (ΔG'/G'0) increased dramatically with increasing electric field strength. The pristine hydrogel possessed the highest storage modulus sensitivity value of 5.87, a relatively high value when compared with other previously studied electroactive polymers. With the addition of conductive PCZ in SF hydrogel, the storage modulus sensitivity and the relative dielectric constant decreased; the conductive polymer thus provided the softening effect under electric field. In the deflection response, the dielectrophoresis force and deflection distance increased monotonically with electric field strength, where the pure SF hydrogel showed the highest deflection distance and dielectrophoresis force. Copyright © 2015 Elsevier B.V. All rights reserved.

Phase Transition in Biopolymer Hydrogels Based on Glycine (g), Valine (v), Proline (p), and Isoleucine (i)

NASA Astrophysics Data System (ADS)

Lee, Jonghwi; Urry, Dan W.; Macosko, Christopher W.

2000-03-01

Selectively modified elastic protein-based polymers demonstrate diverse energy conversions by means of the control of a phase transition resulting from the sensitivity to stimuli of the hydrophobic association. Among these polymers, poly(GVGVP), poly(GVGIP) and analogues of poly(GVGVP) containing carboxylic acid or amino functional groups as side chains were cross-linked and their swelling behavior was studied. Regardless of cross-linking method, reversible phase transitions can be observed in the swelling of all cross-linked polymers by changing temperature and pH, where relevant. Decreased cross-link density leads to increased swelling ratio as the transition becomes more pronounced. Fibers, chemically cross-linked after formation, exhibit anisotropic dimensional changes on changing the temperature. Gamma-irradiation cross-linked poly(GVGVP) exhibited a more distinct phase transition than modified poly(GVGVP) with ion pairs between side chains, which were partially converted to amide cross-links.

Bioactive Hydrogels Made from Step-Growth Derived PEG-Peptide Macromers

PubMed Central

Miller, Jordan S.; Shen, Colette J.; Legant, Wesley R.; Baranski, Jan D.; Blakely, Brandon L.; Chen, Christopher S.

2010-01-01

Synthetic hydrogels based on poly(ethylene glycol) (PEG) have been used as biomaterials for cell biology and tissue engineering investigations. Bioactive PEG-based gels have largely relied on heterobifunctional or multi-arm PEG precursors that can be difficult to synthesize and characterize or expensive to obtain. Here, we report an alternative strategy, which instead uses inexpensive and readily available PEG precursors to simplify reactant sourcing. This new approach provides a robust system in which to probe cellular interactions with the microenvironment. We used the step-growth polymerization of PEG diacrylate (PEGDA, 3400 Da) with bis-cysteine matrix metalloproteinase (MMP)-sensitive peptides via Michael-type addition to form biodegradable photoactive macromers of the form acrylate-PEG-(peptide-PEG)m-acrylate. The molecular weight (MW) of these macromers is controlled by the stoichiometry of the reaction, with a high proportion of resultant macromer species greater than 500 kDa. In addition, the polydispersity of these materials was nearly identical for three different MMP-sensitive peptide sequences subjected to the same reaction conditions. When photopolymerized into hydrogels, these high MW materials exhibit increased swelling and sensitivity to collagenase-mediated degradation as compared to previously published PEG hydrogel systems. Cell-adhesive acrylate-PEG-CGRGDS was synthesized similarly and its immobilization and stability in solid hydrogels was characterized with a modified Lowry assay. To illustrate the functional utility of this approach in a biological setting, we applied this system to develop materials that promote angiogenesis in an ex vivo aortic arch explant assay. We demonstrate the formation and invasion of new sprouts mediated by endothelial cells into the hydrogels from embedded embryonic chick aortic arches. Furthermore, we show that this capillary sprouting and three-dimensional migration of endothelial cells can be tuned by engineering the MMP-susceptibility of the hydrogels and the presence of functional immobilized adhesive ligands (CGRGDS vs. CGRGES peptide). The facile chemistry described and significant cellular responses observed suggest the usefulness of these materials in a variety of in vitro and ex vivo biologic investigations, and may aid in the design or refinement of material systems for a range of tissue engineering approaches. PMID:20138664

Study of the influence of the agarose hydrogel layer thickness on sensitivity of the coated silica microsphere resonator to humidity.

PubMed

Mallik, Arun Kumar; Farrell, Gerald; Wu, Qiang; Semenova, Yuliya

2017-05-10

In this paper, we investigate both theoretically and experimentally the influence of the agarose hydrogel layer thickness on the sensitivity of a proposed relative humidity (RH) sensor based on a silica microsphere resonator coated with agarose hydrogel. The operating principle of the sensor relies on excitation of whispering gallery modes (WGMs) in the coated silica microsphere using the evanescent field of a tapered fiber. A change in the ambient relative humidity is detected by measuring the wavelength shift of the WGMs in the transmission spectrum of the tapered fiber. Using perturbation theory, we analyze the influence of the agarose coating thickness on the sensitivity of the proposed sensor and compare the results of this analysis with experimental findings for different coating layer thicknesses. We demonstrate that an increase in the coating layer thickness initially leads to an increase in the sensitivity to RH and reaches saturation at higher values of the agarose layer thickness. The results of the study are useful for the design and optimization of microsphere sensor parameters to meet a performance specification.

Autonomous Rhythmic Drug Delivery Systems Based on Chemical and Biochemomechanical Oscillators

NASA Astrophysics Data System (ADS)

Siegel, Ronald A.

While many drug delivery systems target constant, or zero-order drug release, certain drugs and hormones must be delivered in rhythmic pulses in order to achieve their optimal effect. Here we describe studies with two model autonomous rhythmic delivery systems. The first system is driven by a pH oscillator that modulates the ionization state of a model drug, benzoic acid, which can permeate through a lipophilic membrane when the drug is uncharged. The second system is based on a nonlinear negative feedback instability that arises from coupling of swelling of a hydrogel membrane to an enzymatic reaction, with the hydrogel controlling access of substrate to the enzyme, and the enzyme's product controlling the hydrogel's swelling state. The latter system, whose autonomous oscillations are driven by glucose at constant external activity, is shown to deliver gonadotropin releasing hormone (GnRH) in rhythmic pulses, with periodicity of the same order as observed in sexually mature adult humans. Relevant experimental results and some mathematical models are reviewed.

Systematic studies of tannin–formaldehyde aerogels: preparation and properties

PubMed Central

Amaral-Labat, Gisele; Szczurek, Andrzej; Fierro, Vanessa; Pizzi, Antonio; Celzard, Alain

2013-01-01

Gelation of tannin–formaldehyde (TF) solutions was systematically investigated by changing pH and concentration of TF resin in water. In this way we constructed the TF phase diagram, from which chemical hydrogels could be described, and also synthesized thermoreversible tannin-based hydrogels. Conditions of non-gelation were also determined. Hydrogels were dried in supercritical CO2, leading to a broad range of TF aerogels. The latter were investigated for volume shrinkage, total porosity, micro-, meso- and macropore volumes, Brunauer–Emmett–Teller (BET) surface area, microscopic texture, mechanical and thermal properties. All these properties are discussed in relation to each other, leading to an accurate and self-consistent description of these bioresource-based highly porous materials. The conditions for obtaining the highest BET surface area or mesopore volume were determined and explained in relation to the preparation conditions. The highest BET surface area, 880 m2 g−1, is remarkably high for organic aerogels derived from a natural resource. PMID:27877559

Systematic studies of tannin-formaldehyde aerogels: preparation and properties

NASA Astrophysics Data System (ADS)

Amaral-Labat, Gisele; Szczurek, Andrzej; Fierro, Vanessa; Pizzi, Antonio; Celzard, Alain

2013-02-01

Gelation of tannin-formaldehyde (TF) solutions was systematically investigated by changing pH and concentration of TF resin in water. In this way we constructed the TF phase diagram, from which chemical hydrogels could be described, and also synthesized thermoreversible tannin-based hydrogels. Conditions of non-gelation were also determined. Hydrogels were dried in supercritical CO2, leading to a broad range of TF aerogels. The latter were investigated for volume shrinkage, total porosity, micro-, meso- and macropore volumes, Brunauer-Emmett-Teller (BET) surface area, microscopic texture, mechanical and thermal properties. All these properties are discussed in relation to each other, leading to an accurate and self-consistent description of these bioresource-based highly porous materials. The conditions for obtaining the highest BET surface area or mesopore volume were determined and explained in relation to the preparation conditions. The highest BET surface area, 880 m2 g-1, is remarkably high for organic aerogels derived from a natural resource.

In vitro analysis of the physical properties of contact lens blister pack solutions.

PubMed

Menzies, Kara L; Jones, Lyndon

2011-04-01

Since the initial development of silicone hydrogels, many modifications to the bulk and surface properties of the lenses have been undertaken to improve the wettability and comfort of the lenses. Recently, manufacturers have incorporated various "wetting agents" or surface-active agents into the blister packaging solutions (BPSs) of the lenses to improve initial comfort of the lens on eye. The purpose of this study was to measure and compare the pH, surface tension (ST), viscosity, and osmolality of BPSs for a variety of silicone hydrogel and polyHEMA-based hydrogel lenses. In addition, two saline solutions were tested for comparison purposes. The pH, osmolality, ST, and viscosity were measured for the BPSs for lotrafilcon B and lotrafilcon A and lotrafilcon B with a "modified BPS" (m-lotrafilcon A, m-lotrafilcon B) (CIBA Vision, Duluth, GA); balafilcon A (Bausch & Lomb, Rochester, NY); galyfilcon A, senofilcon A, and narafilcon A (Johnson & Johnson, Jacksonville, FL); and comfilcon A and enfilcon A (CooperVision, Pleasanton, CA) and BPSs from two conventional polyHEMA-based materials-etafilcon A (Johnson & Johnson) and omafilcon A (CooperVision). The two saline solutions tested were Unisol (Alcon, Fort Worth, TX) and Softwear Saline (CIBA Vision). The pH results for the two saline solutions and all BPSs remained in the pH range of tears (6.6-7.8). The ST of the modified BPS was significantly lower (p < 0.01) than the original non-modified BPS. Viscosity measurements ranged between 0.90 and 1.00 cP for all BPSs and saline solutions, except for the modified BPS, which had significantly higher viscosities (p < 0.001). Osmolality measurements were not significantly different (p > 0.05) between BPSs made by the same manufacturer but were significantly different compared with BPSs made by different manufacturers (p < 0.05). The incorporation of wetting agents and surfactants into BPSs does alter the physical properties of the BPSs, which may have clinical implications regarding initial in-eye comfort.

Evaluation of superabsorbent linseed-polysaccharides as a novel stimuli-responsive oral sustained release drug delivery system.

PubMed

Haseeb, Muhammad Tahir; Hussain, Muhammad Ajaz; Bashir, Sajid; Ashraf, Muhammad Umer; Ahmad, Naveed

2017-03-01

Advancement in technology has transformed the conventional dosage forms to intelligent drug delivery systems. Such systems are helpful for targeted and efficient drug delivery with minimum side effects. Drug release from these systems is governed and controlled by external stimuli (pH, enzymes, ions, glucose, etc.). Polymeric biomaterial having stimuli-responsive properties has opened a new area in drug delivery approach. Potential of a polysaccharide (rhamnogalacturonan)-based hydrogel from Linseeds (Linum usitatissimum L.) was investigated as an intelligent drug delivery material. Different concentrations of Linseed hydrogel (LSH) were used to prepare caffeine and diacerein tablets and further investigated for pH and salt solution-responsive swelling, pH-dependent drug release, and release kinetics. Morphology of tablets was observed using SEM. LSH tablets exhibited dynamic swelling-deswelling behavior with tendency to swell at pH 7.4 and in deionized water while deswell at pH 1.2, in normal saline and ethanol. Consequently, pH controlled release of the drugs was observed from tablets with lower release (<10%) at pH 1.2 and higher release at pH 6.8 and 7.4. SEM showed elongated channels in swollen then freeze-dried tablets. The drug release was greatly influenced by the amount of LSH in the tablets. Drug release from LSH tablets was governed by the non-Fickian diffusion. These finding indicates that LSH holds potential to be developed as sustained release material for tablet.

Supramolecular Hydrogels Based on DNA Self-Assembly.

PubMed

Shao, Yu; Jia, Haoyang; Cao, Tianyang; Liu, Dongsheng

2017-04-18

Extracellular matrix (ECM) provides essential supports three dimensionally to the cells in living organs, including mechanical support and signal, nutrition, oxygen, and waste transportation. Thus, using hydrogels to mimic its function has attracted much attention in recent years, especially in tissue engineering, cell biology, and drug screening. However, a hydrogel system that can merit all parameters of the natural ECM is still a challenge. In the past decade, deoxyribonucleic acid (DNA) has arisen as an outstanding building material for the hydrogels, as it has unique properties compared to most synthetic or natural polymers, such as sequence designability, precise recognition, structural rigidity, and minimal toxicity. By simple attachment to polymers as a side chain, DNA has been widely used as cross-links in hydrogel preparation. The formed secondary structures could confer on the hydrogel designable responsiveness, such as response to temperature, pH, metal ions, proteins, DNA, RNA, and small signal molecules like ATP. Moreover, single or multiple DNA restriction enzyme sites could be incorporated into the hydrogels by sequence design and greatly expand the latitude of their responses. Compared with most supramolecular hydrogels, these DNA cross-linked hydrogels could be relatively strong and easily adjustable via sequence variation, but it is noteworthy that these hydrogels still have excellent thixotropic properties and could be easily injected through a needle. In addition, the quick formation of duplex has also enabled the multilayer three-dimensional injection printing of living cells with the hydrogel as matrix. When the matrix is built purely by DNA assembly structures, the hydrogel inherits all the previously described characteristics; however, the long persistence length of DNA structures excluded the small size meshes of the network and made the hydrogel permeable to nutrition for cell proliferation. This unique property greatly expands the cell viability in the three-dimensional matrix to several weeks and also provides an easy way to prepare interpenetrating double network materials. In this Account, we outline the stream of hydrogels based on DNA self-assembly and discuss the mechanism that brings outstanding properties to the materials. Unlike most reported hydrogel systems, the all-in-one character of the DNA hydrogel avoids the "cask effect" in the properties. We believe the hydrogel will greatly benefit cell behavior studies especially in the following aspects: (1) stem cell differentiation can be studied with solely tunable mechanical strength of the matrix; (2) the dynamic nature of the network can allow cell migration through the hydrogel, which will help to build a more realistic model to observe the migration of cancer cells in vivo; (3) combination with rapidly developing three-dimension printing technology, the hydrogel will boost the construction of three-dimensional tissues and artificial organs.

Cold-set hydrogels made of whey protein nanofibrils with different divalent cations.

PubMed

Mohammadian, Mehdi; Madadlou, Ashkan

2016-08-01

Whey protein nanofibrils are gaining interest to fabricate cold-set hydrogels due to their ability to gel at lower concentrations than parent proteins. In the present research, fibrillated protein solution was gelled with three different divalent cation salts including CaCl2, MnCl2 and ZnCl2 and the textural and functional characteristics of the resulting hydrogel samples were studied. Atomic force microscopy indicated that the flexible micron-scaled fibrils with nanometric thickness (up to 8.0nm) that formed at pH 2.0 underwent breaking in length upon post-formation pH rise to 7.5. Whilst heat-denatured protein solution failed to form self-supporting gel at pH 7.5, fibrillated protein solution gelled by all three types of cations. Fibrillation increased the protein solution consistency coefficient (K) much more than heat denaturation. It was suggested based on Fourier-transform infra-red (FT-IR) spectra that some hydrogen bonds were disrupted by fibrillation. Zn(2+)-induced gel was firmer, had a higher water holding capacity and a more compact microstructure, as well, required a higher compressive stress to fracture than its counterparts. Nonetheless, the Mn(2+)- and Ca(2+)-induced gels disintegrated to a much lesser extent in both pepsin-free and pepsin-present simulated gastric juice than Zn(2+)-induced sample. Chitosan coating approximately halved the simulated degradability of all gel samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Photonic crystal fiber as lab-in-fiber optofluidic platform for sensing and process monitoring

NASA Astrophysics Data System (ADS)

Tian, Fei

The ability to design and fabricate photonic crystal fiber (PCF) of vastly different microstructural and optical characteristics is arguably one of the most significant recent advances in the field of fiber optics. This dissertation aims to advance the PCF research frontier by exploring long-period fiber gratings (LPG) inscribed in PCF for sensing and process monitoring via combined numerical and experimental investigation. Specifically, a mode solver based on the Finite Element Method (FEM) has been employed to calculate the mode field distribution, the phase matching condition, and the dispersive characteristics associated with LPG-induced coupling of the fundamental core mode (LP01) to various cladding modes (LPmn, m=0,1; n=2,3, ...) in an endlessly single mode PCF. The numerical results have been used to guide the design and fabrication of LPG in PCF by CO2 laser inscription to maximize index sensitivity in gas or liquid medium. Cascaded PCF-LPG has been fabricated and shown to exhibit record sensitivity in excess of 1700 nm/RIU with high resolution for index measurements of gas phase. The inherent interference fringes in the transmission spectrum of cascaded PCF-LPG have been utilized to analyze mode coupling behaviour. In addition, we have developed and implemented a reflective mirror-aided method to allow symmetrical CO2 laser irradiation of PCF during LPG inscription. Both numerical analysis and experimental measurements have shown significantly improved mode coupling behaviour, mode field distribution, as well as reproducibility in LPG fabrication, critical for practical exploitation of the PCF-LPG platform. We have further exploited the high index sensitivity of PCF-LPG to monitor layer-by-layer (LbL) self-assembly of poly(vinyl pyrrolidone) (PVPON) and poly(methacrylic acid) (PMAA) polyelectrolyte layers as well as the pH responsiveness of the cross-linked PMAA hydrogel films. A shift of ˜1.625 nm in the resonance wavelength per polyelectrolyte layer deposited inside PCF-LPG has been registered with robust pH response of the hydrogel. These findings have demonstrated the significant potential of PCF-LPG as a novel lab-in-fiber optofluidic platform for basic and applied studies of LbL in confined geometry for nanosensors and nano-actuators based on stimuli-responsive polyelectrolyte thin films.

Dramatically Promoted Swelling of a Hydrogel by Pillar[6]arene-Ferrocene Complexation with Multistimuli Responsiveness.

PubMed

Ni, Mengfei; Zhang, Ning; Xia, Wei; Wu, Xuan; Yao, Chenhao; Liu, Xin; Hu, Xiao-Yu; Lin, Chen; Wang, Leyong

2016-05-25

The swelling-shrinking transition of hydrogels is crucial for their wide applications such as actuators and drug delivery. We hereby fabricated a smart hydrogel with ferrocene groups on pendant of polymer networks. While it was immersed in the water-soluble pillar[6]arene (WP6) aqueous solution, the hydrogel was dramatically swollen, which was an approximately 11-fold promotion in weight compared with that in pure water, due to the formation of the inclusion complexes between WP6 and ferrocene groups in the hydrogel. In particular, the well-swollen hydrogel exhibited good responsiveness to multistimuli including temperature, pH, redox, and competitive guests by tuning the dissociation/formation of WP6-ferrocene inclusion complexes or the strength of their charges. Meanwhile, potential application of such a smart hydrogel in pH-responsive drug release was demonstrated as well.

Polymer gel dosimeter with AQUAJOINT® as hydrogel matrix

NASA Astrophysics Data System (ADS)

Maeyama, Takuya; Ishida, Yasuhiro; Kudo, Yoshihiro; Fukasaku, Kazuaki; Ishikawa, Kenichi L.; Fukunishi, Nobuhisa

2018-05-01

We report a polymer gel dosimeter based on a new gel matrix (AQUAJOINT®) that is a thermo-irreversible hydrogel formed by mixing two types of water-based liquids at room temperature. Normoxic N-vinylpyrrolidone-based polymer gels were prepared with AQUAJOINT® instead of gelatin. This AQUAJOINT®-based gel dosimeter exhibits a 2.5-fold increase in sensitivity over a gelatin-based gel dosimeter and a linear dose-response in the dose range of 0-8 Gy. This gel has heat resistance in a jar and controlled gel properties such as viscoelastic and mechanical characters, which may be useful for deformable polymer gel dosimetry.

Fabrication of a microfluidic device for studying the in situ drug-loading/release behavior of graphene oxide-encapsulated hydrogel beads.

PubMed

Veerla, Sarath Chandra; Kim, Da Reum; Yang, Sung Yun

2018-01-01

Controlled drug delivery system is highly important for not only prolonged the efficacy of drug but also cellular development for tissue engineering. A number of biopolymer composites and nanostructured carriers behave been used for the controlled drug delivery of therapeutics. Recently, in vitro microfluidic devices that mimic the human body have been developed for drug-delivery applications. A microfluidic channel was fabricated via a two-step process: (i) polydimethyl siloxane (PDMS) and curing agent were poured with a 10:2 mass ratio onto an acrylic mold with two steel pipes, and (ii) calcium alginate beads were synthesized using sodium alginate and calcium chloride solutions. Different amounts (10, 25, 50 μg) of graphene oxide (GO) were then added by Hummers method, and studies on the encapsulation and release of the model drug, risedronate (Ris), were performed using control hydrogel beads (pH 6.3), GO-containing beads (10GO, 25GO and 50GO), and different pH conditions. MC3T3 osteoblastic cells were cultured in a microchannel with Ris-loaded GO-hydrogel beads, and their proliferation, viability, attachment and spreading were assessed for a week. The spongy and textured morphology of pristine hydrogel beads was converted to flowery and rod-shaped structures in drug-loaded hydrogel beads at reduced pH (6.3) and at a lower concentration (10 μg) of GO. These latter 10GO drug-loaded beads rapidly released their cargo owing to the calcium phosphate deposited on the surface. Notably, beads containing a higher amount of GO (50GO) exhibited an extended drug-release profile. We further found that MC3T3 cells proliferated continuously in vitro in the microfluidic channel containing the GO-hydrogel system. MTT and live/dead assays showed similar proliferative potential of MC3T3 cells. Therefore, a microfluidic device with microchannels containing hydrogel beads formulated with different amounts of GO and tested under various pH conditions could be a promising system for controlled drug release. The GO and drug (risedronate, Rig) were directed loaded into a hydrogel placed in a microchannel. Through interactions such as hydrogen bonding between Go and the Rig-loaded GO-hydrogel beads, the bead-loaded microfluidic device supported MC3T3 proliferation and development as osteoblast without additional osteogenic differentiation supplements.

Analyte-Responsive Hydrogels: Intelligent Materials for Biosensing and Drug Delivery.

PubMed

Culver, Heidi R; Clegg, John R; Peppas, Nicholas A

2017-02-21

Nature has mastered the art of molecular recognition. For example, using synergistic non-covalent interactions, proteins can distinguish between molecules and bind a partner with incredible affinity and specificity. Scientists have developed, and continue to develop, techniques to investigate and better understand molecular recognition. As a consequence, analyte-responsive hydrogels that mimic these recognitive processes have emerged as a class of intelligent materials. These materials are unique not only in the type of analyte to which they respond but also in how molecular recognition is achieved and how the hydrogel responds to the analyte. Traditional intelligent hydrogels can respond to environmental cues such as pH, temperature, and ionic strength. The functional monomers used to make these hydrogels can be varied to achieve responsive behavior. For analyte-responsive hydrogels, molecular recognition can also be achieved by incorporating biomolecules with inherent molecular recognition properties (e.g., nucleic acids, peptides, enzymes, etc.) into the polymer network. Furthermore, in addition to typical swelling/syneresis responses, these materials exhibit unique responsive behaviors, such as gel assembly or disassembly, upon interaction with the target analyte. With the diverse tools available for molecular recognition and the ability to generate unique responsive behaviors, analyte-responsive hydrogels have found great utility in a wide range of applications. In this Account, we discuss strategies for making four different classes of analyte-responsive hydrogels, specifically, non-imprinted, molecularly imprinted, biomolecule-containing, and enzymatically responsive hydrogels. Then we explore how these materials have been incorporated into sensors and drug delivery systems, highlighting examples that demonstrate the versatility of these materials. For example, in addition to the molecular recognition properties of analyte-responsive hydrogels, the physicochemical changes that are induced upon analyte binding can be exploited to generate a detectable signal for sensing applications. As research in this area has grown, a number of creative approaches for improving the selectivity and sensitivity (i.e., detection limit) of these sensors have emerged. For applications in drug delivery systems, therapeutic release can be triggered by competitive molecular interactions or physicochemical changes in the network. Additionally, including degradable units within the network can enable sustained and responsive therapeutic release. Several exciting examples exploiting the analyte-responsive behavior of hydrogels for the treatment of cancer, diabetes, and irritable bowel syndrome are discussed in detail. We expect that creative and combinatorial approaches used in the design of analyte-responsive hydrogels will continue to yield materials with great potential in the fields of sensing and drug delivery.

In vivo imaging of the morphology and changes in pH along the gastrointestinal tract of Japanese medaka by photonic band-gap hydrogel microspheres.

PubMed

Du, Xuemin; Lei, Ngai-Yu; Hu, Peng; Lei, Zhang; Ong, Daniel Hock-Chun; Ge, Xuewu; Zhang, Zhicheng; Lam, Michael Hon-Wah

2013-07-17

Colloidal crystalline microspheres with photonic band-gap properties responsive to media pH have been developed for in vivo imaging purposes. These colloidal crystalline microspheres were constructed from monodispersed core-shell nano-size particles with poly(styrene-co-acrylic acid) (PS-co-PAA) cores and poly(acrylic acid-co-N-isopropylacrylamide) (PAA-co-PNIPAM) hydrogel shells cross-linked by N,N'-methylenebisacrylamide. A significant shift in the photonic band-gap properties of these colloidal crystalline microspheres was observed in the pH range of 4-5. This was caused by the discontinuous volume phase transition of the hydrogel coating, due to the protonation/deprotonation of its acrylic acid moieties, on the core-shell nano-sized particles within the microspheres. The in vivo imaging capability of these pH-responsive photonic microspheres was demonstrated on a test organism - Japanese medaka, Oryzia latipes - in which the morphology and change in pH along their gastrointestinal (GI) tracts were revealed under an ordinary optical microscope. This work illustrates the potential of stimuli-responsive photonic band-gap materials in tissue-/organ-level in vivo bio-imaging. Copyright © 2013 Elsevier B.V. All rights reserved.

Photothermal-modulated drug delivery and magnetic relaxation based on collagen/poly(γ-glutamic acid) hydrogel.

PubMed

Cho, Sun-Hee; Kim, Ahreum; Shin, Woojung; Heo, Min Beom; Noh, Hyun Jong; Hong, Kwan Soo; Cho, Jee-Hyun; Lim, Yong Taik

2017-01-01

Injectable and stimuli-responsive hydrogels have attracted attention in molecular imaging and drug delivery because encapsulated diagnostic or therapeutic components in the hydrogel can be used to image or change the microenvironment of the injection site by controlling various stimuli such as enzymes, temperature, pH, and photonic energy. In this study, we developed a novel injectable and photoresponsive composite hydrogel composed of anticancer drugs, imaging contrast agents, bio-derived collagen, and multifaceted anionic polypeptide, poly (γ-glutamic acid) (γ-PGA). By the introduction of γ-PGA, the intrinsic temperature-dependent phase transition behavior of collagen was modified to a low viscous sol state at room temperature and nonflowing gel state around body temperature. The modified temperature-dependent phase transition behavior of collagen/γ-PGA hydrogels was also evaluated after loading of near-infrared (NIR) fluorophore, indocyanine green (ICG), which could transform absorbed NIR photonic energy into thermal energy. By taking advantage of the abundant carboxylate groups in γ-PGA, cationic-charged doxorubicin (Dox) and hydrophobic MnFe 2 O 4 magnetic nanoparticles were also incorporated successfully into the collagen/γ-PGA hydrogels. By illumination of NIR light on the collagen/γ-PGA/Dox/ICG/MnFe 2 O 4 hydrogels, the release kinetics of Dox and magnetic relaxation of MnFe 2 O 4 nanoparticles could be modulated. The experimental results suggest that the novel injectable and NIR-responsive collagen/γ-PGA hydrogels developed in this study can be used as a theranostic platform after loading of various molecular imaging probes and therapeutic components.

Chitosan-containing hydrogel wound dressings prepared by radiation technique

NASA Astrophysics Data System (ADS)

Mozalewska, Wiktoria; Czechowska-Biskup, Renata; Olejnik, Alicja K.; Wach, Radoslaw A.; Ulański, Piotr; Rosiak, Janusz M.

2017-05-01

The aim of the study was to develop an antimicrobial hydrogel wound dressing by means of radiation-initiated crosslinking of hydrophilic polymers, i.e. by well-established technology comprising gel manufacturing and its sterilization in one process. The approach included admixture of chitosan of relatively low molecular weight dissolved in lactic acid (LA) into the initial regular components of the conventional hydrogel dressing based on poly(N-vinyl pyrrolidone) (PVP) and agar. Molecular weight of chitosan was regulated by radiation-initiated degradation in the range of 39-132 kg mol-1. Optimum total concentration of LA in the resultant hydrogel dressing was evaluated as 0.05 mol dm-3, that is ca. 0.5%. Presence of LA in the system influenced essential radiation and technological parameters of hydrogel manufacturing. The setting temperature of the pre-hydrogel mixture, resulting from agar ability to congeal, was reduced with LA concentration, yet remained significantly above the room temperature. 0.5% of chitosan was effectively dissolved in aqueous solution of lactic acid due to its pH (lower than 5.5). Radiation parameters of PVP crosslinking in the presence of LA, as determined with generalized Charlesby-Pinner equation, were reflected in slight reduction of the maximum gel fraction and increase in gelation dose and in the factor comparing yields of scission to crosslinking. Nevertheless, essentially physical characteristics of the hydrogel was not affected, except for somewhat increased water uptake capacity, what in turn improves functionality of the dressing as extensive exudate for the wound can be efficiently absorbed. Preliminary microbiological studies showed antimicrobial character of the chitosan-containing hydrogel towards Gram-positive bacterial strain.

Novel Osteoinductive Photo-cross-linkable Chitosan-lactide-fibrinogen Hydrogels Enhance Bone Regeneration in Critical Size Segmental Bone Defects

DTIC Science & Technology

2014-08-01

an absorbable collagen sponge (ACS) is the FDA-approved device for clinical applications including lumbar spine fusion, open tibial fractures, and...fibrinogen on the morphological change of the CL hydrogels was observed. The hydrogel samples were incubated into PBS (pH 7.4) at 37°C for 1 day and... morphology was observed qualitatively using a Zeiss Axiovert 200 microscope (Carl Zeiss Microimaging, Thornwood, NY). Photomicrographs of cells

Synthesis and characterization of a biocompatible chitosan-based hydrogel cross-linked via 'click' chemistry for controlled drug release.

PubMed

Guaresti, O; García-Astrain, C; Palomares, T; Alonso-Varona, A; Eceiza, A; Gabilondo, N

2017-09-01

A chemically cross-linked chitosan-based hydrogel was successfully synthesized through Diels-Alder (DA) reaction and characterized. The final product was obtained after different steps; on the one hand, furan-modified chitosan (Cs-Fu) was synthesized by the reaction of furfural with the free amino groups of chitosan. On the other hand, highlighting the novelty of the present research, maleimide-functionalized chitosan (Cs-AMI) was prepared by the reaction of a maleimide-modified aminoacid with the amino groups of chitosan through amide coupling. The two complementary chitosan derivatives were cross-linked to the final hydrogel network. Both modification reactions were confirmed by FTIR and 1 H NMR, obtaining a degree of substitution (DS) of 31% and 26% for Cs-Fu and Cs-AMI, respectively. The as-designed hydrogel was analyzed in terms of microstructure, swelling capacity and rheological behaviour. The hydrogel showed pH-sensitivity, biocompatibility and inhibitory bacterial activity, promising features for biomedical applications, particularly for targeted-drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Production of lignin based insoluble polymers (anionic hydrogels) by C. versicolor.

PubMed

Brzonova, Ivana; Kozliak, Evguenii I; Andrianova, Anastasia A; LaVallie, Audrey; Kubátová, Alena; Ji, Yun

2017-12-13

Unlike previous lignin biodegradation studies, white rot fungi were used to produce functional biopolymers from Kraft lignin. Lignin-based polymers (hydrogel precursors) partially soluble in both aqueous and organic solvents were produced employing a relatively fast (6 days) enzymation of Kraft lignin with basidiomycetes, primarily Coriolus versicolor, pre-grown on kenaf/lignin agar followed by either vacuum evaporation or acid precipitation. After drying followed by a treatment with alkaline water, this intermediate polymer became a pH-sensitive anionic hydrogel insoluble in either aqueous or organic solvents. The yield of this polymer increased from 20 to 72 wt% with the addition of 2% dimethylsulfoxide to distilled water used as a medium. The mechanical stability and buffering capacity of this hydrogel can be adjusted by washing the intermediate polymer/hydrogel precursor prior to drying with solvents of different polarity (water, methanol or ethanol). Any of these polymers featured a significant thermal resilience assessed as a high thermostable "coked" fraction in thermal carbon analysis, apparently resulting from significant covalent cross-linking that occurs during the treatment of their intermediate precursors.

Temperature-responsive in situ nanoparticle hydrogels based on hydrophilic pendant cyclic ether modified PEG-PCL-PEG.

PubMed

Feng, Zujian; Zhao, Junqiang; Li, Yin; Xu, Shuxin; Zhou, Junhui; Zhang, Jianhua; Deng, Liandong; Dong, Anjie

2016-10-20

Thermo-sensitive injectable hydrogels based on poly(ε-caprolactone)/poly(ethylene glycol) (PCL/PEG) block copolymers have attracted considerable attention for sustained drug release and tissue engineering applications. Previously, we have reported a thermo-sensitive hydrogel of P(CL-co-TOSUO)-PEG-P(CL-co-TOSUO) (PECT) triblock copolymers modified by hydrophilic cyclic ether pendant groups 1,4,8-trioxa-[4.6]spiro-9-undecanone (TOSUO). Unfortunately, the low gel modulus of PECT (only 50-70 Pa) may limit its applications. Herein, another kind of thermogelling triblock copolymer of a pendant cyclic ether-modified caprolactonic poloxamer analog, PEG-P(CL-co-TOSUO)-PEG (PECTE), was successfully prepared by control of the hydrophilicity/hydrophobicity balance and chemical compositions of the copolymers. PECTE powder could directly disperse in water to form a stable nanoparticle (NP) aqueous dispersion and underwent sol-gel-sol transition behavior at a higher concentration with the temperature increasing from ambient or lower temperatures. Significantly, the microstructure parameters (e.g., different chemical compositions of the hydrophobic block and topology) played a critical role in the phase transition behavior. Furthermore, comparison studies on PECTE and PEG-PCL-PEG (PECE) showed that the introduction of pendant cyclic ether groups into PCL blocks could avoid unexpected ahead-of-time gelling of the PECE aqueous solution. In addition, the rheological analysis of PECTE and PECT indicated that the storage modulus of the PECTE hydrogel could be 100 times greater than that of the PECT hydrogel under the same mole ratios of TOSUO/CL and lower molecular weight. Consequently, PECTE thermal hydrogel systems are believed to be promising as in situ gel-forming biomaterials for drug delivery and tissue engineering.

Autonomously Self-Adhesive Hydrogels as Building Blocks for Additive Manufacturing.

PubMed

Deng, Xudong; Attalla, Rana; Sadowski, Lukas P; Chen, Mengsu; Majcher, Michael J; Urosev, Ivan; Yin, Da-Chuan; Selvaganapathy, P Ravi; Filipe, Carlos D M; Hoare, Todd

2018-01-08

We report a simple method of preparing autonomous and rapid self-adhesive hydrogels and their use as building blocks for additive manufacturing of functional tissue scaffolds. Dynamic cross-linking between 2-aminophenylboronic acid-functionalized hyaluronic acid and poly(vinyl alcohol) yields hydrogels that recover their mechanical integrity within 1 min after cutting or shear under both neutral and acidic pH conditions. Incorporation of this hydrogel in an interpenetrating calcium-alginate network results in an interfacially stiffer but still rapidly self-adhesive hydrogel that can be assembled into hollow perfusion channels by simple contact additive manufacturing within minutes. Such channels withstand fluid perfusion while retaining their dimensions and support endothelial cell growth and proliferation, providing a simple and modular route to produce customized cell scaffolds.

Dynamic Coordination of Eu-Iminodiacetate to Control Fluorochromic Response of Polymer Hydrogels to Multistimuli.

PubMed

Weng, Gengsheng; Thanneeru, Srinivas; He, Jie

2018-03-01

New fluorochromic materials that reversibly change their emission properties in response to their environment are of interest for the development of sensors and light-emitting materials. A new design of Eu-containing polymer hydrogels showing fast self-healing and tunable fluorochromic properties in response to five different stimuli, including pH, temperature, metal ions, sonication, and force, is reported. The polymer hydrogels are fabricated using Eu-iminodiacetate (IDA) coordination in a hydrophilic poly(N,N-dimethylacrylamide) matrix. Dynamic metal-ligand coordination allows reversible formation and disruption of hydrogel networks under various stimuli which makes hydrogels self-healable and injectable. Such hydrogels show interesting switchable ON/OFF luminescence along with the sol-gel transition through the reversible formation and dissociation of Eu-IDA complexes upon various stimuli. It is demonstrated that Eu-containing hydrogels display fast and reversible mechanochromic response as well in hydrogels having interpenetrating polymer network. Those multistimuli responsive fluorochromic hydrogels illustrate a new pathway to make smart optical materials, particularly for biological sensors where multistimuli response is required. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ionic polysaccharide hydrogels via the Passerini and Ugi multicomponent condensations: synthesis, behavior and solid-state NMR characterization.

PubMed

de Nooy, A E; Capitani, D; Masci, G; Crescenzi, V

2000-01-01

Original data are provided demonstrating that the title condensations are simple and versatile methods for the synthesis of hydrogels based on a variety of carboxylated polysaccharides. In this work, the biopolymers considered are sodium hyaluronate and sodium alginate. Nonnatural carboxylated polysaccharides were commercial (carboxymethyl)cellulose or were obtained by carboxymethylation or selective oxidation of primary alcohol groups of scleroglucan and dextran. Hydrogels prepared via the Passerini reaction were transparent, alkali labile materials whereas the transparency of the Ugi gels depended on the polysaccharide, the cross-linker, and the degree of cross-linking. The Ugi gels were stable for several months at a pH ranging from 1.3 to 11 and up to temperatures over 90 degrees C. The structure of the networks was studied by means of 13C CP-MAS and 15N CP-MAS NMR spectroscopy. A quantitative NMR analysis and elemental analysis of the dry gels allowed us to estimate the efficiency of the reactions, i.e., the actual degree of cross-linking, which appeared to be about 80% of theoretical. The influence of added salt and pH on the swelling of several Ugi gels with different degrees of cross-linking was studied in a qualitative manner.

Development of polymer-polysaccharide hydrogels for controlling drug delivery

NASA Astrophysics Data System (ADS)

Baldwin, Aaron David

The use of polymers as biomaterials has evolved over the past several decades, encompassing an expanding synthetic toolbox and many bio-mimetic approaches. Both synthetic and natural polymers have been used as components for biomaterials as their unique chemical structures can provide specific functions for desired applications. Of these materials, heparin, a highly sulfated naturally occurring polysaccharide, has been investigated extensively as a core component in drug delivery platforms and tissue engineering. The goal of this work was to further explore the use of heparin via conjugation with synthetic polymers for applications in drug delivery. We begin by investigating low molecular weight heparin (LMWH), a depolymerized heparin that is used medicinally in the prevention of thrombosis by subcutaneous injection or intravenous drip. Certain disease states or disorders require frequent administration with invasive delivery modalities leading to compliance issues for individuals on prolonged therapeutic courses. To address these issues, a long-term delivery method was developed for LMWH via subcutaneous injection of in situ hydrogelators. This therapy was accomplished by chemical modification of LMWH with maleimide functionality so that it may be crosslinked into continuous hydrogel networks with four-arm thiolated polyethylene glycol (PEG-SH). These hydrogels degrade via hydrolysis over a period of weeks and release bioactive LMWH with first-order kinetics as determined by in vitro and in vivo models, thus indicating the possibility of an alternative means of heparin delivery over current accepted methodologies. Evaluation of the maleimide-thiol chemistries applied in the LMWH hydrogels revealed reversibility for some conjugates under reducing conditions. Addition chemistries, such as maleimide-thiol reactions, are widely employed in biological conjugates and are generally accepted as stable. Here we show that the resulting succinimide thioether formed by the Michael type addition of thiol derivatives to N-ethylmaleimide (NEM) undergoes retro and exchange reactions in the presence of other thiol compounds at physiological pH and temperature. Model studies of NEM conjugated to various thiols (4-mercaptophenylacetic acid (MPA), N-acetylcysteine, or 3-mercaptopropionic acid (MP)), incubated with a naturally occurring reducing agent, glutathione, showed half-lives from 20-80 hrs with extents of conversion from 20-90% for MPA and N-acetylcysteine conjugates. The kinetics of the retro reactions and extent of exchange can be modulated by the Michael donor's reactivity; therefore the degradation of maleimide-thiol adducts could be tuned for controlled release of drugs or degradation of materials at timescales different than those currently possible via disulfide-mediated release. The reduction sensitive maleimide-thiol chemistry was then investigated as a crosslinking mechanism for LMWH hydrogels. Crosslinking maleimide functionalized LMWH with PEG functionalized with thiophenyl functionalities imparted glutathione sensitivity. 4-mercaptophenylpropionic acid and 2,2-dimethyl-3-(4-mercaptophenyl)propionic acid, induced sensitivity to glutathione as shown by a decrease in degradation time of 4x and 5x respectively. The pseudo-first order retro reaction constants were approximately an order of magnitude slower than hydrogels crosslinked via disulfide linkages, indicating the potential use of the retro succinimide-thioether covalent bonds for reduction mediated release and/or degradation with increased blood stability and prolonged drug delivery timescales compared to disulfide chemistries. In summary, this work highlights the use of polymer-polysaccharide hydrogels composed of LMWH and PEG as investigated for drug delivery and as a tool for elucidating a novel reduction sensitive controlled release mechanism.

Synthesis and characterization of hydrogel films of carboxymethyl tamarind gum using citric acid.

PubMed

Mali, Kailas K; Dhawale, Shashikant C; Dias, Remeth J

2017-12-01

The objective of this study was to synthesize and characterize citric acid crosslinked carboxymethyl tamarind gum (CMTG) hydrogels films. The hydrogel films were characterized by Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, solid state 13 C-nuclear magnetic resonance ( 13 C NMR) spectroscopy and differential scanning calorimeter (DSC). The prepared hydrogel films were evaluated for the carboxyl content and swelling ratio. The model drug moxifloxacin hydrochloride was loaded into hydrogels films and drug release was studied at pH 7.4. The hemolysis assay was used to study the biocompatibility of hydrogel films. The results of ATR-FTIR, solid state 13 C NMR and DSC confirmed the formation of ester crosslinks between citric acid and CMTG. The total carboxyl content of hydrogel film was found to be decreased when amount of CMTG was increased. The swelling of hydrogel film was found to be decreased with increase in curing temperature and time. CMTG hydrogel films showed high drug loading with non-Fickian release mechanism suggesting controlled release of drug. The hydrogel films were found to be biocompatible. It can be concluded that the citric acid can be used for the preparation of CMTG hydrogel films. Further, CMTG hydrogel film can be used potentially for controlled release of drug. Copyright © 2017 Elsevier B.V. All rights reserved.

Radiofrequency treatment enhances the catalytic function of an immobilized nanobiohybrid catalyst

NASA Astrophysics Data System (ADS)

San, Boi Hoa; Ha, Eun-Ju; Paik, Hyun-Jong; Kim, Kyeong Kyu

2014-05-01

Biocatalysis, the use of enzymes in chemical transformation, has undergone intensive development for a wide range of applications. As such, maximizing the functionality of enzymes for biocatalysis is a major priority to enable industrial use. To date, many innovative technologies have been developed to address the future demand of enzymes for these purposes, but maximizing the catalytic activity of enzymes remains a challenge. In this study, we demonstrated that the functionality of a nanobiocatalyst could be enhanced by combining immobilization and radiofrequency (RF) treatment. Aminopeptidase PepA-encapsulating 2 nm platinum nanoparticles (PepA-PtNPs) with the catalytic activities of hydrolysis and hydrogenation were employed as multifunctional nanobiocatalysts. Immobilizing the nanobiocatalysts in a hydrogel using metal chelation significantly enhanced their functionalities, including catalytic power, thermal-stability, pH tolerance, organic solvent tolerance, and reusability. Most importantly, RF treatment of the hydrogel-immobilized PepA-PtNPs increased their catalytic power by 2.5 fold greater than the immobilized PepA. Our findings indicate that the catalytic activities and functionalities of PepA-PtNPs are greatly enhanced by the combination of hydrogel-immobilization and RF treatment. Based on our findings, we propose that RF treatment of nanobiohybrid catalysts immobilized on the bulk hydrogel represents a new strategy for achieving efficient biocatalysis.Biocatalysis, the use of enzymes in chemical transformation, has undergone intensive development for a wide range of applications. As such, maximizing the functionality of enzymes for biocatalysis is a major priority to enable industrial use. To date, many innovative technologies have been developed to address the future demand of enzymes for these purposes, but maximizing the catalytic activity of enzymes remains a challenge. In this study, we demonstrated that the functionality of a nanobiocatalyst could be enhanced by combining immobilization and radiofrequency (RF) treatment. Aminopeptidase PepA-encapsulating 2 nm platinum nanoparticles (PepA-PtNPs) with the catalytic activities of hydrolysis and hydrogenation were employed as multifunctional nanobiocatalysts. Immobilizing the nanobiocatalysts in a hydrogel using metal chelation significantly enhanced their functionalities, including catalytic power, thermal-stability, pH tolerance, organic solvent tolerance, and reusability. Most importantly, RF treatment of the hydrogel-immobilized PepA-PtNPs increased their catalytic power by 2.5 fold greater than the immobilized PepA. Our findings indicate that the catalytic activities and functionalities of PepA-PtNPs are greatly enhanced by the combination of hydrogel-immobilization and RF treatment. Based on our findings, we propose that RF treatment of nanobiohybrid catalysts immobilized on the bulk hydrogel represents a new strategy for achieving efficient biocatalysis. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr00407h

Building a polysaccharide hydrogel capsule delivery system for control release of ibuprofen.

PubMed

Chen, Zhi; Wang, Ting; Yan, Qing

2018-02-01

Development of a delivery system which can effectively carry hydrophobic drugs and have pH response is becoming necessary. Here we demonstrate that through preparation of β-cyclodextrin polymer (β-CDP), a hydrophobic drug molecule of ibuprofen (IBU) was incorporated into our prepared β-CDP inner cavities, aiming to improve the poor water solubility of IBU. A core-shell capsule structure has been designed for achieving the drug pH targeted and sustained release. This delivery system was built with polysaccharide polymer of Sodium alginate (SA), sodium carboxymethylcellulose (CMC) and hydroxyethyl cellulose (HEC) by physical cross-linking. The drug pH-response control release is this hydrogel system's chief merit, which has potential value for synthesizing enteric capsule. Besides, due to our simple preparing strategy, optimal conditions can be readily determined and the synthesis process can be accurately controlled, leading to consistent and reproducible hydrogel capsules. In addition, phase-solubility method was used to investigate the solubilization effect of IBU by β-CDP. SEM was used to prove the forming of core and shell structure. FT-IR and 1 H-NMR were also used to perform structural characteristics. By the technique of UV determination, the pH targeted and sustained release study were also performed. The results have proved that our prepared polysaccharide hydrogel capsule delivery system has potential applications as oral drugs delivery in the field of biomedical materials.

Design and fabrication of a chitosan hydrogel with gradient structures via a step-by-step cross-linking process.

PubMed

Xu, Yongxiang; Yuan, Shenpo; Han, Jianmin; Lin, Hong; Zhang, Xuehui

2017-11-15

The development of scaffolds to mimic the gradient structure of natural tissue is an important consideration for effective tissue engineering. In the present study, a physical cross-linking chitosan hydrogel with gradient structures was fabricated via a step-by-step cross-linking process using sodium tripolyphosphate and sodium hydroxide as sequential cross-linkers. Chitosan hydrogels with different structures (single, double, and triple layers) were prepared by modifying the gelling process. The properties of the hydrogels were further adjusted by varying the gelling conditions, such as gelling time, pH, and composition of the crosslinking solution. Slight cytotoxicity was showed in MTT assay for hydrogels with uncross-linking chitosan solution and non-cytotoxicity was showed for other hydrogels. The results suggest that step-by-step cross-linking represents a practicable method to fabricate scaffolds with gradient structures. Copyright © 2017. Published by Elsevier Ltd.

Encapsulation of mesenchymal stem cells in chitosan/β-glycerophosphate hydrogel for seeding on a novel calcium phosphate cement scaffold.

PubMed

Liu, Tao; Li, Jian; Shao, Zengwu; Ma, Kaige; Zhang, Zhicai; Wang, Baichuan; Zhang, Yannan

2018-06-01

Due to its moldability, biocompatibility, osteoconductivity and resorbability, calcium phosphate cement (CPC) is a highly promising scaffold material for orthopedic applications. However, pH changes and ionic activity during the CPC setting reaction may adversely affect cells seeded directly on CPC. Moreover, a lack of macropores in CPC limits ingrowth of new bone. The objectives of this study were to prepare macroporous CPC scaffolds via porogen leaching, using mannitol crystals as the porogen and to evaluate the in vitro proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) encapsulated in chitosan/β-glycerophosphate (C/GP) hydrogel prior to exposure to the novel CPC scaffold. MSCs were found to be adhered to the surfaces of CPC macropores via scanning electron microscopy. The viability and osteogenic differentiation of MSCs in C/GP hydrogel with or without exposure to CPC constructs containing mannitol crystals indicated that coating with C/GP hydrogel protected the cells during cement mixing and setting. In conclusion, novel, macroporous CPC scaffolds were prepared, and our data indicate that a hydrogel encapsulation-based strategy can be used to protect cells during scaffold formation. Thus, the MSC-laden CPC scaffolds show promise for the delivery of stem cells to promote bone regeneration. Copyright © 2018 IPEM. Published by Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perovic, Iva; Davidyants, Anastasia; Evans, John Spencer

In the mollusk shell there exists a framework silk fibroin-polysaccharide hydrogel coating around nacre aragonite tablets, and this coating facilitates the synthesis and organization of mineral nanoparticles into mesocrystals. In this report, we identify that a protein component of this coating, n16.3, is a hydrogelator. Due to the presence of intrinsic disorder, aggregation-prone regions, and nearly equal balance of anionic and cationic side chains, this protein assembles to form porous mesoscale hydrogel particles in solution and on mica surfaces. These hydrogel particles change their dimensionality, organization, and internal structure in response to pH and ions, particularly Ca(II), which indicates thatmore » these behave as ion-responsive or “smart” hydrogels. Thus, in addition to silk fibroins, the gel phase of the mollusk shell nacre framework layer may actually consist of several framework hydrogelator proteins, such as n16.3, which can promote mineral nanoparticle organization and assembly during the nacre biomineralization process and also serve as a model system for designing ion-responsive, composite, and smart hydrogels.« less

Seeing diabetes: visual detection of glucose based on the intrinsic peroxidase-like activity of MoS2 nanosheets

NASA Astrophysics Data System (ADS)

Lin, Tianran; Zhong, Liangshuang; Guo, Liangqia; Fu, Fengfu; Chen, Guonan

2014-09-01

Molybdenum disulfide (MoS2) has attracted increasing research interest recently due to its unique physical, optical and electrical properties, correlated with its 2D ultrathin atomic-layered structure. Until now, however, great efforts have focused on its applications such as lithium ion batteries, transistors, and hydrogen evolution reactions. Herein, for the first time, MoS2 nanosheets are discovered to possess an intrinsic peroxidase-like activity and can catalytically oxidize 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 to produce a color reaction. The catalytic activity follows the typical Michaelis-Menten kinetics and is dependent on temperature, pH, H2O2 concentration, and reaction time. Based on this finding, a highly sensitive and selective colorimetric method for H2O2 and glucose detection is developed and applied to detect glucose in serum samples. Moreover, a simple, inexpensive, instrument-free and portable test kit for the visual detection of glucose in normal and diabetic serum samples is constructed by utilizing agarose hydrogel as a visual detection platform.Molybdenum disulfide (MoS2) has attracted increasing research interest recently due to its unique physical, optical and electrical properties, correlated with its 2D ultrathin atomic-layered structure. Until now, however, great efforts have focused on its applications such as lithium ion batteries, transistors, and hydrogen evolution reactions. Herein, for the first time, MoS2 nanosheets are discovered to possess an intrinsic peroxidase-like activity and can catalytically oxidize 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 to produce a color reaction. The catalytic activity follows the typical Michaelis-Menten kinetics and is dependent on temperature, pH, H2O2 concentration, and reaction time. Based on this finding, a highly sensitive and selective colorimetric method for H2O2 and glucose detection is developed and applied to detect glucose in serum samples. Moreover, a simple, inexpensive, instrument-free and portable test kit for the visual detection of glucose in normal and diabetic serum samples is constructed by utilizing agarose hydrogel as a visual detection platform. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr03393k

Autoinducer Sensing Microarrays by Reporter Bacteria Encapsulated in Hybrid Supramolecular-Polysaccharide Hydrogels.

PubMed

Li, Ping; Dou, Xiaoqiu; Müller, Mareike; Feng, Chuanliang; Chang, Matthew Wook; Frettlöh, Martin; Schönherr, Holger

2017-11-01

A generally applicable strategy to obtain mechanically robust hydrogels for the incorporation and containment of functional reporter bacteria for the microarray and microparticle-based detection and signaling of N-acyl homoserine lactone autoinducers (3OC 12 HSL) at relevant concentrations is reported. For reinforcing hydrogels of 1,4-bi(phenylalanine-diglycol)-benzene (PDB), a hybrid hydrogel is formed by the combination of PDB self-assembly with Ca 2+ mediated alginate crosslinking. The different assembly mechanisms are shown not to interfere with each other and despite the more than four-fold increased moduli of the hydrogels, diffusion of autoinducers into the gels remains efficient and Escherichia coli pLuxR-green fluorescent protein (GFP) reporter bacteria are proliferating. Templating affords reporter bacteria-loaded hydrogels with controllable shape and size. Upon exposure to 3OC 12 HSL, the embedded bacteria exhibit an up to 12 ± 3 times increase in fluorescence intensity due to autoinducer-triggered GFP expression. This approach can serve as a potentially generally applicable strategy to sensitively detect bacteria via their secreted autoinducers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mesenchymal stem cell-laden anti-inflammatory hydrogel enhances diabetic wound healing

PubMed Central

Chen, Shixuan; Shi, Junbin; Zhang, Min; Chen, Yinghua; Wang, Xueer; Zhang, Lei; Tian, Zhihui; Yan, Yuan; Li, Qinglin; Zhong, Wen; Xing, Malcolm; Zhang, Lu; Zhang, Lin

2015-01-01

The purpose of this study was to permit bone marrow mesenchymal stem cells (BMSCs) to reach their full potential in the treatment of chronic wounds. A biocompatible multifunctional crosslinker based temperature sensitive hydrogel was developed to deliver BMSCs, which improve the chronic inflammation microenvironments of wounds. A detailed in vitro investigation found that the hydrogel is suitable for BMSC encapsulation and can promote BMSC secretion of TGF-β1 and bFGF. In vivo, full-thickness skin defects were made on the backs of db/db mice to mimic diabetic ulcers. It was revealed that the hydrogel can inhibit pro-inflammatory M1 macrophage expression. After hydrogel association with BMSCs treated the wound, significantly greater wound contraction was observed in the hydrogel + BMSCs group. Histology and immunohistochemistry results confirmed that this treatment contributed to the rapid healing of diabetic skin wounds by promoting granulation tissue formation, angiogenesis, extracellular matrix secretion, wound contraction, and re-epithelialization. These results show that a hydrogel laden with BMSCs may be a promising therapeutic strategy for the management of diabetic ulcers. PMID:26643550

Highly Photostable Near-Infrared Fluorescent pH Indicators and Sensors Based on BF2-Chelated Tetraarylazadipyrromethene Dyes

PubMed Central

2012-01-01

In this study, a series of new BF2-chelated tetraarylazadipyrromethane dyes are synthesized and are shown to be suitable for the preparation of on/off photoinduced electron transfer modulated fluorescent sensors. The new indicators are noncovalently entrapped in polyurethane hydrogel D4 and feature absorption maxima in the range 660–710 nm and fluorescence emission maxima at 680–740 nm. Indicators have high molar absorption coefficients of ∼80 000 M–1 cm–1, good quantum yields (up to 20%), excellent photostability and low cross-sensitivity to the ionic strength. pKa values of indicators are determined from absorbance and fluorescence measurements and range from 7 to 11, depending on the substitution pattern of electron-donating and -withdrawing functionalities. Therefore, the new indicators are suitable for exploitation and adaptation in a diverse range of analytical applications. Apparent pKa values in sensor films derived from fluorescence data show 0.5–1 pH units lower values in comparison with those derived from the absorption data due to Förster resonance energy transfer from protonated to deprotonated form. A dual-lifetime referenced sensor is prepared, and application for monitoring of pH in corals is demonstrated. PMID:22738322

Towards a quantitative understanding of oxygen tension and cell density evolution in fibrin hydrogels.

PubMed

Demol, Jan; Lambrechts, Dennis; Geris, Liesbet; Schrooten, Jan; Van Oosterwyck, Hans

2011-01-01

The in vitro culture of hydrogel-based constructs above a critical size is accompanied by problems of unequal cell distribution when diffusion is the primary mode of oxygen transfer. In this study, an experimentally-informed mathematical model was developed to relate cell proliferation and death inside fibrin hydrogels to the local oxygen tension in a quantitative manner. The predictive capacity of the resulting model was tested by comparing its outcomes to the density, distribution and viability of human periosteum derived cells (hPDCs) that were cultured inside fibrin hydrogels in vitro. The model was able to reproduce important experimental findings, such as the formation of a multilayered cell sheet at the hydrogel periphery and the occurrence of a cell density gradient throughout the hydrogel. In addition, the model demonstrated that cell culture in fibrin hydrogels can lead to complete anoxia in the centre of the hydrogel for realistic values of oxygen diffusion and consumption. A sensitivity analysis also identified these two parameters, together with the proliferation parameters of the encapsulated cells, as the governing parameters for the occurrence of anoxia. In conclusion, this study indicates that mathematical models can help to better understand oxygen transport limitations and its influence on cell behaviour during the in vitro culture of cell-seeded hydrogels. Copyright © 2010 Elsevier Ltd. All rights reserved.

Aragonite-Associated Mollusk Shell Protein Aggregates To Form Mesoscale “Smart” Hydrogels

DOE PAGES

Perovic, Iva; Davidyants, Anastasia; Evans, John Spencer

2016-11-30

In the mollusk shell there exists a framework silk fibroin-polysaccharide hydrogel coating around nacre aragonite tablets, and this coating facilitates the synthesis and organization of mineral nanoparticles into mesocrystals. In this report, we identify that a protein component of this coating, n16.3, is a hydrogelator. Due to the presence of intrinsic disorder, aggregation-prone regions, and nearly equal balance of anionic and cationic side chains, this protein assembles to form porous mesoscale hydrogel particles in solution and on mica surfaces. These hydrogel particles change their dimensionality, organization, and internal structure in response to pH and ions, particularly Ca(II), which indicates thatmore » these behave as ion-responsive or “smart” hydrogels. Thus, in addition to silk fibroins, the gel phase of the mollusk shell nacre framework layer may actually consist of several framework hydrogelator proteins, such as n16.3, which can promote mineral nanoparticle organization and assembly during the nacre biomineralization process and also serve as a model system for designing ion-responsive, composite, and smart hydrogels.« less

Flocculation and adsorption properties of biodegradable gum-ghatti-grafted poly(acrylamide-co-methacrylic acid) hydrogels.

PubMed

Mittal, H; Jindal, R; Kaith, B S; Maity, A; Ray, S S

2015-01-22

This study reports the microwave-assisted synthesis of gum-ghatti (Gg)-grafted poly(acrylamide-co-methacrylic acid) (AAm-co-MAA) hydrogels for the development of biodegradable flocculants and adsorbents. The synthesized hydrogels were characterized using TGA, FTIR and SEM. TGA studies revealed that the synthesized hydrogels were thermally more stable than pristine Gg and exhibited maximum swelling capacity of 1959% at 60°C in neutral pH. The optimal Gg-cl-P(AAm-co-MAA) hydrogel was successfully employed for the removal of saline water from various petroleum fraction-saline emulsions. The maximum flocculation efficiency was achieved in an acidic clay suspension with a 15 mg polymer dose at 40°C. Moreover, the synthesized hydrogel adsorbed 94% and 75% of Pb(2+) and Cu(2+), respectively, from aqueous solutions. Finally, the Gg-cl-P(AAm-co-MAA) hydrogel could be degraded completely within 50 days. In summary, the Gg-cl-P(AAm-co-MAA) hydrogel was demonstrated to have potential for use as flocculants and heavy metal absorbents for industrial waste water treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hybrid nanocomposites based on electroactive hydrogels and cellulose nanocrystals for high-sensitivity electro-mechanical underwater actuation

NASA Astrophysics Data System (ADS)

Santaniello, Tommaso; Migliorini, Lorenzo; Locatelli, Erica; Monaco, Ilaria; Yan, Yunsong; Lenardi, Cristina; Comes Franchini, Mauro; Milani, Paolo

2017-08-01

We report the synthesis, fabrication and characterization of a hybrid hydrogel/cellulose nanocomposite, which exhibits high-performance electro-mechanical underwater actuation and high sensitivity in response to electrical stimuli below the standard potential of water electrolysis. The macromolecular structure of the material is constituted by an electroactive hydrogel, obtained through a photo-polymerization reaction with the use of three vinylic co-monomers: Na-4-vinylbenzenesulfonate, 2-hydroxyethylmethacrylate, and acrylonitrile. Different amounts (from 0.1% to 1.4% w/w) of biodegradable cellulose nanocrystals (CNCs) with sulfonate surface groups, obtained through the acidic hydrolysis of sulphite pulp lapsheets, are physically incorporated into the gel matrix during the synthesis step. Freestanding thin films of the nanocomposites are molded, and their swelling, mechanical and responsive properties are fully characterized. We observed that the embedding of the CNCs enhanced both the material Young’s modulus and its sensitivity to the applied electric field in the sub-volt regime (down to 5 mV cm-1). A demonstrator integrating multiple actuators that cooperatively bend together, mimicking the motion of an electro-valve, is also prototyped and tested. The presented nanocomposite is suitable for the development of soft smart components for bio-robotic applications and cells-based and bio-hybrid fluidic devices fabrication.

In situ-forming hydrogels for sustained ophthalmic drug delivery.

PubMed

Nanjawade, Basavaraj K; Manvi, F V; Manjappa, A S

2007-09-26

Ophthalmic drug delivery is one of the most interesting and challenging endeavors facing the pharmaceutical scientist. The conventional ocular drug delivery systems like solutions, suspensions, and ointments show drawbacks such as increased precorneal elimination, high variability in efficiency, and blurred vision respectively. In situ-forming hydrogels are liquid upon instillation and undergo phase transition in the ocular cul-de-sac to form visco-elastic gel and this provides a response to environmental changes. In the past few years, an impressive number of novel temperature, pH, and ion induced in situ-forming systems have been reported for sustain ophthalmic drug delivery. Each system has its own advantages and drawbacks. The choice of a particular hydrogel depends on its intrinsic properties and envisaged therapeutic use. This review includes various temperature, pH, and ion induced in situ-forming polymeric systems used to achieve prolonged contact time of drugs with the cornea and increase their bioavailability.

A pure DNA hydrogel with stable catalytic ability produced by one-step rolling circle amplification.

PubMed

Huang, Yishun; Xu, Wanlin; Liu, Guoyuan; Tian, Leilei

2017-03-09

A rolling-circle-amplification method was developed to produce DNA hydrogels with horseradish-peroxidase-like catalytic capability. The catalytic hydrogel exhibits highly improved stability at elevated temperatures or during a long-term storage. Integrated with glucose oxidase, the complex hydrogel can be applied to the sensitive and reliable detection of glucose.

Tunable Nanocomposite Membranes for Water Remediation and Separations

NASA Astrophysics Data System (ADS)

Sierra, Sebastian Hernandez

Nano-structured material fabrication using functionalized membranes with polyelectrolytes is a promising research field for water pollution, catalytic and mining applications. These responsive polymers react to external stimuli like temperature, pH, radiation, ionic strength or chemical composition. Such nanomaterials provide novel hybrid properties and can also be self-supported in addition to the membranes. Polyelectrolytes (as hydrogels) have pH responsiveness. The hydrogel moieties gain or lose protons based on the pH, displaying swelling properties. These responsive materials can be exploited to synthesize metal nanoparticles in situ using their functional groups, or to immobilize other polyelectrolytes and biomolecules. Due to their properties, these responsive materials prevent the loss of nanomaterials to the environment and improve reactivity due to their larger surface areas, expanding their range of applications. The present work describes different techniques used to create nanocomposites based on poly(vinylidene fluoride) (PVDF) hollow fiber and flat sheet membranes, both thick sponge-like and thin. Due to their hydrophobicity, hollow fiber membranes were hydrophilized by a water-based green process of cross-linking polyvinylpyrrolidone (PVP) onto their surface. Commercial hydrophilic and hydrophilized lab-prepared membranes were subsequently functionalized with a poly(acrylic acid) (PAA) hydrogel through free radical polymerizations. This work advanced membrane functionalization, specifically flat sheet membranes, from lab-scale to full-scale by modifications of the polymerization procedures. The hydrogel functionalized membranes by redox polymerization showed an expected responsive behavior, represented by permeability variation at various pH values (4.0 ≤ pH ≤ 9.0), from 53.9 to 3.4 L/(m2EhEbar) and a change in effective pore size from 222 to 111 nm, being 3800 L/(m 2EhEbar) and 650 nm the former permeability and pore size values of the non-functionalized membrane. Then, throughout a double ion exchange of sodium/iron and a subsequent reduction, bimetallic Fe/Pd nanoparticles were synthesized in-situ. Similarly, it was possible to use the reacted accelerants of the redox polymerization to synthesize Fe0 nanoparticles. These hydrogel-membrane systems with Fe/Pd nanoparticles were studied throughout the reduction of trichloroethylene (TCE). This work has demonstrated an effective improvement in TCE reduction by the variation of the supporting membrane types and the functionalization (polymerization and nanoparticle synthesis) processes. The TCE normalized dechlorination rates (k sa) are 3 times greater and 8 times for hollow fiber and sponge-like flat sheet membranes, respectively, than previous studies. For membrane supported Fe/Pd nanoparticles by redox functionalization, the dechlorination rates are similar to previous works in flat sheet membranes; and for the redox polymerized hydrogel, the dechlorination rates are the highest results with 1.3 times greater than the rates of solution-phase nanoparticles and 10 times the rate values of the membranes. All supports showed nonsignificant nanoparticle loss (up to 1%). Up to 80% of reduction was achieved within 2 hours with chloride production near to stoichiometric values (3:1), demonstrating absence of intermediates. As an extension of the membrane functionalization, it was possible to immobilize Outer membrane protein F precursor (OmpF) from Escherichia coli within the PVDF membrane pore structure, using layer-by-layer (LbL) assembly of polyeletrolytes. This LbL technique allows to reuse the membranes numerous times, having reproducibility and greater selective rejections of uncharged (organic species) over charged solutes (small ions) than similar functionalized membranes without OmpF: 1.7 times and 2.0 times higher for Organic/CaCl2 and Organic/NaCl, respectively. Additionally, the permeability of OmpFmembranes is almost double of the non-OmpF: 2.6 to 1.5 L/(m2˙h˙bar).

Design of multimodal degradable hydrogels for controlled therapeutic delivery

NASA Astrophysics Data System (ADS)

Kharkar, Prathamesh Madhav

Hydrogels are of growing interest for the delivery of therapeutics to specific sites in the body. For localized drug delivery, hydrophilic polymeric precursors often are laden with bioactive moieties and then directly injected to the site of interest for in situ gel formation. The release of physically entrapped cargo is dictated by Fickian diffusion, degradation of the drug carrier, or a combination of both. The goal of this work was to design and characterize degradable hydrogel formulations that are responsive to multiple biologically relevant stimuli for degradation-mediated delivery of cargo molecules such as therapeutic proteins, growth factors, and immunomodulatory agents. We began by demonstrating the use of cleavable click linkages formed by Michael-type addition reactions in conjunction with hydrolytically cleavable functionalities for the degradation of injectable hydrogels by endogenous stimuli for controlled protein release. Specifically, the reaction between maleimides and thiols was utilized for hydrogel formation, where thiol selection dictates the degradability of the resulting linkage under thiol-rich reducing conditions. Relevant microenvironments where degradation would occur in vivo include those rich in glutathione (GSH), a tripeptide that is found at elevated concentrations in carcinoma tissues. Degradation of the hydrogels was monitored with rheometry and volumetric swelling measurements. Arylthiol-based thioether succinimide linkages underwent degradation via click cleavage and thiol exchange reaction in the presence of GSH and via ester hydrolysis, whereas alkylthiol-based thioether succinimide linkages only undergo degradation by only ester hydrolysis. The resulting control over the degradation rate within a reducing microenvironment resulted in 2.5 fold differences in the release profile of the model protein, a fluorescently-labeled bovine serum albumin, from dually degradable hydrogels compared to non-degradable hydrogels, where the thiol exchange reaction facilitated rapid and responsive protein release in the presence of GSH. A photolabile o-nitrobenzyl ether group (o-NB) was subsequently incorporated within the PEG-based, gel-forming monomers to demonstrate cargo release triggered by exogenous stimuli for patient-specific therapies. Upon the application of cytocompatible doses of light, the photolabile o-NB linkage underwent irreversible cleavage yielding ketone and carboxylic acid-based cleavage products. Hydrogel degradation kinetics was characterized in response to externally applied cytocompatible light or GSH in aqueous microenvironments. By incorporating a photodegradable o-nitrobenzyl ether group, a thiol-sensitive succinimide thioether linkage, and ester linkages within the hydrogels, we demonstrated unique control over degradation via surface erosion or bulk degradation mechanisms, respectively, with degradation rate constants ranging from 10-1 min-1 to 10-4 min-1. As a proof of concept, the controlled release of nanobeads from the hydrogel was demonstrated in a preprogrammed and stimuli-responsive fashion. The multimodal degradable hydrogels were then investigated for the local controlled release of small molecular weight proteins, which are of interest for regulating various cellular functions and fates in vivo. Low molecular weight heparin, a highly sulfated polysaccharide was incorporated within the hydrogel network by Michael-type reaction due to its affinity with biologics such as growth factors and immunomodulatory proteins. Incorporation of reduction-sensitive linkages resulted in 2.3 fold differences in the release profile of fibroblast growth factor-2 (FGF-2) in the presence of GSH compared to non-reducing microenvironment. Bioactivity of released FGF-2 was comparable to pristine FGF-2, indicating the ability of the hydrogel to retain bioactivity of cargo molecules during encapsulation and release. Further, preliminary in vivo studies demonstrated control over hydrogel degradation by varying % degradable contents. Collectively, this research developed injectable hydrogels that are responsive to various endogenous and exogenous stimuli, establishing a platform for stimuli-responsive drug delivery carriers.

Structural Design and Physicochemical Foundations of Hydrogels for Biomedical Applications.

PubMed

Li, Qingyong; Ning, Zhengxiang; Ren, Jiaoyan; Liao, Wenzhen

2018-01-01

Biomedical research, known as medical research, is conducive to support and promote the development of knowledge in the field of medicine. Hydrogels have been extensively used in many biomedical fields due to their highly absorbent and flexible properties. The smart hydrogels, especially, can respond to a broad range of external stimuli such as temperature, pH value, light, electric and magnetic fields. With excellent biocompatibility, tunable rheology, mechanical properties, porosity, and hydrated molecular structure, hydrogels are considered as promising candidate for simulating local tissue microenvironment. In this review article, we mainly focused on the most recent development of engineering synthetic hydrogels; moreover, the classification, properties, especially the biomedical applications including tissue engineering and cell scaffolding, drug and gene delivery, immunotherapies and vaccines, are summarized and discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A large deformation viscoelastic model for double-network hydrogels

NASA Astrophysics Data System (ADS)

Mao, Yunwei; Lin, Shaoting; Zhao, Xuanhe; Anand, Lallit

2017-03-01

We present a large deformation viscoelasticity model for recently synthesized double network hydrogels which consist of a covalently-crosslinked polyacrylamide network with long chains, and an ionically-crosslinked alginate network with short chains. Such double-network gels are highly stretchable and at the same time tough, because when stretched the crosslinks in the ionically-crosslinked alginate network rupture which results in distributed internal microdamage which dissipates a substantial amount of energy, while the configurational entropy of the covalently-crosslinked polyacrylamide network allows the gel to return to its original configuration after deformation. In addition to the large hysteresis during loading and unloading, these double network hydrogels also exhibit a substantial rate-sensitive response during loading, but exhibit almost no rate-sensitivity during unloading. These features of large hysteresis and asymmetric rate-sensitivity are quite different from the response of conventional hydrogels. We limit our attention to modeling the complex viscoelastic response of such hydrogels under isothermal conditions. Our model is restricted in the sense that we have limited our attention to conditions under which one might neglect any diffusion of the water in the hydrogel - as might occur when the gel has a uniform initial value of the concentration of water, and the mobility of the water molecules in the gel is low relative to the time scale of the mechanical deformation. We also do not attempt to model the final fracture of such double-network hydrogels.

Injectable self-healing carboxymethyl chitosan-zinc supramolecular hydrogels and their antibacterial activity.

PubMed

Wahid, Fazli; Zhou, Ya-Ning; Wang, Hai-Song; Wan, Tong; Zhong, Cheng; Chu, Li-Qiang

2018-04-07

Injectable and self-healing hydrogels have found numerous applications in drug delivery, tissue engineering and 3D cell culture. Herein, we report an injectable self-healing carboxymethyl chitosan (CMCh) supramolecular hydrogels cross-linked by zinc ions (Zn 2+ ). Supramolecular hydrogels were obtained by simple addition of metal ions solution to CMCh solution at an appropriate pH value. The mechanical properties of these hydrogels were adjustable by the concentration of Zn 2+ . For example, the hydrogel with the highest concentration of Zn 2+ (CMCh-Zn4) showed strongest mechanical properties (storage modulus~11,000Pa) while hydrogel with the lowest concentration of Zn 2+ (CMCh-Zn1) showed weakest mechanical properties (storage modulus~220Pa). As observed visually and confirmed rheologically, the CMCh-Zn1 hydrogel with the lowest Zn 2+ concentration showed thixotropic property. CMCh-Zn1 hydrogel also presented injectable property. Moreover, the antibacterial properties of the prepared supramolecular hydrogels were studied against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) by agar well diffusion method. The results revealed Zn 2+ dependent antibacterial properties against both kinds of strains. The inhibition zones were ranging from ~11-24mm and ~10-22mm against S. aureus and E. coli, respectively. We believe that the prepared supramolecular hydrogels could be used as a potential candidate in biomedical fields. Copyright © 2018 Elsevier B.V. All rights reserved.

Polyvinyl alcohol-based nanocomposite hydrogels containing magnetic laponite RD to remove cadmium.

PubMed

Mola Ali Abasiyan, Sara; Mahdavinia, Gholam Reza

2018-05-01

In this study, magnetic nanocomposite hydrogels based on polyvinyl alcohol were synthesized. Magnetic polyvinyl alcohol/laponite RD (PVA-mLap) nanocomposites were characterized by scanning electron microscopy, X-ray diffraction, transmission electron microscopy, and Fourier transform infrared spectroscopy. The results indicated that PVA-mLap had desirable magnetic-sorption properties and magnetic-laponite nanoparticles were successfully synthesized and added to polyvinyl alcohol. The present nanocomposites were applied to remove Cd 2+ from aqueous solution. The influence of initial Cd 2+ concentration, magnetic-laponite concentration, pH, and ionic strength on adsorption isotherm was investigated. Heterogeneity of adsorption sites was intensified by increasing magnetic concentration of adsorbents and by rising pH value. Results of ionic strength studies indicated that by increasing ionic strength more than four times, the adsorption of Cd 2+ has only decreased around 15%. According to the results, the dominant mechanism of Cd 2+ sorption by the present adsorbents was determined chemical and specific sorption. Therefore, the use of the present nanocomposites as a powerful adsorbent of Cd 2+ in the wastewater treatment is suggested. Isotherm data were described by using Freundlich and Langmuir models, and better fitting was introduced Langmuir model.

Influence of pH on Cr(VI) ions removal from aqueous solutions using carboxymethyl cellulose-based hydrogel as adsorbent

NASA Astrophysics Data System (ADS)

Anah, L.; Astrini, N.

2017-03-01

The major problem in heavy metal pollution is that these metals are not biodegradable and accordingly accumulate in the bodies of living organisms, causing dangerous diseases and serious cell disorder. According to World Health Organization (WHO), the long term exposure of Cr(VI) levels of over 0.1 ppm causes respiratory problems, liver and kidney damage, and carcinogenicity.Due to its easy operation and of various cheap adsorbents development, adsorption has been proved to be efficient and most economically attractive technique and feasible to the removal of toxic heavy metal from wastewater. The study aimed to report the removal of Cr(VI) ions from aqueous solutions through adsorption process using carboxymethyl cellulose-graft-poly(acrylic acid) (CMC-g-PAA) hydrogel as adsorbent.Effect of pH was studied to remove hexavalent chromium.Graft copolymerization of poly(acrylic acid) onto carboxymethyl cellulose was carried out in the presence of benzoyl peroxide redox initiator and methylenbisacrylamide as crosslinker agent. Batch experiments were carried out to investigate the effects ofinitial pH.The adsorption of Cr(VI) ions as a function of pH was conducted in the initial pH range of 1 to 8. The results indicated that acidic pH strongly favored the adsorption. The optimum pH for adsorption of Cr(VI) ranged from 1 to 3, and the maximum uptake of Cr(VI) from the solution was 6.53 mg/g at pH 1 and 30°C. FTIR spectroscopy, SEM analyses were performed on the adsorbent before and after Cr(VI) binding. All analyses confirmed the complexation of Cr(VI) ions on the adsorbent.

Hydrogel microphones for stealthy underwater listening

PubMed Central

Gao, Yang; Song, Jingfeng; Li, Shumin; Elowsky, Christian; Zhou, You; Ducharme, Stephen; Chen, Yong Mei; Zhou, Qin; Tan, Li

2016-01-01

Exploring the abundant resources in the ocean requires underwater acoustic detectors with a high-sensitivity reception of low-frequency sound from greater distances and zero reflections. Here we address both challenges by integrating an easily deformable network of metal nanoparticles in a hydrogel matrix for use as a cavity-free microphone. Since metal nanoparticles can be densely implanted as inclusions, and can even be arranged in coherent arrays, this microphone can detect static loads and air breezes from different angles, as well as underwater acoustic signals from 20 Hz to 3 kHz at amplitudes as low as 4 Pa. Unlike dielectric capacitors or cavity-based microphones that respond to stimuli by deforming the device in thickness directions, this hydrogel device responds with a transient modulation of electric double layers, resulting in an extraordinary sensitivity (217 nF kPa−1 or 24 μC N−1 at a bias of 1.0 V) without using any signal amplification tools. PMID:27554792

Photopolymerized dynamic hydrogels with tunable viscoelastic properties through thioester exchange.

PubMed

Brown, Tobin E; Carberry, Benjamin J; Worrell, Brady T; Dudaryeva, Oksana Y; McBride, Matthew K; Bowman, Christopher N; Anseth, Kristi S

2018-04-04

The extracellular matrix (ECM) constitutes a viscoelastic environment for cells. A growing body of evidence suggests that the behavior of cells cultured in naturally-derived or synthetic ECM mimics is influenced by the viscoelastic properties of these substrates. Adaptable crosslinking strategies provide a means to capture the viscoelasticity found in native soft tissues. In this work, we present a covalent adaptable hydrogel based on thioester exchange as a biomaterial for the in vitro culture of human mesenchymal stem cells. Through control of pH, gel stoichiometry, and crosslinker structure, viscoelastic properties in these crosslinked networks can be modulated across several orders of magnitude. We also propose a strategy to alter these properties in existing networks by the photo-uncaging of the catalyst 4-mercaptophenylacetic acid. Mesenchymal stem cells encapsulated in thioester hydrogels are able to elongate in 3D and display increased proliferation relative to those in static networks. Copyright © 2018 Elsevier Ltd. All rights reserved.

Extremely stretchable thermosensitive hydrogels by introducing slide-ring polyrotaxane cross-linkers and ionic groups into the polymer network.

PubMed

Bin Imran, Abu; Esaki, Kenta; Gotoh, Hiroaki; Seki, Takahiro; Ito, Kohzo; Sakai, Yasuhiro; Takeoka, Yukikazu

2014-10-08

Stimuli-sensitive hydrogels changing their volumes and shapes in response to various stimulations have potential applications in multiple fields. However, these hydrogels have not yet been commercialized due to some problems that need to be overcome. One of the most significant problems is that conventional stimuli-sensitive hydrogels are usually brittle. Here we prepare extremely stretchable thermosensitive hydrogels with good toughness by using polyrotaxane derivatives composed of α-cyclodextrin and polyethylene glycol as cross-linkers and introducing ionic groups into the polymer network. The ionic groups help the polyrotaxane cross-linkers to become well extended in the polymer network. The resulting hydrogels are surprisingly stretchable and tough because the cross-linked α-cyclodextrin molecules can move along the polyethylene glycol chains. In addition, the polyrotaxane cross-linkers can be used with a variety of vinyl monomers; the mechanical properties of the wide variety of polymer gels can be improved by using these cross-linkers.

Extremely stretchable thermosensitive hydrogels by introducing slide-ring polyrotaxane cross-linkers and ionic groups into the polymer network

PubMed Central

Bin Imran, Abu; Esaki, Kenta; Gotoh, Hiroaki; Seki, Takahiro; Ito, Kohzo; Sakai, Yasuhiro; Takeoka, Yukikazu

2014-01-01

Stimuli-sensitive hydrogels changing their volumes and shapes in response to various stimulations have potential applications in multiple fields. However, these hydrogels have not yet been commercialized due to some problems that need to be overcome. One of the most significant problems is that conventional stimuli-sensitive hydrogels are usually brittle. Here we prepare extremely stretchable thermosensitive hydrogels with good toughness by using polyrotaxane derivatives composed of α-cyclodextrin and polyethylene glycol as cross-linkers and introducing ionic groups into the polymer network. The ionic groups help the polyrotaxane cross-linkers to become well extended in the polymer network. The resulting hydrogels are surprisingly stretchable and tough because the cross-linked α-cyclodextrin molecules can move along the polyethylene glycol chains. In addition, the polyrotaxane cross-linkers can be used with a variety of vinyl monomers; the mechanical properties of the wide variety of polymer gels can be improved by using these cross-linkers. PMID:25296246

Energy conversion in polyelectrolyte hydrogels

NASA Astrophysics Data System (ADS)

Olvera de La Cruz, Monica; Erbas, Aykut; Olvera de la Cruz Team

Energy conversion and storage have been an active field of research in nanotechnology parallel to recent interests towards renewable energy. Polyelectrolyte (PE) hydrogels have attracted considerable attention in this field due to their mechanical flexibility and stimuli-responsive properties. Ideally, when a hydrogel is deformed, applied mechanical work can be converted into electrostatic, elastic and steric-interaction energies. In this talk, we discuss the results of our extensive molecular dynamics simulations of PE hydrogels. We demonstrate that, on deformation, hydrogels adjust their deformed state predominantly by altering electrostatic interactions between their charged groups rather than excluded-volume and bond energies. This is due to the hydrogel's inherent tendency to preserve electro-neutrality in its interior, in combination with correlations imposed by backbone charges. Our findings are valid for a wide range of compression ratios and ionic strengths. The electrostatic-energy alterations that we observe in our MD simulations may induce pH or redox-potential changes inside the hydrogels. The resulting energetic difference can be harvested, for instance, analogously to a Carnot engine, or facilitated for sensor applications. Center for Bio-inspired Energy Science (CBES).

Nanofibril scaffold assisted MEMS artificial hydrogel neuromasts for enhanced sensitivity flow sensing

PubMed Central

Kottapalli, Ajay Giri Prakash; Bora, Meghali; Asadnia, Mohsen; Miao, Jianmin; Venkatraman, Subbu S.; Triantafyllou, Michael

2016-01-01

We present the development and testing of superficial neuromast-inspired flow sensors that also attain high sensitivity and resolution through a biomimetic hyaulronic acid-based hydrogel cupula dressing. The inspiration comes from the spatially distributed neuromasts of the blind cavefish that live in completely dark undersea caves; the sensors enable the fish to form three-dimensional flow and object maps, enabling them to maneuver efficiently in cluttered environments. A canopy shaped electrospun nanofibril scaffold, inspired by the cupular fibrils, assists the drop-casting process allowing the formation of a prolate spheroid-shaped artificial cupula. Rheological and nanoindentation characterizations showed that the Young’s modulus of the artificial cupula closely matches the biological cupula (10–100 Pa). A comparative experimental study conducted to evaluate the sensitivities of the naked hair cell sensor and the cupula-dressed sensor in sensing steady-state flows demonstrated a sensitivity enhancement by 3.5–5 times due to the presence of hydrogel cupula. The novel strategies of sensor development presented in this report are applicable to the design and fabrication of other biomimetic sensors as well. The developed sensors can be used in the navigation and maneuvering of underwater robots, but can also find applications in biomedical and microfluidic devices. PMID:26763299

Dynamic Manipulation of Hydrogels to Control Cell Behavior: A Review

PubMed Central

Vats, Kanika

2013-01-01

For many tissue engineering applications and studies to understand how materials fundamentally affect cellular functions, it is important to have the ability to synthesize biomaterials that can mimic elements of native cell–extracellular matrix interactions. Hydrogels possess many properties that are desirable for studying cell behavior. For example, hydrogels are biocompatible and can be biochemically and mechanically altered by exploiting the presentation of cell adhesive epitopes or by changing hydrogel crosslinking density. To establish physical and biochemical tunability, hydrogels can be engineered to alter their properties upon interaction with external driving forces such as pH, temperature, electric current, as well as exposure to cytocompatible irradiation. Additionally, hydrogels can be engineered to respond to enzymes secreted by cells, such as matrix metalloproteinases and hyaluronidases. This review details different strategies and mechanisms by which biomaterials, specifically hydrogels, can be manipulated dynamically to affect cell behavior. By employing the appropriate combination of stimuli and hydrogel composition and architecture, cell behavior such as adhesion, migration, proliferation, and differentiation can be controlled in real time. This three-dimensional control in cell behavior can help create programmable cell niches that can be useful for fundamental cell studies and in a variety of tissue engineering applications. PMID:23541134

Reduction of Non-Specific Protein Adsorption Using Poly(ethylene) Glycol (PEG) Modified Polyacrylate Hydrogels In Immunoassays for Staphylococcal Enterotoxin B Detection

PubMed Central

Charles, Paul T.; Stubbs, Veronte R.; Soto, Carissa M.; Martin, Brett D.; White, Brandy J.; Taitt, Chris R.

2009-01-01

Three PEG molecules (PEG-methacrylate, -diacrylate and -dimethacrylate) were incorporated into galactose-based polyacrylate hydrogels and their relative abilities to reduce non-specific protein adsorption in immunoassays were determined. Highly crosslinked hydrogels containing amine-terminated functionalities were formed and used to covalently attach antibodies specific for staphylococcal enterotoxin B (SEB). Patterned arrays of immobilized antibodies in the PEG-modified hydrogels were created with a PDMS template containing micro-channels for use in sandwich immunoassays to detect SEB. Different concentrations of the toxin were applied to the hydrogel arrays, followed with a Cy3-labeled tracer antibody specific for the two toxins. Fluorescence laser scanning confocal microscopy of the tracer molecules provided both qualitative and quantitative measurements on the detection sensitivity and the reduction in non-specific binding as a result of PEG incorporation. Results showed the PEG-modified hydrogel significantly reduced non-specific protein binding with a detection limit for SEB of 1 ng/mL. Fluorescence signals showed a 10-fold decrease in the non-specific binding and a 6-fold increase in specific binding of SEB. PMID:22389622

Degradable Hydrogels and Nanogels for the Delivery of Cells and Therapeutics

NASA Astrophysics Data System (ADS)

Boehnke, Natalie

Degradable polymeric materials such as hydrogels are extensively utilized as delivery vehicles due to their biocompatibility and tunable properties. Encapsulating therapeutic agents inside hydrogels stabilizes the cargo by preventing degradation, extending circulation time, and also allows for targeted release and delivery. Due to their small size and tunable properties, nano-scale hydrogels, or nanogels, are frequently utilized to deliver therapeutics to areas difficult to reach, such as tumors and the cytoplasm, through traditional means. To control hydro- and nanogel function, degradable cross-links can be installed, allowing for cargo release in response to specific stimuli, such as hydrolysis or reduction. This dissertation offers three degradable strategies that can be applied to synthesize hydrogels and nanogels for the stabilization and release of therapeutic cargo. In the first example, mixed imine cross-linking chemistry was applied to synthesize poly(ethylene glycol) (PEG)-based hydrogels with tunable degradability to encapsulate and deliver cells. Time to degradation of the gels could be controlled from 24 hours to more than 7 days by varying the hydrazone structure and the ratio of hydrazone and oxime cross-links. Encapsulated cells exhibited high viability up to at least 7 days, suggesting this system may be useful for cell delivery applications. In the second example, disulfide cross-links were utilized to form redox-responsive nanogels comprised of trehalose copolymers. The synthesis of a methacrylate trehalose monomer (TrMA) was optimized, improving the overall yield from 14% to 42%. TrMA was subsequently copolymerized with pyridyl disulfide ethyl methacrylate (PDSMA) using free radical polymerization conditions to form copolymers with two monomer ratios (1:1 and 2:1) which were cross-linked with 1 kDa PEG-dithiol via disulfide exchange to form uniform nanogels approximately 9 nm in diameter. The addition of a cross-linker eliminated the need to add reducing agent to facilitate cross-linking and nanogel formation, making this approach ideal for the encapsulation of sensitive therapeutic agents. Next, PDSMA-co-TrMA nanogels were utilized to encapsulate, stabilize, and release glucagon, an unstable peptide hormone used to treat hypoglycemia. The amines on glucagon were modified with thiol groups while retaining their positive charges for reversible conjugation and cross-linking. Glucagon-nanogel conjugates were synthesized with >80% conjugation yield, and the reversible disulfide linkage between peptide and polymer allowed for efficient cargo release under mild reducing conditions. The nanogels stabilized glucagon against aggregation in solution up to five days as well as solubilized the peptide at neutral pH. In vitro bioactivity of the modified peptide was found to be comparable to native glucagon, suggesting this may be a promising formulation strategy for further in vivo study. Finally, a series of dual-enzyme responsive peptides was synthesized by masking the epsilon-amine of lysine with protease substrates. After unmasking the amine by enzymatic cleavage, a second enzyme was able to cleave at the C terminus of lysine, which was monitored colorimetrically. Three different dual-enzyme responsive peptides were prepared, (AcAAF)K-pNA, (AcFG)K-pNA, and (AcDEVD)K-pNA, for chymotrypsin, papain, and caspase 3 sensitivity, respectively, followed by trypsin sensitivity after cleavage by the first enzyme. This modular peptide design could be useful for selective drug delivery, studies on dual enzyme activity, as well as for diagnostic enzyme screening.

Rapid self-healing hydrogels

PubMed Central

Phadke, Ameya; Zhang, Chao; Arman, Bedri; Hsu, Cheng-Chih; Mashelkar, Raghunath A.; Lele, Ashish K.; Tauber, Michael J.; Arya, Gaurav; Varghese, Shyni

2012-01-01

Synthetic materials that are capable of autonomous healing upon damage are being developed at a rapid pace because of their many potential applications. Despite these advancements, achieving self-healing in permanently cross-linked hydrogels has remained elusive because of the presence of water and irreversible cross-links. Here, we demonstrate that permanently cross-linked hydrogels can be engineered to exhibit self-healing in an aqueous environment. We achieve this feature by arming the hydrogel network with flexible-pendant side chains carrying an optimal balance of hydrophilic and hydrophobic moieties that allows the side chains to mediate hydrogen bonds across the hydrogel interfaces with minimal steric hindrance and hydrophobic collapse. The self-healing reported here is rapid, occurring within seconds of the insertion of a crack into the hydrogel or juxtaposition of two separate hydrogel pieces. The healing is reversible and can be switched on and off via changes in pH, allowing external control over the healing process. Moreover, the hydrogels can sustain multiple cycles of healing and separation without compromising their mechanical properties and healing kinetics. Beyond revealing how secondary interactions could be harnessed to introduce new functions to chemically cross-linked polymeric systems, we also demonstrate various potential applications of such easy-to-synthesize, smart, self-healing hydrogels. PMID:22392977

Photodegradable, Photoadaptable Hydrogels via Radical-Mediated Disulfide Fragmentation Reaction.

PubMed

Fairbanks, Benjamin D; Singh, Samir P; Bowman, Christopher N; Anseth, Kristi S

2011-04-26

Various techniques have been adopted to impart a biological responsiveness to synthetic hydrogels for the delivery of therapeutic agents as well as the study and manipulation of biological processes and tissue development. Such techniques and materials include polyelectrolyte gels that swell and deswell with changes in pH, thermosensitive gels that contract at physiological temperatures, and peptide cross-linked hydrogels that degrade upon peptidolysis by cell-secreted enzymes. Herein we report a unique approach to photochemically deform and degrade disulfide cross-linked hydrogels, mitigating the challenges of light attenuation and low quantum yield, permitting the degradation of hydrogels up to 2 mm thick within 120 s at low light intensities (10 mW/cm(2) at 365 nm). Hydrogels were formed by the oxidation of thiol-functionalized 4-armed poly(ethylene glycol) macromolecules. These disulfide cross-linked hydrogels were then swollen in a lithium acylphosphinate photoinitiator solution. Upon exposure to light, photogenerated radicals initiate multiple fragmentation and disulfide exchange reactions, permitting and promoting photodeformation, photowelding, and photodegradation. This novel, but simple, approach to generate photoadaptable hydrogels portends the study of cellular response to mechanically and topographically dynamic substrates as well as novel encapsulations by the welding of solid substrates. The principles and techniques described herein hold implications for more than hydrogel materials but also for photoadaptable polymers more generally.

Eco-friendly polyvinyl alcohol/carboxymethyl cellulose hydrogels reinforced with graphene oxide and bentonite for enhanced adsorption of methylene blue.

PubMed

Dai, Hongjie; Huang, Yue; Huang, Huihua

2018-04-01

Eco-friendly polyvinyl alcohol/carboxymethyl cellulose (isolated from pineapple peel) hydrogels reinforced with graphene oxide and bentonite were prepared as efficient adsorbents for methylene blue (MB). The structure and morphology of the prepared hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), X-ray diffraction (XRD), thermogravimetry (TG) and differential scanning calorimetry (DSC). Introducing graphene oxide and bentonite into the hydrogels evidently enhanced the thermal stability, swelling ability and MB adsorption capacity. The effects of initial concentration of MB, pH, contact time and temperature on MB adsorption capacity of the prepared hydrogels were investigated. Adsorption kinetics and equilibrium adsorption isotherm fitted pseudo-second-order kinetic model and Langmuir isotherm model well, respectively. After introducing graphene oxide and bentonite into the hydrogels, the maximum adsorption capacity calculated from the Langmuir isotherm model reached 172.14 mg/g at 30 °C, obviously higher than the hydrogels prepared without these additions (83.33 mg/g). Furthermore, all the prepared hydrogels also displayed good reusability for the efficient removal of MB. Consequently, the prepared hydrogels could be served as eco-friendly, stable, efficient and reusable adsorbents for anionic dyes in wastewater treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bio-inspired layered chitosan/graphene oxide nanocomposite hydrogels with high strength and pH-driven shape memory effect.

PubMed

Zhang, Yaqian; Zhang, Min; Jiang, Haoyang; Shi, Jinli; Li, Feibo; Xia, Yanhong; Zhang, Gongzheng; Li, Huanjun

2017-12-01

The layered nanocomposite hydrogel films containing chitosan (CS) and graphene oxide (GO) have been prepared by water evaporation induced self-assembly and subsequent physical cross-linking in alkaline solution. The layered CS/GO hydrogel films obtained have a nacre-like brick-and-mortar microstructure, which contributes to their excellent mechanical properties. The tensile strength and elongation at break of the hydrogel films with 5wt% GO are 5.35MPa and 193.5%, respectively, which are comparable to natural costal cartilage. Furthermore, the CS/GO hydrogel films exhibited pH-driven shape memory effect, and this unique phenomenon is mainly attributed to the reversible transition of partial physically cross-linking corresponding to hydrogen bondings and hydrophobic interactions between CS polymer chains due to pH changing. Copyright © 2017 Elsevier Ltd. All rights reserved.

The preparations of novel cellulose/phenylboronic acid composite intelligent bio-hydrogel and its glucose, pH-responsive behaviors.

PubMed

Peng, Huafeng; Ning, Xiaoyu; Wei, Gang; Wang, Shaopeng; Dai, Guoliang; Ju, Anqi

2018-09-01

Novel intelligent cellulose/4-vinyl-phenylboronic acid (VPBA) composite bio-hydrogels with glucose and pH-responsiveness were successfully prepared via electron beam irradiation technology at room temperature. The composites were characterized by Fourier transform infrared spectrum (FT-IR) and X-ray photoelectron spectroscopy (XPS). The electron beam irradiation results in the appearance of carbonyl in the polymerization of 4-ethenyl-phenylboronic acid, grafting and cross linking reaction in composites, and a novel composite hydrogel was formed between the poly-4-ethenyl-phenylboronic acid and cellulose matrix. By means of the incorporation of phenylboronic acid groups, the composite hydrogels with pH and glucose responsive properties was produced, and glucose responsive properties were investigated by the self-regulation of insulin release of composite hydrogel through a serial glucose solution with different concentrations, which is having great potential applications in many fields. Copyright © 2018 Elsevier Ltd. All rights reserved.

Genotyping by alkaline dehybridization using graphically encoded particles.

PubMed

Zhang, Huaibin; DeConinck, Adam J; Slimmer, Scott C; Doyle, Patrick S; Lewis, Jennifer A; Nuzzo, Ralph G

2011-03-01

This work describes a nonenzymatic, isothermal genotyping method based on the kinetic differences exhibited in the dehybridization of perfectly matched (PM) and single-base mismatched (MM) DNA duplexes in an alkaline solution. Multifunctional encoded hydrogel particles incorporating allele-specific oligonucleotide (ASO) probes in two distinct regions were fabricated by using microfluidic-based stop-flow lithography. Each particle contained two distinct ASO probe sequences differing at a single base position, and thus each particle was capable of simultaneously probing two distinct target alleles. Fluorescently labeled target alleles were annealed to both probe regions of a particle, and the rate of duplex dehybridization was monitored by using fluorescence microscopy. Duplex dehybridization was achieved through an alkaline stimulus using either a pH step function or a temporal pH gradient. When a single target probe sequence was used, the rate of mismatch duplex dehybridization could be discriminated from the rate of perfect match duplex dehybridization. In a more demanding application in which two distinct probe sequences were used, we found that the rate profiles provided a means to discriminate probe dehybridizations from both of the two mismatched duplexes as well as to distinguish at high certainty the dehybridization of the two perfectly matched duplexes. These results demonstrate an ability of alkaline dehybridization to correctly discriminate the rank hierarchy of thermodynamic stability among four sets of perfect match and single-base mismatch duplexes. We further demonstrate that these rate profiles are strongly temperature dependent and illustrate how the sensitivity can be compensated beneficially by the use of an actuating gradient pH field. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of pH on the rheological properties of borate crosslinked hydroxypropyl guar gum hydrogel and hydroxypropyl guar gum.

PubMed

Wang, Shibin; Tang, Hongbiao; Guo, Jianchun; Wang, Kunjie

2016-08-20

pH is an important factor affecting the performance of polymer fluid. The rheological properties of hydroxypropyl guar gum (HPG) base fluid and the structural strength, rheological properties, viscoelastic properties and thixotropy properties of HPG gel depend largely on the pH values. For the base fluid, an apparent viscosity-increasing effect was observed over the pH range from 7 to 11, and the apparent viscosity gradually decreased at pH 11.5-14, exhibiting electrostatic repulsion behavior and steric effects. For the HPG gel, at pH 7-12.5, the gel possessed higher apparent viscosity, higher elastic modulus (G'), lower tanδ (the ratio of the viscous modulus to the elastic modulus) and an "8"-shaped hysteresis loop, indicating stronger gel structure strength and the elastic dominant property. At pH 13-13.5, the gel samples exhibited the transition from a pseudoplastic fluid to a Newtonian fluid, and their viscosity, elastic modulus decreased but tanδ increased with the increase in pH values, exhibiting gradually weakened elastic properties. When the pH was 14, the gel mainly exhibited viscous characteristics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Retention of heavy metal ions on comb-type hydrogels based on acrylic acid and 4-vinylpyridine, synthesized by gamma radiation

NASA Astrophysics Data System (ADS)

González-Gómez, Roberto; Ortega, Alejandra; Lazo, Luz M.; Burillo, Guillermina

2014-09-01

Two novel comb-type hydrogels based on pH-sensitive monomers (acrylic acid (AAc) and 4-vinylpyridine (4VP) were synthesized by gamma radiation. The systems were as follows: a) comb-type hydrogels of an AAc network followed by grafting of 4VP ((net-PAAc)-g-4VP) and b) comb-type hydrogels of an AAc network grafted onto polypropylene (PP) followed by grafting of 4VP (net-(PP-g-AAc)-g-4VP). The equilibrium isotherms and kinetics were evaluated for copper and zinc ions in aqueous solutions. The Zn(II) retention obtained was 480 mg g-1 and 1086 mg g-1 for (net-PAAc)-g-4VP and net-(PP-g-AAc)-g-4VP, respectively. At concentrations as low as ppm, retention efficiencies of approximately 90% were achieved for Cu(II) on (net-PAAc)-g-4VP and for Zn(II) on net-(PP-g-AAc)-g-4VP. Desorption of the hydrogels was also studied, and the results indicated that they can be used repeatedly in aqueous solutions. For both systems, the adsorption of Cu(II) and Zn(II) obeyed the Freundlich model, indicating heterogeneous sorption, and the retention process occurred by chemisorption. The sorption process follows a pseudo-second-order model.

Interaction of Human Plasma Proteins with Thin Gelatin-Based Hydrogel Films: A QCM-D and ToF-SIMS Study

PubMed Central

2015-01-01

In the fields of surgery and regenerative medicine, it is crucial to understand the interactions of proteins with the biomaterials used as implants. Protein adsorption directly influences cell-material interactions in vivo and, as a result, regulates, for example, cell adhesion on the surface of the implant. Therefore, the development of suitable analytical techniques together with well-defined model systems allowing for the detection, characterization, and quantification of protein adsorbates is essential. In this study, a protocol for the deposition of highly stable, thin gelatin-based films on various substrates has been developed. The hydrogel films were characterized morphologically and chemically. Due to the obtained low thickness of the hydrogel layer, this setup allowed for a quantitative study on the interaction of human proteins (albumin and fibrinogen) with the hydrogel by Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D). This technique enables the determination of adsorbant mass and changes in the shear modulus of the hydrogel layer upon adsorption of human proteins. Furthermore, Secondary Ion Mass Spectrometry and principal component analysis was applied to monitor the changed composition of the topmost adsorbate layer. This approach opens interesting perspectives for a sensitive screening of viscoelastic biomaterials that could be used for regenerative medicine. PMID:24956040

Synthesis and evaluation of chondroitin sulfate based hydrogels of loxoprofen with adjustable properties as controlled release carriers.

PubMed

Khalid, Ikrima; Ahmad, Mahmood; Usman Minhas, Muhammad; Barkat, Kashif

2018-02-01

Mixtures of polymer (chondroitin sulfate) and monomer (AMPS) in the presence of co-monomer (MBA) were employed for the production of hydrogels, with adjustable properties, following free radical copolymerization. The hydrogel's structural properties were assessed by FTIR, DSC, TGA, SEM and XRD which confirmed the development and stability of synthesized structure. The results from FTIR analysis showed that CS react with the AMPS monomer during the polymerization process and confirmed the grafting of AMPS chains onto CS backbone. The surface morphology of CS-co-poly(AMPS) hydrogels, as evident by SEM, corresponds to their improved swelling ability due to high porosity. Thermal analysis showed that crosslinking formed a stable hydrogel network which is thermally more stable than its basic ingredients. The effects of pH revealed an increasing trend in swelling with increasing concentration of either CS or AMPS. In addition, different modalities for drug loading were studied with respect to drug homogeneous distribution; loxoprofen sodium was employed as model drug and was loaded by swelling-diffusion method. In vitro drug release profiles and kinetics were assessed to confirm their reproducibility and reliability. Higuchi model is the best fit model to explain drug release from formed gels indicating diffusion-controlled release. Similarly, Korsmeyer-Peppas model yields remarkably good adjustments where release kinetics involves a combination of diffusion in hydrated matrix and polymer relaxation. Conclusively, CS-co-poly(AMPS) hydrogels could be a potential alternate to conventional dosage forms for controlled delivery of loxoprofen sodium for extended period of time. Copyright © 2017. Published by Elsevier Ltd.

Textural and cargo release attributes of trisodium citrate cross-linked starch hydrogel.

PubMed

Abhari, Negar; Madadlou, Ashkan; Dini, Ali; Hosseini Naveh, Ozra

2017-01-01

An alkaline starch suspension was charged with citric acid and incubated for different durations (0, 8.5 or 17h). The suspension was then supplemented with caffeine and gelatinized to fabricate hydrogels which were subsequently stored for varying periods (0, 24 or 48h). Charging of the well-dissolved alkaline starch suspension with citric acid decreased at first both the flow index and consistency coefficient (K); however, starch cross-linking over time by the generated trisodium citrate increased the K value. The latter also inhibited gel syneresis and increased its water-holding capacity. Trisodium citrate did not nonetheless influence the gel hardness except for the sample incubated for maximum duration and stored for the longest period. The amount of the caffeine released from hydrogel decreased by citrate cross-linking and was higher at neutral pH than pH 2.0. Fourier-transform infra-red spectroscopy suggested that caffeine was enclosed within the gel network via non-covalent interactions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bio-based topical system for enhanced salicylic acid delivery: preparation and performance of gels.

PubMed

Langasco, Rita; Spada, Gianpiera; Tanriverdi, Sakine Tuncay; Rassu, Giovanna; Giunchedi, Paolo; Özer, Özgen; Gavini, Elisabetta

2016-08-01

New salicylic acid (SA)-loaded gels were developed using excipients made from renewable materials, and our goal was to improve drug permeation in the topical treatment of acne vulgaris. We studied the preparation parameters to obtain suitable gel formulations. Only naturally occurring polymers were used as gelling agents. Two hydrogels and three lipogels were selected and characterized in terms of drug loading, pH, viability cells, rheology, mechanical properties and in vitro permeation; these hydrogels and lipogels were compared with the traditional ointment. We also evaluated skin parameters before and after gel application. The formulations that we studied are non-Newtonian fluids; they have high drug loading and suitable mechanical properties. Lipogels exhibit a slower and more linear in vitro permeation profile compared with hydrogels. The different vehicles that we used affected drug permeation and improve patient compliance. Cytotoxicity studies suggest that all of the formulations are non-toxic. Lipogels demonstrate appropriate technological features and improved performance compared with the traditional ointment with regard to their composition. Lipogels may represent a new bio-based topical system for SA delivery. The use of 'green' excipients leads to 'skin-friendly' formulations that are able to satisfy environmental safety. © 2016 Royal Pharmaceutical Society.

Effective genetic modification and differentiation of hMSCs upon controlled release of rAAV vectors using alginate/poloxamer composite systems.

PubMed

Díaz-Rodríguez, P; Rey-Rico, A; Madry, H; Landin, M; Cucchiarini, M

2015-12-30

Viral vectors are common tools in gene therapy to deliver foreign therapeutic sequences in a specific target population via their natural cellular entry mechanisms. Incorporating such vectors in implantable systems may provide strong alternatives to conventional gene transfer procedures. The goal of the present study was to generate different hydrogel structures based on alginate (AlgPH155) and poloxamer PF127 as new systems to encapsulate and release recombinant adeno-associated viral (rAAV) vectors. Inclusion of rAAV in such polymeric capsules revealed an influence of the hydrogel composition and crosslinking temperature upon the vector release profiles, with alginate (AlgPH155) structures showing the fastest release profiles early on while over time vector release was more effective from AlgPH155+PF127 [H] capsules crosslinked at a high temperature (50°C). Systems prepared at room temperature (AlgPH155+PF127 [C]) allowed instead to achieve a more controlled release profile. When tested for their ability to target human mesenchymal stem cells, the different systems led to high transduction efficiencies over time and to gene expression levels in the range of those achieved upon direct vector application, especially when using AlgPH155+PF127 [H]. No detrimental effects were reported on either cell viability or on the potential for chondrogenic differentiation. Inclusion of PF127 in the capsules was also capable of delaying undesirable hypertrophic cell differentiation. These findings are of promising value for the further development of viral vector controlled release strategies. Copyright © 2015 Elsevier B.V. All rights reserved.

One-pot synthesis of pH-responsive hybrid nanogel particles for the intracellular delivery of small interfering RNA

PubMed Central

Parodi, Alessandro; Evangelopoulos, Michael; Corbo, Claudia; Scaria, Shilpa; Hu, Ye; Haddix, Seth G.; Corradetti, Bruna; Salvatore, Francesco; Tasciotti, Ennio

2016-01-01

This report describes a novel, one-pot synthesis of hybrid nanoparticles formed by a nanostructured inorganic silica core and an organic pH-responsive hydrogel shell. This easy-to-perform, oil-in-water emulsion process synthesizes fluorescently-doped silica nanoparticles wrapped within a tunable coating of cationic poly(2-diethylaminoethyl methacrylate) hydrogel in one step. Transmission electron microscopy and dynamic light scattering analysis demonstrated that the hydrogel-coated nanoparticles are uniformly dispersed in the aqueous phase. The formation of covalent chemical bonds between the silica and the polymer increases the stability of the organic phase around the inorganic core as demonstrated by thermogravimetric analysis. The cationic nature of the hydrogel is responsible for the pH buffering properties of the nanostructured system and was evaluated by titration experiments. Zeta-potential analysis demonstrated that the charge of the system was reversed when transitioned from acidic to basic pH and vice versa. Consequently, small interfering RNA (siRNA) can be loaded and released in an acidic pH environment thereby enabling the hybrid particles and their payload to avoid endosomal sequestration and enzymatic degradation. These nanoparticles, loaded with specific siRNA molecules directed towards the transcript of the membrane receptor CXCR4, significantly decreased the expression of this protein in a human breast cancer cell line (i.e., MDA-MB-231). Moreover, intravenous administration of siRNA-loaded nanoparticles demonstrated a preferential accumulation at the tumor site that resulted in a reduction of CXCR4 expression. PMID:26901429

Hydrogels with Modulated Ionic Load for Mammalian Cell Harvesting with Reduced Bacterial Adhesion.

PubMed

Gallardo, Alberto; Martínez-Campos, Enrique; García, Carolina; Cortajarena, Aitziber L; Rodríguez-Hernández, Juan

2017-05-08

In this manuscript, we describe the fabrication of hydrogel supports for mammalian cell handling that can simultaneously prevent materials from microbial contamination and therefore allow storage in aqueous media. For that purpose, hydrogels based on the antifouling polymer polyvinylpyrrolidone (PVP) were functionalized with different ionic groups (anionic, cationic, or two types of zwitterions). In order to prevent bacterial adhesion in the long-term, we took advantage of the synergistic effect of inherently antifouling PVP and additional antifouling moieties incorporated within the hydrogel structure. We evaluated, in a separated series of experiments, both the capability of the materials to act as supports for the growth of mammalian cell monolayers for transplantation (using C-166-GFP endothelial cell line), as well their antifouling properties against Staphylococcus aureus, were studied. All of the hydrogels are structurally pseudodouble networks with high swelling (around 90%) and similar mechanical properties (in the low range for hydrogel materials with Young modulus below 1250 kPa). With some differences, all the charged hydrogels were capable of hosting mouse endothelial cell line C166-GFP to confluence, as well as a monolayer detachment and transplantation through simple mechanical agitation. On the contrary, the uncharged hydrogel was not capable to detach a full monolayer for transplantation. Bacterial adhesion and proliferation was highly sensitive to the functionality (type of charge and density). In particular, we evidenced that monomers bearing zwitterionic sulfobetaine groups, those negatively charged as well as "electro neutral" hydrogels fabricated from stoichiometric amounts of positive and negative units, exhibit excellent antifouling properties both at initial adhesion times and during longer periods up to 72 h.

Design and synthesis of target-responsive hydrogel for portable visual quantitative detection of uranium with a microfluidic distance-based readout device.

PubMed

Huang, Yishun; Fang, Luting; Zhu, Zhi; Ma, Yanli; Zhou, Leiji; Chen, Xi; Xu, Dunming; Yang, Chaoyong

2016-11-15

Due to uranium's increasing exploitation in nuclear energy and its toxicity to human health, it is of great significance to detect uranium contamination. In particular, development of a rapid, sensitive and portable method is important for personal health care for those who frequently come into contact with uranium ore mining or who investigate leaks at nuclear power plants. The most stable form of uranium in water is uranyl ion (UO2(2+)). In this work, a UO2(2+) responsive smart hydrogel was designed and synthesized for rapid, portable, sensitive detection of UO2(2+). A UO2(2+) dependent DNAzyme complex composed of substrate strand and enzyme strand was utilized to crosslink DNA-grafted polyacrylamide chains to form a DNA hydrogel. Colorimetric analysis was achieved by encapsulating gold nanoparticles (AuNPs) in the DNAzyme-crosslinked hydrogel to indicate the concentration of UO2(2+). Without UO2(2+), the enzyme strand is not active. The presence of UO2(2+) in the sample activates the enzyme strand and triggers the cleavage of the substrate strand from the enzyme strand, thereby decreasing the density of crosslinkers and destabilizing the hydrogel, which then releases the encapsulated AuNPs. As low as 100nM UO2(2+) was visually detected by the naked eye. The target-responsive hydrogel was also demonstrated to be applicable in natural water spiked with UO2(2+). Furthermore, to avoid the visual errors caused by naked eye observation, a previously developed volumetric bar-chart chip (V-Chip) was used to quantitatively detect UO2(2+) concentrations in water by encapsulating Au-Pt nanoparticles in the hydrogel. The UO2(2+) concentrations were visually quantified from the travelling distance of ink-bar on the V-Chip. The method can be used for portable and quantitative detection of uranium in field applications without skilled operators and sophisticated instruments. Copyright © 2016 Elsevier B.V. All rights reserved.

Nanocellulose-alginate hydrogel for cell encapsulation.

PubMed

Park, Minsung; Lee, Dajung; Hyun, Jinho

2015-02-13

TEMPO-oxidized bacterial cellulose (TOBC)-sodium alginate (SA) composites were prepared to improve the properties of hydrogel for cell encapsulation. TOBC fibers were obtained using a TEMPO/NaBr/NaClO system at pH 10 and room temperature. The fibrillated TOBCs mixed with SA were cross-linked in the presence of Ca(2+) solution to form hydrogel composites. The compression strength and chemical stability of the TOBC/SA composites were increased compared with the SA hydrogel, which indicated that TOBC performed an important function in enhancing the structural, mechanical and chemical stability of the composites. Cells were successfully encapsulated in the TOBC/SA composites, and the viability of cells was investigated. TOBC/SA composites can be a potential candidate for cell encapsulation engineering. Copyright © 2014 Elsevier Ltd. All rights reserved.

'Smart' polymers in biotechnology and medicine

NASA Astrophysics Data System (ADS)

Galaev, Igor Yu

1995-05-01

'Smart' water-soluble polymers and hydrogels are capable of responding reversibly to slight changes in the properties of the medium (pH, temperature, ionic strength, the presence of certain substances, illumination, electric field), the response of the system being readily seen with the naked eye (the formation of a new phase in a hitherto homogeneous solution, sudden swelling or contraction of the hydrogel). The properties of such polymers and hydrogels are examined. The use of 'smart' polymers and hydrogels for the concentration of protein solutions and the dehydration of suspensions, for the creation of membranes with a controllable permeability, for the isolation and purification of biomolecules, for the immobilisation of biocatalysts, and for the creation of sensor systems and systems for the controlled release of medicinal drugs is discussed. The bibliography includes 261 references.

DNA sequence-directed shape change of photopatterned hydrogels via high-degree swelling

NASA Astrophysics Data System (ADS)

Cangialosi, Angelo; Yoon, ChangKyu; Liu, Jiayu; Huang, Qi; Guo, Jingkai; Nguyen, Thao D.; Gracias, David H.; Schulman, Rebecca

2017-09-01

Shape-changing hydrogels that can bend, twist, or actuate in response to external stimuli are critical to soft robots, programmable matter, and smart medicine. Shape change in hydrogels has been induced by global cues, including temperature, light, or pH. Here we demonstrate that specific DNA molecules can induce 100-fold volumetric hydrogel expansion by successive extension of cross-links. We photopattern up to centimeter-sized gels containing multiple domains that undergo different shape changes in response to different DNA sequences. Experiments and simulations suggest a simple design rule for controlled shape change. Because DNA molecules can be coupled to molecular sensors, amplifiers, and logic circuits, this strategy introduces the possibility of building soft devices that respond to diverse biochemical inputs and autonomously implement chemical control programs.

Poly (3-hydroxyalkanoates)-co-(6-hydroxyhexanoate) hydrogel promotes angiogenesis and collagen deposition during cutaneous wound healing in rats.

PubMed

Gumel, Ahmad Mohammed; Razaif-Mazinah, Mohd Rafais Mohd; Anis, Siti Nor Syairah; Annuar, Mohamad Suffian Mohamad

2015-07-08

Wound management and healing in several physiological or pathological conditions, particularly when comorbidities are involved, usually proves to be difficult. This presents complications leading to socio-economic and public health burdens. The accelerative wound healing potential of biocompatible poly(3-hydroxyalkanoates)-co-(6-hydroxyhexanoate) (PHA-PCL) composite hydrogel is reported herein. The biosynthesized PHA-PCL macromer was cross-linked with PEGMA to give a hydrogel. Twenty-four rats weighing 200-250 g each were randomly assigned to four groups of six rats. Rats in group I (negative control) were dressed with sterilized gum acacia paste in 10% normal saline while PEGMA-alone hydrogel (PH) was used to dress group II (secondary control) rats. Group III rats were dressed with PHAs-PCL cross-linked PEGMA hydrogel (PPH). For the positive control (group IV), the rats were dressed with Intrasite(®) gel. Biochemical, histomorphometric and immunohistomorphometric analyses revealed a significant difference in area closure and re-epithelialization on days 7 and 14 in PPH or Intrasite(®) gel groups compared to gum acacia or PEGMA-alone groups. Furthermore, wounds dressed with PPH or Intrasite(®) gel showed evident collagen deposition, enhanced fibrosis and extensively organized angiogenesis on day 14 compared to the negative control group. While improvement in wound healing of the PH dressed group could be observed, there was no significant difference between the negative control group and the PH dressed group in any of the tests. The findings suggested that topical application of PPH accelerated the rats' wound healing process by improving angiogenesis attributed to the increased microvessel density (MVD) and expressions of VEGF-A in tissue samples. Thus, PPH has been demonstrated to be effective in the treatment of cutaneous wounds in rats, and could be a potential novel agent in the management and acceleration of wound healing in humans and animals.

Thermosensitive multilayer hydrogels of poly(N-vinylcaprolactam) as nanothin films and shaped capsules.

PubMed

Liang, Xing; Kozlovskaya, Veronika; Chen, Yi; Zavgorodnya, Oleksandra; Kharlampieva, Eugenia

2012-08-09

We report on nanothin multilayer hydrogels of cross-linked poly(N-vinylcaprolactam) (PVCL) that exhibit distinctive and reversible thermoresponsive behavior. The single-component PVCL hydrogels were produced by selective cross-linking of PVCL in layer-by-layer films of PVCL-NH(2) copolymers assembled with poly(methacrylic acid) (PMAA) via hydrogen bonding. The degree of the PVCL hydrogel film shrinkage, defined as the ratio of wet thicknesses at 25°C to 50°C, was demonstrated to be 1.9±0.1 and 1.3±0.1 for the films made from PVCL-NH(2)-7 and PVCL-NH(2)-14 copolymers, respectively. No temperature-responsive behavior was observed for non-cross-linked two-component films due to the presence of PMAA. We also demonstrated that temperature-sensitive PVCL capsules of cubical and spherical shapes could be fabricated as hollow hydrogel replicas of inorganic templates. The cubical (PVCL)(7) capsules retained their cubical shape when temperature was elevated from 25°C to 50°C exhibiting 21±1% decrease in the capsule size. Spherical hydrogel capsules demonstrated similar shrinkage of 23±1%. The temperature-triggered capsule size changes were completely reversible. Our work opens new prospects for developing biocompatible and nanothin hydrogel-based coatings and containers for temperate-regulating drug delivery, cellular uptake, sensing, and transport behavior in microfluidic devices.

Intratumoral Delivery of Doxorubicin on Folate-Conjugated Graphene Oxide by In-Situ Forming Thermo-Sensitive Hydrogel for Breast Cancer Therapy

PubMed Central

Fong, Yi Teng; Chen, Chih-Hao

2017-01-01

By taking advantage of the pH-sensitive drug release property of graphene oxide (GO) after intracellular uptake, we prepared folic acid (FA)-conjugated GO (GOFA) for targeted delivery of the chemotherapeutic drug doxorubicin (DOX). GOFA-DOX was further encapsulated in an injectable in-situ forming thermo-sensitive hyaluronic acid-chitosan-g-poly(N-isopropylacrylamide) (HACPN) hydrogel for intratumoral delivery of DOX. As the degradation time of HACPN could be extended up to 3 weeks, intratumoral delivery of GOFA-DOX/HACPN could provide controlled and targeted delivery of DOX through slow degradation HACPN and subsequent cellular uptake of released GOFA-DOX by tumor cells through interactions of GOFA with folate receptors on the tumor cell’s surface. GOFA nano-carrier and HACPN hydrogel were first characterized for the physico-chemical properties. The drug loading experiments indicated the best preparation condition of GOFA-DOX was by reacting 0.1 mg GOFA with 2 mg DOX. GOFA-DOX showed pH-responsive drug release with ~5 times more DOX released at pH 5.5 than at pH 7.4 while only limited DOX was released from GOFA-DOX/HACPN at pH 7.4. Intracellular uptake of GOFA by endocytosis and release of DOX from GOFA-DOX in vitro could be confirmed from transmission electron microscopic and confocal laser scanning microscopic analysis with MCF-7 breast cancer cells. The targeting effect of FA was revealed when intracellular uptake of GOFA was blocked by excess FA. This resulted in enhanced in vitro cytotoxicity as revealed from the lower half maximal inhibitory concentration (IC50) value of GOFA-DOX (7.3 μg/mL) compared with that of DOX (32.5 μg/mL) and GO-DOX (10 μg/mL). The flow cytometry analysis indicated higher apoptosis rates for cells treated with GOFA-DOX (30%) compared with DOX (8%) and GO-DOX (11%). Animal studies were carried out with subcutaneously implanted MCF-7 cells in BALB/c nude mice and subject to intratumoral administration of drugs. The relative tumor volumes of control (saline) and GOFA-DOX/HACPN groups at day 21 were 2.17 and 1.79 times that at day 0 with no significant difference. In comparison, the relative tumor volumes of treatment groups at the same time were significantly different at 1.02, 0.67 and 0.48 times for DOX, GOFA-DOX and GOFA-DOX/HACPN groups, respectively. The anti-tumor efficacy was also supported by images from an in vivo imaging system (IVIS) using MCF-7 cells transfected with luciferase (MCF-7/Luc). Furthermore, tissue biopsy examination and blood analysis indicated that intratumoral delivery of DOX using GOFA-DOX/HACPN did not elicit acute toxicity. Taken together, GOFA-DOX/HACPN could be deemed as a safe and efficient intratumoral drug delivery system for breast cancer therapy. PMID:29135959

Albumin Hydrogels Formed by Electrostatically Triggered Self-Assembly and Their Drug Delivery Capability

PubMed Central

2015-01-01

Biological hydrogels are fundamentally biocompatible and have intrinsic similarities to extracellular matrices in medical applications and drug delivery systems. Herein we demonstrate the ability to form drug-eluting protein hydrogels using a novel mechanism that involves the electrostatically triggered partial denaturation and self-assembly of the protein via changes in pH. Partial denaturation increases the protein’s solvent exposed hydrophobic surface area, which then drives self-assembly of the protein into a hydrogel within 10 min at 37 °C. We describe the properties of an albumin hydrogel formed by this mechanism. Intrinsic drug binding properties of albumin to all-trans retinoic acid (atRA) are conserved through the partial denaturation process, as confirmed by fluorescence quenching. atRA released from the hydrogel inhibited smooth muscle cell migration as per an in vitro scratch wound assay. Atomistic molecular dynamics and potential of mean force calculations show the preservation and potential creation of new atRA binding sites with a binding energy of −41 kJ/mol. The resulting hydrogel is also biocompatible and exhibits rapid postgelation degradation after its implantation in vivo. This interdisciplinary work provides a new tool for the development of biocompatible protein hydrogel drug delivery systems. PMID:25148603

Synthesis and characterization of microparticles based on poly-methacrylic acid with glucose oxidase for biosensor applications.

PubMed

Hervás Pérez, J P; López-Ruiz, B; López-Cabarcos, E

2016-01-01

In the line of the applicability of biocompatible monomers pH and temperature dependent, we assayed poly-methacrylic acid (p-MAA) microparticles as immobilization system in the design of enzymatic biosensors. Glucose oxidase was used as enzyme model for the study of microparticles as immobilization matrices and as biological material in the performance of glucose biosensors. The enzyme immobilization method was optimized by investigating the influence of monomer concentration and cross-linker content (N',N'-methylenebisacrylamide), used in the preparation of the microparticles in the response of the biosensors. The kinetics of the polymerization and the effects of the temperature were studied, also the conversion of the polymerization was determinates by a weight method. The structure of the obtained p-MAA microparticles were studied through scanning electron microscopy (SEM) and differential scanning microscopy (DSC). The particle size measurements were performed with a Galai-Cis 1 particle analyzer system. Furthermore, the influence of the swelling behavior of hydrogel matrix as a function of pH and temperature were studied. Analytical properties such as sensitivity, linear range, response time and detection limit were studied for the glucose biosensors. The sensitivity for glucose detection obtained with poly-methacrylic acid (p-MAA) microparticles was 11.98mAM(-1)cm(-2) and 10μM of detection limit. A Nafion® layer was used to eliminate common interferents of the human serum such as uric and ascorbic acids. The biosensors were used to determine glucose in human serum samples with satisfactory results. When stored in a frozen phosphate buffer solution (pH 6.0) at -4°C, the useful lifetime of all biosensors was at least 550 days. Copyright © 2015 Elsevier B.V. All rights reserved.

Antimicrobial hydrogels: promising materials for medical application

PubMed Central

Yang, Kerong; Han, Qing; Chen, Bingpeng; Zheng, Yuhao; Zhang, Kesong; Li, Qiang; Wang, Jincheng

2018-01-01

The rapid emergence of antibiotic resistance in pathogenic microbes is becoming an imminent global public health problem. Local application of antibiotics might be a solution. In local application, materials need to act as the drug delivery system. The drug delivery system should be biodegradable and prolonged antibacterial effect should be provided to satisfy clinical demand. Hydrogel is a promising material for local antibacterial application. Hydrogel refers to a kind of biomaterial synthesized by a water-soluble natural polymer or a synthesized polymer, which turns into gel according to the change in different signals such as temperature, ionic strength, pH, ultraviolet exposure etc. Because of its high hydrophilicity, unique three-dimensional network, fine biocompatibility and cell adhesion, hydrogel is one of the suitable biomaterials for drug delivery in antimicrobial areas. In this review, studies from the past 5 years were reviewed, and several types of antimicrobial hydrogels according to different ingredients, different preparations, different antimicrobial mechanisms, different antimicrobial agents they contained and different applications, were summarized. The hydrogels loaded with metal nanoparticles as a potential method to solve antibiotic resistance were highlighted. Finally, future prospects of development and application of antimicrobial hydrogels are suggested. PMID:29695904

Tunable Collagen I Hydrogels for Engineered Physiological Tissue Micro-Environments

PubMed Central

Antoine, Elizabeth E.; Vlachos, Pavlos P.; Rylander, Marissa N.

2015-01-01

Collagen I hydrogels are commonly used to mimic the extracellular matrix (ECM) for tissue engineering applications. However, the ability to design collagen I hydrogels similar to the properties of physiological tissues has been elusive. This is primarily due to the lack of quantitative correlations between multiple fabrication parameters and resulting material properties. This study aims to enable informed design and fabrication of collagen hydrogels in order to reliably and reproducibly mimic a variety of soft tissues. We developed empirical predictive models relating fabrication parameters with material and transport properties. These models were obtained through extensive experimental characterization of these properties, which include compression modulus, pore and fiber diameter, and diffusivity. Fabrication parameters were varied within biologically relevant ranges and included collagen concentration, polymerization pH, and polymerization temperature. The data obtained from this study elucidates previously unknown fabrication-property relationships, while the resulting equations facilitate informed a priori design of collagen hydrogels with prescribed properties. By enabling hydrogel fabrication by design, this study has the potential to greatly enhance the utility and relevance of collagen hydrogels in order to develop physiological tissue microenvironments for a wide range of tissue engineering applications. PMID:25822731

Dual-Functional Hydrazide-Reactive and Anhydride-Containing Oligomeric Hydrogel Building Blocks.

PubMed

Kascholke, Christian; Loth, Tina; Kohn-Polster, Caroline; Möller, Stephanie; Bellstedt, Peter; Schulz-Siegmund, Michaela; Schnabelrauch, Matthias; Hacker, Michael C

2017-03-13

Biomimetic hydrogels are advanced biomaterials that have been developed following different synthetic routes. Covalent postfabrication functionalization is a promising strategy to achieve efficient matrix modification decoupled of general material properties. To this end, dual-functional macromers were synthesized by free radical polymerization of maleic anhydride with diacetone acrylamide (N-(1,1-dimethyl-3-oxobutyl)acrylamide) and pentaerythritol diacrylate monostearate. Amphiphilic oligomers (M n < 7.5 kDa) with anhydride contents of 7-20% offered cross-linking reactivity to yield rigid hydrogels with gelatinous peptides (E = 4-13 kPa) and good cell adhesion properties. Mildly reactive methyl ketones as second functionality remained intact during hydrogel formation and potential of covalent matrix modification was shown using hydrazide and hydrazine model compounds. Successful secondary dihydrazide cross-linking was demonstrated by an increase of hydrogel stiffness (>40%). Efficient hydrazide/hydrazine immobilization depending on solution pH, hydrogel ketone content as well as ligand concentration for bioconjugation was shown and reversibility of hydrazone formation was indicated by physiologically relevant hydrazide release over 7 days. Proof-of-concept experiments with hydrazido-functionalized hyaluronan demonstrated potential for covalent aECM immobilization. The presented dual-functional macromers have perspective as reactive hydrogel building blocks for various biomedical applications.

Hydrogels constructed via self-assembly of beta-hairpin molecules

NASA Astrophysics Data System (ADS)

Ozbas, Bulent

There is a recent and growing interest in hydrogel materials that are formed via peptide self-assembly for tissue engineering applications. Peptide based materials are excellent candidates for diverse applications in biomedical field due to their responsive behavior and complex self-assembled structures. However, there is very limited information on the self-assembly and resultant network and mechanical properties of these types of hydrogels. The main goal of this dissertation is to investigate the self-assembly mechanism and viscoelastic properties of hydrogels that can be altered by changing solution conditions as well as the primary structure of the peptide. These hydrogels are formed via intramolecular folding and consequent self-assembly of 20 amino acid long beta-hairpin peptide molecules (Max1). The peptide molecules are locally amphiphilic with two linear strands of alternating hydrophobic valine and hydrophilic lysine amino acids connected with a Dproline-LProline turn sequence. Circular dichroism and FTIR spectroscopy show that at physiological conditions peptides are unfolded in the absence of salt. By raising the ionic strength of the solution electrostatic interactions between charged lysines are screened and the peptide arms are forced into a beta-sheet secondary structure stabilized by the turn sequence. These folded molecules intermolecularly assemble via hydrophobic collapse and hydrogen bonding into a three dimensional network. Folding and self-assembly of these molecules can also be triggered by increasing temperature and/or pH of the peptide solution. In addition, the random-coil to beta-sheet transition of the beta-hairpin peptides is pH and, with proper changes in the peptide sequence, thermally reversible. Rheological measurements demonstrate that the resultant supramolecular structure forms an elastic material, whose structure, and thus modulus, can be tuned by magnitude of the stimulus. Hydrogels recover their initial viscoelastic properties after cessation of high magnitude of strain due to the physically crosslinked network structure and strong inter-fibrillar interactions. These interactions can be turned off by either condensing anions or covalently attaching PEG chains on lysine-decorated fibrillar surfaces. TEM, SANS, and rheological data reveal that the elasticity arises from a network consisting of semiflexible fibrillar assemblies that are monodisperse in width. The experimental results are compared with scaling relationships developed for permanently crosslinked semiflexible biopolymer networks. (Abstract shortened by UMI.)

Modeling the controllable pH-responsive swelling and pore size of networked alginate based biomaterials.

PubMed

Chan, Ariel W; Neufeld, Ronald J

2009-10-01

Semisynthetic network alginate polymer (SNAP), synthesized by acetalization of linear alginate with di-aldehyde, is a pH-responsive tetrafunctionally linked 3D gel network, and has potential application in oral delivery of protein therapeutics and active biologicals, and as tissue bioscaffold for regenerative medicine. A constitutive polyelectrolyte gel model based on non-Gaussian polymer elasticity, Flory-Huggins liquid lattice theory, and non-ideal Donnan membrane equilibria was derived, to describe SNAP gel swelling in dilute and ionic solutions containing uni-univalent, uni-bivalent, bi-univalent or bi-bi-valent electrolyte solutions. Flory-Huggins interaction parameters as a function of ionic strength and characteristic ratio of alginates of various molecular weights were determined experimentally to numerically predict SNAP hydrogel swelling. SNAP hydrogel swells pronouncedly to 1000 times in dilute solution, compared to its compact polymer volume, while behaving as a neutral polymer with limited swelling in high ionic strength or low pH solutions. The derived model accurately describes the pH-responsive swelling of SNAP hydrogel in acid and alkaline solutions of wide range of ionic strength. The pore sizes of the synthesized SNAP hydrogels of various crosslink densities were estimated from the derived model to be in the range of 30-450 nm which were comparable to that measured by thermoporometry, and diffusion of bovine serum albumin. The derived equilibrium swelling model can characterize hydrogel structure such as molecular weight between crosslinks and crosslinking density, or can be used as predictive model for swelling, pore size and mechanical properties if gel structural information is known, and can potentially be applied to other point-link network polyelectrolytes such as hyaluronic acid gel.

Effect of drug loading method against the dissolution mechanism of encapsulated amoxicillin trihidrate drug in matrix of semi-IPN chitosan-poly (N-vinyl pyrrolidone) hydrogel with pore forming agent CaCO3

NASA Astrophysics Data System (ADS)

Nurjannah, Yanah; Budianto, Emil

2018-04-01

Heliobacter pylori (H.pylori) is a type of bacteria that causes inflammation in the lining of the stomach. The treatment of the bacterial infection by using conventional medicine which is amoxicillin trihidrate has a very short retention time in the stomach which is about 1-1,5 hours. Floating drug delivery system is expected to have a long retention time in the stomach so the efficiency of drug can be achieved. In this study, has been synthesized matrix of semi-IPN chitosan-Poly(N-vinil pyrrolidone) hydrogel with a pore-forming agent of CaCO3 under optimum conditions. Amoxicillin is encapsulated in a matrix hydrogel to be applied as a floating drug delivery system by in situ loading and post loading methods. The encapsulation efficiency and dissolution of in situ loading and post loading hydrogels are performed in vitro on gastric pH. In situ loading hydrogel shows higer percentage of encapsulation efficiency and dissolution compared to post loading hydrogel. The encapsulation efficiency of in situ and post loading hydrogels were 92,1% and 89,4%, respectively. The aim of drug dissolution by mathematical equation model is to know kinetics and the mecanism of dissolution. The kinetics release of in situ hydrogel tends to follow first order kinetics, while the post loading hydrogel follow the Higuchi model. The dissolution mecanism of hydrogels is erosion.

A fast pH-switchable and self-healing supramolecular hydrogel carrier for guided, local catheter injection in the infarcted myocardium.

PubMed

Bastings, Maartje M C; Koudstaal, Stefan; Kieltyka, Roxanne E; Nakano, Yoko; Pape, A C H; Feyen, Dries A M; van Slochteren, Frebus J; Doevendans, Pieter A; Sluijter, Joost P G; Meijer, E W; Chamuleau, Steven A J; Dankers, Patricia Y W

2014-01-01

Minimally invasive intervention strategies after myocardial infarction use state-of-the-art catheter systems that are able to combine mapping of the infarcted area with precise, local injection of drugs. To this end, catheter delivery of drugs that are not immediately pumped out of the heart is still challenging, and requires a carrier matrix that in the solution state can be injected through a long catheter, and instantaneously gelates at the site of injection. To address this unmet need, a pH-switchable supramolecular hydrogel is developed. The supramolecular hydrogel is switched into a liquid at pH > 8.5, with a viscosity low enough to enable passage through a 1-m long catheter while rapidly forming a hydrogel in contact with tissue. The hydrogel has self-healing properties taking care of adjustment to the injection site. Growth factors are delivered from the hydrogel thereby clearly showing a reduction of infarct scar in a pig myocardial infarction model. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fabrication and evaluation of thermosensitive chitosan/collagen/α, β-glycerophosphate hydrogels for tissue regeneration.

PubMed

Dang, Qifeng; Liu, Kai; Zhang, Zhenzhen; Liu, Chengsheng; Liu, Xi; Xin, Ying; Cheng, Xiaoyu; Xu, Tao; Cha, Dongsu; Fan, Bing

2017-07-01

Thermosensitive hydrogels whose physiological properties are similar to extracellular matrix have been extensively used for tissue regeneration. Polysaccharides and proteins, as biocompatible substrates similar to bio-macromolecules that could be recognized by human body, are two preferred polymers for fabrication of such hydrogels. A series of novel thermosensitive hydrogels (CS-ASC-HGs) containing chitosan (CS) and acid-soluble collagen (ASC) were thus prepared, in the presence of α, β-glycerophosphate, to mimic extracellular microenvironment for tissue regeneration. Rheological measurements demonstrated excellent thermosensitivity. FT-IR and SEM indicated CS-ASC-HGs possessed 3D porous architectures with fibrous ASC, and the molecular structure of ASC was well-maintained in hydrogels. Hemolysis, acute toxicity, and cytotoxicity tests suggested CS-ASC-HGs were of good biocompatibility. CS-ASC-HGs were able to support the survival and proliferation of L929 cells encapsulated in them. Moreover, CS-ASC-HGs had better pH stability and biocompatibility than pure CS hydrogel. These results suggested that CS-ASC-HGs could serve as promising scaffolds for tissue regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Doxorubicin-induced co-assembling nanomedicines with temperature-sensitive acidic polymer and their in-situ-forming hydrogels for intratumoral administration.

PubMed

Wan, Jiangshan; Geng, Shinan; Zhao, Hao; Peng, Xiaole; Zhou, Qing; Li, Han; He, Ming; Zhao, Yanbing; Yang, Xiangliang; Xu, Huibi

2016-08-10

Doxorubicin (DOX)-induced co-assembling nanomedicines (D-PNAx) with temperature-sensitive PNAx triblock polymers have been developed for regional chemotherapy against liver cancer via intratumoral administration in the present work. Owing to the formation of insoluble DOX carboxylate, D-PNAx nanomedicines showed high drug-loading and entrapment efficacy via a simple mixing of doxorubicin hydrochloride and PNAx polymers. The sustained releasing profile of D-PNA100 nanomedicines indicated that only 9.4% of DOX was released within 1day, and 60% was released during 10days. Based on DOX-induced co-assembling behavior and their temperature sensitive in-situ-forming hydrogels, D-PNA100 nanomedicines showed excellent antitumor activity against H22 tumor using intratumoral administration. In contrast to that by free DOX solution (1.13±0.04 times at 9days) and blank PNA100 (2.11±0.34 times), the tumor volume treated by D-PNA100 had been falling to only 0.77±0.13 times of original tumor volume throughout the experimental period. In vivo biodistribution of DOX indicated that D-PNA100 nanomedicines exhibited much stronger DOX retention in tumor tissues than free DOX solution via intratumoral injection. D-PNA100 nanomedicines were hopeful to be developed as new temperature sensitive in-situ-forming hydrogels via i.t. injection for regional chemotherapy. Copyright © 2016. Published by Elsevier B.V.

Novel Polyethylenimine–Acrylamide/SiO 2 Hybrid Hydrogel Sorbent for Rare-Earth-Element Recycling from Aqueous Sources

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Qiuming; Wilfong, Walter C.; Kail, Brian W.

Recycling rare earth elements (REEs) becomes increasingly important due to their supply vulnerability and increasing demands in industry, agriculture, and national security. Hybrid hydrogel sorbents were outstanding due to their high stability and selectivity. Organic-inorganic hybrid hydrogels were synthesized by thermo-polymerization of acrylamide onto PEI polymer chain with N,N’-methylene bisacrylamide as a crosslinker. The grafted network was evidenced by DRIFTS and XPS. The porous structure was observed by SEM. Crosslink degree, PEI grafting degree, and SiO 2 concentration were studied to optimize the REEs adsorption. The pH value of the medium greatly affected REE adsorption capacity, where the nearly neutralmore » conditions gave the strongest bonding of REEs to active sites. Moreover, kinetic studies showed that the rate-determining step of the adsorption process was chemical sorption, and that REE diffusion within micropores was the control step for, specifically, intraparticle diffusion. The adsorbents showed excellent selectivity and recyclability for REEs through 5 adsorption-desorption cycles in contact with synthetic acid mine drainage solution. A high separation toward REEs over fouling metals was achieved by using a citrate-based buffer eluent solution. This hybrid hydrogel shows promise for the recycling of REEs from aqueous solutions.« less

Novel Polyethylenimine–Acrylamide/SiO 2 Hybrid Hydrogel Sorbent for Rare-Earth-Element Recycling from Aqueous Sources

DOE PAGES

Wang, Qiuming; Wilfong, Walter C.; Kail, Brian W.; ...

2017-09-14

Recycling rare earth elements (REEs) becomes increasingly important due to their supply vulnerability and increasing demands in industry, agriculture, and national security. Hybrid hydrogel sorbents were outstanding due to their high stability and selectivity. Organic-inorganic hybrid hydrogels were synthesized by thermo-polymerization of acrylamide onto PEI polymer chain with N,N’-methylene bisacrylamide as a crosslinker. The grafted network was evidenced by DRIFTS and XPS. The porous structure was observed by SEM. Crosslink degree, PEI grafting degree, and SiO 2 concentration were studied to optimize the REEs adsorption. The pH value of the medium greatly affected REE adsorption capacity, where the nearly neutralmore » conditions gave the strongest bonding of REEs to active sites. Moreover, kinetic studies showed that the rate-determining step of the adsorption process was chemical sorption, and that REE diffusion within micropores was the control step for, specifically, intraparticle diffusion. The adsorbents showed excellent selectivity and recyclability for REEs through 5 adsorption-desorption cycles in contact with synthetic acid mine drainage solution. A high separation toward REEs over fouling metals was achieved by using a citrate-based buffer eluent solution. This hybrid hydrogel shows promise for the recycling of REEs from aqueous solutions.« less

Cyclodextrin controlled release of poorly water-soluble drugs from hydrogels.

PubMed

Woldum, Henriette Sie; Larsen, Kim Lambertsen; Madsen, Flemming

2008-01-01

The effect of 2-hydroxypropyl-beta-cyclodextrin and gamma-cyclodextrin on the release of ibuprofen, ketoprofen and prednisolone was studied. Stability constants calculated for inclusion complexes show size dependence for complexes with both cyclodextrins. Hydrogels were prepared by ultraviolet irradiation and release of each model drug was studied. For drugs formulated using cyclodextrins an increase in the achievable concentration and in the release from hydrogels was obtained due to increased solubility, although the solubility of all gamma-cyclodextrin complexes was limited. The load also was increased by adjusting pH for the acidic drugs and this exceeds the increase obtained with gamma-cyclodextrin addition.

Quantifying the bending of bilayer temperature-sensitive hydrogels

NASA Astrophysics Data System (ADS)

Dong, Chenling; Chen, Bin

2017-04-01

Stimuli-responsive hydrogels can serve as manipulators, including grippers, sensors, etc., where structures can undergo significant bending. Here, a finite-deformation theory is developed to quantify the evolution of the curvature of bilayer temperature-sensitive hydrogels when subjected to a temperature change. Analysis of the theory indicates that there is an optimal thickness ratio to acquire the largest curvature in the bilayer and also suggests that the sign or the magnitude of the curvature can be significantly affected by pre-stretches or small pores in the bilayer. This study may provide important guidelines in fabricating temperature-responsive bilayers with desirable mechanical performance.

In vivo triarylmethyl radical stabilization through encapsulation in Pluronic F-127 hydrogel

NASA Astrophysics Data System (ADS)

Abbas, Kahina; Boutier-Pischon, Audrey; Auger, Florian; Françon, Dominique; Almario, Antonio; Frapart, Yves-Michel

2016-09-01

In vivo electron paramagnetic resonance (EPR) imaging and spectroscopy are non-invasive technologies used to specifically detect and quantify paramagnetic species. However, the relative instability of spin probes such as triarylmethyl radicals limits their application to conduct oxygen quantification and mapping. In this study we encapsulated tetrathiatriarylmethyl radical (TAM; known as "Finland" probe) in Pluronic F-127 hydrogel (PF-127) in order to limit its degradation and evaluate its in vitro and in vivo EPR properties as a function of oxygen. Our results show that the EPR signal of encapsulated TAM in PF-127 hydrogel is similar to the one in solution. Although it is less sensitive to oxygen, it is suitable for oximetry. We also demonstrated that the incorporation of TAM in PF-127 hydrogel leads to an improved in vivo EPR stability of the radical under anesthesia. This new formulation enables high quality EPR imaging and oximetry and paves the way for the application of TAM radical-based probes in various biomedical fields.

Biomimetic hydrogels gate transport of calcium ions across cell culture inserts.

PubMed

Kotanen, Christian N; Wilson, A Nolan; Wilson, Ann M; Ishihara, Kazuhiko; Guiseppi-Elie, Anthony

2012-06-01

Control of the in vitro spatiotemporal availability of calcium ions is one means by which the microenvironments of hematopoietic stem cells grown in culture may be reproduced. The effects of cross-linking density on the diffusivity of calcium ions through cell culture compatible poly(2-hydroxyethyl methacrylate) [poly(HEMA)]-based bioactive hydrogels possessing 1.0 mol% 2-methacryloyloxyethyl phosphorylcholine (MPC), 5 mol% N,N-(dimethylamino)ethylmethacrylate (DMAEMA) and ca. 17 mol% n-butyl acrylate (n-BA) have been investigated to determine if varying cross-link density is a viable approach to controlling transport of calcium across hydrogel membranes. Cross-linking density was varied by changing the composition of cross-linker, tetraethyleneglycol diacrylate (TEGDA). The hydrogel membranes were formed by sandwich casting onto the external surface of track-etched polycarbonate membranes (T = 10 μm, φ = 0.4 μm pores) of cell culture inserts, polymerized in place by UV light irradiation and immersed in buffered (0.025 HEPES, pH 7.4) 0.10 M calcium chloride solution. The transport of calcium ions across the hydrogel membrane was monitored using a calcium ion selective electrode set within the insert. Degree of hydration (21.6 ± 1.0%) and void fraction were found to be constant across all cross-linking densities. Diffusion coefficients, determined using time-lag analysis, were shown to be strongly dependent on and to exponentially decrease with increasing cross-linking density. Compared to that found in buffer (2.0-2.5 × 10⁻⁶ cm²/s), diffusion coefficients ranged from 1.40 × 10⁻⁶ cm²/s to 1.80 × 10⁻⁷ cm²/s and tortuosity values ranged from 1.7 to 10.0 for the 1 and 12 mol% TEGDA cross-linked hydrogels respectively. Changes in tortuosity arising from variations in cross-link density were found to be the primary modality for controlling diffusivity through novel n-BA containing poly(HEMA)-based bioactive hydrogels.

New Hydrogels Enriched with Antioxidants from Saffron Crocus Can Find Applications in Wound Treatment and/or Beautification.

PubMed

Zeka, Keti; Ruparelia, Ketan C; Sansone, Claudia; Macchiarelli, Guido; Continenza, Maria Adelaide; Arroo, Randolph R J

2018-01-01

Saffron extracts have a long history of application as skin protectant, possibly due to their ability to scavenge free radicals. In this work, the performance of a hydrogel enriched with antioxidant compounds isolated from saffron crocus (Crocus sativus L.) petals was tested. These hydrogels could be considered as new drug delivery system. Hydrogels are crosslinked polymer networks that absorb large quantities of water but retain the properties of a solid, thus making ideal dressings for sensitive skin. We tested antioxidant-enriched hydrogels on primary mouse fibroblasts. Hydrogels enriched with kaempferol and crocin extracted from saffron petals showed good biocompatibility with in vitro cultured fibroblasts. These new types of hydrogels may find applications in wound treatment and/or beautification. © 2018 S. Karger AG, Basel.

A novel injectable temperature-sensitive zinc doped chitosan/β-glycerophosphate hydrogel for bone tissue engineering.

PubMed

Niranjan, Ramesh; Koushik, Chandru; Saravanan, Sekaran; Moorthi, Ambigapathi; Vairamani, Mariappanadar; Selvamurugan, Nagarajan

2013-03-01

Hydrogels are hydrophilic polymers that have a wide range of biomedical applications including bone tissue engineering. In this study we report preparation and characterization of a thermosensitive hydrogel (Zn-CS/β-GP) containing zinc (Zn), chitosan (CS) and beta-glycerophosphate (β-GP) for bone tissue engineering. The prepared hydrogel exhibited a liquid state at room temperature and turned into a gel at body temperature. The hydrogel was characterized by SEM, EDX, XRD, FT-IR and swelling studies. The hydrogel enhanced antibacterial activity and promoted osteoblast differentiation. Thus, we suggest that the Zn-CS/β-GP hydrogel could have potential impact as an injectable in situ forming scaffold for bone tissue engineering applications. Copyright © 2012 Elsevier B.V. All rights reserved.

Glucose-Sensitive Hydrogel Optical Fibers Functionalized with Phenylboronic Acid.

PubMed

Yetisen, Ali K; Jiang, Nan; Fallahi, Afsoon; Montelongo, Yunuen; Ruiz-Esparza, Guillermo U; Tamayol, Ali; Zhang, Yu Shrike; Mahmood, Iram; Yang, Su-A; Kim, Ki Su; Butt, Haider; Khademhosseini, Ali; Yun, Seok-Hyun

2017-04-01

Hydrogel optical fibers are utilized for continuous glucose sensing in real time. The hydrogel fibers consist of poly(acrylamide-co-poly(ethylene glycol) diacrylate) cores functionalized with phenylboronic acid. The complexation of the phenylboronic acid and cis-diol groups of glucose enables reversible changes of the hydrogel fiber diameter. The analyses of light propagation loss allow for quantitative glucose measurements within the physiological range. © 2017 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rapid and efficient treatment of wastewater with high-concentration heavy metals using a new type of hydrogel-based adsorption process.

PubMed

Zhou, Guiyin; Liu, Chengbin; Chu, Lin; Tang, Yanhong; Luo, Shenglian

2016-11-01

In this study, a new type of double-network hydrogel sorbent was developed to remove heavy metals in wastewater. The amino-functionalized Starch/PAA hydrogel (NH2-Starch/PAA) could be conducted in a wide pH and the adsorption process could rapidly achieve the equilibrium. The adsorption capacity got to 256.4mg/g for Cd(II). Resultantly, even though Cd(II) concentration was as high as 180mg/L, the Cd(II) could be entirely removed using 1g/L sorbent. Furthermore, the desirable mechanical durability of the adsorbent allowed easy separation and reusability. In the fixed-bed column experiments, the treatment volume of the effluent with a high Cd(II) concentration of 200mg/L reached 2400BV (27.1L) after eight times cycle. The NH2-Starch/PAA overcame the deficiency of conventional sorbents that could not effectively treat the wastewater with relatively high metal concentrations. This work provides a new insight into omnidirectional enhancement of sorbents for removing high-concentration heavy metals in wastewater. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gel integration for microfluidic applications.

PubMed

Zhang, Xuanqi; Li, Lingjun; Luo, Chunxiong

2016-05-21

Molecular diffusive membranes or materials are important for biological applications in microfluidic systems. Hydrogels are typical materials that offer several advantages, such as free diffusion for small molecules, biocompatibility with most cells, temperature sensitivity, relatively low cost, and ease of production. With the development of microfluidic applications, hydrogels can be integrated into microfluidic systems by soft lithography, flow-solid processes or UV cure methods. Due to their special properties, hydrogels are widely used as fluid control modules, biochemical reaction modules or biological application modules in different applications. Although hydrogels have been used in microfluidic systems for more than ten years, many hydrogels' properties and integrated techniques have not been carefully elaborated. Here, we systematically review the physical properties of hydrogels, general methods for gel-microfluidics integration and applications of this field. Advanced topics and the outlook of hydrogel fabrication and applications are also discussed. We hope this review can help researchers choose suitable methods for their applications using hydrogels.

Photoinitiator-Free Synthesis of Endothelial Cell Adhesive and Enzymatically Degradable Hydrogels

PubMed Central

Jones, Derek R.; Marchant, Roger E.; von Recum, Horst; Gupta, Anirban Sen; Kottke-Marchant, Kandice

2015-01-01

We report on a photoinitiator-free synthetic method of incorporating bioactivity into poly(ethylene glycol) (PEG) hydrogels in order to control physical properties, enzymatic biodegradability and cell-specific adhesiveness of the polymer network, while eliminating the need for UV-mediated photopolymerization. To accomplish this, hydrogel networks were polymerized using Michael addition with four-arm PEG acrylate (10 kDa), using a collagenase sensitive peptide (CSP) as a crosslinker, and introducing an endothelial cell adhesive peptide either terminally (RGD) or attached to the crosslinking peptide sequence (CSP-RGD). The efficiency of the Michael addition reactions were determined by NMR and Ellman’s assay. Successful decoupling of cell adhesivity and physical properties was demonstrated by quantifying and comparing the swelling ratios and Young’s Moduli of various hydrogel formulations. Degradation profiles were established by incubating functionalized hydrogels in collagenase solutions (0.0 – 1.0 µg/mL), demonstrating that functionalized hydrogels degraded at a rate dependent upon collagenase concentration. Moreover, it was shown that the degradation rate was independent of CSP-RGD concentration. Cell attachment and proliferation on functionalized hydrogels were compared for various RGD concentrations, providing evidence that cell attachment and proliferation were directly related to relative amounts of the CSP-RGD combination peptide. An increase in cell viability was achieved using Michael addition techniques when compared to UV-polymerization, and was assessed by a LIVE/DEAD fluorescence assay. This photoinitiator-free method shows promise in creating hydrogel-based tissue engineering scaffolds allow for decoupled cell adhesivity and physical properties and that render greater cell viability. PMID:25462848

Dual-functional transdermal drug delivery system with controllable drug loading based on thermosensitive poloxamer hydrogel for atopic dermatitis treatment

NASA Astrophysics Data System (ADS)

Wang, Wenyi; Wat, Elaine; Hui, Patrick C. L.; Chan, Ben; Ng, Frency S. F.; Kan, Chi-Wai; Wang, Xiaowen; Hu, Huawen; Wong, Eric C. W.; Lau, Clara B. S.; Leung, Ping-Chung

2016-04-01

The treatment of atopic dermatitis (AD) has long been viewed as a problematic issue by the medical profession. Although a wide variety of complementary therapies have been introduced, they fail to combine the skin moisturizing and drug supply for AD patients. This study reports the development of a thermo-sensitive Poloxamer 407/Carboxymethyl cellulose sodium (P407/CMCs) composite hydrogel formulation with twin functions of moisture and drug supply for AD treatment. It was found that the presence of CMCs can appreciably improve the physical properties of P407 hydrogel, which makes it more suitable for tailored drug loading. The fabricated P407/CMCs composite hydrogel was also characterized in terms of surface morphology by field emission scanning electron microscopy (FE-SEM), rheological properties by a rheometer, release profile in vitro by dialysis method and cytotoxicity test. More importantly, the findings from transdermal drug delivery behavior revealed that P407/CMCs showed desirable percutaneous performance. Additionally, analysis of cytotoxicity test suggested that P407/CMCs composite hydrogel is a high-security therapy for clinical trials and thus exhibits a promising way to treat AD with skin moisturizing and medication.

Dual-functional transdermal drug delivery system with controllable drug loading based on thermosensitive poloxamer hydrogel for atopic dermatitis treatment

PubMed Central

Wang, Wenyi; Wat, Elaine; Hui, Patrick C. L.; Chan, Ben; Ng, Frency S. F.; Kan, Chi-Wai; Wang, Xiaowen; Hu, Huawen; Wong, Eric C. W.; Lau, Clara B. S.; Leung, Ping-Chung

2016-01-01

The treatment of atopic dermatitis (AD) has long been viewed as a problematic issue by the medical profession. Although a wide variety of complementary therapies have been introduced, they fail to combine the skin moisturizing and drug supply for AD patients. This study reports the development of a thermo-sensitive Poloxamer 407/Carboxymethyl cellulose sodium (P407/CMCs) composite hydrogel formulation with twin functions of moisture and drug supply for AD treatment. It was found that the presence of CMCs can appreciably improve the physical properties of P407 hydrogel, which makes it more suitable for tailored drug loading. The fabricated P407/CMCs composite hydrogel was also characterized in terms of surface morphology by field emission scanning electron microscopy (FE-SEM), rheological properties by a rheometer, release profile in vitro by dialysis method and cytotoxicity test. More importantly, the findings from transdermal drug delivery behavior revealed that P407/CMCs showed desirable percutaneous performance. Additionally, analysis of cytotoxicity test suggested that P407/CMCs composite hydrogel is a high-security therapy for clinical trials and thus exhibits a promising way to treat AD with skin moisturizing and medication. PMID:27090158

A novel multiphysic model for simulation of swelling equilibrium of ionized thermal-stimulus responsive hydrogels

NASA Astrophysics Data System (ADS)

Li, Hua; Wang, Xiaogui; Yan, Guoping; Lam, K. Y.; Cheng, Sixue; Zou, Tao; Zhuo, Renxi

2005-03-01

In this paper, a novel multiphysic mathematical model is developed for simulation of swelling equilibrium of ionized temperature sensitive hydrogels with the volume phase transition, and it is termed the multi-effect-coupling thermal-stimulus (MECtherm) model. This model consists of the steady-state Nernst-Planck equation, Poisson equation and swelling equilibrium governing equation based on the Flory's mean field theory, in which two types of polymer-solvent interaction parameters, as the functions of temperature and polymer-network volume fraction, are specified with or without consideration of the hydrogen bond interaction. In order to examine the MECtherm model consisting of nonlinear partial differential equations, a meshless Hermite-Cloud method is used for numerical solution of one-dimensional swelling equilibrium of thermal-stimulus responsive hydrogels immersed in a bathing solution. The computed results are in very good agreements with experimental data for the variation of volume swelling ratio with temperature. The influences of the salt concentration and initial fixed-charge density are discussed in detail on the variations of volume swelling ratio of hydrogels, mobile ion concentrations and electric potential of both interior hydrogels and exterior bathing solution.

Development, fabrication, and modeling of highly sensitive conjugated polymer based piezoresistive sensors in electronic skin applications

NASA Astrophysics Data System (ADS)

Khalili, Nazanin; Naguib, Hani E.; Kwon, Roy H.

2016-04-01

Human intervention can be replaced through development of tools resulted from utilizing sensing devices possessing a wide range of applications including humanoid robots or remote and minimally invasive surgeries. Similar to the five human senses, sensors interface with their surroundings to stimulate a suitable response or action. The sense of touch which arises in human skin is among the most challenging senses to emulate due to its ultra high sensitivity. This has brought forth novel challenging issues to consider in the field of biomimetic robotics. In this work, using a multiphase reaction, a polypyrrole (PPy) based hydrogel is developed as a resistive type pressure sensor with an intrinsically elastic microstructure stemming from three dimensional hollow spheres. Furthermore, a semi-analytical constriction resistance model accounting for the real contact area between the PPy hydrogel sensors and the electrode along with the dependency of the contact resistance change on the applied load is developed. The model is then solved using a Monte Carlo technique and the sensitivity of the sensor is obtained. The experimental results showed the good tracking ability of the proposed model.

Bioengineering and regenerative medicine: Keeping track

NASA Astrophysics Data System (ADS)

Ziv, Keren; Gambhir, Sanjiv S.

2013-03-01

Assessing when cell death occurs following in vivo transplantation of stem cells is challenging. Now, pH-sensitive hydrogel capsules containing arginine-based liposomes are shown to act as magnetic resonance imaging contrast agents, allowing cell death to be monitored within the capsules.

Soft poly(2-chloroaniline)/pectin hydrogel and its electromechanical properties.

PubMed

Kongkaew, Wanar; Sangwan, Watchara; Lerdwijitjarud, Wanchai; Sirivat, Anuvat

2018-01-01

Pectin hydrogels were successfully fabricated with various physical crosslinkers and concentrations for soft actuator applications. A small amount of synthesized P2ClAn was added as a dispersed phase into the pectin matrix. The electromechanical properties of the pectin hydrogels and blends were investigated under the effects of electric field strength, ionic crosslinker type and concentration, and P2ClAn concentration. The electromechanical properties of the pectin hydrogel as crosslinked by Fe 2+ were superior to other pectin hydrogels. The pristine pectin hydrogel and the P2ClAn/Pectin hydrogel blended with 0.10%v/v P2ClAn provided the high storage modulus sensitivity values of 8.61 and 14.01, respectively, under the electric field strength of 800 V/mm. The P2ClAn/Pectin hydrogel blend responded to the electric field with higher dielectrophoretic forces, but lower deflections relative to the pristine pectin hydrogel due to the additional P2ClAn polarization and the latter lower rigidity.

Controlled release behaviors of chitosan/α, β-glycerophosphate thermo-sensitive hydrogels

NASA Astrophysics Data System (ADS)

Liu, Wei-Fang; Kang, Chuan-Zhen; Kong, Ming; Li, Yang; Su, Jing; Yi, An; Cheng, Xiao-Jie; Chen, Xi-Guang

2012-09-01

Chitosan/α, β-glycerophosphate (CS/α, β-GP) thermo-sensitive hydrogels presented flowable solution state at low temperature and semisolid hydrogel when the ambient temperature increased. In this research, different concentrations of metronidazole encapsulated, CS and α, β-GP, as well as different acid solvents, were chosen to evaluate their influences on the drug release behaviors from CS/α, β-GP hydrogels. It was found that there was a sustaining release during the first 3 h followed by a plateau. SEM images showed that drugs were located both on the surface and in the interior of hydrogels. The optimal preparation conditions of this hydrogel for drug release were as follows: 1.8% (w/v) CS in HAc solvent, 5.6% (w/v) α, β-GP and 5 g/L metronidazole encapsulation. Cytotoxicity evaluation found no toxic effect. In order to control the release rate, 2.5 g/L chitosan microspheres with spherical shape and smooth surface were incorporated, and it was found that the initial release process was alleviated, while drug concentration had no obvious effect on the release rate. It could be concluded that the metronidzole release behaviors could be optimized according to practical applications.

Dextran hydrogel coated surface plasmon resonance imaging (SPRi) sensor for sensitive and label-free detection of small molecule drugs

NASA Astrophysics Data System (ADS)

Li, Shaopeng; Yang, Mo; Zhou, Wenfei; Johnston, Trevor G.; Wang, Rui; Zhu, Jinsong

2015-11-01

The label-free and sensitive detection of small molecule drugs on SPRi is still a challenging task, mainly due to the limited surface immobilization capacity of the sensor. In this research, a dextran hydrogel-coated gold sensor chip for SPRi was successfully fabricated via photo-cross-linking for enhanced surface immobilization capacity. The density of the dextran hydrogel was optimized for protein immobilization and sensitive small molecule detection. The protein immobilization capacity of the hydrogel was 10 times greater than a bare gold surface, and 20 times greater than an 11-mercaptoundecanoic acid (MUA) surface. Such a drastic improvement in immobilization capacity allowed the SPRi sensor to detect adequate response signals when probing small molecule binding events. The binding signal of 4 nM liquid-phase biotin to streptavidin immobilized on the dextran surface reached 435 RU, while no response was observed on bare gold or MUA surfaces. The dextran hydrogel-coated SPRi sensor was also applied in a kinetic study of the binding between an immunosuppressive drug (FK506) and its target protein (FKBP12) in a high-throughput microarray format. The measured binding affinity was shown to be consistent with reported literature values, and a detection limit of 0.5 nM was achieved.

Effects of pore forming agents of potassium bicarbonate and drug loading method against dissolution mechanisms of amoxicillin drugs encapsulated in hydrogel full-Ipn chitosan-poly(N-vinylcaprolactam) as a floating drug delivery system

NASA Astrophysics Data System (ADS)

Aini, Nurul; Rahayu, Dyah Utami Cahyaning; Budianto, Emil

2018-04-01

The limitation of amoxicillin trihydrate in the treatment of H. pylori bacteria is relatively short retention time in the stomach. The FDDS (Floating Drug Delivery System) amoxicillin trihydrate into a chitosan-poly(N-vinylcaprolactam) full-Ipn hydrogel matrix using a pore-forming agent KHCO3 is expected to overcome these limitations. The pore-forming agent to be used is 15% KHCO3 compound. Chemical kinetics approach is performed to determine the dissolution mechanism of amoxicillin trihydrate from K-PNVCL hydrogel in vitro on gastric pH and characterization using SEM performed to confirm the dissolution mechanism. Hydrogels with the addition of pore-forming agents will be loading in situ loading and post loading. Fourier Transform Infra Red (FTIR) spectroscopy was used to characterize K-PNVCL and UV-Vis hydrogels used to calculate the efficiency of encapsulation and drug dissolution rate in K-PNVCL hydrogel. Hydrogel K-PNVCL / KHCO3 that encapsulated by in situ loading method resulted in an encapsulation efficiency of 93.5% and dissolution of 93.4%. While the Hydrogel K-PNVCL / KHCO3 which is drug encapsulation resulted in an encapsulation efficiency of 87.2% with dissolution of 81.5%. Chemical kinetics approach to in situ encapsulation of loading and post loading shows the dissolution mechanism occurring in the K-PNVCL / KHCO3 hydrogel matrix occurs by diffusion. Observation using optical microscope and SEM showed the mechanism of drug dissolution in Hydrogel K-PNVCL occurred by diffusion.

Responsive Photonic Crystal Carbohydrate Hydrogel Sensor Materials for Selective and Sensitive Lectin Protein Detection.

PubMed

Cai, Zhongyu; Sasmal, Aniruddha; Liu, Xinyu; Asher, Sanford A

2017-10-27

Lectin proteins, such as the highly toxic lectin protein, ricin, and the immunochemically important lectin, jacalin, play significant roles in many biological functions. It is highly desirable to develop a simple but efficient method to selectively detect lectin proteins. Here we report the development of carbohydrate containing responsive hydrogel sensing materials for the selective detection of lectin proteins. The copolymerization of a vinyl linked carbohydrate monomer with acrylamide and acrylic acid forms a carbohydrate hydrogel that shows specific "multivalent" binding to lectin proteins. The resulting carbohydrate hydrogels are attached to 2-D photonic crystals (PCs) that brightly diffract visible light. This diffraction provides an optical readout that sensitively monitors the hydrogel volume. We utilize lactose, galactose, and mannose containing hydrogels to fabricate a series of 2-D PC sensors that show strong selective binding to the lectin proteins ricin, jacalin, and concanavalin A (Con A). This binding causes a carbohydrate hydrogel shrinkage which significantly shifts the diffraction wavelength. The resulting 2-D PC sensors can selectively detect the lectin proteins ricin, jacalin, and Con A. These unoptimized 2-D PC hydrogel sensors show a limit of detection (LoD) of 7.5 × 10 -8 M for ricin, a LoD of 2.3 × 10 -7 M for jacalin, and a LoD of 3.8 × 10 -8 M for Con A, respectively. This sensor fabrication approach may enable numerous sensors for the selective detection of numerous lectin proteins.

Dynamic modeling of the hydrogel molecular filter in a metamaterial biosensing system for glucose concentration estimation.

PubMed

Teutsch, T; Mesch, M; Giessen, H; Tarin, C

2014-01-01

We present a novel concept for ophthalmic glucose sensing using a biosensing system that consists of plasmonic dipole metamaterial covered by a layer of functionalized hydrogel. The metamaterial together with the hydrogel can be integrated into a contact lens. This optical sensor changes its properties such as reflectivity upon the ambient glucose concentration, which allows in situ measurements in the eye. The functionalization of the sensor with hydrogel allows for a glucose-specific detection, providing both selectivity and sensitivity. As a result of the presented work we derive a dynamic model of the hydrogel that can be used for further simulation studies.

Photonic hydrogel sensors.

PubMed

Yetisen, Ali K; Butt, Haider; Volpatti, Lisa R; Pavlichenko, Ida; Humar, Matjaž; Kwok, Sheldon J J; Koo, Heebeom; Kim, Ki Su; Naydenova, Izabela; Khademhosseini, Ali; Hahn, Sei Kwang; Yun, Seok Hyun

2016-01-01

Analyte-sensitive hydrogels that incorporate optical structures have emerged as sensing platforms for point-of-care diagnostics. The optical properties of the hydrogel sensors can be rationally designed and fabricated through self-assembly, microfabrication or laser writing. The advantages of photonic hydrogel sensors over conventional assay formats include label-free, quantitative, reusable, and continuous measurement capability that can be integrated with equipment-free text or image display. This Review explains the operation principles of photonic hydrogel sensors, presents syntheses of stimuli-responsive polymers, and provides an overview of qualitative and quantitative readout technologies. Applications in clinical samples are discussed, and potential future directions are identified. Copyright © 2015 Elsevier Inc. All rights reserved.

Synthesis and colon-specific drug delivery of a poly(acrylic acid-co-acrylamide)/MBA nanosized hydrogel.

PubMed

Ray, Debajyoti; Mohapatra, Dillip K; Mohapatra, Ranjit K; Mohanta, Guru P; Sahoo, Prafulla K

2008-01-01

Intravenous administration of 5-fluorouracil (5-FU) for colon cancer therapy produces severe systemic side-effects due to its cytotoxic effect on normal cells. The main objective of the present study was to develop novel oral site-specific delivery of 5-FU to the colon with less drug being released in the stomach or small intestine using biodegradable hydrogel, hydrogel nanoparticles and comparing the targeting efficiency of 5-FU to colon from both. Poly(acrylic acid-co-acrylamide) (P(AA-co-Am)) normal hydrogel and hydrogel nanoparticles (HN) were synthesized by free radical polymerization using N,N-methylene-bis-acrylamide (MBA) as cross-linker, potassium persulfate as reaction initiator and 5-FU was loaded. HN were found to be degradable in physiological medium and showed comparatively higher swelling in rat caecal medium (RCM). 5-FU entrapment was increased by increasing Am (wt%) monomer feed. In vitro release of 5-FU from normal hydrogel and HN in pH progressive medium, it was found that a AA/Am ratio of 25:75 showed higher release in RCM. The Higuchi model yielded good adjustment of in vitro release kinetics. A higher amount of 5-FU reached the colon in HN (61 +/- 2.1%) than normal hydrogel (40 +/- 3.6%) by organ biodistribution studies in albino rats.

Design and development of hydrogel nanoparticles for mercaptopurine

PubMed Central

Senthil, V.; Kumar, R. Suresh; Nagaraju, C. V. V.; Jawahar, N.; Ganesh, G. N. K.; Gowthamarajan, K.

2010-01-01

Hydrogel nanoparticles have gained attention in recent years as they demonstrate the features and characters of hydrogels and nanoparticles at the same time. In the present study chitosan and carrageenan have been used, as hydrogel nanoparticles of mercaptopurine are developed using natural, biodegradable, and biocompatible polymers like chitosan and carrageenan. As these polymers are hydrophilic in nature, the particles will have a long life span in systemic circulation. Hydrogel nanoparticles with mercaptopurine is form an antileukemia drug by the counter polymer gelation method. Fourier-Transform Infrared (FT-IR) studies have shown a compatibility of polymers with the drug. The diameter of hydrogel nanoparticles was about 370 – 800 nm with a positive zeta potential of 26 – 30 mV. The hydrogel nanoparticles were almost spherical in shape, as revealed by scanning electron microscopy (SEM). Drug loading varied from 9 to 17%. Mercaptopurine released from the nanoparticles at the end of the twenty-fourth hour was about 69.48 – 76.52% at pH 7.4. The drug release from the formulation was following zero order kinetics, which was evident from the release kinetic studies and the mechanism of drug release was anomalous diffusion, which indicated that the drug release was controlled by more than one process. PMID:22247867

Tough Composite Hydrogels with High Loading and Local Release of Biological Drugs.

PubMed

Li, Jianyu; Weber, Eckhard; Guth-Gundel, Sabine; Schuleit, Michael; Kuttler, Andreas; Halleux, Christine; Accart, Nathalie; Doelemeyer, Arno; Basler, Anne; Tigani, Bruno; Wuersch, Kuno; Fornaro, Mara; Kneissel, Michaela; Stafford, Alexander; Freedman, Benjamin R; Mooney, David J

2018-05-01

Hydrogels are under active development for controlled drug delivery, but their clinical translation is limited by low drug loading capacity, deficiencies in mechanical toughness and storage stability, and poor control over the drug release that often results in burst release and short release duration. This work reports a design of composite clay hydrogels, which simultaneously achieve a spectrum of mechanical, storage, and drug loading/releasing properties to address the critical needs from translational perspectives. The clay nanoparticles provide large surface areas to adsorb biological drugs, and assemble into microparticles that are physically trapped within and toughen hydrogel networks. The composite hydrogels demonstrate feasibility of storage, and extended release of large quantities of an insulin-like growth factor-1 mimetic protein (8 mg mL -1 ) over four weeks. The release rate is primarily governed by ionic exchange and can be upregulated by low pH, which is typical for injured tissues. A rodent model of Achilles tendon injury is used to demonstrate that the composite hydrogels allow for highly extended and localized release of biological drugs in vivo, while demonstrating biodegradation and biocompatibility. These attributes make the composite hydrogel a promising system for drug delivery and regenerative medicine. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Injectable, degradable, electroactive nanocomposite hydrogels containing conductive polymer nanoparticles for biomedical applications

PubMed Central

Wang, Qinmei; Wang, Qiong; Teng, Wei

2016-01-01

Injectable electroactive hydrogels (eGels) are promising in regenerative medicine and drug delivery, however, it is still a challenge to obtain such hydrogels simultaneously possessing other properties including uniform structure, degradability, robustness, and biocompatibility. An emerging strategy to endow hydrogels with desirable properties is to incorporate functional nanoparticles in their network. Herein, we report the synthesis and characterization of an injectable hydrogel based on oxidized alginate (OA) crosslinking gelatin reinforced by electroactive tetraaniline-graft-OA nanoparticles (nEOAs), where nEOAs are expected to impart electroactivity besides reinforcement without significantly degrading the other properties of hydrogels. Assays of transmission electron microscopy, 1H nuclear magnetic resonance, and dynamic light scattering reveal that EOA can spontaneously and quickly self-assemble into robust nanoparticles in water, and this nanoparticle structure can be kept at pH 3~9. Measurement of the gel time by rheometer and the stir bar method confirms the formation of the eGels, and their gel time is dependent on the weight content of nEOAs. As expected, adding nEOAs to hydrogels does not cause the phase separation (scanning electron microscopy observation), but it improves mechanical strength up to ~8 kPa and conductivity up to ~10−6 S/cm in our studied range. Incubating eGels in phosphate-buffered saline leads to their further swelling with an increase of water content <6% and gradual degradation. When growing mesenchymal stem cells on eGels with nEOA content ≤14%, the growth curves and morphology of cells were found to be similar to that on tissue culture plastic; when implanting these eGels on a chick chorioallantoic membrane for 1 week, mild inflammation response appeared without any other structural changes, indicating their good in vitro and in vivo biocompatibility. With injectability, uniformity, degradability, electroactivity, relative robustness, and biocompatibility, these eGels may have a huge potential as scaffolds for tissue regeneration and matrix for stimuli responsive drug release. PMID:26792990

Silk Electrogel Based Gastroretentive Drug Delivery System

NASA Astrophysics Data System (ADS)

Wang, Qianrui

Gastric cancer has become a global pandemic and there is imperative to develop efficient therapies. Oral dosing strategy is the preferred route to deliver drugs for treating the disease. Recent studies suggested silk electro hydrogel, which is pH sensitive and reversible, has potential as a vehicle to deliver the drug in the stomach environment. The aim of this study is to establish in vitro electrogelation e-gel based silk gel as a gastroretentive drug delivery system. We successfully extended the duration of silk e-gel in artificial gastric juice by mixing silk solution with glycerol at different ratios before the electrogelation. Structural analysis indicated the extended duration was due to the change of beta sheet content. The glycerol mixed silk e-gel had good doxorubicin loading capability and could release doxorubicin in a sustained-release profile. Doxorubicin loaded silk e-gels were applied to human gastric cancer cells. Significant cell viability decrease was observed. We believe that with further characterization as well as functional analysis, the silk e-gel system has the potential to become an effective vehicle for gastric drug delivery applications.

Novel Polysaccharide Based Polymers and Nanoparticles for Controlled Drug Delivery and Biomedical Imaging

NASA Astrophysics Data System (ADS)

Shalviri, Alireza

The use of polysaccharides as building blocks in the development of drugs and contrast agents delivery systems is rapidly growing. This can be attributed to the outstanding virtues of polysaccharides such as biocompatibility, biodegradability, upgradability, multiple reacting groups and low cost. The focus of this thesis was to develop and characterize novel starch based hydrogels and nanoparticles for delivery of drugs and imaging agents. To this end, two different systems were developed. The first system includes polymer and nanoparticles prepared by graft polymerization of polymethacrylic acid and polysorbate 80 onto starch. This starch based platform nanotechnology was developed using the design principles based on the pathophysiology of breast cancer, with applications in both medical imaging and breast cancer chemotherapy. The nanoparticles exhibited a high degree of doxorubicin loading as well as sustained pH dependent release of the drug. The drug loaded nanoparticles were significantly more effective against multidrug resistant human breast cancer cells compared to free doxorubicin. Systemic administration of the starch based nanoparticles co-loaded with doxorubicin and a near infrared fluorescent probe allowed for non-invasive real time monitoring of the nanoparticles biodistribution, tumor accumulation, and clearance. Systemic administration of the clinically relevant doses of the drug loaded particles to a mouse model of breast cancer significantly enhanced therapeutic efficacy while minimizing side effects compared to free doxorubicin. A novel, starch based magnetic resonance imaging (MRI) contrast agent with good in vitro and in vivo tolerability was formulated which exhibited superior signal enhancement in tumor and vasculature. The second system is a co-polymeric hydrogel of starch and xanthan gum with adjustable swelling and permeation properties. The hydrogels exhibited excellent film forming capability, and appeared to be particularly useful in controlled delivery applications of larger molecular size compounds. The starch based hydrogels, polymers and nanoparticles developed in this work have shown great potentials for controlled drug delivery and biomedical imaging applications.

Microsphere erosion in outer hydrogel membranes creating macroscopic porosity to counter biofouling-induced sensor degradation.

PubMed

Vaddiraju, S; Wang, Y; Qiang, L; Burgess, D J; Papadimitrakopoulos, F

2012-10-16

Biofouling and tissue inflammation present major challenges toward the realization of long-term implantable glucose sensors. Following sensor implantation, proteins and cells adsorb on sensor surfaces to not only inhibit glucose flux but also signal a cascade of inflammatory events that eventually lead to permeability-reducing fibrotic encapsulation. The use of drug-eluting hydrogels as outer sensor coatings has shown considerable promise to mitigate these problems via the localized delivery of tissue response modifiers to suppress inflammation and fibrosis, along with reducing protein and cell absorption. Biodegradable poly (lactic-co-glycolic) acid (PLGA) microspheres, encapsulated within a poly (vinyl alcohol) (PVA) hydrogel matrix, present a model coating where the localized delivery of the potent anti-inflammatory drug dexamethasone has been shown to suppress inflammation over a period of 1-3 months. Here, it is shown that the degradation of the PLGA microspheres provides an auxiliary venue to offset the negative effects of protein adsorption. This was realized by: (1) the creation of fresh porosity within the PVA hydrogel following microsphere degradation (which is sustained until the complete microsphere degradation) and (2) rigidification of the PVA hydrogel to prevent its complete collapse onto the newly created void space. Incubation of the coated sensors in phosphate buffered saline (PBS) led to a monotonic increase in glucose permeability (50%), with a corresponding enhancement in sensor sensitivity over a 1 month period. Incubation in serum resulted in biofouling and consequent clogging of the hydrogel microporosity. This, however, was partially offset by the generated macroscopic porosity following microsphere degradation. As a result of this, a 2-fold recovery in sensor sensitivity for devices with microsphere/hydrogel composite coatings was observed as opposed to similar devices with blank hydrogel coatings. These findings suggest that the use of macroscopic porosity can reduce sensitivity drifts resulting from biofouling, and this can be achieved synergistically with current efforts to mitigate negative tissue responses through localized and sustained drug delivery.

In vitro and in vivo testing of glucose-responsive insulin-delivery microdevices in diabetic rats.

PubMed

Chu, Michael K L; Chen, Jian; Gordijo, Claudia R; Chiang, Simon; Ivovic, Alexander; Koulajian, Khajag; Giacca, Adria; Wu, Xiao Yu; Sun, Yu

2012-07-21

We have developed glucose-responsive implantable microdevices for closed-loop delivery of insulin and conducted in vivo testing of these devices in diabetic rats. The microdevices consist of an albumin-based bioinorganic membrane that utilizes glucose oxidase (GOx), catalase (CAT) and manganese dioxide (MnO(2)) nanoparticles to convert a change in the environmental glucose level to a pH stimulus, which regulates the volume of pH-sensitive hydrogel nanoparticles and thereby the permeability of the membrane. The membrane is integrated with microfabricated PDMS (polydimethylsiloxane) structures to form compact, stand-alone microdevices, which do not require tethering wires or tubes. During in vitro testing, the microdevices showed glucose-responsive insulin release over multiple cycles at clinically relevant glucose concentrations. In vivo, the microdevices were able to counter hyperglycemia in diabetic rats over a one-week period. The in vitro and in vivo testing results demonstrated the efficacy of closed-loop biosensing and rapid response of the 'smart' insulin delivery devices.

Clinical and economic benefit of enzymatic debridement of pressure ulcers compared to autolytic debridement with a hydrogel dressing.

PubMed

Waycaster, Curtis; Milne, Catherine T

2013-07-01

The purpose of this study was to determine the cost-effectiveness of enzymatic debridement using collagenase relative to autolytic debridement with a hydrogel dressing for the treatment of pressure ulcers. A 3-stage Markov model was used to determine the expected costs and outcomes of wound care for collagenase and hydrogel dressings. Outcome data used in the analysis were taken from a randomized clinical trial that directly compared collagenase and hydrogel dressings. The primary outcome in the clinical trial was the proportion of patients achieving a closed epithelialized wound. Transition probabilities for the Markov states were estimated from the clinical trial. A 1-year time horizon was used to determine the expected number of closed wound days and the expected costs for the two alternative debridement therapies. Resource utilization was based on the wound care treatment regimen used in the clinical trial. Resource costs were derived from standard cost references and medical supply wholesalers. The economic perspective taken was that of the long-term care facility. No cost discounting was performed due to the short time horizon of the analysis. A deterministic sensitivity analysis was conducted to analyze economic uncertainty. The number of expected wound days for the collagenase and hydrogel cohorts are estimated at 48 and 147, respectively. The expected direct cost per patient for pressure ulcer care was $2003 for collagenase and $5480 for hydrogel debridement. The number of closed wound days was 1.5-times higher for collagenase (317 vs 218 days) than with the hydrogel. The estimated cost/closed wound day was 4-times higher for the hydrogel ($25) vs collagenase ($6). In this Markov model based on a randomized trial of pressure ulcer care in a long-term care setting collagenase debridement was economically dominant over autolytic debridement, yielding better outcomes at a lower total cost. Since it was a single institution study with a small sample size, the results should be interpreted with caution. Specifically, the findings may not necessarily be generalized to other hydrogel dressings, healthcare settings, age groups, or to wounds of other etiologies.

Strengthening injectable thermo-sensitive NIPAAm-g-chitosan hydrogels using chemical cross-linking of disulfide bonds as scaffolds for tissue engineering.

PubMed

Wu, Shu-Wei; Liu, Xifeng; Miller, A Lee; Cheng, Yu-Shiuan; Yeh, Ming-Long; Lu, Lichun

2018-07-15

In the present study, we fabricated non-toxic, injectable, and thermo-sensitive NIPAAm-g-chitosan (NC) hydrogels with thiol modification for introduction of disulfide cross-linking strategy. Previously, NIPAAm and chitosan copolymer has been proven to have excellent biocompatibility, biodegradability and rapid phase transition after injection, suitable to serve as cell carriers or implanted scaffolds. However, weak mechanical properties significantly limit their potential for biomedical fields. In order to overcome this issue, we incorporated thiol side chains into chitosan by covalently conjugating N-acetyl-cysteine (NAC) with carbodiimide chemistry to strengthen mechanical properties. After oxidation of thiols into disulfide bonds, modified NC hydrogels did improve the compressive modulus over 9 folds (11.4 kPa). Oscillatory frequency sweep showed a positive correlation between storage modulus and cross-liking density as well. Additionally, there was no cytotoxicity observed to mesenchymal stem cells, fibroblasts and osteoblasts. We suggested that the thiol-modified thermo-sensitive polysaccharide hydrogels are promising to be a cell-laden biomaterial for tissue regeneration. Copyright © 2018 Elsevier Ltd. All rights reserved.

Formulation, and physical, in vitro and ex vivo evaluation of transdermal ibuprofen hydrogels containing turpentine oil as penetration enhancer.

PubMed

Khan, N R; Khan, G M; Wahab, A; Khan, A R; Hussain, A; Nawaz, A; Akhlaq, M

2011-11-01

The aim of the present study was to investigate the transdermal permeation enhancing capability of turpentine oil for ibuprofen from hydrogels. Ibuprofen 1% w/v hydrogels were developed with carboxypolymethylene with and without turpentine oil. Turpentine oil was incorporated in increasing concentrations, i.e. 0.5, 1, 1.5, 2, 2.5 and 3% of the total gel formulation, and its permeation enhancing effect was examined. Gels were examined physically for pH, viscosity, spreadability, extrudability, smoothness and appearance. To study the in vitro and ex vivo permeation potential of formulated gels, permeation studies were performed with a Franz diffusion cell using cellulose membrane and excised rabbit abdominal skin. Ibuprofen hydrogel with 3% turpentine oil showed a maximum flux of 10.87 mg/cm2/h across artificial skin and 17.26 mg/cm2/h across rabbit abdominal skin.

Hydrogels for Atopic Dermatitis and Wound Management: A Superior Drug Delivery Vehicle.

PubMed

Harrison, Ian P; Spada, Fabrizio

2018-06-14

Wound management, in addition to presenting a significant burden to patients and their families, also contributes significantly to a country’s healthcare costs. Treatment strategies are numerous, but in most cases not ideal. Hydrogels, three-dimensional polymeric materials that can withstand a great degree of swelling without losing structural integrity, are drawing great attention for their use as topical wound management solutions in the form of films and as vehicles for drug delivery, due to their unique properties of high water content, biocompatibility, and flexibility. Hydrogels, both naturally and synthetically derived, can be tuned to respond to specific stimuli such as pH, temperature and light and they are ideally suited as drug delivery vehicles. Here we provide a brief overview of the history and characteristics of hydrogels, assess their uses in wound management and drug delivery, and compare them with other types of common drug delivery vehicle.

Mechanistic Studies of an Autonomously Pulsing Hydrogel/Enzyme System for Rhythmic Hormone Delivery

PubMed Central

Bhalla, Amardeep S.; Siegel, Ronald A.

2014-01-01

Numerous hormones are known to be endogenously secreted in a pulsatile manner. In particular, gonadotropin replacing hormone (GnRH) is released in rhythmic pulses, and disruption of this rhythm is associated with pathologies of reproduction and sexual development. In an effort to develop an implantable, rhythmic delivery system, a scheme has been demonstrated involving a negative feedback instability between a pH-sensitive membrane and enzymes that convert endogenous glucose to hydrogen ion. A bench prototype system based on this scheme was previously shown to produce near rhythmic oscillations in internal pH and in GnRH delivery over a period of one week. In the present work, a systematic study of conditions permitting such oscillations is presented, along with a study of factors causing period of oscillations to increase with time and ultimately cease. Membrane composition, glucose concentration, and surface area of marble (CaCO3), which is incorporated as a reactant, were found to affect the capacity of the system to oscillate, and the pH range over which oscillations occur. Accumulation of gluconate- and Ca2+ in the system over time correlated with lengthening of oscillation period, and possibly with cessation of oscillations. Enzyme degradation may also be a factor. These studies provide the groundwork for future improvements in device design. PMID:25450402

Preparation, fabrication and biocompatibility of novel injectable temperature-sensitive chitosan/glycerophosphate/collagen hydrogels.

PubMed

Song, Kedong; Qiao, Mo; Liu, Tianqing; Jiang, Bo; Macedo, Hugo M; Ma, Xuehu; Cui, Zhanfeng

2010-10-01

This paper introduces a novel type of injectable temperature-sensitive chitosan/glycerophosphate/collagen (C/GP/Co) hydrogel that possesses great biocompatibility for the culture of adipose tissue-derived stem cells. The C/GP/Co hydrogel is prepared by mixing 2.2% (v/v) chitosan with 50% (w/w) β-glycerophosphate at different proportions and afterwards adding 2 mg/ml of collagen. The gelation time of the prepared solution at 37°C was found to be of around 12 min. The inner structure of the hydrogel presented a porous spongy structure, as observed by scanning electron microscopy. Moreover, the osmolality of the medium in contact with the hydrogel was in the range of 310-330 mmol kg(-1). These analyses have shown that the C/GP/Co hydrogels are structurally feasible for cell culture, while their biocompatibility was further examined. Human adipose tissue-derived stem cells (ADSCs) were seeded into the developed C/GP and C/GP/Co hydrogels (The ratios of C/GP and C/GP/Co were 5:1 and 5:1:6, respectively), and the cellular growth was periodically observed under an inverted microscope. The proliferation of ADSCs was detected using cck-8 kits, while cell apoptosis was determined by a Live/Dead Viability/Cytotoxicity kit. After 7 days of culture, cells within the C/GP/Co hydrogels displayed a typical adherent cell morphology and good proliferation with very high cellular viability. It was thus demonstrated that the novel C/GP/Co hydrogel herein described possess excellent cellular compatibility, representing a new alternative as a scaffold for tissue engineering, with the added advantage of being a gel at the body's temperature that turns liquid at room temperature.

An electrochemical impedance biosensor for Hg2+ detection based on DNA hydrogel by coupling with DNAzyme-assisted target recycling and hybridization chain reaction.

PubMed

Cai, Wei; Xie, Shunbi; Zhang, Jin; Tang, Dianyong; Tang, Ying

2017-12-15

In this work, an electrochemical impedance biosensor for high sensitive detection of Hg 2+ was presented by coupling with Hg 2+ -induced activation of Mg 2+ -specific DNAzyme (Mg 2+ -DNAzyme) for target cycling and hybridization chain reaction (HCR) assembled DNA hydrogel for signal amplification. Firstly, we synthesized two different copolymer chains P1 and P2 by modifying hairpin DNA H3 and H4 with acrylamide polymer, respectively. Subsequently, Hg 2+ was served as trigger to activate the Mg 2+ -DNAzyme for selectively cleavage ribonucleobase-modified substrate in the presence of Mg 2+ . The partial substrate strand could dissociate from DNAzyme structure, and hybridize with capture probe H1 to expose its concealed sequence for further hybridization. With the help of the exposed sequence, the HCR between hairpin DNA H3 and H4 in P1 and P2 was initiated, and assembled a layer of DNA cross-linked hydrogel on the electrode surface. The formed non-conductive DNA hydrogel film could greatly hinder the interfacial electronic transfer which provided a possibility for us to construct a high sensitive impedance biosensor for Hg 2+ detection. Under the optimal conditions, the impedance biosensor showed an excellent sensitivity and selectivity toward Hg 2+ in a concentration range of 0.1pM - 10nM with a detection limit of 0.042pM Moreover, the real sample analysis reveal that the proposed biosensor is capable of discriminating Hg 2+ ions in reliable and quantitative manners, indicating this method has a promising potential for preliminary application in routine tests. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional nucleic acid-based hydrogels for bioanalytical and biomedical applications

PubMed Central

Mo, Liuting; Lu, Chun-Hua; Fu, Ting

2016-01-01

Hydrogels are crosslinked hydrophilic polymers that can absorb a large amount of water. By their hydrophilic, biocompatible and highly tunable nature, hydrogels can be tailored for applications in bioanalysis and biomedicine. Of particular interest are DNA-based hydrogels owing to the unique features of nucleic acids. Since the discovery of DNA double helical structure, interest in DNA has expanded beyond its genetic role to applications in nanotechnology and materials science. In particular, DNA-based hydrogels present such remarkable features as stability, flexibility, precise programmability, stimuli-responsive DNA conformations, facile synthesis and modification. Moreover, functional nucleic acids (FNAs) have allowed the construction of hydrogels based on aptamers, DNAzymes, i-motif nanostructures, siRNAs and CpG oligodeoxynucleotides to provide additional molecular recognition, catalytic activities and therapeutic potential, making them key players in biological analysis and biomedical applications. To date, a variety of applications have been demonstrated with FNA-based hydrogels, including biosensing, environmental analysis, controlled drug release, cell adhesion and targeted cancer therapy. In this review, we focus on advances in the development of FNA-based hydrogels, which have fully incorporated both the unique features of FNAs and DNA-based hydrogels. We first introduce different strategies for constructing DNA-based hydrogels. Subsequently, various types of FNAs and the most recent developments of FNA-based hydrogels for bioanalytical and biomedical applications are described with some selected examples. Finally, the review provides an insight into the remaining challenges and future perspectives of FNA-based hydrogels. PMID:26758955

Transparent crosslinked ultrashort peptide hydrogel dressing with high shape-fidelity accelerates healing of full-thickness excision wounds

NASA Astrophysics Data System (ADS)

Seow, Wei Yang; Salgado, Giorgiana; Lane, E. Birgitte; Hauser, Charlotte A. E.

2016-09-01

Wound healing is a major burden of healthcare systems worldwide and hydrogel dressings offer a moist environment conducive to healing. We describe cysteine-containing ultrashort peptides that self-assemble spontaneously into hydrogels. After disulfide crosslinking, the optically-transparent hydrogels became significantly stiffer and exhibited high shape fidelity. The peptide sequence (LIVAGKC or LK6C) was then chosen for evaluation on mice with full-thickness excision wounds. Crosslinked LK6C hydrogels are handled easily with forceps during surgical procedures and offer an improvement over our earlier study of a non-crosslinked peptide hydrogel for burn wounds. LK6C showed low allergenic potential and failed to provoke any sensitivity when administered to guinea pigs in the Magnusson-Kligman maximization test. When applied topically as a dressing, the medium-infused LK6C hydrogel accelerated re-epithelialization compared to controls. The peptide hydrogel is thus safe for topical application and promotes a superior rate and quality of wound healing.

Nanocomposite PAAm/methyl cellulose/montmorillonite hydrogel: evidence of synergistic effects for the slow release of fertilizers.

PubMed

Bortolin, Adriel; Aouada, Fauze A; Mattoso, Luiz H C; Ribeiro, Caue

2013-08-07

In this work, we synthesized a novel series of hydrogels composed of polyacrylamide (PAAm), methylcellulose (MC), and calcic montmorillonite (MMt) appropriate for the controlled release of fertilizers, where the components presented a synergistic effect, giving very high fertilizer loading in their structure. The synthesized hydrogel was characterized in relation to morphological, hydrophilic, spectroscopic, structural, thermal, and kinetic properties. After those characterizations, the application potential was verified through sorption and desorption studies of a nitrogenated fertilizer, urea (CO(NH2)2). The swelling degree results showed that the clay loading considerably reduces the water absorption capability; however, the hydrolysis process favored the urea adsorption in the hydrogel nanocomposites, increasing the load content according to the increase of the clay mass. The FTIR spectra indicated that there was incorporation of the clay with the polymeric matrix of the hydrogel and that incorporation increased the water absorption speed (indicated by the kinetic constant k). By an X-ray diffraction technique, good nanodispersion (intercalation) and exfoliation of the clay platelets in the hydrogel matrix were observed. Furthermore, the presence of the montmorillonite in the hydrogel caused the system to liberate the nutrient in a more controlled manner than that with the neat hydrogel in different pH ranges. In conclusion, excellent results were obtained for the controlled desorption of urea, highlighting the hydrolyzed hydrogels containing 50% calcic montmorillonite. This system presented the best desorption results, releasing larger amounts of nutrient and almost 200 times slower than pure urea, i.e., without hydrogel. The total values of nutrients present in the system show that this material is potentially viable for application in agriculture as a nutrient carrier vehicle.

Investigation of hydrogel membranes containing combination of gentamicin and dexamethasone for ocular delivery

PubMed Central

Prabhu, Prabhakara; Dubey, Akhilesh; Parth, Vinod; Ghate, Vivek

2015-01-01

Background: Hydrogel is a cross-linked network of polymers. Water penetrates these network causing swelling and giving the hydrogel a soft and rubbery consistency and there by maintaining the integrity of the membrane. Due to the drawback of conventional therapy for ocular delivery, hydrogel membranes containing the combination of gentamicin (GT) sulfate and dexamethasone (DX) were formulated for the treatment of conjunctivitis. The objective of this study was to formulate and evaluate the hydrogel membranes containing the combination of GT and DX for the treatment of conjunctivitis. Materials and Methods: In the present investigation, hydrogel membranes were prepared by using polymers such as gelatin, polyvinyl alcohol, and chitosan, which were cross-linked using physical/chemical methods. Results: The cross-linking of the membranes was confirmed by Fourier transform infra-red studies. The pH of the membranes ranged from 7.19 to 7.45 and drug content ranged from 69.82% to 89.19%. The hydrogels showed a considerably good swelling ratio ranging from 22.5% to 365.56%. The in vitro drug release study showed that there was a slow and sustained release of the drug from the membranes which were sufficiently cross-linked and followed zero order release. In vivo studies showed that the severity of conjunctivitis was remarkably lowered at day 3 with hydrogel membrane compared to marketed eye drops. Results of unpaired t-test of significance between two groups indicated that the hydrogel membrane showed a better response in the treatment of conjunctivitis compared to the marketed products. Stability studies proved that the formulations could be stable when stored at room temperature. Conclusion: Results of the study indicated that it is possible to develop a safe and physiologically effective hydrogels which are patient compliant. PMID:26682192

A novel biodegradable β-cyclodextrin-based hydrogel for the removal of heavy metal ions.

PubMed

Huang, Zhanhua; Wu, Qinglin; Liu, Shouxin; Liu, Tian; Zhang, Bin

2013-09-12

A novel biodegradable β-cyclodextrin-based gel (CAM) was prepared and applied to the removal of Cd(2+), Pb(2+) and Cu(2+) ions from aqueous solutions. CAM hydrogel has a typical three-dimensional network structure, and showed excellent capability for the removal of heavy metal ions. The effect of different experimental parameters, such as initial pH, adsorbent dosage and initial metal ion concentration, were investigated. The adsorption isotherm data fitted well to the Freundlich model. The adsorption capacity was in the order Pb(2+)>Cu(2+)>Cd(2+) under the same experimental conditions. The maximum adsorption capacities for the metal ions in terms of mg/g of dry gel were 210.6 for Pb(2+), 116.41 for Cu(2+), and 98.88 for Cd(2+). The biodegradation efficiency of the resin reached 79.4% for Gloeophyllum trabeum. The high adsorption capacity and kinetics results indicate that CAM can be used as an alternative adsorbent to remove heavy metals from aqueous solution. Published by Elsevier Ltd.

Temporal Control of Gelation and Polymerization Fronts Driven by an Autocatalytic Enzyme Reaction.

PubMed

Jee, Elizabeth; Bánsági, Tamás; Taylor, Annette F; Pojman, John A

2016-02-05

Chemical systems that remain kinetically dormant until activated have numerous applications in materials science. Herein we present a method for the control of gelation that exploits an inbuilt switch: the increase in pH after an induction period in the urease-catalyzed hydrolysis of urea was used to trigger the base-catalyzed Michael addition of a water-soluble trithiol to a polyethylene glycol diacrylate. The time to gelation (minutes to hours) was either preset through the initial concentrations or the reaction was initiated locally by a base, thus resulting in polymerization fronts that converted the mixture from a liquid into a gel (ca. 0.1 mm min -1 ). The rate of hydrolytic degradation of the hydrogel depended on the initial concentrations, thus resulting in a gel lifetime of hours to months. In this way, temporal programming of gelation was possible under mild conditions by using the output of an autocatalytic enzyme reaction to drive both the polymerization and subsequent degradation of a hydrogel.

Thermoresponsive Polymers and Inverse Opal Hydrogels for the Detection of Diols.

PubMed

Couturier, Jean-Philippe; Wischerhoff, Erik; Bernin, Robert; Hettrich, Cornelia; Koetz, Joachim; Sütterlin, Martin; Tiersch, Brigitte; Laschewsky, André

2016-05-03

Responsive inverse opal hydrogels functionalized by boroxole moieties were synthesized and explored as sensor platforms for various low molar mass as well as polymeric diols and polyols, including saccharides, glycopolymers and catechols, by exploiting the diol induced modulation of their structural color. The underlying thermoresponsive water-soluble copolymers and hydrogels exhibit a coil-to-globule or volume phase transition, respectively, of the LCST-type. They were prepared from oligoethylene oxide methacrylate (macro)monomers and functionalized via copolymerization to bear benzoboroxole moieties. The resulting copolymers represent weak polyacids, which can bind specifically to diols within an appropriate pH window. Due to the resulting modulation of the overall hydrophilicity of the systems and the consequent shift of their phase transition temperature, the usefulness of such systems for indicating the presence of catechols, saccharides, and glycopolymers was studied, exploiting the diol/polyol induced shifts of the soluble polymers' cloud point, or the induced changes of the hydrogels' swelling. In particular, the increased acidity of benzoboroxoles compared to standard phenylboronic acids allowed performing the studies in PBS buffer (phosphate buffered saline) at the physiologically relevant pH of 7.4. The inverse opals constructed of these thermo- and analyte-responsive hydrogels enabled following the binding of specific diols by the induced shift of the optical stop band. Their highly porous structure enabled the facile and specific optical detection of not only low molar mass but also of high molar mass diol/polyol analytes such as glycopolymers. Accordingly, such thermoresponsive inverse opal systems functionalized with recognition units represent attractive and promising platforms for the facile sensing of even rather big analytes by simple optical means, or even by the bare eye.

From Biological Cilia to Artificial Flow Sensors: Biomimetic Soft Polymer Nanosensors with High Sensing Performance

NASA Astrophysics Data System (ADS)

Asadnia, Mohsen; Kottapalli, Ajay Giri Prakash; Karavitaki, K. Domenica; Warkiani, Majid Ebrahimi; Miao, Jianmin; Corey, David P.; Triantafyllou, Michael

2016-09-01

We report the development of a new class of miniature all-polymer flow sensors that closely mimic the intricate morphology of the mechanosensory ciliary bundles in biological hair cells. An artificial ciliary bundle is achieved by fabricating bundled polydimethylsiloxane (PDMS) micro-pillars with graded heights and electrospinning polyvinylidenefluoride (PVDF) piezoelectric nanofiber tip links. The piezoelectric nature of a single nanofiber tip link is confirmed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Rheology and nanoindentation experiments are used to ensure that the viscous properties of the hyaluronic acid (HA)-based hydrogel are close to the biological cupula. A dome-shaped HA hydrogel cupula that encapsulates the artificial hair cell bundle is formed through precision drop-casting and swelling processes. Fluid drag force actuates the hydrogel cupula and deflects the micro-pillar bundle, stretching the nanofibers and generating electric charges. Functioning with principles analogous to the hair bundles, the sensors achieve a sensitivity and threshold detection limit of 300 mV/(m/s) and 8 μm/s, respectively. These self-powered, sensitive, flexible, biocompatibale and miniaturized sensors can find extensive applications in navigation and maneuvering of underwater robots, artificial hearing systems, biomedical and microfluidic devices.

From Biological Cilia to Artificial Flow Sensors: Biomimetic Soft Polymer Nanosensors with High Sensing Performance.

PubMed

Asadnia, Mohsen; Kottapalli, Ajay Giri Prakash; Karavitaki, K Domenica; Warkiani, Majid Ebrahimi; Miao, Jianmin; Corey, David P; Triantafyllou, Michael

2016-09-13

We report the development of a new class of miniature all-polymer flow sensors that closely mimic the intricate morphology of the mechanosensory ciliary bundles in biological hair cells. An artificial ciliary bundle is achieved by fabricating bundled polydimethylsiloxane (PDMS) micro-pillars with graded heights and electrospinning polyvinylidenefluoride (PVDF) piezoelectric nanofiber tip links. The piezoelectric nature of a single nanofiber tip link is confirmed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Rheology and nanoindentation experiments are used to ensure that the viscous properties of the hyaluronic acid (HA)-based hydrogel are close to the biological cupula. A dome-shaped HA hydrogel cupula that encapsulates the artificial hair cell bundle is formed through precision drop-casting and swelling processes. Fluid drag force actuates the hydrogel cupula and deflects the micro-pillar bundle, stretching the nanofibers and generating electric charges. Functioning with principles analogous to the hair bundles, the sensors achieve a sensitivity and threshold detection limit of 300 mV/(m/s) and 8 μm/s, respectively. These self-powered, sensitive, flexible, biocompatibale and miniaturized sensors can find extensive applications in navigation and maneuvering of underwater robots, artificial hearing systems, biomedical and microfluidic devices.

Ex vivo cultures of glioblastoma in three-dimensional hydrogel maintain the original tumor growth behavior and are suitable for preclinical drug and radiation sensitivity screening

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiguet Jiglaire, Carine, E-mail: carine.jiguet-jiglaire@univ-amu.fr; CRO2, UMR 911, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille Cedex; INSERM, U911, 13005 Marseille

Identification of new drugs and predicting drug response are major challenges in oncology, especially for brain tumors, because total surgical resection is difficult and radiation therapy or chemotherapy is often ineffective. With the aim of developing a culture system close to in vivo conditions for testing new drugs, we characterized an ex vivo three-dimensional culture system based on a hyaluronic acid-rich hydrogel and compared it with classical two-dimensional culture conditions. U87-MG glioblastoma cells and seven primary cell cultures of human glioblastomas were subjected to radiation therapy and chemotherapy drugs. It appears that 3D hydrogel preserves the original cancer growth behaviormore » and enables assessment of the sensitivity of malignant gliomas to radiation and drugs with regard to inter-tumoral heterogeneity of therapeutic response. It could be used for preclinical assessment of new therapies. - Highlights: • We have compared primary glioblastoma cell culture in a 2D versus 3D-matrix system. • In 3D morphology, organization and markers better recapitulate the original tumor. • 3D-matrix culture might represent a relevant system for more accurate drug screening.« less

Fundamentals and Bioengineering of Enzymatic Fuel Cells. Part 1. Bioengineering of Enzymes as Electrocatalysts

DTIC Science & Technology

2012-01-31

assembles to form a thermostable. 3-dimensionaI supramolecular hydrogel that has aldo-keto reductase ( AKR ) activity. This is again accomplished... AKR activity, AdhD from Pyrococcus furiosus2*. The monomers are able to self-assemble into a bioactive enzymatic hydrogel that is stable to...temperatures in excess of 60 °C. AdhD is a member of the AKR superfamily that catalyzes the oxidation of secondary alcohols under basic conditions (optimum pH

Facile preparation of antibacterial chitosan/graphene oxide-Ag bio-nanocomposite hydrogel beads for controlled release of doxorubicin.

PubMed

Rasoulzadehzali, Monireh; Namazi, Hassan

2018-04-27

The present project describes the facile preparation of novel pH-sensitive bio-nanocomposite hydrogel beads based on chitosan (CH) and GO-Ag nanohybrid particles for controlled release of anti-cancer drugs such as doxorubicin (DOX). The loading efficiency of doxorubicin into test beads was measured via UV-vis spectroscopy analysis and was found to be high. The formation of silver nanoparticles on the GO sheets and structural characteristics were evaluated via FT-IR, TEM, XRD, and SEM techniques. In addition, the antibacterial activity, swelling and drug release profiles of prepared nanocomposite beads were evaluated. Also, in vitro drug release test was performed in order to investigate the efficiency of CH/GO-Ag nanocomposite hydrogel beads as a drug carrier for controlled release of anti-cancer drugs such as doxorubicin (DOX). A more sustained and controlled drug release profile was observed for CH/GO-Ag nanocomposite hydrogel beads that enhanced by increasing the GO-Ag nanohybrid particles content. Copyright © 2018 Elsevier B.V. All rights reserved.

A Bioinspired Mineral Hydrogel as a Self-Healable, Mechanically Adaptable Ionic Skin for Highly Sensitive Pressure Sensing.

PubMed

Lei, Zhouyue; Wang, Quankang; Sun, Shengtong; Zhu, Wencheng; Wu, Peiyi

2017-06-01

In the past two decades, artificial skin-like materials have received increasing research interests for their broad applications in artificial intelligence, wearable devices, and soft robotics. However, profound challenges remain in terms of imitating human skin because of its unique combination of mechanical and sensory properties. In this work, a bioinspired mineral hydrogel is developed to fabricate a novel type of mechanically adaptable ionic skin sensor. Due to its unique viscoelastic properties, the hydrogel-based capacitive sensor is compliant, self-healable, and can sense subtle pressure changes, such as a gentle finger touch, human motion, or even small water droplets. It might not only show great potential in applications such as artificial intelligence, human/machine interactions, personal healthcare, and wearable devices, but also promote the development of next-generation mechanically adaptable intelligent skin-like devices. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tough and Conductive Hybrid Hydrogels Enabling Facile Patterning.

PubMed

Zhu, Fengbo; Lin, Ji; Wu, Zi Liang; Qu, Shaoxing; Yin, Jun; Qian, Jin; Zheng, Qiang

2018-04-25

Conductive polymer hydrogels (CPHs) that combine the unique properties of hydrogels and electronic properties of conductors have shown their great potentials in wearable/implantable electronic devices, where materials with remarkable mechanical properties, high conductivity, and easy processability are demanding. Here, we have developed a new type of polyion complex/polyaniline (PIC/PAni) hybrid hydrogels that are tough, conductive, and can be facilely patterned. The incorporation of conductive phase (PAni) into PIC matrix through phytic acid resulted in hybrid gels with ∼65 wt % water; high conductivity while maintaining the key viscoelasticity of the tough matrix. The gel prepared from 1 M aniline (Ani) exhibited the breaking strain, fracture stress, tensile modulus, and electrical conductivity of 395%, 1.15 MPa, 5.31 MPa, and 0.7 S/m, respectively, superior to the most existing CPHs. The mechanical and electrical performance of PIC/PAni hybrid hydrogels exhibited pronounced rate-dependent and self-recovery behaviors. The hybrid gels can effectively detect subtle human motions as strain sensors. Alternating conductive/nonconductive patterns can be readily achieved by selective Ani polymerization using stencil masks. This facile patterning method based on PIC/PAni gels can be readily scaled up for fast fabrication of wavy gel circuits and multichannel sensor arrays, enabling real-time monitoring of the large-extent and large-area deformations with various sensitivities.

Immobilizing enzymes onto electrode arrays by hydrogel photolithography to fabricate multi-analyte electrochemical biosensors.

PubMed

Yan, Jun; Pedrosa, Valber A; Simonian, Aleksandr L; Revzin, Alexander

2010-03-01

This paper describes a biomaterial microfabrication approach for interfacing functional biomolecules (enzymes) with electrode arrays. Poly (ethylene glycol) (PEG) hydrogel photopatterning was employed to integrate gold electrode arrays with the enzymes glucose oxidase (GOX) and lactate oxidase (LOX). In this process, PEG diacrylate (DA)-based prepolymer containing enzyme molecules as well as redox species (vinylferrocene) was spin-coated, registered, and UV cross-linked on top of an array of gold electrodes. As a result, enzyme-carrying circular hydrogel structures (600 microm diameter) were fabricated on top of 300 microm diameter gold electrodes. Importantly, when used with multiple masks, hydrogel photolithography allowed us to immobilize GOX and LOX molecules on adjacent electrodes within the same electrode array. Cyclic voltammetry and amperometry were used to characterize biosensor electrode arrays. The response of the biosensor array was linear for up to 20 mM glucose with sensitivity of 0.9 microA cm(-2) mM(-1) and 10 mM lactate with sensitivity of 1.1 microA cm(-2) mM(-1). Importantly, simultaneous detection of glucose and lactate from the same electrode array was demonstrated. A novel strategy for integrating biological and electrical components of a biosensor described in this paper provides the flexibility to spatially resolve and register different biorecognition elements with individual members of a miniature electrode array. Of particular interest to us are future applications of these miniature electrodes for real-time monitoring of metabolite fluxes in the vicinity of living cells.

Silk protein-based hydrogels: Promising advanced materials for biomedical applications.

PubMed

Kapoor, Sonia; Kundu, Subhas C

2016-02-01

Hydrogels are a class of advanced material forms that closely mimic properties of the soft biological tissues. Several polymers have been explored for preparing hydrogels with structural and functional features resembling that of the extracellular matrix. Favourable material properties, biocompatibility and easy processing of silk protein fibers into several forms make it a suitable material for biomedical applications. Hydrogels made from silk proteins have shown a potential in overcoming limitations of hydrogels prepared from conventional polymers. A great deal of effort has been made to control the properties and to integrate novel topographical and functional characteristics in the hydrogel composed from silk proteins. This review provides overview of the advances in silk protein-based hydrogels with a primary emphasis on hydrogels of fibroin. It describes the approaches used to fabricate fibroin hydrogels. Attempts to improve the existing properties or to incorporate new features in the hydrogels by making composites and by improving fibroin properties by genetic engineering approaches are also described. Applications of the fibroin hydrogels in the realms of tissue engineering and controlled release are reviewed and their future potentials are discussed. This review describes the potentiality of silk fibroin hydrogel. Silk Fibroin has been widely recognized as an interesting biomaterial. Due to its properties including high mechanical strength and excellent biocompatibility, it has gained wide attention. Several groups are exploring silk-based materials including films, hydrogels, nanofibers and nanoparticles for different biomedical applications. Although there is a good amount of literature available on general properties and applications of silk based biomaterials, there is an inadequacy of extensive review articles that specifically focus on silk based hydrogels. Silk-based hydrogels have a strong potential to be utilized in biomedical applications. Our work is an effort to highlight the research that has been done in the area of silk-based hydrogels. It aims to provide an overview of the advances that have been made and the future course available. It will provide an overview of the silk-based hydrogels as well as may direct the readers to the specific areas of application. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Biocompatible hydrogel membranes for the protection of RNA aptamer-based electrochemical sensors

NASA Astrophysics Data System (ADS)

Schoukroun-Barnes, Lauren R.; Wagan, Samiullah; Liu, Juan; Leach, Jennie B.; White, Ryan J.

2013-05-01

Electrochemical-aptamer based (E-AB) sensors represent a universal specific, selective, and sensitive sensing platform for the detection of small molecule targets. Their specific detection abilities are afforded by oligonucleotide (RNA or DNA) aptamers employed as electrode-bound biorecognition elements. Sensor signaling is predicated on bindinginduced changes in conformation and/or flexibility of the aptamer that is readily measurable electrochemically. While sensors fabricated using DNA aptamers can achieve specific and selective detection even in unadulterated sample matrices, such as blood serum, RNA-based sensors fail when challenged in the same sample matrix without significant sample pretreatment. This failure is at least partially a result of enzymatic degradation of the RNA sensing element. This degradation destroys the sensing aptamer inhibiting the quantitative measurement of the target analyte and thus limits the application of E-AB sensors constructed with RNA aptamer. To circumvent this, we demonstrate that a biocompatible hydrogel membrane protects the RNA aptamer sensor surface from enzymatic degradation for at least 3 hours - a remarkable improvement over the rapid (~minutes) degradation of unprotected sensors. To demonstrate this, we characterize the response of sensors fabricated with representative DNA and RNA aptamers directed against the aminoglycoside antibiotic, tobramycin in blood serum both protected and unprotected by a polyacrylamide membrane. Furthermore, we find encapsulation of the sensor surface with the hydrogel does not significantly impede the detection ability of aptamer-based sensors. This hydrogel-aptamer interface will thus likely prove useful for the long-term monitoring of therapeutics in complex biological media.

Grafting of GMA and some comonomers onto chitosan for controlled release of diclofenac sodium.

PubMed

Sharma, Rajeev Kr; Lalita; Singh, Anirudh P; Chauhan, Ghanshyam S

2014-03-01

In order to develop pH sensitive hydrogels for controlled drug release we have graft copolymerized glycidyl methacrylate (GMA) with comonomers acrylic acid, acrylamide and acrylonitrile, onto chitosan (Ch) by using potassium persulphate (KPS) as free radical initiator in aqueous solution. The optimum percent grafting for GMA was recorded for 1g chitosan at [KPS]=25.00 × 10(-3)mol/L, [GMA]=0.756 × 10(-3)mol/L, reaction temperature=60 °C and reaction time=1h in 20 mL H2O. Binary monomers were grafted for five different concentrations at optimum grafting conditions evaluated for GMA alone onto chitosan. The graft copolymers were characterized by FTIR, XRD, TGA and SEM. The swelling properties of chitosan and graft copolymers were investigated at different pH to define their end uses in sustained release of an anti-inflammatory drug, diclofenac sodium. Percent drug release w.r.t. drug loaded in polymeric sample was studied as function of time in buffer solutions of pH 2.0 and 7.4. In vitro release data was analyzed using Fick's Law. Chitosan grafted with binary monomers, GMA-co-AAm and GMA-co-AN showed very good results for sustained release of drug at 7.4 pH. Copyright © 2014 Elsevier B.V. All rights reserved.

Immobilization of Cell-Adhesive Laminin Peptides in Degradable PEGDA Hydrogels Influences Endothelial Cell Tubulogenesis

PubMed Central

Ali, Saniya; Saik, Jennifer E.; Gould, Dan J.; Dickinson, Mary E.

2013-01-01

Abstract Attachment, spreading, and organization of endothelial cells into tubule networks are mediated by interactions between cells in the extracellular microenvironment. Laminins are key extracellular matrix components and regulators of cell adhesion, migration, and proliferation. In this study, laminin-derived peptides were conjugated to poly(ethylene glycol) (PEG) monoacrylate and covalently incorporated into degradable PEG diacrylate (PEGDA) hydrogels to investigate the influence of these peptides on endothelial cellular adhesion and function in organizing into tubule networks. Degradable PEGDA hydrogels were synthesized by incorporating a matrix metalloproteinase (MMP)–sensitive peptide, GGGPQGIWGQGK (abbreviated PQ), into the polymer backbone. The secretion of MMP-2 and MMP-9 by endothelial cells promotes polymer degradation and consequently cell migration. We demonstrate the formation of extensive networks of tubule-like structures by encapsulated human umbilical vein endothelial cells in hydrogels with immobilized synthetic peptides. The resulting structures were stabilized by pericyte precursor cells (10T1/2s) in vitro. During tubule formation and stabilization, extracellular matrix proteins such as collagen IV and laminin were deposited. Tubules formed in the matrix of metalloproteinase sensitive hydrogels were visualized from 7 days to 4 weeks in response to different combination of peptides. Moreover, hydrogels functionalized with laminin peptides and transplanted in a mouse cornea supported the ingrowth and attachment of endothelial cells to the hydrogel during angiogenesis. Results of this study illustrate the use of laminin-derived peptides as potential candidates for modification of biomaterials to support angiogenesis. PMID:23914330

[Construction of injectable tissue engineered nucleus pulposus in vitro].

PubMed

Tian, Huake; Wang, Jian; Chen, Chao; Liu, Jie; Zhou, Yue

2009-02-01

To investigate the feasibility of using thermo-sensitive chitosan hydrogen as a scaffold to construct tissue engineered injectable nucleus pulposus (NP). Three-month-old neonatal New Zealand rabbits (male or female) weighing 150-200 g were selected to isolate and culture NP cells. The thermo-sensitive chitosan hydrogel scaffold was made of chitosan, disodium beta-glycerophosphate and hydroxyethyl cellulose. Its physical properties and gross condition were observed. The tissue engineered NP was constructed by compounding the scaffold and rabbit NP cells. Then, the viability of NP cells in the chitosan hydrogel was observed 2 days after compound culture and the growth condition of NP cells on the scaffold was observed by SEM 7 days after compound culture. NP cells went through histology and immunohistochemistry detection and their secretion of aggrecan and expression of Col II mRNA were analyzed by RT-PCR 21 days after compound culture. The thermo-sensitive chitosan hydrogel was liquid at room temperature and solidified into gel at 37 degrees C (15 minutes) due to crosslinking reaction. Acridine orange-propidium iodide staining showed that the viability rate of NP cells in chitosan hydrogel was above 90%. Scanning electron microscope observation demonstrated that the NP cells were distributed in the reticulate scaffold, with ECM on their surfaces. The results of HE, toluidine blue, safranin O and histology and immunohistochemistry staining confirmed that the NP cells in chitosan hydrogel were capable of producing ECM. RT-PCR results showed that the secretion of Col II and aggrecan mRNA in NP cells cultured three-dimensionally by chitosan hydrogen scaffold were 0.631 +/- 0.064 and 0.832 +/- 0.052, respectively, showing more strengths of producing matrix than that of monolayer culture (0.528 +/- 0.039, 0.773 +/- 0.046) with a significant difference (P < 0.05). With good cellular compatibilities, the thermo-sensitive chitosan hydrogel makes it possible for NP cells to maintain their normal morphology and secretion after compound culture, and may be a potential NP cells carrier for tissue engineered NP.

Improvement in the water retention characteristics of sandy loam soil using a newly synthesized poly(acrylamide-co-acrylic acid)/AlZnFe2O4 superabsorbent hydrogel nanocomposite material.

PubMed

Shahid, Shaukat Ali; Qidwai, Ansar Ahmad; Anwar, Farooq; Ullah, Inam; Rashid, Umer

2012-08-03

The use of some novel and efficient crop nutrient-based superabsorbent hydrogel nanocomposites (SHNCs), is currently becoming increasingly important to improve the crop yield and productivity, due to their water retention properties. In the present study a poly(Acrylamide-co-acrylic acid)/AlZnFe2O4 superabsorbent hydrogel nanocomposite was synthesized and its physical properties characterized using Energy Dispersive X-ray (EDX), FE-SEM and FTIR spectroscopic techniques. The effects of different levels of SHNC were studied to evaluate the moisture retention properties of sandy loam soil (sand 59%, silt 21%, clay 19%, pH 7.4, EC 1.92 dS/m). The soil amendment with 0.1, 0.2, 0.3 and 0.4 w/w% of SHNC enhanced the moisture retention significantly at field capacity compared to the untreated soil. Besides, in a separate experiment, seed germination and seedling growth of wheat was found to be notably improved with the application of SHNC. A delay in wilting of seedlings by 5-8 days was observed for SHNC-amended soil, thereby improving wheat plant growth and establishment.

Regenerable Photovoltaic Devices with a Hydrogel-Embedded Microvascular Network

PubMed Central

Koo, Hyung-Jun; Velev, Orlin D.

2013-01-01

Light-driven degradation of photoactive molecules could be one of the major obstacles to stable long term operation of organic dye-based solar light harvesting devices. One solution to this problem may be mimicking the regeneration functionality of a plant leaf. We report an organic dye photovoltaic system that has been endowed with such microfluidic regeneration functionality. A hydrogel medium with embedded channels allows rapid and uniform supply of photoactive reagents by a convection-diffusion mechanism. A washing-activation cycle enables reliable replacement of the organic component in a dye-sensitized photovoltaic system. Repetitive restoration of photovoltaic performance after intensive device degradation is demonstrated. PMID:23912814

Design of self-assembling beta-hairpin pepide-based hydrogels for tissue engineering applications

NASA Astrophysics Data System (ADS)

Butterick, Lisa Ann

The field of tissue engineering aims to repair damaged tissues and organs with diminished function. One approach used in tissue engineering is to introduce cells and/or growth factors to the damaged tissue in either one of two ways. The first method is an invasive procedure where cells are introduced to a preformed scaffold and cultured in vitro. The scaffold is then inserted into the host by making an incision at the site of interest, which must be as large as the preformed scaffold. The second method is a minimally invasive procedure where cells are suspended in a polymeric solution and injected via syringe. After leaving the syringe, the material undergoes a phase transition to form a hydrogel at the site of introduction. Regardless of the delivery mechanism employed, development of an appropriate scaffold conducive to cellular proliferation and extracellular matrix production is critical to the success of the implanted material in persuading the body to repair itself. In working toward this goal, we have developed a family of beta-hairpin peptides, based on the design MAX1, that undergoes intramolecular folding and self-assembly to form rigid hydrogels in response to changes in pH, ionic strength, and temperature. From a molecular design standpoint of view, site specific N-methylation of MAX1 was performed to determine the importance of forming hydrogen bonds during the self-assembly event and its effect on hydrogelation. The remainder of this thesis is dedicated to the development of materials and minimally methodologies to deliver gel/cell constructs via syringe to target sites to aid in tissue repair. A peptide, MAX7CNB was designed that undergoes folding and assembly in response to ultraviolet light to form hydrogel material. In addition, MAX8 was rationally designed to display the appropriate hydrogelation kinetics to achieve homogenous cellular encapsulation throughout the gel matrix. MAX8 gel/cell scaffolds can be easily delivered via syringe to secondary target sites while maintaining cellular homogeneity, viability and remain fixed at the site of introduction. Additionally, preliminary in vitro based studies employing mouse peritoneal macrophages suggest the MAX8 gels are non-inflammatory in nature and may not elicit an in vivo immune response upon implantation. It has been demonstrated throughout this thesis that by employing amino acids as fundamental building blocks, peptide sequences can be designed to undergo molecular recognition, resulting in hydrogel material for use in tissue engineering applications.

Characterization of human adipose tissue-derived stem cells in vitro culture and in vivo differentiation in a temperature-sensitive chitosan/β- glycerophosphate/collagen hybrid hydrogel.

PubMed

Song, Kedong; Li, Liying; Yan, Xinyu; Zhang, Wen; Zhang, Yu; Wang, Yiwei; Liu, Tianqing

2017-01-01

In this study, the interaction of human adipose tissue-derived stem cells (ADSCs) with chitosan/β-glycerophosphate/collagen (C/GP/Co) hybrid hydrogel was test, followed by investigating the capability of engineered adipose tissue formation using this ADSCs seeded hydrogel. The ADSCs were harvested and mixed with a C/GP/Co hydrogel followed by a gelation at 37°C and an in vitro culture. The results showed that the ADSCs within C/GP/Co hydrogels achieved a 30% of expansion over 7days in culture medium and encapsulated cell in C/GP/Co hydrogel demonstrated a characteristic morphology with high viability over 5days. C/GP/Co hydrogel were subcutaneous injected into SD-rats to assess the biocompatibility. The induced ADSCs-C/GP/Co hydrogel and non-induced ADSCs-C/GP/Co hydrogel were subcutaneously injected into nude mice for detecting potential of adipogenic differentiation. It has shown that C/GP/Co hydrogel were well tolerated in SD rats where they had persisted over 4weeks post implantation. Histology analysis indicated that induced ADSCs-C/GP/Co hydrogel has a greater number of adipocytes and vascularized adipose tissues compared with non-induced ADSCs-C/GP/Co hydrogel. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Modified gum arabic cross-linked gelatin scaffold for biomedical applications.

PubMed

Sarika, P R; Cinthya, Kuriakose; Jayakrishnan, A; Anilkumar, P R; James, Nirmala Rachel

2014-10-01

The present work deals with development of modified gum arabic cross-linked gelatin scaffold for cell culture. A new biocompatible scaffold was developed by cross-linking gelatin (Gel) with gum arabic, a polysaccharide. Gum arabic was subjected to periodate oxidation to obtain gum arabic aldehyde (GAA). GAA was reacted with gelatin under appropriate pH to prepare the cross-linked hydrogel. Cross-linking occurred due to Schiff's base reaction between aldehyde groups of oxidized gum arabic and amino groups of gelatin. The scaffold prepared from the hydrogel was characterized by swelling properties, degree of cross-linking, in vitro degradation and scanning electron microscopy (SEM). Cytocompatibility evaluation using L-929 and HepG2 cells confirmed non-cytotoxic and non-adherent nature of the scaffold. These properties are essential for generating multicellular spheroids and hence the scaffold is proposed to be a suitable candidate for spheroid cell culture. Copyright © 2014 Elsevier B.V. All rights reserved.

Genetically engineered silk-collagen-like copolymer for biomedical applications: production, characterization and evaluation of cellular response.

PubMed

Włodarczyk-Biegun, Małgorzata K; Werten, Marc W T; de Wolf, Frits A; van den Beucken, Jeroen J J P; Leeuwenburgh, Sander C G; Kamperman, Marleen; Cohen Stuart, Martien A

2014-08-01

Genetically engineered protein polymers (GEPP) are a class of multifunctional materials with precisely controlled molecular structure and property profile. Representing a promising alternative for currently used materials in biomedical applications, GEPP offer multiple benefits over natural and chemically synthesized polymers. However, producing them in sufficient quantities for preclinical research remains challenging. Here, we present results from an in vitro cellular response study of a recombinant protein polymer that is soluble at low pH but self-organizes into supramolecular fibers and physical hydrogels at neutral pH. It has a triblock structure denoted as C2S(H)48C2, which consists of hydrophilic collagen-inspired and histidine-rich silk-inspired blocks. The protein was successfully produced by the yeast Pichia pastoris in laboratory-scale bioreactors, and it was purified by selective precipitation. This efficient and inexpensive production method provided material of sufficient quantities, purity and sterility for cell culture study. Rheology and erosion studies showed that it forms hydrogels exhibiting long-term stability, self-healing behavior and tunable mechanical properties. Primary rat bone marrow cells cultured in direct contact with these hydrogels remained fully viable; however, proliferation and mineralization were relatively low compared to collagen hydrogel controls, probably because of the absence of cell-adhesive motifs. As biofunctional factors can be readily incorporated to improve material performance, our approach provides a promising route towards biomedical applications. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Hydrogels for efficient light delivery in optogenetic applications

NASA Astrophysics Data System (ADS)

Johannsmeier, S.; Torres, M. L.; Ripken, T.; Heinemann, D.; Heisterkamp, A.

2018-02-01

Light-based therapies have been established for various indications, such as skin conditions, cancer or neonatal jaundice. Advances in the field of optogenetics open up new horizons for light-tissue interactions with an organism-wide impact. Excitable tissues, such as nerve and muscle tissues, can be controlled by light after the introduction of light-sensitive ion channels. Since these organs are generally not easily accessible to illumination in vivo, there is an increasing need for effective biocompatible waveguides for light delivery. These devices not only have to guide and distribute the light as desired with minimal losses, they should also mimic the mechanical properties of the surrounding tissue to ensure compatibility. In this project, we are tuning the properties of hydrogels from poly(ethylene glycol) derivatives to achieve compatibility with muscle tissue as well as optimal light guiding and distribution for optogenetic applications at the heart. The excitation light is coupled into the hydrogel with a biocompatible fiber. Properties of the hydrogel are mainly tuned by monomer length and concentration. Total reflection can be achieved by embedding a fiber-like hydrogel with a high refractive index into a second, low refractive index gel. Different geometries and scattering microparticles are used for light distribution in a flat gel patch. Targeted cell attachment can be achieved by introducing a protein layer to the otherwise bioinert gel. After optimization, the hydrogel may be used to deliver light for the excitation of genetically altered cardiomyocytes for controlled contraction.

Evaluation of the Growth Environment of a Hydrostatic Force Bioreactor for Preconditioning of Tissue-Engineered Constructs

PubMed Central

Reinwald, Yvonne; Leonard, Katherine H.L.; Henstock, James R.; Whiteley, Jonathan P.; Osborne, James M.; Waters, Sarah L.; Levesque, Philippe

2015-01-01

Bioreactors have been widely acknowledged as valuable tools to provide a growth environment for engineering tissues and to investigate the effect of physical forces on cells and cell-scaffold constructs. However, evaluation of the bioreactor environment during culture is critical to defining outcomes. In this study, the performance of a hydrostatic force bioreactor was examined by experimental measurements of changes in dissolved oxygen (O2), carbon dioxide (CO2), and pH after mechanical stimulation and the determination of physical forces (pressure and stress) in the bioreactor through mathematical modeling and numerical simulation. To determine the effect of hydrostatic pressure on bone formation, chick femur skeletal cell-seeded hydrogels were subjected to cyclic hydrostatic pressure at 0–270 kPa and 1 Hz for 1 h daily (5 days per week) over a period of 14 days. At the start of mechanical stimulation, dissolved O2 and CO2 in the medium increased and the pH of the medium decreased, but remained within human physiological ranges. Changes in physiological parameters (O2, CO2, and pH) were reversible when medium samples were placed in a standard cell culture incubator. In addition, computational modeling showed that the distribution and magnitude of physical forces depends on the shape and position of the cell-hydrogel constructs in the tissue culture format. Finally, hydrostatic pressure was seen to enhance mineralization of chick femur skeletal cell-seeded hydrogels. PMID:24967717

Evaluation of the growth environment of a hydrostatic force bioreactor for preconditioning of tissue-engineered constructs.

PubMed

Reinwald, Yvonne; Leonard, Katherine H L; Henstock, James R; Whiteley, Jonathan P; Osborne, James M; Waters, Sarah L; Levesque, Philippe; El Haj, Alicia J

2015-01-01

Bioreactors have been widely acknowledged as valuable tools to provide a growth environment for engineering tissues and to investigate the effect of physical forces on cells and cell-scaffold constructs. However, evaluation of the bioreactor environment during culture is critical to defining outcomes. In this study, the performance of a hydrostatic force bioreactor was examined by experimental measurements of changes in dissolved oxygen (O2), carbon dioxide (CO2), and pH after mechanical stimulation and the determination of physical forces (pressure and stress) in the bioreactor through mathematical modeling and numerical simulation. To determine the effect of hydrostatic pressure on bone formation, chick femur skeletal cell-seeded hydrogels were subjected to cyclic hydrostatic pressure at 0-270 kPa and 1 Hz for 1 h daily (5 days per week) over a period of 14 days. At the start of mechanical stimulation, dissolved O2 and CO2 in the medium increased and the pH of the medium decreased, but remained within human physiological ranges. Changes in physiological parameters (O2, CO2, and pH) were reversible when medium samples were placed in a standard cell culture incubator. In addition, computational modeling showed that the distribution and magnitude of physical forces depends on the shape and position of the cell-hydrogel constructs in the tissue culture format. Finally, hydrostatic pressure was seen to enhance mineralization of chick femur skeletal cell-seeded hydrogels.

Target-responsive DNAzyme cross-linked hydrogel for visual quantitative detection of lead.

PubMed

Huang, Yishun; Ma, Yanli; Chen, Yahong; Wu, Xuemeng; Fang, Luting; Zhu, Zhi; Yang, Chaoyong James

2014-11-18

Because of the severe health risks associated with lead pollution, rapid, sensitive, and portable detection of low levels of Pb(2+) in biological and environmental samples is of great importance. In this work, a Pb(2+)-responsive hydrogel was prepared using a DNAzyme and its substrate as cross-linker for rapid, sensitive, portable, and quantitative detection of Pb(2+). Gold nanoparticles (AuNPs) were first encapsulated in the hydrogel as an indicator for colorimetric analysis. In the absence of lead, the DNAzyme is inactive, and the substrate cross-linker maintains the hydrogel in the gel form. In contrast, the presence of lead activates the DNAzyme to cleave the substrate, decreasing the cross-linking density of the hydrogel and resulting in dissolution of the hydrogel and release of AuNPs for visual detection. As low as 10 nM Pb(2+) can be detected by the naked eye. Furthermore, to realize quantitative visual detection, a volumetric bar-chart chip (V-chip) was used for quantitative readout of the hydrogel system by replacing AuNPs with gold-platinum core-shell nanoparticles (Au@PtNPs). The Au@PtNPs released from the hydrogel upon target activation can efficiently catalyze the decomposition of H2O2 to generate a large volume of O2. The gas pressure moves an ink bar in the V-chip for portable visual quantitative detection of lead with a detection limit less than 5 nM. The device was able to detect lead in digested blood with excellent accuracy. The method developed can be used for portable lead quantitation in many applications. Furthermore, the method can be further extended to portable visual quantitative detection of a variety of targets by replacing the lead-responsive DNAzyme with other DNAzymes.

Doxorubicin loaded carboxymethyl cellulose/graphene quantum dot nanocomposite hydrogel films as a potential anticancer drug delivery system.

PubMed

Javanbakht, Siamak; Namazi, Hassan

2018-06-01

Creating anticancer properties in the hydrogel film could make it as a candidate for treating cancer tissues. In this work, a novel hydrogel nanocomposite films with anticancer properties were designed via incorporation of graphene quantum dot (GQD) as a nanoparticle into carboxymethyl cellulose (CMC) hydrogel and using doxorubicin (DOX) as drug model with broad-spectrum anticancer properties. Drug release studies carried out at two different pHs and the MTT assay was evaluated for DOX-loaded CMC/GQD nanocomposite hydrogel films against blood cancer cells (K562). The prepared nanocomposite hydrogel films were characterized using Fourier transform infrared (FT-IR), UV-Vis spectroscopy, scanning electron microscopy (SEM), permeability and mechanical properties. The prepared CMC/GQD nanocomposite hydrogel films showed an improvement in vitro swelling, degradation, water vapor permeability and pH-sensitive drug delivery properties along with not significant toxicity against blood cancer cells (K562). According to the obtained results, this nanocomposite hydrogel films can be proposed to use as an anticancer film and drug delivery system. Copyright © 2018 Elsevier B.V. All rights reserved.

Preparation and antibacterial properties of O-carboxymethyl chitosan/lincomycin hydrogels.

PubMed

He, Guanghua; Chen, Xiang; Yin, Yihua; Cai, Weiquan; Ke, Wanwan; Kong, Yahui; Zheng, Hua

2016-01-01

In this study, O-carboxymethyl chitosan (O-CMCS) was synthesized from chitosan and monochloroacetic acid. Then O-CMCS hydrogel was prepared by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) in which the lincomycin was packaged. The Fourier transform infrared spectrum and scanning electron microscopy were adopted to characterize the structure and morphology of the product. The influences of dosage of EDC/NHS and concentration of O-CMCS on the swelling properties of the hydrogels were investigated. The hydrogels performed good swelling capacities and obvious pH-sensitive properties. The antibacterial activities of the hydrogels were tested against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). Compared with pure O-CMCS hydrogels, the antibacterial activities of O-CMCS/lincomycin hydrogels were significantly improved with the increase in the concentration of lincomycin against E. coli and S. aureus. With the increase in dosage of crosslinking agent or concentration of O-CMCS, the antibacterial activities both decreased gradually against the two bacteria. O-CMCS/lincomycin hydrogel was expected to be used for antibacterial material in view of its significant antibacterial activities.

Hierarchical nanostructured conducting polymer hydrogel with high electrochemical activity

PubMed Central

Pan, Lijia; Yu, Guihua; Zhai, Dongyuan; Lee, Hye Ryoung; Zhao, Wenting; Liu, Nian; Wang, Huiliang; Tee, Benjamin C.-K.; Shi, Yi; Cui, Yi; Bao, Zhenan

2012-01-01

Conducting polymer hydrogels represent a unique class of materials that synergizes the advantageous features of hydrogels and organic conductors and have been used in many applications such as bioelectronics and energy storage devices. They are often synthesized by polymerizing conductive polymer monomer within a nonconducting hydrogel matrix, resulting in deterioration of their electrical properties. Here, we report a scalable and versatile synthesis of multifunctional polyaniline (PAni) hydrogel with excellent electronic conductivity and electrochemical properties. With high surface area and three-dimensional porous nanostructures, the PAni hydrogels demonstrated potential as high-performance supercapacitor electrodes with high specific capacitance (∼480 F·g-1), unprecedented rate capability, and cycling stability (∼83% capacitance retention after 10,000 cycles). The PAni hydrogels can also function as the active component of glucose oxidase sensors with fast response time (∼0.3 s) and superior sensitivity (∼16.7 μA·mM-1). The scalable synthesis and excellent electrode performance of the PAni hydrogel make it an attractive candidate for bioelectronics and future-generation energy storage electrodes. PMID:22645374

The osteogenic differentiation of dog bone marrow mesenchymal stem cells in a thermo-sensitive injectable chitosan/collagen/β-glycerophosphate hydrogel: in vitro and in vivo.

PubMed

Sun, Bin; Ma, Wei; Su, Fang; Wang, Yi; Liu, Jiaqiang; Wang, Dongshen; Liu, Hongchen

2011-09-01

Type I collagen was added to the composite chitosan solution in a ratio of 1:2 to build a physical cross-linked self-forming chitosan/collagen/β-GP hydrogel. Osteogenic properties of this novel injectable hydrogel were evaluated. Gelation time was about 8 min which offered enough time for handling a mixture containing cells and the subsequent injection. Scanning electronic microscopy (SEM) observations indicated good spreading of bone marrow mesenchymal stem cells (BMSCs) in this hydrogel scaffold. Mineral nodules were found in the dog-BMSCs inoculated hydrogel by SEM after 28 days. After subcutaneous injection into nude mouse dorsum for 4 weeks, partial bone formation was observed in the chitosan/collagen/β-GP hydrogel loaded with pre-osteodifferentiated dog-BMSCs, which indicated that chitosan/collagen/β-GP hydrogel composite could induce osteodifferentiation in BMSCs without exposure to a continual supply of external osteogenic factors. In conclusion, the novel chitosan/collagen/β-GP hydrogel composite should prove useful as a bone regeneration scaffold.

Synthesis, characterization and in vivo evaluation of biocompatible ferrogels

NASA Astrophysics Data System (ADS)

Lopez-Lopez, M. T.; Rodriguez, I. A.; Rodriguez-Arco, L.; Carriel, V.; Bonhome-Espinosa, A. B.; Campos, F.; Zubarev, A.; Duran, J. D. G.

2017-06-01

A hydrogel is a 3-D network of polymer chains in which water is the dispersion medium. Hydrogels have found extensive applications in the biomedical field due to their resemblance to living tissues. Furthermore, hydrogels can be endowed with exceptional properties by addition of synthetic materials. For example, magnetic field-sensitive gels, called ferrogels, are obtained by embedding magnetic particles in the polymer network. Novel living tissues with unique magnetic field-sensitive properties were recently prepared by 3-D cell culture in biocompatible ferrogels. This paper critically reviews the most recent progress and perspectives in their synthesis, characterization and biocompatibility evaluation. Optimization of ferrogels for this novel application requires low-density, strongly magnetic, multi-domain particles. Interestingly, the rheological properties of the resulting ferrogels in the absence of field were largely enhanced with respect to nonmagnetic hydrogels, which can only be explained by the additional cross-linking imparted by the embedded magnetic particles. Remarkably, rheological measurements under an applied magnetic field demonstrated that ferrogels presented reversibly tunable mechanical properties, which constitutes a unique advantage with respect to nonmagnetic hydrogels. In vivo evaluation of ferrogels showed good biocompatibility, with only some local inflammatory response, and no particle migration or damage to distant organs.

Stimulus responsive hydrogel-coated etched fiber Bragg grating for carcinogenic chromium (VI) sensing

NASA Astrophysics Data System (ADS)

Kishore, Pabbisetti Vayu Nandana; Madhuvarasu, Sai Shankar; Moru, Satyanarayana

2018-01-01

This paper proposes a chemo-mechanical-optical sensing approach for the detection of carcinogenic chromium (VI) metal ion using an etched fiber Bragg grating (FBG) coated with stimulus responsive hydrogel. Hydrogel synthesized from the blends of (3-acrylamidopropyl)-trimethylammonium chloride, which is highly responsive to chromium ions suffers a volume change when placed in Cr solution. When the proposed sensor system is exposed to various concentrations of Cr (VI) ion solution, FBG peak shifts due to the mechanical strain induced by the swelling of the hydrogel. The peak shift is correlated with the concentration of the Cr (VI) metal ion. Due to the reduction in the cladding diameter of FBG, wastage of swelling force due to hydrogel on FBG is lowered and utilized for more wavelength peak shift of FBG resulting in the increase in the sensitivity. The resolution of the sensor system is found to be 0.072 ppb. Trace amounts of chromium (VI) ion as low as 10 ppb can be sensed by this method. The sensor has shown good sensitivity, selectivity, and repeatability. The salient features of the sensors are its compact size, light weight, and adoptability for remote monitoring.

Characterisation and in vitro stability of low-dose, lidocaine-loaded poly(vinyl alcohol)-tetrahydroxyborate hydrogels.

PubMed

Abdelkader, D H; Osman, M A; El-Gizawy, S A; Faheem, A M; McCarron, P A

2016-03-16

Poly(vinyl alcohol) hydrogels cross-linked with the tetrahydroxyborate anion possess textural and rheological properties that can be used as novel drug-loaded vehicles for application to traumatic wounds. However, addition of soluble drug substances causes concentration-dependent phase separation and rheological changes. The aim of this work was to investigate the effect of adding a local anaesthetic, but keeping the concentration low in an attempt to prevent these changes. Cross-linked hydrogels prepared from three grades of poly(vinyl alcohol) were characterised rheologically. Temperature sweep studies showed an elevated complex viscosity upon moving from 25°C to 80°C, which remained high for 48 h following completion of the cycle. Adhesion to model dermal surfaces achieved a maximum of 2.62 N cm(-2) and were greater than that observed to epidermal substrates, with a strong dependence on the rate of detachment used during testing. An optimised formulation (6% w/w PVA (31-50; 99) and 2% w/w THB) containing lidocaine hydrochloride loaded to an upper maximum concentration of 1.5% w/w was assessed for phase separation and drug crystallisation. After six months, crystallisation was present in formulations containing 0.7% and 1.5% lidocaine HCl. Changes in pH in response to increases in lidocaine loading were low. Drug release was shown to operate via a non-Fickian process for all three concentrations, with 60% occurring after approximately 24h. It can be concluded that using a low concentration of lidocaine hydrochloride in hydrogels based on poly(vinyl alcohol) will result in crystallisation. Furthermore, these hydrogels are unlikely to induce rapid anaesthesia due to the low loading and slow release kinetics. Copyright © 2016 Elsevier B.V. All rights reserved.

Tailoring the degradation rates of thermally responsive hydrogels designed for soft tissue injection by varying the autocatalytic potential.

PubMed

Zhu, Yang; Jiang, Hongbin; Ye, Sang-Ho; Yoshizumi, Tomo; Wagner, William R

2015-01-01

The ability to modulate the degradation properties of biomaterials such as thermally responsive hydrogels is desirable when exploring new therapeutic strategies that rely on the temporary presence of a placed scaffold or gel. Here we report a method of manipulating the absorption rate of a poly(N-isopropylacrylamide) ((poly(NIPAAm)) based hydrogel across a wide range (from 1 d to 5 mo) by small alterations in the composition. Relying upon the autocatalytic effect, the degradation of poly(NIPAAm-co-HEMA-co-MAPLA), (HEMA = 2-hydroxyethyl methacrylate; MAPLA = methacrylate-polylactide) was greatly accelerated by adding a fourth monomer methacrylic acid (MAA) at no more than 2 mol% to obtain poly(NIPAAm-co-HEMA-co-MAPLA-co-MAA) (pNHMMj) where j reflects the MAA molar % in the reactant mixture. MAA residue introduction decreased the pH inside the hydrogels and in surrounding buffered solutions. Accelerated degradation positively correlated with MAA content in pNHMMj polymers, putatively by the accelerated cleavage of MAPLA residues to raise the transition temperature of the polymer above body temperature. Physical properties including thermal transition behavior and initial mechanical strength did not vary significantly with MAA content. A rat hindlimb injection model generally reflected the in vitro observation that higher MAA content resulted in more rapid degradation and cellular infiltration. The strategy of tuning the degradation of thermally responsive hydrogels where degradation or solubilization is determined by their polyester components might be applied to other tissue engineering and regenerative medicine applications where designed biomaterial degradation behavior is needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hydrogel Biomaterials: A Smart Future?

PubMed Central

Kopeček, Jindřich

2007-01-01

Hydrogels were the first biomaterials developed for human use. The state-of-the-art and potential for the future are discussed. Recently, new designs have produced mechanically strong synthetic hydrogels. Protein based hydrogels and hybrid hydrogels containing protein domains present a novel advance; such biomaterials may self-assemble from block or graft copolymers containing biorecognition domains. One of the domains, the coiled-coil, ubiquitously found in nature, has been used as an example to demonstrate the developments in the design of smart hydrogels. The application potential of synthetic, protein-based, DNA-based, and hybrid hydrogels bodes well for the future of this class of biomaterials. PMID:17697712

Enhancement of 8-methoxypsoralen topical delivery via nanosized niosomal vesicles: Formulation development, in vitro and in vivo evaluation of skin deposition.

PubMed

Kassem, Ahmed Alaa; Abd El-Alim, Sameh Hosam; Asfour, Marwa Hasanein

2017-01-30

The aim of the present study is to enhance the skin penetration and deposition of 8-methoxypsoraln (8-MOP) via niosomal vesicles to increase its local efficacy and safety. 8-MOP niosomes were prepared by the thin film hydration method using Span 60 or Span 40 along with cholesterol at five different molar ratios. The obtained vesicles revealed high entrapment efficiencies (83.04-89.90%) with nanometric vesicle diameters (111.1-198.8nm) of monodisperse distribution (PDI=0.145-0.216), zeta potential values <-48.3mV and spherical morphology under transmission electron microscopy. Optimized niosomal formulations depicted a biphasic in vitro release pattern in phosphate buffer (pH 5.5)/ethanol (7:3v/v) and displayed good physical stability after storage for 6 months at room (20-25°C) and refrigeration (4-8°C) temperatures. The two optimized formulations were incorporated in 5% sodium carboxy methylcellulose based hydrogel matrix which showed optimum pH values (7.37-7.39), pseudoplastic with thixotropic rheological behavior and more retarded 8-MOP release, by 23.82 and 14.89%, compared to niosomal vesicles after 24h. In vitro drug permeation and deposition studies, using rat skins, revealed promoted penetration and accumulation of 8-MOP after 8h. The skin penetration was further confirmed in vivo by confocal laser scanning microscopy, after 2h application period using rhodamine-loaded niosomal hydrogels compared to plain rhodamine hydrogel, as a florescence marker. Therefore, enhanced permeation and skin deposition of 8-MOP delivered by niosomes may help in improving the efficacy and safety of long-term treatment with 8-MOP. Copyright © 2016 Elsevier B.V. All rights reserved.

Fabrication of Micropatterned Dipeptide Hydrogels by Acoustic Trapping of Stimulus-Responsive Coacervate Droplets.

PubMed

Nichols, Madeleine K; Kumar, Ravinash Krishna; Bassindale, Philip G; Tian, Liangfei; Barnes, Adrian C; Drinkwater, Bruce W; Patil, Avinash J; Mann, Stephen

2018-06-01

Acoustic standing waves offer an excellent opportunity to trap and spatially manipulate colloidal objects. This noncontact technique is used for the in situ formation and patterning in aqueous solution of 1D or 2D arrays of pH-responsive coacervate microdroplets comprising poly(diallyldimethylammonium) chloride and the dipeptide N-fluorenyl-9-methoxy-carbonyl-D-alanine-D-alanine. Decreasing the pH of the preformed droplet arrays results in dipeptide nanofilament self-assembly and subsequent formation of a micropatterned supramolecular hydrogel that can be removed as a self-supporting monolith. Guest molecules such as molecular dyes, proteins, and oligonucleotides are sequestered specifically within the coacervate droplets during acoustic processing to produce micropatterned hydrogels containing spatially organized functional components. Using this strategy, the site-specific isolation of multiple enzymes to drive a catalytic cascade within the micropatterned hydrogel films is exploited. © 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polymeric hydrogels for novel contact lens-based ophthalmic drug delivery systems: a review.

PubMed

Xinming, Li; Yingde, Cui; Lloyd, Andrew W; Mikhalovsky, Sergey V; Sandeman, Susan R; Howel, Carol A; Liewen, Liao

2008-04-01

Only about 5% of drugs administrated by eye drops are bioavailable, and currently eye drops account for more than 90% of all ophthalmic formulations. The bioavailability of ophthalmic drugs can be improved by a soft contact lens-based ophthalmic drug delivery system. Several polymeric hydrogels have been investigated for soft contact lens-based ophthalmic drug delivery systems: (i) polymeric hydrogels for conventional contact lens to absorb and release ophthalmic drugs; (ii) polymeric hydrogels for piggyback contact lens combining with a drug plate or drug solution; (iii) surface-modified polymeric hydrogels to immobilize drugs on the surface of contact lenses; (iv) polymeric hydrogels for inclusion of drugs in a colloidal structure dispersed in the lens; (v) ion ligand-containing polymeric hydrogels; (vi) molecularly imprinted polymeric hydrogels which provide the contact lens with a high affinity and selectivity for a given drug. Polymeric hydrogels for these contact lens-based ophthalmic drug delivery systems, their advantages and drawbacks are critically analyzed in this review.

Oral insulin delivery using P(MAA-g-EG) hydrogels: effects of network morphology on insulin delivery characteristics.

PubMed

Nakamura, Koji; Murray, Robert J; Joseph, Jeffrey I; Peppas, Nicholas A; Morishita, Mariko; Lowman, Anthony M

2004-03-24

Hydrogels of poly(methacrylic acid-g-ethylene glycol) were prepared using different reaction water contents in order to vary the network mesh size, swelling behavior and insulin loading/release kinetics. Gels prepared with greater reaction solvent contents swelled to a greater degree and had a larger network mesh size. All of the hydrogels were able to incorporate insulin and protected it from release in acidic media. At higher pH (7.4), the release rates increased with reaction solvent content. Using a closed loop animal model, all of the insulin loaded formulations produced significant insulin absorption in the upper small intestine combined with hypoglycemic effects. In these studies, bioavailabilities ranged from 4.6% to 7.2% and were dependent on reaction solvent content.

A constriction resistance model of conjugated polymer based piezoresistive sensors for electronic skin applications.

PubMed

Khalili, N; Naguib, H E; Kwon, R H

2016-05-14

Human intervention can be replaced through the development of tools resulting from utilization of sensing devices possessing a wide range of applications including humanoid robots or remote and minimally invasive surgeries. Similar to the five human senses, sensors interface with their surroundings to stimulate a suitable response or action. The sense of touch which arises in human skin is among the most challenging senses to emulate due to its ultra high sensitivity. This has brought forth novel challenging issues to consider in the field of biomimetic robotics. In this work, using a multiphase reaction, a polypyrrole (PPy) based hydrogel is developed as a resistive type pressure sensor with an intrinsically elastic microstructure stemming from three dimensional hollow spheres. It is shown that the electrical conductivity of the fabricated PPy based piezoresistive sensors is enhanced as a result of adding conductive fillers and therefore, endowing the sensors with a higher sensitivity. A semi-analytical constriction resistance based model accounting for the real contact area between the PPy hydrogel sensors and the electrode along with the dependency of the contact resistance change on the applied load is developed. The model is then solved using a Monte Carlo technique and its corresponding sensitivity is obtained. Comparing the results with their experimental counterparts, the proposed modeling methodology offers a good tracking ability.

NIR and MR imaging supported hydrogel based delivery system for anti-TNF alpha probiotic therapy of IBD

NASA Astrophysics Data System (ADS)

Janjic, Jelena M.; Berlec, Ales; Bagia, Christina; Liu, Lu S.; Jeric, Irenej; Gach, Michael; Janjic, Bratislav M.; Strukelj, Borut

2016-03-01

Current treatment of inflammatory bowel disease (IBD) is largely symptomatic and consists of anti-inflammatory agents, immune-suppressives or antibiotics, whereby local luminal action is preferred to minimize systemic side-effects. Recently, anti-TNFα therapy has shown considerable success and is now being routinely used. Here we present a novel approach of using perfluorocarbon (PFC) nanoemulsion containing hydrogels (nanoemulgels) as imaging supported delivery systems for anti-TNF alpha probiotic delivery in IBD. To further facilitate image-guided therapy a food-grade lactic acid bacterium Lactococcus lactis capable of TNFα-binding was engineered to incorporate infrared fluorescent protein (IRFP). This modified bacteria was then incorporated into novel PFC nanoemulgels. The nanoemulgels presented here are designed to deliver locally anti-TNFα probiotic in the lower colon and rectum and provide dual imaging signature of gel delivery (MRI) across the rectum and lower colon and bacteria release (NIR). NIR imaging data in vitro demonstrates high IRFP expressing and TNFα-binding bacteria loading in the hydrogel and complete release in 3 hours. Stability tests indicate that gels remain stable for at least 14 days showing no significant change in droplet size, zeta potential and pH. Flow cytometry analyses demonstrate the NIRF expressing bacteria L. lactis binds TNFα in vitro upon release from the gels. Magnetic resonance and near-infrared imaging in vitro demonstrates homogeneity of hydrogels and the imaging capacity of the overall formulation.

Cooperative Assembly of a Peptide Gelator and Silk Fibroin Afford an Injectable Hydrogel for Tissue Engineering.

PubMed

Cheng, Baochang; Yan, Yufei; Qi, Jingjing; Deng, Lianfu; Shao, Zeng-Wu; Zhang, Ke-Qin; Li, Bin; Sun, Ziling; Li, Xinming

2018-04-18

Silk fibroin (SF) from Bombyx mori has received increasing interest in biomedical fields, because of its slow biodegradability, good biocompatibility, and low immunogenicity. Although SF-based hydrogels have been studied intensively as a potential matrix for tissue engineering, weak gelation performance and low mechanical strength are major limitations that hamper their widespread applicability. Therefore, searching for new strategies to improve the SF gelation property is highly desirable in tissue engineering research. Herein, we report a facile approach to induce rapid gelation of SF by a small peptide gelator (e.g., NapFF). Following the simple mixing of SF and NapFF in water, a stable hydrogel of SF was obtained in a short time period at physiological pH, and the minimum gelation concentration of SF can reach as low as 0.1%. In this process of gelation, NapFF not only can behave itself as a gelator for supramolecular self-assembly, but also can trigger the conformational transition of the SF molecule from random coil to β-sheet structure via hydrophobic and hydrogen-bonding interactions. More importantly, for the generation of a scaffold with favorable cell-surface interactions, a new peptide gelator (NapFFRGD) with Arg-Gly-Asp (RGD) domain was applied to functionalize SF hydrogel with improved bioactivity for cell adhesion and growth. Following encapsulating the vascular endothelial growth factor (VEGF), the SF gel was subcutaneously injected in mice, and served as an effective matrix to trigger the generation of new blood capillaries in vivo.

Synthesis of β-cyclodextrin hydrogel nanoparticles for improving the solubility of dexibuprofen: characterization and toxicity evaluation.

PubMed

Khalid, Qandeel; Ahmad, Mahmood; Minhas, Muhammad Usman

2017-11-01

This study was aimed to enhance aqueous solubility of dexibuprofen through designing β-cyclodextrin (βCD) hydrogel nanoparticles and to evaluate toxicological potential through acute toxicity studies in rats. Dexibuprofen is a non-steroidal analgesic and anti-inflammatory drug that is one of safest over the counter medications. However, its clinical effectiveness is hampered due to poor aqueous solubility. βCD hydrogel nanoparticles were prepared and characterized by percent yield, drug loading, solubilization efficiency, FTIR, XRD, DSC, FESEM and in-vitro dissolution studies. Acute oral toxicity study was conducted to assess safety of oral administration of prepared βCD hydrogel nanoparticles. βCD hydrogel nanoparticles dramatically enhanced the drug loading and solubilization efficiency of dexibuprofen in aqueous media. FTIR, TGA and DSC studies confirmed the formation of new and a stable nano-polymeric network and interactions of dexibuprofen with these nanoparticles. Resulting nanoparticles were highly porous with 287 nm in size. XRD analysis revealed pronounced reduction in crystalline nature of dexibuprofen within nanoparticles. Release of dexibuprofen in βCD hydrogel nanoparticles was significantly higher compared with dexibuprofen tablet at pH 1.2 and 6.8. In acute toxicity studies, no significant changes in behavioral, physiological, biochemical or histopathologic parameters of animals were observed. The efficient preparation, high solubility, excellent physicochemical characteristics, improved dissolution and non-toxic βCD hydrogel nanoparticles may be a promising approach for oral delivery of lipophilic drugs.

Aptamer-based hydrogel barcodes for the capture and detection of multiple types of pathogenic bacteria.

PubMed

Xu, Yueshuang; Wang, Huan; Luan, Chengxin; Liu, Yuxiao; Chen, Baoan; Zhao, Yuanjin

2018-02-15

Rapid and sensitive diagnosing hematological infections based on the separation and detection of pathogenic bacteria in the patient's blood is a significant challenge. To address this, we herein present a new barcodes technology that can simultaneously capture and detect multiple types of pathogenic bacteria from a complex sample. The barcodes are poly (ethylene glycol) (PEG) hydrogel inverse opal particles with characteristic reflection peak codes that remain stable during bacteria capture on their surfaces. As the spherical surface of the particles has ordered porous nanostructure, the barcodes can provide not only more surface area for probe immobilization and reaction, but also a nanopatterned platform for highly efficient bioreactions. In addition, the PEG hydrogel scaffold could decrease the non-specificity adsorption by its anti-adhesive effect, and the decorated aptamer probes in the scaffolds could increase the sensitivity, reliability, and specificity of the bacteria capture and detection. Moreover, the tagged magnetic nanoparticles in the PEG scaffold could impart the barcodes with controllable movement under magnetic fields, which can be used to significantly increase the reaction speed and simplify the processing of the bioassays. Based on the describe barcodes, it was demonstrated that the bacteria could be captured and identified even at low bacterial concentrations (100 CFU mL -1 ) within 2.5h, which is effectively shortened in comparison with the "gold standard" in clinic. These features make the barcodes ideal for capturing and detecting multiple bacteria from clinical samples for hematological infection diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

Sterilization of silicone-based hydrogels for biomedical application using ozone gas: Comparison with conventional techniques.

PubMed

Galante, Raquel; Ghisleni, Daniela; Paradiso, Patrizia; Alves, Vitor D; Pinto, Terezinha J A; Colaço, Rogério; Serro, Ana Paula

2017-09-01

Sterilization of hydrogels is challenging due to their often reported sensitivity to conventional methods involving heat or radiation. Although aseptic manufacturing is a possibility, terminal sterilization is safer in biological terms, leading to a higher overall efficiency, and thus should be used whenever it is possible. The main goal of this work was to study the applicability of an innovative ozone gas terminal sterilization method for silicone-based hydrogels and compare its efficacy and effects with those of traditional sterilization methods: steam heat and gamma irradiation. Ozone gas sterilization is a method with potential interest since it is reported as a low cost green method, does not leave toxic residues and can be applied to thermosensitive materials. A hydrogel intended for ophthalmological applications, based on tris(trimethylsiloxy)silyl] propyl methacrylate, was prepared and extensively characterized before and after the sterilization procedures. Alterations regarding transparency, swelling, wettability, ionic permeability, friction coefficient, mechanical properties, topography and morphology and chemical composition were monitored. Efficacy of the ozonation was accessed by performing controlled contaminations and sterility tests. In vitro cytotoxicity testes were also performed. The results show that ozonation may be applied to sterilize the studied material. A treatment with 8 pulses allowed sterilizing the material with bioburdens≤10 3 CFU/mL, preserving all the studied properties within the required known values for contact lenses materials. However, a higher exposure (10 pulses) led to some degradation of the material and induced mild cytotoxicity. Steam heat sterilization led to an increase of swelling capacity and a decrease of the water contact angle. Regarding gamma irradiation, the increase of irradiation dose led to an increase of the friction coefficient. The higher dose (25kGy) originated surface degradation and affected the mechanical properties of the hydrogel by inducing a significant increase of the Young's modulus. Overall, the results show that ozonation may be considered as a valid and promising alternative for the sterilization of silicon-based hydrogels for biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Hybrid lipid-based nanostructures

NASA Astrophysics Data System (ADS)

Dayani, Yasaman

Biological membranes serve several important roles, such as structural support of cells and organelles, regulation of ionic and molecular transport, barriers to non-mediated transport, contact between cells within tissues, and accommodation of membrane proteins. Membrane proteins and other vital biomolecules incorporated into the membrane need a lipid membrane to function. Due to importance of lipid bilayers and their vital function in governing many processes in the cell, the development of various models as artificial lipid membranes that can mimic cell membranes has become a subject of great interest. Using different models of artificial lipid membranes, such as liposomes, planar lipid bilayers and supported or tethered lipid bilayers, we are able to study many biophysical processes in biological membranes. The ability of different molecules to interact with and change the structure of lipid membranes can be also investigated in artificial lipid membranes. An important application of lipid bilayer-containing interfaces is characterization of novel membrane proteins for high throughput drug screening studies to investigate receptor-drug interactions and develop biosensor systems. Membrane proteins need a lipid bilayer environment to preserve their stability and functionality. Fabrication of materials that can interact with biomolecules like proteins necessitates the use of lipid bilayers as a mimic of cell membranes. The objective of this research is to develop novel hybrid lipid-based nanostructures mimicking biological membranes. Toward this aim, two hybrid biocompatible structures are introduced: lipid bilayer-coated multi-walled carbon nanotubes (MWCNTs) and hydrogel-anchored liposomes with double-stranded DNA anchors. These structures have potential applications in biosensing, drug targeting, drug delivery, and biophysical studies of cell membranes. In the first developed nanostructure, lipid molecules are covalently attached to the surfaces of MWCNTs, and then, using a sonication process, a uniform lipid bilayer that supports the incorporation of membrane proteins is formed. These bilayer-coated carbon nanotubes are highly dispersible and stable in aqueous solution, and they can be used in development of various biosensors and energy producing devices. In the other hybrid nanostructure, the lipid bilayer of a liposome is covalently anchored to a biocompatible poly(ethylene) glycol (PEG) hydrogel core using double-stranded DNA (dsDNA) linkers. Release studies shows that nano-size hydrogel-anchored liposomes are exceptionally stable, and they can be used as biomimetic model membranes that mimic the connectivity between the cytoskeleton and the plasma membrane. After lipid bilayer removal, dsDNA linkers can provide programmable nanogels decorated with oligonucleotides with potential sites for further molecular assembly. These stable nanostructures can be useful for oligonucleotide and drug delivery applications. The developed hydrogel-anchored liposomes are exploited for encapsulation and intracellular delivery of therapeutic peptide. Peptides with anti-cancer properties are successfully encapsulated in hydrogel core of pH-sensitive liposomes during rehydration process. Liposomes release their cargo at acidic pH. Confocal microscopy confirms the intracellular delivery of liposomes through an endocytotic pathway.

From Biological Cilia to Artificial Flow Sensors: Biomimetic Soft Polymer Nanosensors with High Sensing Performance

PubMed Central

Asadnia, Mohsen; Kottapalli, Ajay Giri Prakash; Karavitaki, K. Domenica; Warkiani, Majid Ebrahimi; Miao, Jianmin; Corey, David P.; Triantafyllou, Michael

2016-01-01

We report the development of a new class of miniature all-polymer flow sensors that closely mimic the intricate morphology of the mechanosensory ciliary bundles in biological hair cells. An artificial ciliary bundle is achieved by fabricating bundled polydimethylsiloxane (PDMS) micro-pillars with graded heights and electrospinning polyvinylidenefluoride (PVDF) piezoelectric nanofiber tip links. The piezoelectric nature of a single nanofiber tip link is confirmed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Rheology and nanoindentation experiments are used to ensure that the viscous properties of the hyaluronic acid (HA)-based hydrogel are close to the biological cupula. A dome-shaped HA hydrogel cupula that encapsulates the artificial hair cell bundle is formed through precision drop-casting and swelling processes. Fluid drag force actuates the hydrogel cupula and deflects the micro-pillar bundle, stretching the nanofibers and generating electric charges. Functioning with principles analogous to the hair bundles, the sensors achieve a sensitivity and threshold detection limit of 300 mV/(m/s) and 8 μm/s, respectively. These self-powered, sensitive, flexible, biocompatibale and miniaturized sensors can find extensive applications in navigation and maneuvering of underwater robots, artificial hearing systems, biomedical and microfluidic devices. PMID:27622466

Enhancing cisplatin delivery to hepatocellular carcinoma HepG2 cells using dual sensitive smart nanocomposite.

PubMed

Salimi, Farzaneh; Dilmaghani, Karim Akbari; Alizadeh, Effat; Akbarzadeh, Abolfazl; Davaran, Soodabeh

2017-07-07

Targeted entrance and accumulation of higher doses of drugs into malignant cells could help in intensification of tumor specific cytotoxicity. A dual-responsive nanogel, poly(N-isopropylacrylamide)-co-poly(N,N-(dimethylamino)ethyl methacrylate) [P(NIPAM-co-DMA)] containing N-isopropylacrylamide (NIPAM) as thermoresponsive monomer and N,N-(dimethylamino)ethyl methacrylate (DMA) as pH-responsive monomer and methylene-bis-acrylamide (MBA) as cross-linking agent, was synthesized by free radical emulsion polymerization. Cisplatin along with magnetic Fe 3 O 4 nanoparticles (MNPs) was loaded into the nanogel by physically embedding the magnetic nanoparticles into hydrogel matrix after gelation to obtain drug-loaded magnetic nanocomposite [P(NIPAM-co-DMA)/Fe 3 O 4 ]. Drug loading efficiencies and drug release profiles of cisplatin-loaded P(NIPAM-co-DMA) nanogel and P(NIPAM-co-DMA)/Fe 3 O 4 nanocomposite were evaluated in vitro for controlled drug delivery in different temperature and pH conditions. Finally, the anticancer activity of P(NIPAM-co-DMA)/Fe 3 O 4 nanocomposite on human liver HepG2 cells was evaluated. Nanogel and nanocomposite showed significantly higher (p < .05) cisplatin release at 40 °C compared to 37 °C and at pH 5.7 compared to pH 7.4, demonstrating their temperature and pH sensitivity, respectively. The cytotoxicity assay of drug free nanogel on HepG2 cell line indicated that the nanogel is biocompatible and suitable as drug carrier. Moreover, MTT assay revealed that the cisplatin-loaded nanocomposite represented significant superior cytotoxicity (p < .05) to HepG2 cells as compared with free cisplatin.

Controlled drug release by polymer dissolution. II: Enzyme-mediated delivery device.

PubMed

Heller, J; Trescony, P V

1979-07-01

A novel, closed-loop drug delivery system was developed where the presence or absence of an external compound controls drug delivery from a bioerodible polymer. In the described delivery system, hydrocortisone was incorporated into a n-hexyl half-ester of a methyl vinyl ehter-maleic anhydride copolymer, and the polymer-drug mixture was fabricated into disks. These disks were then coated with a hydrogel containing immobilized urease. In a medium of constant pH and in the absence of external urea, the hydrocortisone release was that normally expected for that polymer at the given pH. With external urea, ammonium bicarbonate and ammonium hydroxide were generated within the hydrogel, which accelerated polymer erosion and drug release. The drug delivery rate increase was proportional to the amount of external urea and was reversible; that is, when external urea was removed, the drug release rate gradually returned to its original value.

One-pot template-free synthesis of monodisperse hollow hydrogel microspheres and their resulting properties.

PubMed

Lim, Hyung-Seok; Kwon, Eunji; Lee, Moonjoo; Moo Lee, Young; Suh, Kyung-Do

2013-08-01

Monodisperse poly(methacrylic acid/ethyleneglycoldimethacrylate) (MAA/EGDMA) hollow microcapsules, which exhibit pH-responsive behavior, are prepared by diffusion of cationic surfactants and hydrophobic interaction. During the association of the negatively charged hydrogel microspheres and an oppositely charged surfactant (cetyltrimethylammonium bromide, CTA(+)B), the hydrophobic polymer-surfactant complexes that form are separated from the internal water; consequently, a hollow structure can be formed. Confocal laser scanning microscopy, UV spectro-scopy and zeta potential are employed to study the formation of the hollow structure during the diffusion of the cationic surfactant. The controlled release behavior of methylene blue as a model drug from the as-prepared poly(MAA/EGDMA) microcapsules with a hollow structure is investigated under different pH conditions. The hollow structure can be retained, even during repetitive pH changes. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A novel thermo-sensitive hydrogel based on thiolated chitosan/hydroxyapatite/beta-glycerophosphate.

PubMed

Liu, Xujie; Chen, Yan; Huang, Qianli; He, Wei; Feng, Qingling; Yu, Bo

2014-09-22

In order to get a water-soluble in situ gel-forming system, a thiolated chitosan, chitosan-4-thio-butylamidine (CS-TBA) conjugate was synthesized and used to replace the unmodified chitosan in the application of the in situ gel-forming system. A novel thermo-sensitive hydrogel was prepared based on CS-TBA/hydroxyapatite (HA)/beta-glycerophosphate disodium (β-GP). The gel formation, rheological properties, morphology, degradation, cytotoxicity, as well as protein release process of the novel gel system were investigated in this study. The CS-TBA/HA/β-GP gel showed a higher storage modulus (G') and loss modulus (G″) and a decreased bovine serum albumin (BSA) release rate which was maintained the protein release for a longer time compared with the unmodified chitosan (CS)/HA/β-GP gel, due to the existence of thiol groups and/or disulfide bonds. The CS-TBA/HA/β-GP gel has a porous structure with a uniform distribution of nano-hydroxyapatite, an appropriate degradation rate and low cytotoxicity, showing potential applications in drug delivery and tissue engineering. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mechanistic studies of an autonomously pulsing hydrogel/enzyme system for rhythmic hormone delivery.

PubMed

Bhalla, Amardeep S; Siegel, Ronald A

2014-12-28

Numerous hormones are known to be endogenously secreted in a pulsatile manner. In particular, gonadotropin replacing hormone (GnRH) is released in rhythmic pulses, and disruption of this rhythm is associated with pathologies of reproduction and sexual development. In an effort to develop an implantable, rhythmic delivery system, a scheme has been demonstrated involving a negative feedback instability between a pH-sensitive membrane and enzymes that convert endogenous glucose to hydrogen ion. A bench prototype system based on this scheme was previously shown to produce near rhythmic oscillations in internal pH and in GnRH delivery over a period of one week. In the present work, a systematic study of conditions permitting such oscillations is presented, along with a study of factors causing period of oscillations to increase with time and ultimately cease. Membrane composition, glucose concentration, and surface area of marble (CaCO3), which is incorporated as a reactant, were found to affect the capacity of the system to oscillate, and the pH range over which oscillations occur. Accumulation of gluconate- and Ca2+ in the system over time correlated with lengthening of oscillation period, and possibly with cessation of oscillations. Enzyme degradation may also be a factor. These studies provide the groundwork for future improvements in device design. Copyright © 2014 Elsevier B.V. All rights reserved.

Optical pH Sensor Covering the Range from pH 0-14 Compatible with Mobile-Device Readout and Based on a Set of Rationally Designed Indicator Dyes.

PubMed

Gotor, Raúl; Ashokkumar, Pichandi; Hecht, Mandy; Keil, Karin; Rurack, Knut

2017-08-15

In this work, a family of pH-responsive fluorescent probes has been designed in a rational manner with the aid of quantum chemistry tools, covering the entire pH range from 0-14. Relying on the boron-dipyrromethene (BODIPY) core, all the probes as well as selected reference dyes display very similar spectroscopic properties with ON-OFF fluorescence switching responses, facilitating optical readout in simple devices used for detection and analysis. Embedding of the probes and reference dyes into hydrogel spots on a plastic strip yielded a test strip that reversibly indicates pH with a considerably small uncertainty of ∼0.1 pH units. These strips are not only reusable but, combined with a 3D-printed case that can be attached to a smartphone, the USB port of which drives the integrated LED used for excitation, allows for autonomous operation in on-site or in-the-field applications; the developed Android application software ("app") further simplifies operation for unskilled users.

A hydrogel biosensor for high selective and sensitive detection of amyloid-beta oligomers.

PubMed

Sun, Liping; Zhong, Yong; Gui, Jie; Wang, Xianwu; Zhuang, Xiaorong; Weng, Jian

2018-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive and memory impairment. It is the most common neurological disease that causes dementia. Soluble amyloid-beta oligomers (AβO) in blood or cerebrospinal fluid (CSF) are the pathogenic biomarker correlated with AD. A simple electrochemical biosensor using graphene oxide/gold nanoparticles (GNPs) hydrogel electrode was developed in this study. Thiolated cellular prion protein (PrP C ) peptide probe was immobilized on GNPs of the hydrogel electrode to construct an AβO biosensor. Electrochemical impedance spectroscopy was utilized for AβO analysis. The specific binding between AβO and PrP C probes on the hydrogel electrode resulted in an increase in the electron-transfer resistance. The biosensor showed high specificity and sensitivity for AβO detection. It could selectively differentiate AβO from amyloid-beta (Aβ) monomers or fibrils. Meanwhile, it was highly sensitive to detect as low as 0.1 pM AβO in artificial CSF or blood plasma. The linear range for AβO detection is from 0.1 pM to 10 nM. This biosensor could be used as a cost-effective tool for early diagnosis of AD due to its high electrochemical performance and bionic structure.

Highly Sensitive and Reproducible SERS Sensor for Biological pH Detection Based on a Uniform Gold Nanorod Array Platform.

PubMed

Bi, Liyan; Wang, Yunqing; Yang, Ying; Li, Yuling; Mo, Shanshan; Zheng, Qingyin; Chen, Lingxin

2018-05-09

Conventional research on surface-enhanced Raman scattering (SERS)-based pH sensors often depends on nanoparticle aggregation, whereas the variability in nanoparticle aggregation gives rise to poor repeatability in the SERS signal. Herein, we fabricated a gold nanorod array platform via an efficient evaporative self-assembly method. The platform exhibits great SERS sensitivity with an enhancement factor of 5.6 × 10 7 and maintains excellent recyclability and reproducibility with relative standard deviation (RSD) values of less than 8%. On the basis of the platform, we developed a highly sensitive bovine serum albumin (BSA)-coated 4-mercaptopyridine (4-MPy)-linked (BMP) SERS-based pH sensor to report pH ranging from pH 3.0 to pH 8.0. The intensity ratio variation of 1004 and 1096 cm -1 in 4-MPy showed excellent pH sensitivity, which decreased as the surrounding pH increased. Furthermore, this BMP SERS-based pH sensor was employed to measure the pH value in C57BL/6 mouse blood. We have demonstrated that the pH sensor has great advantages such as good stability, reliability, and accuracy, which could be extended for the design of point-of-care devices.

Delivery of resveratrol, a red wine polyphenol, from solutions and hydrogels via the skin.

PubMed

Hung, Chi-Feng; Lin, Yin-Ku; Huang, Zih-Rou; Fang, Jia-You

2008-05-01

Resveratrol, the main active polyphenol in red wine, has been demonstrated to show benefits against skin disorders. The bioavailability of orally administered resveratrol is insufficient to permit high enough drug concentrations for systemic therapy. In this study, we examined the feasibility of the topical/transdermal delivery of resveratrol. The effects of vehicles on the in vitro permeation and skin deposition from saturated solutions such as aqueous buffers and soybean oil were investigated. The general trend for the delivery from solutions was: pH 6 buffer=pH 8 buffer>10% glycerol formal in pH 6 buffer>pH 9.9 buffer>pH 10.8 buffer>soybean oil. A linear relationship was established between the permeability coefficient (K(p)) and drug accumulation in the skin reservoir. Viable epidermis/dermis served as the predominant barrier for non-ionic resveratrol permeation. On the other hand, both the stratum corneum (SC) and viable skin acted as barriers to anionic resveratrol. Several prototype hydrogel systems were also studied as resveratrol vehicles. The viscosity but not the polarity of the hydrogels controlled resveratrol permeation/deposition. Piceatannol, a derivative of resveratrol with high pharmacological activity, showed 11.6-fold lower skin permeation compared to resveratrol. The safety profiles of resveratrol suggested that the hydrogel caused no SC disruption or skin erythema. It was concluded that delivery via a skin route may be a potent way to achieve the therapeutic effects of resveratrol. This is the first report to establish the permeation profiles for topically applied resveratrol.

In Situ Synthesis of Antimicrobial Silver Nanoparticles within Antifouling Zwitterionic Hydrogels by Catecholic Redox Chemistry for Wound Healing Application.

PubMed

GhavamiNejad, Amin; Park, Chan Hee; Kim, Cheol Sang

2016-03-14

A multifunctional hydrogel that combines the dual functionality of both antifouling and antimicrobial capacities holds great potential for many bioapplications. Many approaches and different materials have been employed to synthesize such a material. However, a systematic study, including in vitro and in vivo evaluation, on such a material as wound dressings is highly scarce at present. Herein, we report on a new strategy that uses catecholic chemistry to synthesize antimicrobial silver nanoparticles impregnated into antifouling zwitterionic hydrogels. For this purpose, hydrophobic dopamine methacrylamide monomer (DMA) was mixed in an aqueous solution of sodium tetraborate decahydrate and DMA monomer became soluble after increasing pH to 9 due to the complexation between catechol groups and boron. Then, cross-linking polymerization of zwitterionic monomer was carried out with the solution of the protected dopamine monomer to produce a new hydrogel. When this new hydrogel comes in contact with a silver nitrate solution, silver nanoparticles (AgNPs) are formed in its structure as a result of the redox property of the catechol groups and in the absence of any other external reducing agent. The results obtained from TEM and XRD measurements indicate that AgNPs with diameters of around 20 nm had formed within the networks. FESEM images confirmed that the silver nanoparticles were homogeneously incorporated throughout the hydrogel network, and FTIR spectroscopy demonstrated that the catechol moiety in the polymeric backbone of the hydrogel is responsible for the reduction of silver ions into the AgNPs. Finally, the in vitro and in vivo experiments suggest that these mussel-inspired, antifouling, antibacterial hydrogels have great potential for use in wound healing applications.

Surface cytologic features on intraocular lenses: can increased biocompatibility have disadvantages?

PubMed

Hollick, E J; Spalton, D J; Ursell, P G

1999-07-01

To compare the anterior surface cytologic features and effect on blood-aqueous barrier of polymethyl methacrylate, silicone, and hydrogel intraocular lens (IOL) implants to give an indication of their biocompatibility. This prospective study was performed at an English-teaching hospital. Ninety eyes were randomized to receive a polymethyl methacrylate, silicone, or hydrogel implant. A standardized surgical protocol was performed by a single surgeon using phacoemulsification. Patients were seen at intervals for 1 year. Measurements of visual acuity, contrast sensitivity, and anterior chamber laser flare and cells were obtained; and an assessment of lens cytologic features using specular microscopy of the anterior IOL surface was performed. Visual acuity and contrast sensitivity were not significantly different among the 3 groups. Hydrogel IOLs were associated with fewer inflammatory cells on their surface than polymethyl methacrylate and silicone IOLs (P<.001), but with significantly more lens epithelial cells (LECs) (P<.001). Patients with hydrogel implants without LECs had greater blood-aqueous barrier breakdown than those with LECs. The hydrogel IOLs were associated with a reduced inflammatory cell reaction but had many more LECs on their anterior surface. Those IOLs associated with increased blood-aqueous barrier damage did not develop LECs. If an IOL is too biocompatible, then it may incite the growth of LECs over its surface, which could have disadvantages.

Temporal Control of Gelation and Polymerization Fronts Driven by an Autocatalytic Enzyme Reaction.

PubMed

Jee, Elizabeth; Bánsági, Tamás; Taylor, Annette F; Pojman, John A

2016-02-05

Chemical systems that remain kinetically dormant until activated have numerous applications in materials science. Herein we present a method for the control of gelation that exploits an inbuilt switch: the increase in pH after an induction period in the urease-catalyzed hydrolysis of urea was used to trigger the base-catalyzed Michael addition of a water-soluble trithiol to a polyethylene glycol diacrylate. The time to gelation (minutes to hours) was either preset through the initial concentrations or the reaction was initiated locally by a base, thus resulting in polymerization fronts that converted the mixture from a liquid into a gel (ca. 0.1 mm min(-1)). The rate of hydrolytic degradation of the hydrogel depended on the initial concentrations, thus resulting in a gel lifetime of hours to months. In this way, temporal programming of gelation was possible under mild conditions by using the output of an autocatalytic enzyme reaction to drive both the polymerization and subsequent degradation of a hydrogel. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.