Influence of natural and synthetic crosslinking reagents on the structural and mechanical properties of chitosan-based hybrid hydrogels.

PubMed

Garnica-Palafox, I M; Sánchez-Arévalo, F M

2016-10-20

The objective of this work was to correlate the physical and chemical properties of chitosan/poly(vinyl alcohol)/genipin (CS/PVA/GEN) and chitosan/poly(vinyl alcohol)/glutaraldehyde (CS/PVA/GA) hydrogels with their structural and mechanical responses. In addition, their molecular structures were determined and confirmed using FTIR spectroscopy. The results indicated that the hybrid hydrogels crosslinked with genipin showed similar crystallinity, thermal properties, elongation ratio and structural parameters as those crosslinked with glutaraldehyde. However, it was found that the elastic moduli of the two hybrid hydrogels were slightly different: 2.82±0.33MPa and 2.08±0.11MPa for GA and GEN, respectively. Although the hybrid hydrogels crosslinked with GEN presented a lower elastic modulus, the main advantage is that GEN is five to ten thousand times less cytotoxic than GA. This means that the structural and mechanical properties of hybrid hydrogels crosslinked with GEN can easily be tuned and could have potential applications in the tissue engineering, regenerative medicine, food, agriculture and environmental industries. Copyright © 2016 Elsevier Ltd. All rights reserved.

Engineered modular biomaterial logic gates for environmentally triggered therapeutic delivery

NASA Astrophysics Data System (ADS)

Badeau, Barry A.; Comerford, Michael P.; Arakawa, Christopher K.; Shadish, Jared A.; Deforest, Cole A.

2018-03-01

The successful transport of drug- and cell-based therapeutics to diseased sites represents a major barrier in the development of clinical therapies. Targeted delivery can be mediated through degradable biomaterial vehicles that utilize disease biomarkers to trigger payload release. Here, we report a modular chemical framework for imparting hydrogels with precise degradative responsiveness by using multiple environmental cues to trigger reactions that operate user-programmable Boolean logic. By specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within material cross-linkers, we show selective control over gel dissolution and therapeutic delivery. To illustrate the versatility of this methodology, we synthesized 17 distinct stimuli-responsive materials that collectively yielded all possible YES/OR/AND logic outputs from input combinations involving enzyme, reductant and light. Using these hydrogels we demonstrate the first sequential and environmentally stimulated release of multiple cell lines in well-defined combinations from a material. We expect these platforms will find utility in several diverse fields including drug delivery, diagnostics and regenerative medicine.

Engineered modular biomaterial logic gates for environmentally triggered therapeutic delivery.

PubMed

Badeau, Barry A; Comerford, Michael P; Arakawa, Christopher K; Shadish, Jared A; DeForest, Cole A

2018-03-01

The successful transport of drug- and cell-based therapeutics to diseased sites represents a major barrier in the development of clinical therapies. Targeted delivery can be mediated through degradable biomaterial vehicles that utilize disease biomarkers to trigger payload release. Here, we report a modular chemical framework for imparting hydrogels with precise degradative responsiveness by using multiple environmental cues to trigger reactions that operate user-programmable Boolean logic. By specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within material cross-linkers, we show selective control over gel dissolution and therapeutic delivery. To illustrate the versatility of this methodology, we synthesized 17 distinct stimuli-responsive materials that collectively yielded all possible YES/OR/AND logic outputs from input combinations involving enzyme, reductant and light. Using these hydrogels we demonstrate the first sequential and environmentally stimulated release of multiple cell lines in well-defined combinations from a material. We expect these platforms will find utility in several diverse fields including drug delivery, diagnostics and regenerative medicine.

Nature-inspired multifunctional membrane fabricated by adaptive hybridization of PNIPAm and PPy

NASA Astrophysics Data System (ADS)

Kim, Hyejeong; Kim, Kiwoong; Lee, Sang Joon

2017-11-01

Specialized plant organs, such as guard cells of stomata, consist of soft materials with deformability and electrochemical properties in response to various environmental stimuli. Stimulus-responsive hydrogels with electrochemical properties are good candidates for imitating such functionalities having great potential in a wide range of applications. However, conductive hydrogels are usually mechanically rigid and the fabrication technology of structured hydrogels has low reproducibility. Here, inspired by stimulus-responsive functionalities of plants, a thermo-responsive multifunctional hybrid membrane (HM) is synthesized through the in situ hybridization of conductive poly(pyrrole)(PPy) on a photopolymerized poly(N-isopropylacrylamide)(PNIPAm) membrane. The various properties of the HM are investigated to characterize its multiple functions. In terms of morphology, the HM can be easily fabricated into various structures, and exhibits thermo-responsive deformability. In terms of functionality, it exhibits various electrical and charge responses to thermal stimuli. This simple and efficient fabrication method can be used as a promising platform for fabricating a variety of functional devices, such as actuators, biosensors, and filtration membranes. This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIP) (No. 2017R1A2B3005415).

Injectable dual redox responsive diselenide-containing poly(ethylene glycol) hydrogel.

PubMed

Gong, Chu; Shan, Meng; Li, Bingqiang; Wu, Guolin

2017-09-01

An injectable dual redox responsive diselenide-containing poly(ethylene glycol) (PEG) hydrogel was successfully developed by combining the conceptions of injectable hydrogels and dual redox responsive diselenides. In the first step, four-armed PEG was modified with N-hydroxysuccinimide (NHS)-activated esters and thereafter, crosslinked by selenocystamine crosslinkers to form injectable hydrogels via the rapid reaction between NHS-activated esters and amino groups. The cross-sectional morphology, mechanical properties, and crosslinking modes of hydrogels were well characterized via scanning electron microscope (SEM), rheological measurements, and Fourier transform infrared spectra, respectively. In addition, the oxidation- and reduction-responsive degradation behaviors of hydrogels were observed and analyzed. The model drug, rhodamine B, was encapsulated in the hydrogel. The drug-loaded hydrogel exhibited a dual redox responsive release profile, which was consistent with the degradation experiments. The results of all experiments indicated that the formulated injectable dual redox responsive diselenide-containing PEG hydrogel can have potential applications in various biomedical fields such as drug delivery and stimuli-responsive drug release. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2451-2460, 2017. © 2017 Wiley Periodicals, Inc.

Thiol–ene click hydrogels for therapeutic delivery

PubMed Central

Kharkar, Prathamesh M.; Rehmann, Matthew S.; Skeens, Kelsi M.; Maverakis, Emanual; Kloxin, April M.

2016-01-01

Hydrogels are of growing interest for the delivery of therapeutics to specific sites in the body. For use as a delivery vehicle, hydrophilic precursors are usually laden with bioactive moieties and then directly injected to the site of interest for in situ gel formation and controlled release dictated by precursor design. Hydrogels formed by thiol–ene click reactions are attractive for local controlled release of therapeutics owing to their rapid reaction rate and efficiency under mild aqueous conditions, enabling in situ formation of gels with tunable properties often responsive to environmental cues. Herein, we will review the wide range of applications for thiol–ene hydrogels, from the prolonged release of anti-inflammatory drugs in the spine to the release of protein-based therapeutics in response to cell-secreted enzymes, with a focus on their clinical relevance. We will also provide a brief overview of thiol–ene click chemistry and discuss the available alkene chemistries pertinent to macromolecule functionalization and hydrogel formation. These chemistries include functional groups susceptible to Michael type reactions relevant for injection and radically-mediated reactions for greater temporal control of formation at sites of interest using light. Additionally, mechanisms for the encapsulation and controlled release of therapeutic cargoes are reviewed, including i) tuning the mesh size of the hydrogel initially and temporally for cargo entrapment and release and ii) covalent tethering of the cargo with degradable linkers or affinity binding sequences to mediate release. Finally, myriad thiol–ene hydrogels and their specific applications also are discussed to give a sampling of the current and future utilization of this chemistry for delivery of therapeutics, such as small molecule drugs, peptides, and biologics. PMID:28361125

Reduced Graphene Oxide-Containing Smart Hydrogels with Excellent Electro-Response and Mechanical Properties for Soft Actuators.

PubMed

Yang, Chao; Liu, Zhuang; Chen, Chen; Shi, Kun; Zhang, Lei; Ju, Xiao-Jie; Wang, Wei; Xie, Rui; Chu, Liang-Yin

2017-05-10

A novel reduced graphene oxide/poly(2-acrylamido-2-methylpropanesulfonic acid-co-acrylamide) (rGO/poly(AMPS-co-AAm)) nanocomposite hydrogel that possesses excellent electro-response and mechanical properties has been successfully developed. The rGO nanosheets that homogeneously dispersed in the hydrogels could provide prominent conductive platforms for promoting the ion transport inside the hydrogels to generate significant osmotic pressure between the outside and inside of such nanocomposite hydrogels. Thus, the electro-responsive rate and degree of the hydrogel for both deswelling and bending performances become rapid and remarkable. Moreover, the enhanced mechanical properties including both the tensile strength and compressive strength of rGO/poly(AMPS-co-AAm) hydrogels are improved by the hydrogen-bond interactions between the rGO nanosheets and polymer chains, which could dissipate the strain energy in the polymeric networks of the hydrogels. The proposed rGO/poly(AMPS-co-AAm) nanocomposite hydrogels with improved mechanical properties exhibit rapid, significant, and reversible electro-response, which show great potential for developing remotely controlled electro-responsive hydrogel systems, such as smart actuators and soft manipulators.

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

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.

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.

Study on temperature and near-infrared driving characteristics of hydrogel actuator fabricated via molding and 3D printing.

PubMed

Zhao, Qian; Liang, Yunhong; Ren, Lei; Qiu, Feng; Zhang, Zhihui; Ren, Luquan

2018-02-01

A hydrogel material system which was fit for molding and 3D printing was developed to fabricate bilayer hydrogel actuators with controllable temperature and near infrared laser responses. Polymerization on interface boundary of layered structure enhanced the bonding strength of hydrogel actuators. By utilizing anisotropic of microstructure along with thickness direction, bilayer hydrogel actuators fabricated via molding realized intelligent bending/shrinking responses, which guided the preparation of hydrogel ink for 3D printing. In-situ free radical polymerization under vacuum realized the solidification of printed hydrogel actuators with graphene oxide. Based on anisotropic swelling/deswelling behaviors of precise structure fabricated via 3D printing, the printed bilayer hydrogel actuators achieved temperature and near infrared laser responsive deformation. Changes of programmable printing path effectively resulted in corresponding deformation patterns. Combination of advantages of molding and 3D printing can promote the design and fabrication of hydrogel actuators with high mechanical strength, response speed and deformation ability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hydrogels from Amorphous Calcium Carbonate and Polyacrylic Acid: Bio-Inspired Materials for "Mineral Plastics".

PubMed

Sun, Shengtong; Mao, Li-Bo; Lei, Zhouyue; Yu, Shu-Hong; Cölfen, Helmut

2016-09-19

Given increasing environmental issues due to the large usage of non-biodegradable plastics based on petroleum, new plastic materials, which are economic, environmentally friendly, and recyclable are in high demand. One feasible strategy is the bio-inspired synthesis of mineral-based hybrid materials. Herein we report a facile route for an amorphous CaCO3 (ACC)-based hydrogel consisting of very small ACC nanoparticles physically cross-linked by poly(acrylic acid). The hydrogel is shapeable, stretchable, and self-healable. Upon drying, the hydrogel forms free-standing, rigid, and transparent objects with remarkable mechanical performance. By swelling in water, the material can completely recover the initial hydrogel state. As a matrix, thermochromism can also be easily introduced. The present hybrid hydrogel may represent a new class of plastic materials, the "mineral plastics". © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Rapidly responsive silk fibroin hydrogels as an artificial matrix for the programmed tumor cells death.

PubMed

Ribeiro, Viviana P; Silva-Correia, Joana; Gonçalves, Cristiana; Pina, Sandra; Radhouani, Hajer; Montonen, Toni; Hyttinen, Jari; Roy, Anirban; Oliveira, Ana L; Reis, Rui L; Oliveira, Joaquim M

2018-01-01

Timely and spatially-regulated injectable hydrogels, able to suppress growing tumors in response to conformational transitions of proteins, are of great interest in cancer research and treatment. Herein, we report rapidly responsive silk fibroin (SF) hydrogels formed by a horseradish peroxidase (HRP) crosslinking reaction at physiological conditions, and demonstrate their use as an artificial biomimetic three-dimensional (3D) matrix. The proposed SF hydrogels presented a viscoelastic nature of injectable hydrogels and spontaneous conformational changes from random coil to β-sheet conformation under physiological conditions. A human neuronal glioblastoma (U251) cell line was used for screening cell encapsulation and in vitro evaluation within the SF hydrogels. The transparent random coil SF hydrogels promoted cell viability and proliferation up to 10 days of culturing, while the crystalline SF hydrogels converted into β-sheet structure induced the formation of TUNEL-positive apoptotic cells. Therefore, this work provides a powerful tool for the investigation of the microenvironment on the programed tumor cells death, by using rapidly responsive SF hydrogels as 3D in vitro tumor models.

UV-crosslinkable and thermo-responsive chitosan hybrid hydrogel for NIR-triggered localized on-demand drug delivery.

PubMed

Wang, Lei; Li, Baoqiang; Xu, Feng; Xu, Zheheng; Wei, Daqing; Feng, Yujie; Wang, Yaming; Jia, Dechang; Zhou, Yu

2017-10-15

Innovative drug delivery technologies based on smart hydrogels for localized on-demand drug delivery had aroused great interest. To acquire smart UV-crosslinkable chitosan hydrogel for NIR-triggered localized on-demanded drug release, a novel UV-crosslinkable and thermo-responsive chitosan was first designed and synthesized by grafting with poly N-isopropylacrylamide, acetylation of methacryloyl groups and embedding with photothermal carbon. The UV-crosslinkable unit (methacryloyl groups) endowed chitosan with gelation via UV irradiation. The thermo-responsive unit (poly N-isopropylacrylamide) endowed chitosan hydrogel with temperature-triggered volume shrinkage and reversible swelling/de-swelling behavior. The chitosan hybrid hydrogel embedded with photothermal carbon exhibited distinct NIR-triggered volume shrinkage (∼42% shrinkage) in response to temperature elevation as induced by NIR laser irradiation. As a demonstration, doxorubicin release rate was accelerated and approximately 40 times higher than that from non-irradiated hydrogels. The UV-crosslinkable and thermal-responsive hybrid hydrogel served as in situ forming hydrogel-based drug depot is developed for NIR-triggered localized on-demand release. Copyright © 2017 Elsevier Ltd. All rights reserved.

Design of protein-responsive micro-sized hydrogels for self-regulating microfluidic systems

NASA Astrophysics Data System (ADS)

Hirayama, Mayu; Tsuruta, Kazuhiro; Kawamura, Akifumi; Ohara, Masayuki; Shoji, Kan; Kawano, Ryuji; Miyata, Takashi

2018-03-01

Diagnosis sensors using micro-total analysis systems (µ-TAS) have been developed for detecting target biomolecules such as proteins and saccharides because they are signal biomolecules for monitoring body conditions and diseases. In this study, biomolecularly stimuli-responsive micro-sized hydrogels that exhibited quick shrinkage in response to lectin concanavalinA (ConA) were prepared in a microchannel by photopolymerization using a fluorescence microscope. In preparing the micro-size hydrogels, glycosyloxyethyl methacrylate (GEMA) as a ligand monomer was copolymerized with a crosslinker in the presence of template ConA in molecular imprinting. The ConA-imprinted micro-hydrogel showed greater shrinkage in response to target ConA than nonimprinted micro-hydrogel. When a buffer solution was switched to an aqueous ConA solution in the Y-shaped microchannel, the flow rates changed quickly because of the responsive shrinkage of the micro-hydrogel prepared in the microchannel. These results suggest that the ConA-imprinted micro-hydrogel acted as a self-regulated microvalve in microfluidic systems.

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

Recent Advances in Edible Polymer Based Hydrogels as a Sustainable Alternative to Conventional Polymers.

PubMed

Ali, Akbar; Ahmed, Shakeel

2018-06-26

The over increasing demand of eco-friendly materials to counter various problems, such as environmental issues, economics, sustainability, biodegradability, and biocompatibility, open up new fields of research highly focusing on nature-based products. Edible polymer based materials mainly consisting of polysaccharides, proteins, and lipids could be a prospective contender to handle such problems. Hydrogels based on edible polymer offer many valuable properties compared to their synthetic counterparts. Edible polymers can contribute to the reduction of environmental contamination, advance recyclability, provide sustainability, and thereby increase its applicability along with providing environmentally benign products. This review is highly emphasizing on toward the development of hydrogels from edible polymer, their classification, properties, chemical modification, and their potential applications. The application of edible polymer hydrogels covers many areas including the food industry, agricultural applications, drug delivery to tissue engineering in the biomedical field and provide more safe and attractive products in the pharmaceutical, agricultural, and environmental fields, etc.

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.

Worldwide Emerging Environmental Issues Affecting the U.S. Military. December 2008 Report

DTIC Science & Technology

2008-12-01

Environmental Security Implications……………..…3 7.1 New Protection for Plastic Electronics……………………………………………….3 7.2 Reusable Hydrogels Detect and Remove...www.nanowerk.com/spotlight/spotid=8555.php 7.2 Reusable Hydrogels Detect and Remove Heavy Metals from Contaminated Water Scientists at the...Department of Chemistry, University of California at Berkeley developed a group of low cost protein-cross-linked hydrogels , incorporating pea

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.

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.

Photothermal fabrication of microscale patterned DNA hydrogels

NASA Astrophysics Data System (ADS)

Shimomura, Suguru; Nishimura, Takahiro; Ogura, Yusuke; Tanida, Jun

2018-02-01

This paper introduces a method for fabricating microscale DNA hydrogels using irradiation with patterned light. Optical fabrication allows for the flexible and tunable formation of DNA hydrogels without changing the environmental conditions. Our scheme is based on local heat generation via the photothermal effect, which is induced by light irradiation on a quenching species. We demonstrate experimentally that, depending on the power and irradiation time, light irradiation enables the creation of local microscale DNA hydrogels, while the shapes of the DNA hydrogels are controlled by the irradiation patterns.

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.

Tunable poly(methacrylic acid-co-acrylamide) nanoparticles through inverse emulsion polymerization.

PubMed

Zhong, Justin X; Clegg, John R; Ander, Eric W; Peppas, Nicholas A

2018-06-01

Environmentally responsive biomaterials have played key roles in the design of biosensors and drug delivery vehicles. Their physical response to external stimuli, such as temperature or pH, can transduce a signal or trigger the release of a drug. In this work, we designed a robust, highly tunable, pH-responsive nanoscale hydrogel system. We present the design and characterization of poly(methacrylic acid-co-acrylamide) hydrogel nanoparticles, crosslinked with methylenebisacrylamide, through inverse emulsion polymerization. The effects of polymerization parameters (i.e., identities and concentrations of monomer and surfactant) and polymer composition (i.e., weight fraction of ionic and crosslinking monomers) on the nanoparticles' bulk and environmentally responsive properties were determined. We generated uniform, spherical nanoparticles which, through modulation of crosslinking, exhibit a volume swelling of 1.77-4.07, relative to the collapsed state in an acidic environment. We believe our system has potential as a base platform for the targeted, injectable delivery of hydrophilic therapeutics. With equal importance, however, we hope that our systematic analysis of the individual impacts of polymerization and purification conditions on nanoparticle composition, morphology, and performance can be used to expedite the development of alternate hydrophilic nanomaterials for a range of biomedical applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1677-1686, 2018. © 2018 Wiley Periodicals, Inc.

Bioinspired Smart Actuator Based on Graphene Oxide-Polymer Hybrid Hydrogels.

PubMed

Wang, Tao; Huang, Jiahe; Yang, Yiqing; Zhang, Enzhong; Sun, Weixiang; Tong, Zhen

2015-10-28

Rapid response and strong mechanical properties are desired for smart materials used in soft actuators. A bioinspired hybrid hydrogel actuator was designed and prepared by series combination of three trunks of tough polymer-clay hydrogels to accomplish the comprehensive actuation of "extension-grasp-retraction" like a fishing rod. The hydrogels with thermo-creep and thermo-shrinking features were successively irradiated by near-infrared (NIR) to execute extension and retraction, respectively. The GO in the hydrogels absorbed the NIR energy and transformed it into thermo-energy rapidly and effectively. The hydrogel with adhesion or magnetic force was adopted as the "hook" of the hybrid hydrogel actuator for grasping object. The hook of the hybrid hydrogel actuator was replaceable according to applications, even with functional materials other than hydrogels. This study provides an innovative concept to explore new soft actuators through combining response hydrogels and programming the same stimulus.

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.

Immunologic responses of bison to vaccination with Brucella abortus strain RB51: comparison of parenteral to ballistic delivery via compressed pellets or photopolymerized hydrogels.

PubMed

Olsen, Steven C; Christie, R J; Grainger, D W; Stoffregen, W S

2006-02-27

This study compared responses of bison calves to 10(10)CFU of Brucella abortus strain RB51 (SRB51) delivered by parenteral or ballistic methods. Two types of biobullet payloads were evaluated; compacted SRB51 pellets or SRB51 encapsulated in photopolymerized poly(ethylene glycol) hydrogels. Bison were vaccinated with saline, parenteral SRB51 alone, or in combination with Spirovac, or ballistically with compressed SRB51 or hydrogel biobullets. Bison parenterally vaccinated with SRB51 had greater (P<0.05) immunologic responses when compared to control bison. Co-administration of Spirovac as an adjuvant did not influence immunologic responses. As compared to compressed SRB51 biobullets, ballistic vaccination with hydrogel biobullets increased cellular immune responses at some sampling times. Our data suggest that hydrogel formulations of SRB51 may be a superior alternative to compressed SRB51 tablets for ballistic vaccination of bison. Although preliminary, data suggests that immunologic responses of bison to SRB51 hydrogel bullets are similar to responses after parenteral vaccination with SRB51.

Zwitterionic PEG-PC Hydrogels Modulate the Foreign Body Response in a Modulus-Dependent Manner.

PubMed

Jansen, Lauren E; Amer, Luke D; Chen, Esther Y-T; Nguyen, Thuy V; Saleh, Leila S; Emrick, Todd; Liu, Wendy F; Bryant, Stephanie J; Peyton, Shelly R

2018-05-15

Reducing the foreign body response (FBR) to implanted biomaterials will enhance their performance in tissue engineering. Poly(ethylene glycol) (PEG) hydrogels are increasingly popular for this application due to their low cost, ease of use, and the ability to tune their compliance via molecular weight and cross-linking densities. PEG hydrogels can elicit chronic inflammation in vivo, but recent evidence has suggested that extremely hydrophilic, zwitterionic materials and particles can evade the immune system. To combine the advantages of PEG-based hydrogels with the hydrophilicity of zwitterions, we synthesized hydrogels with comonomers PEG and the zwitterion phosphorylcholine (PC). Recent evidence suggests that stiff hydrogels elicit increased immune cell adhesion to hydrogels, which we attempted to reduce by increasing hydrogel hydrophilicity. Surprisingly, hydrogels with the highest amount of zwitterionic comonomer elicited the highest FBR. Lowering the hydrogel modulus (165 to 3 kPa), or PC content (20 to 0 wt %), mitigated this effect. A high density of macrophages was found at the surface of implants associated with a high FBR, and mass spectrometry analysis of the proteins adsorbed to these gels implicated extracellular matrix, immune response, and cell adhesion protein categories as drivers of macrophage recruitment. Overall, we show that modulus regulates macrophage adhesion to zwitterionic-PEG hydrogels, and demonstrate that chemical modifications to hydrogels should be studied in parallel with their physical properties to optimize implant design.

Effect of Extreme Cold Treatment on Morphology and Behavior of Hydrogels and Microgels (Poster Session)

DTIC Science & Technology

2017-08-20

UNCLASSIFIED Effect of Extreme Cold Treatment on Morphology and Behavior of Hydrogels and Microgels BACKGROUND • Stimuli responsive hydrogel systems...particularly for cold weather and Arctic uniforms, • The effect of extreme cold on gel responsiveness however is not well studied • This project seeks...to understand the effect of cold temperature ( down to -80 ° C) on hydrogel and microgel particles properties and response to thermal stimuli • We

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.

Visual and portable strategy for copper(II) detection based on a striplike poly(thymine)-caged and microwell-printed hydrogel.

PubMed

Qing, Zhihe; Mao, Zhengui; Qing, Taiping; He, Xiaoxiao; Zou, Zhen; He, Dinggeng; Shi, Hui; Huang, Jin; Liu, Jianbo; Wang, Kemin

2014-11-18

Due to its importance to develop strategies for copper(II) (Cu(2+)) detection, we here report a visual and portable strategy for Cu(2+) detection based on designing and using a strip-like hydrogel. The hydrogel is functionalized through caging poly(thymine) as probes, which can effectively template the formation of fluorescent copper nanoparticles (CuNPs) in the presence of the reductant (ascorbate) and Cu(2+). On the hydrogel's surface, uniform wells of microliter volume (microwells) are printed for sample-injection. When the injected sample is stained by Cu(2+), fluorescent CuNPs will be in situ templated by poly T in the hydrogel. With ultraviolet (UV) irradiation, the red fluorescence of CuNPs can be observed by naked-eye and recorded by a common camera without complicated instruments. Thus, the strategy integrates sample-injection, reaction and indication with fast signal response, providing an add-and-read manner for visual and portable detection of Cu(2+), as well as a strip-like strategy. Detection ability with a detectable minimum concentration of 20 μM and practically applicable properties have been demonstrated, such as resistance to environmental interference and good constancy, indicating that the strategy holds great potential and significance for popular detection of Cu(2+), especially in remote regions. We believe that the strip-like hydrogel-based methodology is also applicable to other targets by virtue of altering probes.

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.

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.

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.

Thermo-responsive methylcellulose hydrogels as temporary substrate for cell sheet biofabrication.

PubMed

Altomare, Lina; Cochis, Andrea; Carletta, Andrea; Rimondini, Lia; Farè, Silvia

2016-05-01

Methylcellulose (MC), a water-soluble polymer derived from cellulose, was investigated as a possible temporary substrate having thermo-responsive properties favorable for cell culturing. MC-based hydrogels were prepared by a dispersion technique, mixing MC powder (2, 4, 6, 8, 10, 12 % w/v) with selected salts (sodium sulphate, Na2SO4), sodium phosphate, calcium chloride, or phosphate buffered saline, to evaluate the influence of different compositions on the thermo-responsive behavior. The inversion test was used to determine the gelation temperatures of the different hydrogel compositions; thermo-mechanical properties and thermo-reversibility of the MC hydrogels were investigated by rheological analysis. Gelation temperatures and rheological behavior depended on the MC concentration and type and concentration of salt used in hydrogel preparation. In vitro cytotoxicity tests, performed using L929 mouse fibroblasts, showed no toxic release from all the tested hydrogels. Among the investigated compositions, the hydrogel composed of 8 % w/v MC with 0.05 M Na2SO4 had a thermo-reversibility temperature at 37 °C. For that reason, this formulation was thus considered to verify the possibility of inducing in vitro spontaneous detachment of cells previously seeded on the hydrogel surface. A continuous cell layer (cell sheet) was allowed to grow and then detached from the hydrogel surface without the use of enzymes, thanks to the thermo-responsive behavior of the MC hydrogel. Immunofluorescence observation confirmed that the detached cell sheet was composed of closely interacting cells.

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.

Weak Bond-Based Injectable and Stimuli Responsive Hydrogels for Biomedical Applications

PubMed Central

Ding, Xiaochu; Wang, Yadong

2017-01-01

Here we define hydrogels crosslinked by weak bonds as physical hydrogels. They possess unique features including reversible bonding, shear thinning and stimuli-responsiveness. Unlike covalently crosslinked hydrogels, physical hydrogels do not require triggers to initiate chemical reactions for in situ gelation. The drug can be fully loaded in a pre-formed hydrogel for delivery with minimal cargo leakage during injection. These benefits make physical hydrogels useful as delivery vehicles for applications in biomedical engineering. This review focuses on recent advances of physical hydrogels crosslinked by weak bonds: hydrogen bonds, ionic interactions, host-guest chemistry, hydrophobic interactions, coordination bonds and π-π stacking interactions. Understanding the principles and the state of the art of gels with these dynamic bonds may give rise to breakthroughs in many biomedical research areas including drug delivery and tissue engineering. PMID:29062484

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

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

A double-imprinted diffraction-grating sensor based on a virus-responsive super-aptamer hydrogel derived from an impure extract.

PubMed

Bai, Wei; Spivak, David A

2014-02-17

The detection of viruses is of interest for a number of fields including biomedicine, environmental science, and biosecurity. Of particular interest are methods that do not require expensive equipment or trained personnel, especially if the results can be read by the naked eye. A new "double imprinting" method was developed whereby a virus-bioimprinted hydrogel is further micromolded into a diffraction grating sensor by using imprint-lithography techniques to give a "Molecularly Imprinted Polymer Gel Laser Diffraction Sensor" (MIP-GLaDiS). A simple laser transmission apparatus was used to measure diffraction, and the system can read by the naked eye to detect the Apple Stem Pitting Virus (ASPV) at concentrations as low as 10 ng mL(-1), thus setting the limit of detection of these hydrogels as low as other antigen-binding methods such as ELISA or fluorescence-tag systems. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel Injectable Pentablock Copolymer Based Thermoresponsive Hydrogels for Sustained Release Vaccines.

PubMed

Bobbala, Sharan; Tamboli, Viral; McDowell, Arlene; Mitra, Ashim K; Hook, Sarah

2016-01-01

The need for multiple vaccinations to enhance the immunogenicity of subunit vaccines may be reduced by delivering the vaccine over an extended period of time. Here, we report two novel injectable pentablock copolymer based thermoresponsive hydrogels made of polyethyleneglycol-polycaprolactone-polylactide-polycaprolactone-polyethyleneglycol (PEG-PCL-PLA-PCL-PEG) with varying ratios of polycaprolactone (PCL) and polylactide (PLA), as single shot sustained release vaccines. Pentablock copolymer hydrogels were loaded with vaccine-encapsulated poly lactic-co-glycolic acid nanoparticles (PLGA-NP) or with the soluble vaccine components. Incorporation of PLGA-NP into the thermoresponsive hydrogels increased the complex viscosity of the gels, lowered the gelation temperature, and minimized the burst release of antigen and adjuvants. The two pentablock hydrogels stimulated both cellular and humoral responses. The addition of PLGA-NP to the hydrogels sustained immune responses for up to 49 days. The polymer with a higher ratio of PCL to PLA formed a more rigid gel, induced stronger immune responses, and stimulated effective anti-tumor responses in a prophylactic melanoma tumor model.

Highly Swellable, Dual-Responsive Hydrogels Based on PNIPAM and Redox Active Poly(ferrocenylsilane) Poly(ionic liquid)s: Synthesis, Structure, and Properties.

PubMed

Feng, Xueling; Zhang, Kaihuan; Chen, Peng; Sui, Xiaofeng; Hempenius, Mark A; Liedberg, Bo; Vancso, G Julius

2016-12-01

Highly swellable, dual-responsive hydrogels, consisting of thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) and redox-responsive poly(ferrocenylsilane) (PFS) based poly(ionic liquid)s (PILs) are formed by photo-polymerization. PFS chains bearing cross-linkable vinylimidazolium (VIm) side groups are copolymerized with NIPAM in aqueous solutions under ultraviolet light (λ = 365 nm) in the presence of a photoinitiator. The PFS-PILs serve as a macro-cross-linker and also provide redox responsiveness. The swelling ratio, morphology, and lower critical solution temperature (LCST) of the hydrogels are studied as a function of the PNIPAM/PFS ratio. The value of the LCST is dependent on the choice of the counterion of the PIL and the PNIPAM/PFS ratio. The hydrogel is employed as a reducing environment for the in situ fabrication of gold nanoparticles (AuNPs), forming AuNP-hydrogel composites. The localized surface plasmon resonance peak of the as-synthesized Au nanoparticles inside the hydrogel could be tuned by altering the temperature. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gradient Material Strategies for Hydrogel Optimization in Tissue Engineering Applications

PubMed Central

2018-01-01

Although a number of combinatorial/high-throughput approaches have been developed for biomaterial hydrogel optimization, a gradient sample approach is particularly well suited to identify hydrogel property thresholds that alter cellular behavior in response to interacting with the hydrogel due to reduced variation in material preparation and the ability to screen biological response over a range instead of discrete samples each containing only one condition. This review highlights recent work on cell–hydrogel interactions using a gradient material sample approach. Fabrication strategies for composition, material and mechanical property, and bioactive signaling gradient hydrogels that can be used to examine cell–hydrogel interactions will be discussed. The effects of gradients in hydrogel samples on cellular adhesion, migration, proliferation, and differentiation will then be examined, providing an assessment of the current state of the field and the potential of wider use of the gradient sample approach to accelerate our understanding of matrices on cellular behavior. PMID:29485612

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.

Development of smart delivery system for ascorbic acid using pH-responsive P(MAA-co-EGMA) hydrogel microparticles.

PubMed

Lee, Eunmi; Kim, Kyusik; Choi, Moonjae; Lee, Youngmoo; Park, Jin-Won; Kim, Bumsang

2010-11-01

pH-Responsive P(MAA-co-EGMA) hydrogel microparticles were prepared and their feasibility as intelligent delivery carriers was evaluated. P(MAA-co-EGMA) hydrogel microparticles were synthesized via dispersion photopolymerization. There was a drastic change in the swelling ratio of P(MAA-co-EGMA) microparticles at a pH of ~ 5 and, as the amount of MAA in the hydrogel increased, the swelling ratio increased at a pH above 5. The loading efficiency of the ascorbic acid into the hydrogel was affected more by the degree of swelling of the hydrogel than the electrostatic interaction between the hydrogel and the loaded ascorbic acid. The P(MAA-co-EGMA) hydrogel microparticles showed a pH-sensitive release behavior. Thus, at pH 4 almost none of the ascorbic acid permeated through the skin while at pH 6 relatively high skin permeability was obtained. The ascorbic acid loaded in the hydrogel particles was hardly degraded and its stability was maintained at high temperature.

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.

Calcium ion coordinated dexamethasone supramolecular hydrogel as therapeutic alternative for control of non-infectious uveitis.

PubMed

Wu, Wei; Zhang, Zhaoliang; Xiong, Taotao; Zhao, Wenguang; Jiang, Rou; Chen, Hao; Li, Xingyi

2017-10-01

Supramolecular hydrogels formed by the self-assembly of therapeutic agents have received considerable attention due to their high drug payload and carrier-free features. Herein, we constructed a dexamethasone sodium phosphate (Dex) supramolecular hydrogel in combination with Dex and calcium ion (Ca 2+ ) and further demonstrated its therapeutic efficacy in the control of ocular inflammation. The developed supramolecular hydrogel was thoroughly characterized by rheology, TEM, FTIR and XRD. Calcium ions and Dex concentration had a marked influence on the sol-gel transition behaviour of hydrogel and the proposed Dex supramolecular hydrogel displayed thixotropic properties. The drug release rate from Dex supramolecular hydrogel was dependent on the Ca 2+ concentration. In comparison with Dex aqueous solution, single intravitreal injections of Dex supramolecular hydrogel up to 30μg/eye were well tolerated without causing undesirable complications of fundus blood vessel tortuosity and lens opacity, as indicated by electroretinograms (ERGs), fundus photography and histopathology. Moreover, the administration by Dex supramolecular hydrogel exhibited a comparable anti-inflammatory efficacy to native Dex solution on an experimental autoimmune uveitis (EAU) model induced in Lewis rats with IRBP peptide and the therapeutic efficacy had in a dosage-dependent manner. Histological observation and cytokines measurements indicated that both Dex solution and Dex supramolecular hydrogel (30μg/eye) treatment could significantly attenuate the inflammatory response in both anterior and posterior chambers via the downregulation of Th1 and Th17 effector responses. All these data suggested that the developed Dex supramolecular hydrogel might be a therapeutic alternative for non-infectious uveitis with minimal risk of the induction of lens opacity and fundus blood vessel tortuosity. A facile ionic cross-linking strategy was exploited to construct a dexamethasone sodium phosphate (Dex) supramolecular hydrogel composed of Dex and calcium ion. Intravitreal injection of Dex hydrogel displayed excellent intraocular biocompatibility without causing the complications of fundus blood vessel tortuosity and lens opacity. More importantly, the proposed Dex hydrogel exhibited a comparative anti-inflammatory response to native Dex formulation on an experimental autoimmune uveitis (EAU) model via the downregulation of Th1 and Th17 effector responses. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

DNA hydrogel as a template for synthesis of ultrasmall gold nanoparticles for catalytic applications.

PubMed

Zinchenko, Anatoly; Miwa, Yasuyuki; Lopatina, Larisa I; Sergeyev, Vladimir G; Murata, Shizuaki

2014-03-12

DNA cross-linked hydrogel was used as a matrix for synthesis of gold nanoparticles. DNA possesses a strong affinity to transition metals such as gold, which allows for the concentration of Au precursor inside a hydrogel. Further reduction of HAuCl4 inside DNA hydrogel yields well dispersed, non-aggregated spherical Au nanoparticles of 2-3 nm size. The average size of these Au nanoparticles synthesized in DNA hydrogel is the smallest reported so far for in-gel metal nanoparticles synthesis. DNA hybrid hydrogel containing gold nanoparticles showed high catalytic activity in the hydrogenation reaction of nitrophenol to aminophenol. The proposed soft hybrid material is promising as environmentally friendly and sustainable material for catalytic applications.

A study on the swelling behavior of poly(acrylic acid) hydrogels obtained by electron beam crosslinking

NASA Astrophysics Data System (ADS)

Sheikh, N.; Jalili, L.; Anvari, F.

2010-06-01

Poly(acrylic acid) (PAA) hydrogels were prepared by using electron beam (EB) crosslinking of PAA homopolymer from its aqueous solutions. The swelling behavior of the hydrogels was studied as a function of the concentration of PAA solution, radiation dose, pH of the swelling medium and swelling time. Also the environmental pH effect on the water diffusion mode into hydrogels was investigated. These hydrogels clearly showed pH-sensitive swelling behavior with Fickian type of diffusion in the stomach-like pH medium (pH 1.3) and non-Fickian type in the intestine-like pH medium (pH 6.8).

Thermo-responsive in-situ forming hydrogels as barriers to prevent post-operative peritendinous adhesion.

PubMed

Chou, Pang-Yun; Chen, Shih-Heng; Chen, Chih-Hao; Chen, Shih-Hsien; Fong, Yi Teng; Chen, Jyh-Ping

2017-11-01

In this study, we aimed to assess whether thermo-responsive in-situ forming hydrogels based on poly(N-isopropylacrylamide) (PNIPAM) could prevent post-operative peritendinous adhesion. The clinical advantages of the thermo-responsive hydrogels are acting as barrier material to block penetration of fibroblasts, providing mobility and flexibility during application and enabling injection through a small opening to fill spaces of any shape after surgery. The thermo-responsiveness of hydrogels was determined to ensure their clinic uses. By grafting hydrophilic biopolymers chitosan (CS) and hyaluronic acid (HA) to PNIPAM, the copolymer hydrogels show enhanced water retention and lubrication, while reduced volume shrinkage during phase transition. In cell culture experiments, the thermo-responsive hydrogel has good biocompatibility and reduces fibroblast penetration. In animal experiments, the effectiveness of preventing post-operative peritendinous adhesion was studied in a rabbit deep flexor tendon model. From gross examination, histology, bending angles of joints, tendon gliding excursion and pull-out force, HA-CS-PNIPAM (HACPN) was confirmed to be the best barrier material to prevent post-operative peritendinous adhesion compared to PNIPAM and CS-PNIPAM (CPN) hydrogels and a commercial barrier film Seprafilm®. There was no significant difference in the breaking strength of HACPN-treated tendons and spontaneously healed ones, indicating HACPN hydrogel application did not interfere with normal tendon healing. We conclude that HACPN hydrogel can provide the best functional outcomes to significantly prevent post-operative tendon adhesion in vivo. We prepared thermo-responsive in-situ forming hydrogels based on poly(N-isopropylacrylamide) (PNIPAM) to prevent post-operative peritendinous adhesion. The injectable barrier hydrogel could have better anti-adhesive properties than current commercial products by acting as barrier material to block penetration of fibroblasts, providing mobility and flexibility during application and enabling injection through a small opening to fill spaces of any shape after surgery. The effectiveness of preventing post-operative peritendinous adhesion was studied in a rabbit deep flexor tendon model. From gross examination, histology, bending angles of joints, tendon gliding excursion and pull-out force, HA-CS-PNIPAM (HACPN) was confirmed to be the best barrier material to prevent post-operative peritendinous adhesion compared to PNIPAM and CS-PNIPAM (CPN) hydrogels and a commercial barrier film Seprafilm®. Copyright © 2017 Acta Materialia Inc. Published by 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.

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.

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.

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.

Designing degradable hydrogels for orthogonal control of cell microenvironments

PubMed Central

Kharkar, Prathamesh M.

2013-01-01

Degradable and cell-compatible hydrogels can be designed to mimic the physical and biochemical characteristics of native extracellular matrices and provide tunability of degradation rates and related properties under physiological conditions. Hence, such hydrogels are finding widespread application in many bioengineering fields, including controlled bioactive molecule delivery, cell encapsulation for controlled three-dimensional culture, and tissue engineering. Cellular processes, such as adhesion, proliferation, spreading, migration, and differentiation, can be controlled within degradable, cell-compatible hydrogels with temporal tuning of biochemical or biophysical cues, such as growth factor presentation or hydrogel stiffness. However, thoughtful selection of hydrogel base materials, formation chemistries, and degradable moieties is necessary to achieve the appropriate level of property control and desired cellular response. In this review, hydrogel design considerations and materials for hydrogel preparation, ranging from natural polymers to synthetic polymers, are overviewed. Recent advances in chemical and physical methods to crosslink hydrogels are highlighted, as well as recent developments in controlling hydrogel degradation rates and modes of degradation. Special attention is given to spatial or temporal presentation of various biochemical and biophysical cues to modulate cell response in static (i.e., non-degradable) or dynamic (i.e., degradable) microenvironments. This review provides insight into the design of new cell-compatible, degradable hydrogels to understand and modulate cellular processes for various biomedical applications. PMID:23609001

Biosynthetic hydrogels--studies on chemical and physical characteristics on long-term cellular response for tissue engineering.

PubMed

Thankam, Finosh Gnanaprakasam; Muthu, Jayabalan

2014-07-01

Biosynthetic hydrogels can meet the drawbacks caused by natural and synthetic ones for biomedical applications. In the current article we present a novel biosynthetic alginate-poly(propylene fumarate) copolymer based chemically crosslinked hydrogel scaffolds for cardiac tissue engineering applications. Partially crosslinked PA hydrogel and fully cross linked PA-A hydrogel scaffolds were prepared. The influence of chemical and physical (morphology and architecture of hydrogel) characteristics on the long term cellular response was studied. Both these hydrogels were cytocompatible and showed no genotoxicity upon contact with fibroblast cells. Both PA and PA-A were able to resist deleterious effects of reactive oxygen species and sustain the viability of L929 cells. The hydrogel incubated oxidative stress induced cells were capable of maintaining the intra cellular reduced glutathione (GSH) expression to the normal level confirmed their protective effect. Relatively the PA hydrogel was found to be unstable in the cell culture medium. The PA-A hydrogel was able to withstand appreciable cyclic stretching. The cyclic stretching introduced complex macro and microarchitectural features with interconnected pores and more structured bound water which would provide long-term viability of around 250% after the 24th day of culture. All these qualities make PA-A hydrogel form a potent candidate for cardiac tissue engineering. © 2013 Wiley Periodicals, Inc.

Hydrogen peroxide mechanosynthesis in siloxane-hydrogel contact lenses.

PubMed

Tavazzi, Silvia; Ferraro, Lorenzo; Cozza, Federica; Pastori, Valentina; Lecchi, Marzia; Farris, Stefano; Borghesi, Alessandro

2014-11-26

Drug-loaded contact lenses are emerging as the preferred treatment method for several ocular diseases, and efforts are being directed to promote extended and controlled delivery. One strategy is based on delivery induced by environmental triggers. One of these triggers can be hydrogen peroxide, since many platforms based on drug-loaded nanoparticles were demonstrated to be hydrogen-peroxide responsive. This is particularly interesting when hydrogen peroxide is the result of a specific pathophysiological condition. Otherwise, an alternative route to induce drug delivery is here proposed, namely the mechano-synthesis. The present work represents the proof-of-concept of the mechanosynthesis of hydrogen peroxide in siloxane-hydrogel contact lenses as a consequence of the cleavage of siloxane bonds at the interface between the polymer and water in aqueous phase. Their spongy morphology makes contact lenses promising systems for mechanical-to-chemical energy conversion, since the amount of hydrogen peroxide is expected to scale with the interfacial area between the polymer and water. The eyelid pressure during wear is sufficient to induce the hydrogen peroxide synthesis with concentrations which are biocompatible and suitable to trigger the drug release through hydrogen-peroxide-responsive platforms. For possible delivery on demand, the integration of piezoelectric polymers in the siloxane-hydrogel contact lenses could be designed, whose mechanical deformation could be induced by an applied wireless-controlled voltage.

Preparation of Chitosan-based Injectable Hydrogels and Its Application in 3D Cell Culture.

PubMed

Li, Yongsan; Zhang, Yaling; Wei, Yen; Tao, Lei

2017-09-29

The protocol presents a facile, efficient, and versatile method to prepare chitosan-based hydrogels using dynamic imine chemistry. The hydrogel is prepared by mixing solutions of glycol chitosan with a synthesized benzaldehyde terminated polymer gelator, and hydrogels are efficiently obtained in several minutes at room temperature. By varying ratios between glycol chitosan, polymer gelator, and water contents, versatile hydrogels with different gelation times and stiffness are obtained. When damaged, the hydrogel can recover its appearances and modulus, due to the reversibility of the dynamic imine bonds as crosslinkages. This self-healable property enables the hydrogel to be injectable since it can be self-healed from squeezed pieces to an integral bulk hydrogel after the injection process. The hydrogel is also multi-responsive to many bio-active stimuli due to different equilibration statuses of the dynamic imine bonds. This hydrogel was confirmed as bio-compatible, and L929 mouse fibroblast cells were embedded following standard procedures and the cell proliferation was easily assessed by a 3D cell cultivation process. The hydrogel can offer an adjustable platform for different research where a physiological mimic of a 3D environment for cells is profited. Along with its multi-responsive, self-healable, and injectable properties, the hydrogels can potentially be applied as multiple carriers for drugs and cells in future bio-medical applications.

Prodrugs as self-assembled hydrogels: a new paradigm for biomaterials.

PubMed

Vemula, Praveen Kumar; Wiradharma, Nikken; Ankrum, James A; Miranda, Oscar R; John, George; Karp, Jeffrey M

2013-12-01

Prodrug-based self-assembled hydrogels represent a new class of active biomaterials that can be harnessed for medical applications, in particular the design of stimuli responsive drug delivery devices. In this approach, a promoiety is chemically conjugated to a known-drug to generate an amphiphilic prodrug that is capable of forming self-assembled hydrogels. Prodrug-based self-assembled hydrogels are advantageous as they alter the solubility of the drug, enhance drug loading, and eliminate the use of harmful excipients. In addition, self-assembled prodrug hydrogels can be designed to undergo controlled drug release or tailored degradation in response to biological cues. Herein we review the development of prodrug-based self-assembled hydrogels as an emerging class of biomaterials that overcome several common limitations encountered in conventional drug delivery. Published by Elsevier Ltd.

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.

Dual-responsive and Multi-functional Plasmonic Hydrogel Valves and Biomimetic Architectures Formed with Hydrogel and Gold Nanocolloids

PubMed Central

Song, Ji Eun; Cho, Eun Chul

2016-01-01

We present a straightforward approach with high moldability for producing dual-responsive and multi-functional plasmonic hydrogel valves and biomimetic architectures that reversibly change volumes and colors in response to temperature and ion variations. Heating of a mixture of hybrid colloids (gold nanoparticles assembled on a hydrogel colloid) and hydrogel colloids rapidly induces (within 30 min) the formation of hydrogel architectures resembling mold shapes (cylinder, fish, butterfly). The biomimetic fish and butterfly display reversible changes in volumes and colors with variations of temperature and ionic conditions in aqueous solutions. The cylindrical plasmonic valves installed in flow tubes rapidly control water flow rate in on-off manner by responding to these stimuli. They also report these changes in terms of their colors. Therefore, the approach presented here might be helpful in developing new class of biomimetic and flow control systems where liquid conditions should be visually notified (e.g., glucose or ion concentration changes). PMID:27703195

Design of Nanostructured Biological Materials Through Self-Assembly of Peptides and Proteins

DTIC Science & Technology

2002-01-01

of applications, including scaffolding for tissue repair in regenerative medicine, drug delivery and biological surface engineering. Tirrell and...colleagues [2] designed artificial proteins that undergo self-assembly to form hydrogels responsive to pH and other environmental changes. Ghadiri and...showed that other β-sheet peptide systems can also undergo self-assembly into regular nanofiber structures. Although they share no sequence

Superporous thermo-responsive hydrogels by combination of cellulose fibers and aligned micropores.

PubMed

Halake, Kantappa S; Lee, Jonghwi

2014-05-25

In the area of artificial hydrogels, simultaneous engineering of the volume transition characteristics and mechanical properties of stimuli-responsive hydrogels is an important subject. By unrestricted architecting of hierarchical structures, natural hydrogels are able to provide a wide range of swelling and mechanical properties, beyond the limits of artificial hydrogels. Herein, a combination of nanostructures and microstructures was developed to construct superporous hydrogels. Fibers of microfibrillated cellulose (MFC), an eco-friendly reinforcing material, were used as nanostructures, aligned micropores were used as microstructures, and in situ photopolymerization was used to immobilize the two structures together within the gel networks of poly(N-isopropyl acrylamide) (PNIPAm). The introduction of MFC distinctly enhanced volume transition, mainly by decreasing the swelling ratios above the transition. The introduction of directional micropores increased the swelling ratio below the transition and decreased the swelling ratio above the transition, thereby also enhancing the volume transition. Additionally, the formation of aligned micropores achieved fast water infiltration, which is beneficial for superabsorbent applications. The introduction of aligned micropores reduced the elastic modulus, but this could partially be compensated for by reinforcement with MFC. This combination of crystalline nanofibers and aligned micropores has great potential for the development of stimuli-responsive superporous hydrogels outperforming current artificial hydrogels. Copyright © 2014 Elsevier Ltd. All rights reserved.

Polyisocyanopeptide hydrogels: A novel thermo-responsive hydrogel supporting pre-vascularization and the development of organotypic structures.

PubMed

Zimoch, Jakub; Padial, Joan Simó; Klar, Agnes S; Vallmajo-Martin, Queralt; Meuli, Martin; Biedermann, Thomas; Wilson, Christopher J; Rowan, Alan; Reichmann, Ernst

2018-04-01

Molecular and mechanical interactions with the 3D extracellular matrix are essential for cell functions such as survival, proliferation, migration, and differentiation. Thermo-responsive biomimetic polyisocyanopeptide (PIC) hydrogels are promising new candidates for 3D cell, tissue, and organ cultures. This is a synthetic, thermo-responsive and stress-stiffening material synthesized via polymerization of the corresponding monomers using a nickel perchlorate as a catalyst. It can be tailored to meet various demands of cells by modulating its stiffness and through the decoration of the polymer with short GRGDS peptides using copper free click chemistry. These peptides make the hydrogels biocompatible by mimicking the binding sites of certain integrins. This study focuses on the optimization of the PIC polymer properties for efficient cell, tissue and organ development. Screening for the optimal stiffness of the hydrogel and the ideal concentration of the GRGDS ligand conjugated with the polymer, enabled cell proliferation, migration and differentiation of various primary cell types of human origin. We demonstrate that fibroblasts, endothelial cells, adipose-derived stem cells and melanoma cells, do survive, thrive and differentiate in optimized PIC hydrogels. Importantly, these hydrogels support the spontaneous formation of complex structures like blood capillaries in vitro. Additionally, we utilized the thermo-responsive properties of the hydrogels for a rapid and gentle recovery of viable cells. Finally, we show that organotypic structures of human origin grown in PIC hydrogels can be successfully transplanted subcutaneously onto immune-compromised rats, on which they survive and integrate into the surrounding tissue. Molecular and mechanical interactions with the surrounding environment are essential for cell functions. Although 2D culture systems greatly contributed to our understanding of complex biological phenomena, they cannot substitute for crucial interaction that take place in 3D. 3D culture systems aim to overcome limitations of the 2D cultures and answer new questions about cell functions. Thermo-responsive biomimetic polyisocyanopeptide (PIC) hydrogels are promising new candidates for 3D cell, tissue, and organ cultures. They are synthetic and can be tailor to meet certain experimental demands. Additionally, they are characterized by strain-stiffening, a feature crucial for cell behaviour, but rare in hydrogels. Their thermos-responsive properties enable quick recovery of the cells by a simple procedure of lowering the temperature. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Dual Salt- and Thermo-Responsive Programmable Bilayer Hydrogel Actuators with Pseudo-Interpenetrating Double-Network Structures.

PubMed

Xiao, Shengwei; Zhang, Mingzhen; He, Xiaomin; Huang, Lei; Zhang, Yanxian; Ren, Baiping; Zhong, Mingqiang; Chang, Yung; Yang, Jintao; Zheng, Jie

2018-06-07

Development of smart soft actuators is highly important for fundamental research and industrial applications, but has proved to be extremely challenging. In this work, we present a facile, one-pot, one-step method to prepare dual-responsive bilayer hydrogels, consisting of a thermos-responsive poly(N-isopropyl acrylamide) (polyNIPAM) layer and a salt-responsive poly(3-(1-(4-vinylbenzyl)-1H-imidazol-3-ium-3-yl)propane-1-sulfonat) (polyVBIPS) layer. Both polyNIPAM and polyVBIPs layers exhibit a completely opposite swelling/shrinking behavior, where polyNIPAM shrinks (swells) but polyVBIPS swells (shrinks) in salt solution (water) or at high (low) temperatures. By tuning NIPAM:VBIPS ratios, the resulting polyNIPAM/polyVBIPS bilayer hydrogels enable to achieve fast and large-amplitude bidirectional bending in response to temperatures, salt concentrations, and salt types. Such bidirectional bending, bending orientation and degree can be reversibly, repeatedly, and precisely controlled by salt- or temperature-induced cooperative, swelling-shrinking properties from both layers. Based on their fast, reversible, bidirectional bending behavior, we further design two conceptual hybrid hydrogel actuators, serving as a six-arm gripper to capture, transport, and release an object and an electrical circuit switch to turn on-and-off a lamp. Different from the conventional two or multi-step methods for preparation of bilayer hydrogels, our simple, one-pot, one-step method and a new bilayer hydrogel system provide an innovative concept to explore new hydrogel-based actuators through combining different responsive materials that allow to program different stimulus for soft and intelligent materials applications.

In vitro and in vivo acute response towards injectable thermosensitive chitosan/TEMPO-oxidized cellulose nanofiber hydrogel.

PubMed

Nguyen, Trang Ho Minh; Abueva, Celine; Ho, Hai Van; Lee, Sun-Young; Lee, Byong-Taek

2018-01-15

TEMPO-oxidized cellulose nanofiber (TOCNF) is a natural material with many promising properties, including biocompatibility and degradability. In this study, we integrated TOCNF at different concentrations (0.2, 0.4, 0.6, 0.8% w/v) with chitosan (CS) and created a thermosensitive injectable hydrogel intended for biomedical applications. These hydrogels can undergo sol-gel transition at body temperature through interactions between chitosan and β-glycerophosphate. The addition of TOCNF resulted in faster gelation time and increased porosity. These hydrogels with TOCNF showed improved biocompatibility both in vitro and in vivo compared to CS hydrogel. Both MC3T3-E1 pre-osteoblast cells and L929 fibroblast cells showed biocompatibility towards CS/TOCNF 0.4. After 7days of implantation, initial inflammatory response to CS/TOCNF 0.4 was found. Such response was significantly subsided within 14days. Cell infiltration within the hydrogel was also prominent, showing anti-inflammatory or wound healing (M2) macrophage at 14days after implantation. These results showed that the addition of TOCNF could significantly improve the biocompatibility of CS hydrogel as a biomaterial for biomedical application. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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.

A simple route to synthesize conductive stimuli-responsive polypyrrole nanocomposite hydrogel particles with strong magnetic properties and their performance for removal of hexavalent chromium ions from aqueous solution

NASA Astrophysics Data System (ADS)

Ahmad, Hasan; Rahman, Mohammad Mostafizar; Ali, Mohammad Azgar; Minami, Hideto; Tauer, Klaus; Gafur, Mohammad Abdul; Rahman, Mohammad Mahbubor

2016-08-01

A combination of maghemite polypyrrole (PPy/γ-Fe2O3) and stimuli-responsive properties in the same hydrogel microspheres is expected to enhance their application potential in various fields such as tissue engineering, regenerative medicine, biosensors, biomedical applications and removal of heavy metals from waste water, catalysis etc. In this investigation a simple two step process is used to prepare conductive stimuli-responsive polypyrrole (PPy) composite hydrogel particles with strong magnetic properties. Poly(styrene-methacrylic acid-N-isopropylacrylamide-polyethelene glycol methacrylate) or P(S-NIPAM-MAA-PEGMA) hydrogel seed particles are first prepared by soap-free precipitation copolymerization. The copolymer hydrogel particles exhibited both temperature- and pH-responsive volume phase transition. Conductive P(S-NIPAM-MAA-PEGMA)/PPy/γ-Fe2O3 nanocomposite hydrogel particles are then prepared by seeded chemical oxidative polymerization of pyrrole in the presence of P(S-NIPAM-MAA-PEGMA) hydrogel seed particles using FeCl3 as a oxidant and p-toluene sulfonic acid (p-TSA) as a dopant. In the reaction system FeCl3 functioned as a source of Fe(III) for the formation of γ-Fe2O3. This reaction also requires the initial presence of Fe(II) provided by the addition of FeCl2. The size and size distribution, surface structure, and morphology of the prepared conductive composite hydrogel particles are confirmed by FTIR, electron micrographs, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and UV-visible spectroscopy. The performance of nanocomposite hydrogel particles has been evaluated for the removal of hexavalent chromium (Cr) ions from water.

Cellular Response to Reagent-Free Electron-Irradiated Gelatin Hydrogels.

PubMed

Wisotzki, Emilia I; Friedrich, Ralf P; Weidt, Astrid; Alexiou, Christoph; Mayr, Stefan G; Zink, Mareike

2016-06-01

As a biomaterial, it is well established that gelatin exhibits low cytotoxicity and can promote cellular growth. However, to circumvent the potential toxicity of chemical crosslinkers, reagent-free crosslinking methods such as electron irradiation are highly desirable. While high energy irradiation has been shown to exhibit precise control over the degree of crosslinking, these hydrogels have not been thoroughly investigated for biocompatibility and degradability. Here, NIH 3T3 murine fibroblasts are seeded onto irradiated gelatin hydrogels to examine the hydrogel's influence on cellular viability and morphology. The average projected area of cells seeded onto the hydrogels increases with irradiation dose, which correlates with an increase in the hydrogel's shear modulus up to 10 kPa. Cells on these hydrogels are highly viable and exhibits normal cell cycles, particularly when compared to those grown on glutaraldehyde crosslinked gelatin hydrogels. However, proliferation is reduced on both types of crosslinked samples. To mimic the response of the hydrogels in physiological conditions, degradability is monitored in simulated body fluid to reveal strongly dose-dependent degradation times. Overall, given the low cytotoxicity, influence on cellular morphology and variability in degradation times of the electron irradiated gelatin hydrogels, there is significant potential for application in areas ranging from regenerative medicine to mechanobiology. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inherent interfacial mechanical gradients in 3D hydrogels influence tumor cell behaviors.

PubMed

Rao, Shreyas S; Bentil, Sarah; DeJesus, Jessica; Larison, John; Hissong, Alex; Dupaix, Rebecca; Sarkar, Atom; Winter, Jessica O

2012-01-01

Cells sense and respond to the rigidity of their microenvironment by altering their morphology and migration behavior. To examine this response, hydrogels with a range of moduli or mechanical gradients have been developed. Here, we show that edge effects inherent in hydrogels supported on rigid substrates also influence cell behavior. A Matrigel hydrogel was supported on a rigid glass substrate, an interface which computational techniques revealed to yield relative stiffening close to the rigid substrate support. To explore the influence of these gradients in 3D, hydrogels of varying Matrigel content were synthesized and the morphology, spreading, actin organization, and migration of glioblastoma multiforme (GBM) tumor cells were examined at the lowest (<50 µm) and highest (>500 µm) gel positions. GBMs adopted bipolar morphologies, displayed actin stress fiber formation, and evidenced fast, mesenchymal migration close to the substrate, whereas away from the interface, they adopted more rounded or ellipsoid morphologies, displayed poor actin architecture, and evidenced slow migration with some amoeboid characteristics. Mechanical gradients produced via edge effects could be observed with other hydrogels and substrates and permit observation of responses to multiple mechanical environments in a single hydrogel. Thus, hydrogel-support edge effects could be used to explore mechanosensitivity in a single 3D hydrogel system and should be considered in 3D hydrogel cell culture systems.

Temperature responsive hydrogel magnetic nanocomposites for hyperthermia and metal extraction applications

NASA Astrophysics Data System (ADS)

Reddy, N. Narayana; Ravindra, S.; Reddy, N. Madhava; Rajinikanth, V.; Raju, K. Mohana; Vallabhapurapu, Vijaya Srinivasu

2015-11-01

The present work deals with the development of temperature and magnetic responsive hydrogel networks based on poly (N-isopropylacrylamide)/acrylamido propane sulfonic acid. The hydrogel matrices are synthesized by polymerizing N-isopropylacrylamide (NIPAM) monomer in the presence of acrylamido propane sulphonicacid (AMPS) using a cross-linker (N,N-methylenebisacrylamide, MBA) and redox initiating system [ammonium persulphate (APS)/tetramethylethylenediamine (TMEDA)]. The magnetic nanoparticles are generated throughout the hydrogel networks using in situ method by incorporating iron ions and subsequent treatment with ammonia. A series of hydrogel-magnetic nanocomposites (HGMNC) are developed by varying AMPS composition. The synthesized hydrogel magnetic nanocomposites (HGMNC) are characterized by using Fourier Transform Infrared (FTIR) Spectroscopy, X-ray diffraction (XRD), Thermal Analyses and Electron Microscopy analysis (Scanning and Transmission Electron Microscope). The metal extraction capacities of the prepared hydrogel (HG) and hydrogel magnetic nanocomposites (HGMNC) were studied at different temperatures. The results suggest that HGMNCs have higher extraction capacity compared to HG and HG loaded iron ions. This data also reveals that the extraction of metals by hydrogel magnetic nanocomposites (HGMNCs) is higher at higher temperatures than room temperature. The prepared HGMNCs are also subjected to hyperthermia (cancer therapy) studies.

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.

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

Stable environmentally sensitive cationic hydrogels for controlled delivery applications.

PubMed

Deo, Namita; Ruetsch, S; Ramaprasad, K R; Kamath, Y

2010-01-01

New thermosensitive, cationic hydrogels were synthesized by the dispersion copolymerization of N-isopropylacrylamide (NIPAM) and (3-acrylamidopropyl)trimethylammonium chloride (AAPTAC). In the polymerization protocol, an amide-based comonomer, (3-acrylamidopropyl)trimethylammonium chloride, was reacted as a new alternative monomer for introducing positive charges into the thermosensitive hydrogel. The hydrogels were synthesized without making any pH adjustment in the aqueous medium. These hydrogel particles exhibited colloidal stability in the pH range of 1.5 to 11.0, while similar cationic hydrogels were reported to be unstable at pHs higher than 6. The stronger cationic character of the selected comonomer provided higher colloidal stability to the poly(NIPAM-co-AAPTAC) hydrogels. Furthermore, these hydrogels displayed sensitivity towards temperature, pH, and salt concentration. Interestingly, the particle size of hydrogels was found to be decreased significantly with an increase in temperature and salt concentration. In addition, using pyrene fluorescence spectroscopy, it was established that the hydrophobicity/hydrophilicity of the hydrogel particles was largely controlled by both pH and temperature. The thermosensitive hydrogels reported in this paper may be suitable for delivering different actives for cosmetic and medical applications. Although direct application of these hydrogel particles in cosmetics has not been shown at this stage, the methodology of making them and controlling their absorption and release properties as a function of temperature and pH has been demonstrated. Furthermore, these hydrogels may also have applications in scavenging organic and inorganic toxics.

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.

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.

pH-responsive and enzymatically-responsive hydrogel microparticles for the oral delivery of therapeutic proteins: Effects of protein size, crosslinking density, and hydrogel degradation on protein delivery.

PubMed

Koetting, Michael Clinton; Guido, Joseph Frank; Gupta, Malvika; Zhang, Annie; Peppas, Nicholas A

2016-01-10

Two potential platform technologies for the oral delivery of protein therapeutics were synthesized and tested. pH-responsive poly(itaconic acid-co-N-vinyl-2-pyrrolidone) (P(IA-co-NVP)) hydrogel microparticles were tested in vitro with model proteins salmon calcitonin, urokinase, and rituximab to determine the effects of particle size, protein size, and crosslinking density on oral delivery capability. Particle size showed no significant effect on overall delivery potential but did improve percent release of encapsulated protein over the micro-scale particle size range studied. Protein size was shown to have a significant impact on the delivery capability of the P(IA-co-NVP) hydrogel. We show that when using P(IA-co-NVP) hydrogel microparticles with 3 mol% tetra(ethylene glycol) dimethacrylate crosslinker, a small polypeptide (salmon calcitonin) loads and releases up to 45 μg/mg hydrogel while the mid-sized protein urokinase and large monoclonal antibody rituximab load and release only 19 and 24 μg/mg hydrogel, respectively. We further demonstrate that crosslinking density offers a simple method for tuning hydrogel properties to variously sized proteins. Using 5 mol% TEGDMA crosslinker offers optimal performance for the small peptide, salmon calcitonin, whereas lower crosslinking density of 1 mol% offers optimal performance for the much larger protein rituximab. Finally, an enzymatically-degradable hydrogels of P(MAA-co-NVP) crosslinked with the peptide sequence MMRRRKK were synthesized and tested in simulated gastric and intestinal conditions. These hydrogels offer ideal loading and release behavior, showing no degradative release of encapsulated salmon calcitonin in gastric conditions while yielding rapid and complete release of encapsulated protein within 1h in intestinal conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

Thermo-responsive hydrogels for intravitreal injection and biomolecule release

NASA Astrophysics Data System (ADS)

Drapala, Pawel

In this dissertation, we develop an injectable polymer system to enable localized and prolonged release of therapeutic biomolecules for improved treatment of Age-Related Macular Degeneration (AMD). Thermo-responsive hydrogels derived from N-isopropylacrylamide (NIPAAm) and cross-linked with poly(ethylene glycol) (PEG) poly(L-Lactic acid) (PLLA) copolymer were synthesized via free-radical polymerization. These materials were investigated for (a) phase change behavior, (b) in-vitro degradation, (c) capacity for controlled drug delivery, and (d) biocompatibility. The volume-phase transition temperature (VPTT) of the PNIPAAm- co-PEG-b-PLLA hydrogels was adjusted using hydrophilic and hydrophobic moieties so that it is ca. 33°C. These hydrogels did not initially show evidence of degradation at 37°C due to physical cross-links of collapsed PNIPAAm. Only after addition of glutathione chain transfer agents (CTA)s to the precursor did the collapsed hydrogels become fully soluble at 37°C. CTAs significantly affected the release kinetics of biomolecules; addition of 1.0 mg/mL glutathione to 3 mM cross-linker accelerated hydrogel degradation, resulting in 100% release in less than 2 days. This work also explored the effect of PEGylation in order to tether biomolecules to the polymer matrix. It was demonstrated that non-site-specific PEGylation can postpone the burst release of solutes (up to 10 days in hydrogels with 0.5 mg/mL glutathione). Cell viability assays showed that at least two 20-minute buffer extraction steps were needed to remove cytotoxic elements from the hydrogels. Clinically-used therapeutic biomolecules LucentisRTM and AvastinRTM were demonstrated to be both stable and bioactive after release form PNIPAAm-co-PEG-b-PLLA hydrogels. The thermo-responsive hydrogels presented here offer a promising platform for the localized delivery of proteins such as recombinant antibodies.

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…

Injectable Polyethylene Glycol Hydrogel for Islet Encapsulation: an in vitro and in vivo Characterization

PubMed Central

Knobeloch, Tracy; Abadi, Sakineh Esmaeili Mohsen; Bruns, Joseph; Zustiak, Silviya Petrova; Kwon, Guim

2017-01-01

An injection of hydrogel-encapsulated islets that controls blood glucose levels over long term would provide a much needed alternative treatment for type 1 diabetes mellitus (T1DM). To this end, we tested the feasibility of using an injectable polyethylene glycol (PEG) hydrogel as a scaffold for islet encapsulation. Encapsulated islets cultured in vitro for 6 days showed excellent cell viability and released insulin with higher basal and stimulated insulin secretion than control islets. Host responses to PEG hydrogels were studied by injecting PEG hydrogels (no treatment and vehicle controls used) into the peritoneal cavities of B6D2F1 mice and monitoring alterations in body weight, food and water intake, and blood glucose levels. After 2 weeks, peritoneal cavity cells were harvested, followed by hydrogel retrieval, and extraction of spleens. Body weights, food and water intake, and blood glucose levels were unaltered in mice injected with hydrogels compared to no treatment and vehicle-injected control mice. Frozen sections of a hydrogel showed the presence of tissues and small number of immune cells surrounding the hydrogel but no cell infiltration into the hydrogel bulk. Spleen sizes were not significantly different under the experimental conditions. Peritoneal cavity cells were slightly higher in mice injected with hydrogels compared to control mice but no statistical difference between vehicle- and hydrogel-injected mice was noted. As an in vivo feasibility study, streptozotocin-induced diabetic mice were injected with vehicle or hydrogels containing 50 islets each into two sites, the peritoneal cavity and a subcutaneous site on the back. Transient control of blood glucose levels were observed in mice injected with hydrogels containing islets. In summary, we developed an injectable PEG hydrogel that supported islet function and survival in vitro and in vivo and elicited only a mild host response. Our work illustrates the feasibility of using injectable PEG hydrogels for islet encapsulation. PMID:29527325

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

Installing logic-gate responses to a variety of biological substances in supramolecular hydrogel-enzyme hybrids.

PubMed

Ikeda, Masato; Tanida, Tatsuya; Yoshii, Tatsuyuki; Kurotani, Kazuya; Onogi, Shoji; Urayama, Kenji; Hamachi, Itaru

2014-06-01

Soft materials that exhibit stimuli-responsive behaviour under aqueous conditions (such as supramolecular hydrogels composed of self-assembled nanofibres) have many potential biological applications. However, designing a macroscopic response to structurally complex biochemical stimuli in these materials still remains a challenge. Here we show that redox-responsive peptide-based hydrogels have the ability to encapsulate enzymes and still retain their activities. Moreover, cooperative coupling of enzymatic reactions with the gel response enables us to construct unique stimuli-responsive soft materials capable of sensing a variety of disease-related biomarkers. The programmable gel-sol response (even to biological samples) is visible to the naked eye. Furthermore, we built Boolean logic gates (OR and AND) into the hydrogel-enzyme hybrid materials, which were able to sense simultaneously plural specific biochemicals and execute a controlled drug release in accordance with the logic operation. The intelligent soft materials that we have developed may prove valuable in future medical diagnostics or treatments.

Installing logic-gate responses to a variety of biological substances in supramolecular hydrogel-enzyme hybrids

NASA Astrophysics Data System (ADS)

Ikeda, Masato; Tanida, Tatsuya; Yoshii, Tatsuyuki; Kurotani, Kazuya; Onogi, Shoji; Urayama, Kenji; Hamachi, Itaru

2014-06-01

Soft materials that exhibit stimuli-responsive behaviour under aqueous conditions (such as supramolecular hydrogels composed of self-assembled nanofibres) have many potential biological applications. However, designing a macroscopic response to structurally complex biochemical stimuli in these materials still remains a challenge. Here we show that redox-responsive peptide-based hydrogels have the ability to encapsulate enzymes and still retain their activities. Moreover, cooperative coupling of enzymatic reactions with the gel response enables us to construct unique stimuli-responsive soft materials capable of sensing a variety of disease-related biomarkers. The programmable gel-sol response (even to biological samples) is visible to the naked eye. Furthermore, we built Boolean logic gates (OR and AND) into the hydrogel-enzyme hybrid materials, which were able to sense simultaneously plural specific biochemicals and execute a controlled drug release in accordance with the logic operation. The intelligent soft materials that we have developed may prove valuable in future medical diagnostics or treatments.

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.

Synthesis and Characterization of Poly(Ethylene Glycol) Based Thermo-Responsive Hydrogels for Cell Sheet Engineering.

PubMed

Son, Kuk Hui; Lee, Jin Woo

2016-10-20

The swelling properties and thermal transition of hydrogels can be tailored by changing the hydrophilic-hydrophobic balance of polymer networks. Especially, poly( N -isopropylacrylamide) (PNIPAm) has received attention as thermo-responsive hydrogels for tissue engineering because its hydrophobicity and swelling property are transited around body temperature (32 °C). In this study, we investigated the potential of poly(ethylene glycol) diacrylate (PEGDA) as a hydrophilic co-monomer and crosslinker of PNIPAm to enhance biological properties of PNIPAm hydrogels. The swelling ratios, lower critical solution temperature (LCST), and internal pore structure of the synthesized p(NIPAm- co -PEGDA) hydrogels could be varied with changes in the molecular weight of PEGDA and the co-monomer ratios (NIPAm to PEGDA). We found that increasing the molecular weight of PEGDA showed an increase of pore sizes and swelling ratios of the hydrogels. In contrast, increasing the weight ratio of PEGDA under the same molecular weight condition increased the crosslinking density and decreased the swelling ratios of the hydrogels. Further, to evaluate the potential of these hydrogels as cell sheets, we seeded bovine chondrocytes on the p(NIPAm- co -PEGDA) hydrogels and observed the proliferation of the seed cells and their detachment as a cell sheet upon a decrease in temperature. Based on our results, we confirmed that p(NIPAm- co -PEGDA) hydrogels could be utilized as cell sheets with enhanced cell proliferation performance.

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.

Thermo-responsive hydroxybutyl chitosan hydrogel as artery intervention embolic agent for hemorrhage control.

PubMed

Sun, Guohui; Feng, Chao; Jiang, Changqing; Zhang, Tingting; Bao, Zixian; Zuo, Yajun; Kong, Ming; Cheng, Xiaojie; Liu, Ya; Chen, Xiguang

2017-12-01

This work targeted to investigate the potential of thermo-responsive hydroxybutyl chitosan (HBC) hydrogel using as an embolic material for occlusion of selective blood vessels. HBC hydrogel was prepared via an etherification reaction between chitosan (CS) and 1, 2-butene oxide. The hydroxybutyl groups were introduced into CS backbone, which endowed HBC hydrogel with properties of porous structure, favorable hydrophilia and rapid sol-gel interconvertibility. The gelation temperatures and gelation time respectively decreased from 30.7°C to 11.5°C and 79.60±3.19s to 7.70±1.42s at 37°C, with HBC solutions viscoelasticity increased from 3.0% to 7.0%. HBC hydrogel exhibited noncytotoxic to mouse embryo fibroblasts (MEFs) and excellent hemocompatibility with red blood cells (RBCs). After injection HBC solution into rat renal arteries, HBC solution transformed into hydrogel and attached onto blood vessel inner wall tightly, giving immediate blood vessels embolization. Meanwhile, RBCs could aggregate around HBC hydrogel to form moderate coagulation, which was beneficial to avoid hydrogel migration with blood flow. Above results suggested that HBC hydrogel could be applied as a promising embolic agent for hemorrage in the interventional vascular embolization field. Copyright © 2017. Published by Elsevier B.V.

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.

Biodegradation of PVP-CMC hydrogel film: a useful food packaging material.

PubMed

Roy, Niladri; Saha, Nabanita; Kitano, Takeshi; Saha, Petr

2012-06-20

Hydrogels can offer new opportunities for the design of efficient packaging materials with desirable properties (i.e. durability, biodegradability and mechanical strength). It is a promising and emerging concept, as most of the biopolymer based hydrogels are supposed to be biodegradable, they can be considered as alternative eco-friendly packaging materials. This article reports about synthetic (polyvinylpyrrolidone (PVP)) and biopolymer (carboxymethyl cellulose (CMC)) based a novel hydrogel film and its nature of biodegradability under controlled environmental condition. The dry hydrogel films were prepared by solution casting method and designated as 'PVP-CMC hydrogel films'. The hydrogel film containing PVP and CMC in a ratio of 20:80 shows best mechanical properties among all the test samples (i.e. 10:90, 20:80, 50:50, 80:20 and 90:10). Thus, PVP-CMC hydrogel film of 20:80 was considered as a useful food packaging material and further experiments were carried out with this particular hydrogel film. Biodegradation of the PVP-CMC hydrogel films were studied in liquid state (Czapec-Dox liquid medium+soil extracts) until 8 weeks. Variation in mechanical, viscoelastic properties and weight loss of the hydrogel films with time provide the direct evidence of biodegradation of the hydrogels. About 38% weight loss was observed within 8 weeks. FTIR spectra of the hydrogel films (before and after biodegradation) show shifts of the peaks and also change in the peak intensities, which refer to the physico-chemical change in the hydrogel structure and SEM views of the hydrogels show how internal structure of the PVP-CMC film changes in the course of biodegradation. Copyright © 2012 Elsevier Ltd. All rights reserved.

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.

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.

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.

Hydrogels with a Memory: Dual-Responsive, Organometallic Poly(ionic liquid)s with Hysteretic Volume-Phase Transition

PubMed Central

2017-01-01

We report on the synthesis and structure–property relations of a novel, dual-responsive organometallic poly(ionic liquid) (PIL), consisting of a poly(ferrocenylsilane) backbone of alternating redox-active, silane-bridged ferrocene units and tetraalkylphosphonium sulfonate moieties in the side groups. This PIL is redox responsive due to the presence of ferrocene in the backbone and also exhibits a lower critical solution temperature (LCST)-type thermal responsive behavior. The LCST phase transition originates from the interaction between water molecules and the ionic substituents and shows a concentration-dependent, tunable transition temperature in aqueous solution. The PIL’s LCST-type transition temperature can also be influenced by varying the redox state of ferrocene in the polymer main chain. As the polymer can be readily cross-linked and is easily converted into hydrogels, it represents a new dual-responsive materials platform. Interestingly, the as-formed hydrogels display an unusual, strongly hysteretic volume-phase transition indicating useful thermal memory properties. By employing the dispersing abilities of this cationic PIL, CNT-hydrogel composites were successfully prepared. These hybrid conductive composite hydrogels showed bi-stable states and tunable resistance in heating–cooling cycles. PMID:28654756

Responsive hydrogels--structurally and dimensionally optimized smart frameworks for applications in catalysis, micro-system technology and material science.

PubMed

Döring, Artjom; Birnbaum, Wolfgang; Kuckling, Dirk

2013-09-07

Although the technological and scientific importance of functional polymers has been well established over the last few decades, the most recent focus that has attracted much attention has been on stimuli-responsive polymers. This group of materials is of particular interest due to its ability to respond to internal and/or external chemico-physical stimuli, which is often manifested as large macroscopic responses. Aside from scientific challenges of designing stimuli-responsive polymers, the main technological interest lies in their numerous applications ranging from catalysis through microsystem technology and chemomechanical actuators to sensors that have been extensively explored. Since the phase transition phenomenon of hydrogels is theoretically well understood advanced materials based on the predictions can be prepared. Since the volume phase transition of hydrogels is a diffusion-limited process the size of the synthesized hydrogels is an important factor. Consistent downscaling of the gel size will result in fast smart gels with sufficient response times. In order to apply smart gels in microsystems and sensors, new preparation techniques for hydrogels have to be developed. For the up-coming nanotechnology, nano-sized gels as actuating materials would be of great interest.

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.

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.

[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.

Nanoscale functionalization and characterization of surfaces with hydrogel patterns and biomolecules

NASA Astrophysics Data System (ADS)

Dinakar, Hariharasudhan Chirra

The advent of numerous tools, ease of techniques, and concepts related to nanotechnology, in combination with functionalization via simple chemistry has made gold important for various biomedical applications. In this dissertation, the development and characterization of planar gold surfaces with responsive hydrogel patterns for rapid point of care sensing and the functionalization of gold nanoparticles for drug delivery are highlighted. Biomedical micro- and nanoscale devices that are spatially functionalized with intelligent hydrogels are typically fabricated using conventional UV-lithography. Herein, precise 3-D hydrogel patterns made up of temperature responsive crosslinked poly(N-isopropylacrylamide) over gold were synthesized. The XY control of the hydrogel was achieved using microcontact printing, while thickness control was achieved using atom transfer radical polymerization (ATRP). Atomic force microscopy analysis showed that to the ATRP reaction time governed the pattern growth. The temperature dependent swelling ratio was tailored by tuning the mesh size of the hydrogel. While nanopatterns exhibited a broad lower critical solution temperature (LCST) transition, surface roughness showed a sharp LCST transition. Quartz crystal microbalance with dissipation showed rapid response behavior of the thin films, which makes them applicable as functional components in biomedical devices. The easy synthesis, relative biocompatibility, inertness, and easy functionalization of gold nanoparticles (GNPs) have made them useful for various biomedical applications. Although ATRP can be successfully carried out over GNPs, the yield of stable solution based GNPs for biomedical applications prove to be low. As an alternative approach, a novel method of ISOlating, FUnctionalizing, and REleasing nanoparticles (ISOFURE) was proposed. Biodegradable poly(beta-amino ester) hydrogels were used to synthesize ISOFURE-GNP composites. ATRP was performed inside the composite, and the final hydrogel coated GNPs were released via matrix degradation. Response analysis confirmed that the ISOFURE method led to the increased stability and yield of the hydrogel coated ISOFURE-GNPs. The ISOFURE protocol was also utilized in functionalizing GNPs with enzyme catalase in the absence of a stabilizing reagent. Biotin-streptavidin affinity was used as the bioconjugation method. Activity analysis of the conjugated enzyme showed that the ISOFURE-GNPs showed enhanced biomolecular loading relative to solution based stabilizing reagent passivated GNPs. KEYWORDS: Hydrogel, Gold nanoparticle, ISOFURE, Atom transfer radical polymerization, Microcontact printing

PEG-based degradable networks for drug delivery applications

NASA Astrophysics Data System (ADS)

Ostroha, Jamie L.

The controlled delivery of therapeutic agents by biodegradable hydrogels has become a popular mechanism for drug administration in recent years. Hydrogels are three-dimensional networks of polymer chains held together by crosslinks. Although the changes which the hydrogel undergoes in solution are important to a wide range of experimental studies, they have not been investigated systematically and the factors which influence the degree of swelling have not been adequately described. Hydrogels made of poly(ethylene glycol) (PEG) will generally resist degradation in aqueous conditions, while a hydrogel made from a copolymer of poly(lactic acid) (PLA) and PEG will degrade via hydrolysis of the lactic acid group. This ability to degrade makes these hydrogels promising candidates for controlled release drug delivery systems. The goal of this research was to characterize the swelling and degradation of both degradable and non-degradable gels and to evaluate the release of different drugs from these hydrogels, where the key variable is the molecular weight of the PEG segment. These hydrogels were formed by the addition and subsequent chemically crosslinking of methacrylate end groups. During crosslinking, both PEG and LA-PEG-LA hydrogels of varied PEG molecular weight were loaded with Vitamin B12, Insulin, Haloperidol, and Dextran. It was shown that increasing PEG molecular weight produces a hydrogel with larger pores, thus increasing water uptake and degradation rate. While many environmental factors do not affect the swelling behavior, they do significantly impact the degradation of the hydrogel, and thus the release of incorporated therapeutic agents.

The effect of glutathione as chain transfer agent in PNIPAAm-based thermo-responsive hydrogels for controlled release of proteins.

PubMed

Drapala, Pawel W; Jiang, Bin; Chiu, Yu-Chieh; Mieler, William F; Brey, Eric M; Kang-Mieler, Jennifer J; Pérez-Luna, Victor H

2014-03-01

To control degradation and protein release using thermo-responsive hydrogels for localized delivery of anti-angiogenic proteins. Thermo-responsive hydrogels derived from N-isopropylacrylamide (NIPAAm) and crosslinked with poly(ethylene glycol)-co-(L-lactic acid) diacrylate (Acry-PLLA-b-PEG-b-PLLA-Acry) were synthesized via free radical polymerization in the presence of glutathione, a chain transfer agent (CTA) added to modulate their degradation and release properties. Immunoglobulin G (IgG) and the recombinant proteins Avastin® and Lucentis® were encapsulated in these hydrogels and their release was studied. The encapsulation efficiency of IgG was high (75-87%) and decreased with CTA concentration. The transition temperature of these hydrogels was below physiological temperature, which is important for minimally invasive therapies involving these materials. The toxicity from unreacted monomers and free radical initiators was eliminated with a minimum of three buffer extractions. Addition of CTA accelerated degradation and resulted in complete protein release. Glutathione caused the degradation products to become solubilized even at 37°C. Hydrogels prepared without glutathione did not disintegrate nor released protein completely after 3 weeks at 37°C. PEGylation of IgG postponed the burst release effect. Avastin® and Lucentis® released from degraded hydrogels retained their biological activity. These systems offer a promising platform for the localized delivery of proteins.

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.

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.

Low-Cost, Rapidly Responsive, Controllable, and Reversible Photochromic Hydrogel for Display and Storage.

PubMed

Yang, Yongqi; Guan, Lin; Gao, Guanghui

2018-04-25

Traditional optoelectronic devices without stretchable performance could be limited for substrates with irregular shape. Therefore, it is urgent to explore a new generation of flexible, stretchable, and low-cost intelligent vehicles as visual display and storage devices, such as hydrogels. In the investigation, a novel photochromic hydrogel was developed by introducing the negatively charged ammonium molybdate as a photochromic unit into polyacrylamide via ionic and covalent cross-linking. The hydrogel exhibited excellent properties of low cost, easy preparation, stretchable deformation, fatigue resistance, high transparency, and second-order response to external signals. Moreover, the photochromic and fading process of hydrogels could be precisely controlled and repeated under the irradiation of UV light and exposure of oxygen at different time and temperature. The photochromic hydrogel could be considered applied for artificial intelligence system, wearable healthcare device, and flexible memory device. Therefore, the strategy for designing a soft photochromic material would open a new direction to manufacture flexible and stretchable devices.

Physicochemical properties and cytotoxicity of hydrogels based on Beetosan® containing sage and bee pollen.

PubMed

Tyliszczak, Bożena; Drabczyk, Anna; Kudłacik-Kramarczyk, Sonia; Grabowska, Beata; Kędzierska, Magdalena

2017-01-01

Currently, increasing attention is being paid to issues related to environmental protection, waste management, as well as to the development of polymers with useful properties. The research presented here involved preparation of hydrogels based on Beetosan® - a chitosan derived from the multi-stage processing of dead bees. Moreover, hydrogels were additionally modified with natural substances - i.e. bee pollen and extract of Salvia officinalis (sage) that are well known for the presence of many compounds with beneficial properties from a medical point of view. Materials have been first obtained by photopolymerization. Then, their surface morphology, wettability and cytotoxicity to selected cell lines have been determined. It can be stated that such combination of Beetosan® hydrogel matrix and the mentioned additives resulted in a preparation of polymers characterized by negative impact on cancer cells. Impact of hydrogels with sage is slightly more intense due to the presence of substances such as ursalic or rosmaric acid that are characterized to have anticancer activity. Such negative impact has not been observed in case of studies using fibroblasts. Furthermore, addition of natural substances into hydrogels resulted in a more homogeneous surface and in the decrease of wettability angle of the tested polymers. It can be concluded that the use of natural-derived reagents and synthesis of polymers using these reagents (as a result of environmentally friendly photopolymerization) yields materials with interesting properties for medical purposes, with particular emphasis on antitumor activity, and without significant negative impact on fibroblasts.

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.

CMOS image sensor-based implantable glucose sensor using glucose-responsive fluorescent hydrogel.

PubMed

Tokuda, Takashi; Takahashi, Masayuki; Uejima, Kazuhiro; Masuda, Keita; Kawamura, Toshikazu; Ohta, Yasumi; Motoyama, Mayumi; Noda, Toshihiko; Sasagawa, Kiyotaka; Okitsu, Teru; Takeuchi, Shoji; Ohta, Jun

2014-11-01

A CMOS image sensor-based implantable glucose sensor based on an optical-sensing scheme is proposed and experimentally verified. A glucose-responsive fluorescent hydrogel is used as the mediator in the measurement scheme. The wired implantable glucose sensor was realized by integrating a CMOS image sensor, hydrogel, UV light emitting diodes, and an optical filter on a flexible polyimide substrate. Feasibility of the glucose sensor was verified by both in vitro and in vivo experiments.

Silk-ionomer and silk-tropoelastin hydrogels as charged three-dimensional culture platforms for the regulation of hMSC response.

PubMed

Calabrese, Rossella; Raia, Nicole; Huang, Wenwen; Ghezzi, Chiara E; Simon, Marc; Staii, Cristian; Weiss, Anthony S; Kaplan, David L

2017-09-01

The response of human bone marrow-derived mesenchymal stem cells (hMSCs) encapsulated in three-dimensional (3D) charged protein hydrogels was studied. Combining silk fibroin (S) with recombinant human tropoelastin (E) or silk ionomers (I) provided protein composite alloys with tunable physicochemical and biological features for regulating the bioactivity of encapsulated hMSCs. The effects of the biomaterial charges on hMSC viability, proliferation and chondrogenic or osteogenic differentiation were assessed. The silk-tropoelastin or silk-ionomers hydrogels supported hMSC viability, proliferation and differentiation. Gene expression of markers for chondrogenesis and osteogenesis, as well as biochemical and histological analysis, showed that hydrogels with different S/E and S/I ratios had different effects on cell fate. The negatively charged hydrogels upregulated hMSC chondrogenesis or osteogenesis, with or without specific differentiation media, and hydrogels with higher tropoelastin content inhibited the differentiation potential even in the presence of the differentiation media. The results provide insight on charge-tunable features of protein-based biomaterials to control hMSC differentiation in 3D hydrogels, as well as providing a new set of hydrogels for the compatible encapsulation and utility for cell functions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Design and evaluation of novel fast forming pilocarpine-loaded ocular hydrogels for sustained pharmacological response

PubMed Central

Anumolu, SivaNaga S.; Singh, Yashveer; Gao, Dayuan; Stein, Stanley; Sinko, Patrick J.

2009-01-01

Fast forming hydrogels prepared by crosslinking a poly(ethylene glycol) (PEG)-based copolymer containing multiple thiol (SH) groups were evaluated for the controlled ocular delivery of pilocarpine and subsequent pupillary constriction. Physical properties of the hydrogels were characterized using UV-Vis spectrophotometry, transmission electron microscopy (TEM), rheometry, and swelling kinetics. Pilocarpine loading efficiency and release properties were measured in simulated tear fluid. The hydrogel formulations exhibited high drug loading efficiency (~74%). Pilocarpine release was found to be biphasic with release half times of ~2 and 94 h, respectively, and 85–100% of the drug was released over 8-days. Pilocarpine-loaded (2% w/v) hydrogels were evaluated in a rabbit model and compared to a similar dose of drug in aqueous solution. The hydrogels were retained in the eye for the entire period of the study with no observed irritation. Pilocarpine-loaded hydrogels sustained pupillary constriction for 24 h after administration as compared to 3 h for the solution, an 8-fold increase in duration of action. A strong correlation between pilocarpine release and pupillary response was observed. In conclusion, the current studies demonstrate that in situ forming PEG hydrogels possess the viscoelastic, retention, and sustained delivery properties required for an efficient ocular drug delivery system. PMID:19341773

Modulation of cultured neural networks using neurotrophin release from hydrogel-coated microelectrode arrays

NASA Astrophysics Data System (ADS)

Jun, Sang Beom; Hynd, Matthew R.; Dowell-Mesfin, Natalie M.; Al-Kofahi, Yousef; Roysam, Badrinath; Shain, William; Kim, Sung June

2008-06-01

Polyacrylamide and poly(ethylene glycol) diacrylate hydrogels were synthesized and characterized for use as drug release and substrates for neuron cell culture. Protein release kinetics was determined by incorporating bovine serum albumin (BSA) into hydrogels during polymerization. To determine if hydrogel incorporation and release affect bioactivity, alkaline phosphatase was incorporated into hydrogels and a released enzyme activity determined using the fluorescence-based ELF-97 assay. Hydrogels were then used to deliver a brain-derived neurotrophic factor (BDNF) from hydrogels polymerized over planar microelectrode arrays (MEAs). Primary hippocampal neurons were cultured on both control and neurotrophin-containing hydrogel-coated MEAs. The effect of released BDNF on neurite length and process arborization was investigated using automated image analysis. An increased spontaneous activity as a response to the released BDNF was recorded from the neurons cultured on the top of hydrogel layers. These results demonstrate that proteins of biological interest can be incorporated into hydrogels to modulate development and function of cultured neural networks. These results also set the stage for development of hydrogel-coated neural prosthetic devices for local delivery of various biologically active molecules.

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.

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.

Water-Responsive Shape Recovery Induced Buckling in Biodegradable Photo-Cross-Linked Poly(ethylene glycol) (PEG) Hydrogel.

PubMed

Salvekar, Abhijit Vijay; Huang, Wei Min; Xiao, Rui; Wong, Yee Shan; Venkatraman, Subbu S; Tay, Kiang Hiong; Shen, Ze Xiang

2017-02-21

The phenomenon of recovering the permanent shape from a severely deformed temporary shape, but only in the presence of the right stimulus, is known as the shape memory effect (SME). Materials with such an interesting effect are known as shape memory materials (SMMs). Typical stimuli to trigger shape recovery include temperature (heating or cooling), chemical (including water/moisture and pH value), and light. As a SMM is able not only to maintain the temporary shape but also to respond to the right stimulus when it is applied, via shape-shifting, a seamless integration of sensing and actuation functions is achieved within one single piece of material. Hydrogels are defined by their ability to absorb a large amount of water (from 10-20% up to thousands of times their dry weight), which results in significant swelling. On the other hand, dry hydrogels indeed belong to polymers, so they exhibit heat- and chemoresponsive SMEs as most polymers do. While heat-responsive SMEs have been spotted in a handful of wet hydrogels, so far, most dry hydrogels evince the heat and water (moisture)-responsive SMEs. Since water is one of the major components in living biological systems, water-responsive SMMs hold great potential for various implantable applications, including wound healing, intravascular devices, soft tissue reconstruction, and controlled drug delivery. This provides motivation to combine water-activated SMEs and swelling in hydrogels together to enhance the performance. In many applications, such as vascular occlusion via minimally invasive surgery for liver cancer treatment, the operation time (for both start and finish) is required to be well controlled. Due to the gradual and slow manner of water absorption for water-activated SMEs and swelling in hydrogels, even a combination of both effects encounters many difficulties to meet the timerequirements in real procedures of vascular occlusion. Recently, we have reported a bioabsorbable radiopaque water-responsive shape memory embolization plug for temporary vascular occlusion. The plug consists of a composite with a poly(dl-lactide-co-glycolide) (PLGA) core (loaded with radiopaque filler) and cross-linked poly(ethylene glycol) (PEG) hydrogel outer layer. The device can be activated by body fluid (or water) after about 2 min of immersion in water. The whole occlusion process is completed within a few dozens of seconds. The underlying mechanism is water-responsive shape recovery induced buckling, which occurs in an expeditious manner within a short time period and does not require complete hydration of the whole hydrogel. In this paper, we experimentally and analytically investigate the water-activated shape recovery induced buckling in this biodegradable PEG hydrogel to understand the fundamentals in precisely controlling the buckling time. The molecular mechanism responsible for the water-induced SME in PEG hydrogel is also elucidated. The original diameter and amount of prestretching are identified as two influential parameters to tailor the buckling time between 1 and 4 min as confirmed by both experiments and simulation. The phenomenon reported here, chemically induced buckling via a combination of the SME and swelling, is generic, and the study reported here should be applicable to other water- and non-water-responsive gels.

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.

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.

Rheological properties of a biological thermo-responsive hydrogel prepared from vegetable oil

USDA-ARS?s Scientific Manuscript database

Hydrogel is a colloidal gel in which water is the dispersion medium. The unique properties of hydrogels make this kind of materials have many utilization potentials, such as drug delivery, gene therapy, wound care products, breast implant materials, cosmetic products, and tissue engineering. Hydroge...

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

Glucose-Responsive Trehalose Hydrogel for Insulin Stabilization and Delivery.

PubMed

Lee, Juneyoung; Ko, Jeong Hoon; Mansfield, Kathryn M; Nauka, Peter C; Bat, Erhan; Maynard, Heather D

2018-05-01

Effective delivery of therapeutic proteins is important for many biomedical applications. Yet, the stabilization of proteins during delivery and long-term storage remains a significant challenge. Herein, a trehalose-based hydrogel is reported that stabilizes insulin to elevated temperatures prior to glucose-triggered release. The hydrogel is synthesized using a polymer with trehalose side chains and a phenylboronic acid end-functionalized 8-arm poly(ethylene glycol) (PEG). The hydroxyls of the trehalose side chains form boronate ester linkages with the PEG boronic acid cross-linker to yield hydrogels without any further modification of the original trehalose polymer. Dissolution of the hydrogel is triggered upon addition of glucose as a stronger binder to boronic acid (K b = 2.57 vs 0.48 m -1 for trehalose), allowing the insulin that is entrapped during gelation to be released in a glucose-responsive manner. Moreover, the trehalose hydrogel stabilizes the insulin as determined by immunobinding after heating up to 90 °C. After 30 min heating, 74% of insulin is detected by enzyme-linked immunosorbent assay in the presence of the trehalose hydrogel, whereas only 2% is detected without any additives. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Nanocomposite Hydrogel with Potent and Broad-Spectrum Antibacterial Activity.

PubMed

Dai, Tianjiao; Wang, Changping; Wang, Yuqing; Xu, Wei; Hu, Jingjing; Cheng, Yiyun

2018-05-02

Local bacterial infection is a challenging task and still remains a serious threat to human health in clinics. Systemic administration of antibiotics has only short-term antibacterial activity and usually causes adverse effects and bacterial resistance. A bioadhesive hydrogel with broad-spectrum and on-demand antibiotic activity is highly desirable. Here, we designed a pH-responsive nanocomposite hydrogel via a Schiff base linkage between oxidized polysaccharides and cationic dendrimers encapsulated with silver nanoparticles. The antibacterial components, both the cationic dendrimers and silver species, could be released in response to the acidity generated by growing bacteria. The released cationic polymer and silver exhibited a synergistic effect in antibacterial activity, and thus, the nanocomposite hydrogel showed potent antibacterial activity against both Gram-negative ( Escherichia coli and Pseudomonas aeruginosa) and Gram-positive bacteria ( Staphylococcus epidermidis and Staphylococcus aureus). The gel showed superior in vivo antibacterial efficacy against S. aureus infection compared with a commercial silver hydrogel at the same silver concentration. In addition, no obvious hemolytic toxicity, cytotoxicity, and tissue and biochemical toxicity were observed for the antibacterial hydrogel after incubation with cells or implantation. This study provides a facile and promising strategy to develop smart hydrogels to treat local bacterial infections.

CMOS image sensor-based implantable glucose sensor using glucose-responsive fluorescent hydrogel

PubMed Central

Tokuda, Takashi; Takahashi, Masayuki; Uejima, Kazuhiro; Masuda, Keita; Kawamura, Toshikazu; Ohta, Yasumi; Motoyama, Mayumi; Noda, Toshihiko; Sasagawa, Kiyotaka; Okitsu, Teru; Takeuchi, Shoji; Ohta, Jun

2014-01-01

A CMOS image sensor-based implantable glucose sensor based on an optical-sensing scheme is proposed and experimentally verified. A glucose-responsive fluorescent hydrogel is used as the mediator in the measurement scheme. The wired implantable glucose sensor was realized by integrating a CMOS image sensor, hydrogel, UV light emitting diodes, and an optical filter on a flexible polyimide substrate. Feasibility of the glucose sensor was verified by both in vitro and in vivo experiments. PMID:25426316

A precision structured smart hydrogel for sensing applications

NASA Astrophysics Data System (ADS)

Menges, J.; Kleinschmidt, P.; Bart, H.-J.; Oesterschulze, E.

2017-10-01

We report on a macroinitiator based smart hydrogel film applied on a microcantilever for sensing applications. The studied hydrogel features a comparatively wide dynamic range for changes in the electrolyte's ionic strength. Furthermore, it offers a simple spin coating process for thin film deposition as well as the capability to obtain high aspect ratio microstructures by reactive ion etching. This makes the hydrogel compatible to microelectromechanical system integration. As a proof of concept, we study the response of hydrogel functionalized cantilevers in aqueous sodium chloride solutions of varying ionic strength. In contrast to the majority of hydrogel materials reported in the literature, we found that our hydrogel still responds in high ionic strength environments. This may be of future interest for sensing e.g., in sea water or physiological environments like urine.

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.

Shape morphing and motion of responsive hydrogel composites

NASA Astrophysics Data System (ADS)

Hayward, Ryan

Composites of stimuli-responsive hydrogels paired with stiff structural elements or functional inorganic materials offer myriad opportunities to control the shape, properties, and motion of materials. In one example, our group has studied the geometry and mechanics of swelling-induced buckling of polymer trilayer films consisting of patterning rigid layers sandwiching a swellable hydrogel layer. Of particular recent interest has been the formation of helical structures from seedpod-type architectures with perpendicular orientation of stripes on opposite faces. We have studied the concatenation of two or more helical segments, yielding simple geometric design rules for the fabrication of 3D constructs. In a second example, we have considered the light-driven reshaping and motion of hydrogels containing plasmonic nanoparticles as photothermal heating elements. In contrast to systems pre-programmed to take on a single, or perhaps a few, different 3D shapes, this approach enables continuous shape reconfiguration, and correspondingly, directed motion of composite hydrogel sheets.

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.

Humanized mouse model for assessing the human immune response to xenogeneic and allogeneic decellularized biomaterials.

PubMed

Wang, Raymond M; Johnson, Todd D; He, Jingjin; Rong, Zhili; Wong, Michelle; Nigam, Vishal; Behfar, Atta; Xu, Yang; Christman, Karen L

2017-06-01

Current assessment of biomaterial biocompatibility is typically implemented in wild type rodent models. Unfortunately, different characteristics of the immune systems in rodents versus humans limit the capability of these models to mimic the human immune response to naturally derived biomaterials. Here we investigated the utility of humanized mice as an improved model for testing naturally derived biomaterials. Two injectable hydrogels derived from decellularized porcine or human cadaveric myocardium were compared. Three days and one week after subcutaneous injection, the hydrogels were analyzed for early and mid-phase immune responses, respectively. Immune cells in the humanized mouse model, particularly T-helper cells, responded distinctly between the xenogeneic and allogeneic biomaterials. The allogeneic extracellular matrix derived hydrogels elicited significantly reduced total, human specific, and CD4 + T-helper cell infiltration in humanized mice compared to xenogeneic extracellular matrix hydrogels, which was not recapitulated in wild type mice. T-helper cells, in response to the allogeneic hydrogel material, were also less polarized towards a pro-remodeling Th2 phenotype compared to xenogeneic extracellular matrix hydrogels in humanized mice. In both models, both biomaterials induced the infiltration of macrophages polarized towards a M2 phenotype and T-helper cells polarized towards a Th2 phenotype. In conclusion, these studies showed the importance of testing naturally derived biomaterials in immune competent animals and the potential of utilizing this humanized mouse model for further studying human immune cell responses to biomaterials in an in vivo environment. Copyright © 2017 Elsevier Ltd. 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.

Gelam (Melaleuca spp.) Honey-Based Hydrogel as Burn Wound Dressing

PubMed Central

Mohd Zohdi, Rozaini; Abu Bakar Zakaria, Zuki; Yusof, Norimah; Mohamed Mustapha, Noordin; Abdullah, Muhammad Nazrul Hakim

2012-01-01

A novel cross-linked honey hydrogel dressing was developed by incorporating Malaysian honey into hydrogel dressing formulation, cross-linked and sterilized using electron beam irradiation (25 kGy). In this study, the physical properties of the prepared honey hydrogel and its wound healing efficacy on deep partial thickness burn wounds in rats were assessed. Skin samples were taken at 7, 14, 21, and 28 days after burn for histopathological and molecular evaluations. Application of honey hydrogel dressings significantly enhanced (P < 0.05) wound closure and accelerated the rate of re-epithelialization as compared to control hydrogel and OpSite film dressing. A significant decrease in inflammatory response was observed in honey hydrogel treated wounds as early as 7 days after burn (P < 0.05). Semiquantitative analysis using RT-PCR revealed that treatment with honey hydrogel significantly (P < 0.05) suppressed the expression of proinflammatory cytokines (IL-1α, IL-1β, and IL-6). The present study substantiates the potential efficacy of honey hydrogel dressings in accelerating burn wound healing. PMID:21941590

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.

Smart hydrogels from laterally-grafted peptide assembly.

PubMed

Li, Wen; Park, Il-soo; Kang, Seong-Kyun; Lee, Myongsoo

2012-09-11

Small peptides carrying laterally-grafted azobenzene units self-assemble into photo-responsive hydrogels which are applied as a smart matrix for controlling the dye molecules release. We demonstrate that a delicate balance among peptides interactions plays a pivotal role in the photo-responsive gel-sol transition.

Preprogramming Complex Hydrogel Responses using Enzymatic Reaction Networks.

PubMed

Postma, Sjoerd G J; Vialshin, Ilia N; Gerritsen, Casper Y; Bao, Min; Huck, Wilhelm T S

2017-02-06

The creation of adaptive matter is heavily inspired by biological systems. However, it remains challenging to design complex material responses that are governed by reaction networks, which lie at the heart of cellular complexity. The main reason for this slow progress is the lack of a general strategy to integrate reaction networks with materials. Herein we use a systematic approach to preprogram the response of a hydrogel to a trigger, in this case the enzyme trypsin, which activates a reaction network embedded within the hydrogel. A full characterization of all the kinetic rate constants in the system enabled the construction of a computational model, which predicted different hydrogel responses depending on the input concentration of the trigger. The results of the simulation are in good agreement with experimental findings. Our methodology can be used to design new, adaptive materials of which the properties are governed by reaction networks of arbitrary complexity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Hydrogel: Preparation, characterization, and applications: A review

PubMed Central

Ahmed, Enas M.

2013-01-01

Hydrogel products constitute a group of polymeric materials, the hydrophilic structure of which renders them capable of holding large amounts of water in their three-dimensional networks. Extensive employment of these products in a number of industrial and environmental areas of application is considered to be of prime importance. As expected, natural hydrogels were gradually replaced by synthetic types due to their higher water absorption capacity, long service life, and wide varieties of raw chemical resources. Literature on this subject was found to be expanding, especially in the scientific areas of research. However, a number of publications and technical reports dealing with hydrogel products from the engineering points of view were examined to overview technological aspects covering this growing multidisciplinary field of research. The primary objective of this article is to review the literature concerning classification of hydrogels on different bases, physical and chemical characteristics of these products, and technical feasibility of their utilization. It also involved technologies adopted for hydrogel production together with process design implications, block diagrams, and optimized conditions of the preparation process. An innovated category of recent generations of hydrogel materials was also presented in some details. PMID:25750745

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.

3D patterned stem cell differentiation using thermo-responsive methylcellulose hydrogel molds.

PubMed

Lee, Wonjae; Park, Jon

2016-07-06

Tissue-specific patterned stem cell differentiation serves as the basis for the development, remodeling, and regeneration of the multicellular structure of the native tissues. We herein proposed a cytocompatible 3D casting process to recapitulate this patterned stem cell differentiation for reconstructing multicellular tissues in vitro. We first reconstituted the 2D culture conditions for stem cell fate control within 3D hydrogel by incorporating the sets of the diffusible signal molecules delivered through drug-releasing microparticles. Then, utilizing thermo-responsivity of methylcellulose (MC), we developed a cytocompatible casting process to mold these hydrogels into specific 3D configurations, generating the targeted spatial gradients of diffusible signal molecules. The liquid phase of the MC solution was viscous enough to adopt the shapes of 3D impression patterns, while the gelated MC served as a reliable mold for patterning the hydrogel prepolymers. When these patterned hydrogels were integrated together, the stem cells in each hydrogel distinctly differentiated toward individually defined fates, resulting in the formation of the multicellular tissue structure bearing the very structural integrity and characteristics as seen in vascularized bones and osteochondral tissues.

3D patterned stem cell differentiation using thermo-responsive methylcellulose hydrogel molds

NASA Astrophysics Data System (ADS)

Lee, Wonjae; Park, Jon

2016-07-01

Tissue-specific patterned stem cell differentiation serves as the basis for the development, remodeling, and regeneration of the multicellular structure of the native tissues. We herein proposed a cytocompatible 3D casting process to recapitulate this patterned stem cell differentiation for reconstructing multicellular tissues in vitro. We first reconstituted the 2D culture conditions for stem cell fate control within 3D hydrogel by incorporating the sets of the diffusible signal molecules delivered through drug-releasing microparticles. Then, utilizing thermo-responsivity of methylcellulose (MC), we developed a cytocompatible casting process to mold these hydrogels into specific 3D configurations, generating the targeted spatial gradients of diffusible signal molecules. The liquid phase of the MC solution was viscous enough to adopt the shapes of 3D impression patterns, while the gelated MC served as a reliable mold for patterning the hydrogel prepolymers. When these patterned hydrogels were integrated together, the stem cells in each hydrogel distinctly differentiated toward individually defined fates, resulting in the formation of the multicellular tissue structure bearing the very structural integrity and characteristics as seen in vascularized bones and osteochondral tissues.

Thermo-responsive and compression properties of TEMPO-oxidized cellulose nanofiber-modified PNIPAm hydrogels.

PubMed

Wei, Jinguang; Chen, Yufei; Liu, Hongzhi; Du, Chungui; Yu, Huilong; Zhou, Zhongxi

2016-08-20

In this study, TEMPO-oxidized bamboo cellulose nanofibers (TO-CNF) with anionic carboxylate groups on the surfaces were in-situ incorporated into poly(N-isopropylacrylamide) (PNIPAm) matrix to improve its thermo-responsive and mechanical properties during the polymerization. The microstructure, swelling behaviors, and compressive strength of resultant PNIPAm composite hydrogels with varying contents of TO-CNFs (0-10wt%) were then examined, respectively. Modified hydrogels exhibited the similar light transparency to pure PNIPAm one due to the formation of semi-IPN structure between PNIPAm and TO-CNF. FT-IR spectra demonstrated that the presence of TO-CNF did not alter the position of characteristic peaks associated with PNIPAm. SEM observation suggested that the pore size of PNIPAm hydrogels was markedly increased after the incorporation of TO-CNF. Also, the composite hydrogels showed superior swelling behavior and much improved compression properties with respect to pure PNIPAm one. Thus, TO-CNF appeared to be a "green" nanofiller that can simultaneously improve swelling and mechanical properties of PNIPAm hydrogel. Copyright © 2016 Elsevier Ltd. All rights reserved.

3D patterned stem cell differentiation using thermo-responsive methylcellulose hydrogel molds

PubMed Central

Lee, Wonjae; Park, Jon

2016-01-01

Tissue-specific patterned stem cell differentiation serves as the basis for the development, remodeling, and regeneration of the multicellular structure of the native tissues. We herein proposed a cytocompatible 3D casting process to recapitulate this patterned stem cell differentiation for reconstructing multicellular tissues in vitro. We first reconstituted the 2D culture conditions for stem cell fate control within 3D hydrogel by incorporating the sets of the diffusible signal molecules delivered through drug-releasing microparticles. Then, utilizing thermo-responsivity of methylcellulose (MC), we developed a cytocompatible casting process to mold these hydrogels into specific 3D configurations, generating the targeted spatial gradients of diffusible signal molecules. The liquid phase of the MC solution was viscous enough to adopt the shapes of 3D impression patterns, while the gelated MC served as a reliable mold for patterning the hydrogel prepolymers. When these patterned hydrogels were integrated together, the stem cells in each hydrogel distinctly differentiated toward individually defined fates, resulting in the formation of the multicellular tissue structure bearing the very structural integrity and characteristics as seen in vascularized bones and osteochondral tissues. PMID:27381562

Silver nanoparticles-containing dual-function hydrogels based on a guar gum-sodium borohydride system

PubMed Central

Dai, Lei; Nadeau, Ben; An, Xingye; Cheng, Dong; Long, Zhu; Ni, Yonghao

2016-01-01

Dual-function hydrogels, possessing both stimuli-responsive and self-healing properties, have recently attracted attention of both chemists and materials scientists. Here we report a new paradigm using natural polymer (guar gum, GG) and sodium borohydride (NaBH4), for the preparation of silver nanoparticles (AgNPs)-containing smart hydrogels in a simple, fast and economical way. NaBH4 performs as a reducing agent for AgNPs synthesis using silver nitrate (AgNO3) as the precursor. Meanwhile, sodium metaborate (NaBO2) (from NaBH4) behaves as a cross-linking agent between GG molecular chains. The AgNPs/GG hydrogels with excellent viscoelastic properties can be obtained within 3 min at room temperature without the addition of other cross-linkers. The resultant AgNPs/GG hydrogels are flowable and injectable, and they possess excellent pH/thermal responsive properties. Additionally, they exhibit rapid self-healing capacity. This work introduces a facile and scale-up way to prepare a class of hydrogels that can have great potential to biomedical and other industrial applications. PMID:27819289

Collective Cell Behavior in Mechanosensing of Substrate Thickness.

PubMed

Tusan, Camelia G; Man, Yu-Hin; Zarkoob, Hoda; Johnston, David A; Andriotis, Orestis G; Thurner, Philipp J; Yang, Shoufeng; Sander, Edward A; Gentleman, Eileen; Sengers, Bram G; Evans, Nicholas D

2018-06-05

Extracellular matrix stiffness has a profound effect on the behavior of many cell types. Adherent cells apply contractile forces to the material on which they adhere and sense the resistance of the material to deformation-its stiffness. This is dependent on both the elastic modulus and the thickness of the material, with the corollary that single cells are able to sense underlying stiff materials through soft hydrogel materials at low (<10 μm) thicknesses. Here, we hypothesized that cohesive colonies of cells exert more force and create more hydrogel deformation than single cells, therefore enabling them to mechanosense more deeply into underlying materials than single cells. To test this, we modulated the thickness of soft (1 kPa) elastic extracellular-matrix-functionalized polyacrylamide hydrogels adhered to glass substrates and allowed colonies of MG63 cells to form on their surfaces. Cell morphology and deformations of fluorescent fiducial-marker-labeled hydrogels were quantified by time-lapse fluorescence microscopy imaging. Single-cell spreading increased with respect to decreasing hydrogel thickness, with data fitting to an exponential model with half-maximal response at a thickness of 3.2 μm. By quantifying cell area within colonies of defined area, we similarly found that colony-cell spreading increased with decreasing hydrogel thickness but with a greater half-maximal response at 54 μm. Depth-sensing was dependent on Rho-associated protein kinase-mediated cellular contractility. Surface hydrogel deformations were significantly greater on thick hydrogels compared to thin hydrogels. In addition, deformations extended greater distances from the periphery of colonies on thick hydrogels compared to thin hydrogels. Our data suggest that by acting collectively, cells mechanosense rigid materials beneath elastic hydrogels at greater depths than individual cells. This raises the possibility that the collective action of cells in colonies or sheets may allow cells to sense structures of differing material properties at comparatively large distances. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

An adaptive supramolecular hydrogel comprising self-sorting double nanofibre networks

NASA Astrophysics Data System (ADS)

Shigemitsu, Hajime; Fujisaku, Takahiro; Tanaka, Wataru; Kubota, Ryou; Minami, Saori; Urayama, Kenji; Hamachi, Itaru

2018-02-01

Novel soft materials should comprise multiple supramolecular nanostructures whose responses (for example, assembly and disassembly) to external stimuli can be controlled independently. Such multicomponent systems are present in living cells and control the formation and break-up of a variety of supramolecular assemblies made of proteins, lipids, DNA and RNA in response to external stimuli; however, artificial counterparts are challenging to make. Here, we present a hybrid hydrogel consisting of a self-sorting double network of nanofibres in which each network responds to an applied external stimulus independent of the other. The hydrogel can be made to change its mechanical properties and rates of release of encapsulated proteins by adding Na2S2O4 or bacterial alkaline phosphatase. Notably, the properties of the gel depend on the order in which the external stimuli are applied. Multicomponent hydrogels comprising orthogonal stimulus-responsive supramolecular assemblies would be suitable for designing novel adaptive materials.

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.

Hydrogel-coated feed spacers in two-phase flow cleaning in spiral wound membrane elements: a novel platform for eco-friendly biofouling mitigation.

PubMed

Wibisono, Yusuf; Yandi, Wetra; Golabi, Mohsen; Nugraha, Roni; Cornelissen, Emile R; Kemperman, Antoine J B; Ederth, Thomas; Nijmeijer, Kitty

2015-03-15

Biofouling is still a major challenge in the application of nanofiltration and reverse osmosis membranes. Here we present a platform approach for environmentally friendly biofouling control using a combination of a hydrogel-coated feed spacer and two-phase flow cleaning. Neutral (polyHEMA-co-PEG10MA), cationic (polyDMAEMA) and anionic (polySPMA) hydrogels have been successfully grafted onto polypropylene (PP) feed spacers via plasma-mediated UV-polymerization. These coatings maintained their chemical stability after 7 days incubation in neutral (pH 7), acidic (pH 5) and basic (pH 9) environments. Anti-biofouling properties of these coatings were evaluated by Escherichia coli attachment assay and nanofiltration experiments at a TMP of 600 kPag using tap water with additional nutrients as feed and by using optical coherence tomography. Especially the anionic polySPMA-coated PP feed spacer shows reduced attachment of E. coli and biofouling in the spacer-filled narrow channels resulting in delayed biofilm growth. Employing this highly hydrophilic coating during removal of biofouling by two-phase flow cleaning also showed enhanced cleaning efficiency, feed channel pressure drop and flux recoveries. The strong hydrophilic nature and the presence of negative charge on polySPMA are most probably responsible for the improved antifouling behavior. A combination of polySPMA-coated PP feed spacers and two-phase flow cleaning therefore is promising and an environmentally friendly approach to control biofouling in NF/RO systems employing spiral-wound membrane modules. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preparation of the polyelectrolyte complex hydrogel of biopolymers via a semi-dissolution acidification sol-gel transition method and its application in solid-state supercapacitors

NASA Astrophysics Data System (ADS)

Zhao, Jian; Chen, Yu; Yao, Ying; Tong, Zong-Rui; Li, Pu-Wang; Yang, Zi-Ming; Jin, Shao-Hua

2018-02-01

Hydrogels have drawn many attentions as the solid-state electrolytes in flexible solid-state supercapacitors (SCs) recently. Among them, the polyelectrolyte complex hydrogel (PECH) electrolytes of natural polymers are more competitive because of their environmentally friendly property and low cost. However, while mixing two biopolymer solutions with opposite charges, the strong electrostatic interactions between the cationic and anionic biopolymers may result in precipitates instead of hydrogels. Here we report a novel method, semi-dissolution acidification sol-gel transition (SD-A-SGT), for the preparation of the PECH of chitosan (CTS) and sodium alginate (SA), with the controllable sol-gel transition and uniform composition and successfully apply it as the hydrogel electrolyte of solid-state supercapacitors (SCs). The CTS-SA PECH exhibits an extremely high ionic conductivity of 0.051 S·cm-1 and reasonable mechanical properties with a tensile strength of 0.29 MPa and elongation at break of 109.5%. The solid-state SC fabricated with the CTS-SA PECH and conventional polyaniline (PANI) nanowire electrodes provided a high specific capacitance of 234.6 F·g-1 at 5 mV·s-1 and exhibited excellent cycling stability with 95.3% capacitance retention after 1000 cycles. Our work may pave a novel avenue to the preparation of biodegradable PECHs of full natural polymers, and promote the development of environmentally friendly electronic devices.

Nata de coco (NDC) hydrogel as nanoreactors for preparation iron nanoparticles (FeNps) from ferrocenium reduction

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

Andarini, Mellissa; Lazim, Azwan

This study focuses on hydrogel as nano template to produce iron nanoparticles (FeNps). Radical polymerization was used to synthesize the hydrogel from nata de coco (NDC-g-PAA). Ferrocenium (FcCL) with 1 × 10{sup −4} g/ml has successfully incorporated with NDC-g-PAA hydrogel system and reduce using sodium hydroxide (NaOH) at different concentrations. Transmission electron microscopy (TEM) result demonstrates that the size of FeNps produced was about 5 – 20 nm. Morphological analysis of hydrogel is carried out by scanning electron microscopy (SEM), SEM-EDEX is used to determine percentage of iron (Fe) in hydrogel. The results offer a wide range of application inmore » various areas, especially the use of hydrogel system as a responsive template.« less

3D Printing of Living Responsive Materials and Devices.

PubMed

Liu, Xinyue; Yuk, Hyunwoo; Lin, Shaoting; Parada, German Alberto; Tang, Tzu-Chieh; Tham, Eléonore; de la Fuente-Nunez, Cesar; Lu, Timothy K; Zhao, Xuanhe

2018-01-01

3D printing has been intensively explored to fabricate customized structures of responsive materials including hydrogels, liquid-crystal elastomers, shape-memory polymers, and aqueous droplets. Herein, a new method and material system capable of 3D-printing hydrogel inks with programed bacterial cells as responsive components into large-scale (3 cm), high-resolution (30 μm) living materials, where the cells can communicate and process signals in a programmable manner, are reported. The design of 3D-printed living materials is guided by quantitative models that account for the responses of programed cells in printed microstructures of hydrogels. Novel living devices are further demonstrated, enabled by 3D printing of programed cells, including logic gates, spatiotemporally responsive patterning, and wearable devices. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Protein-based hydrogels for tissue engineering

PubMed Central

Schloss, Ashley C.; Williams, Danielle M.; Regan, Lynne J.

2017-01-01

The tunable mechanical and structural properties of protein-based hydrogels make them excellent scaffolds for tissue engineering and repair. Moreover, using protein-based components provides the option to insert sequences associated with the promoting both cellular adhesion to the substrate and overall cell growth. Protein-based hydrogel components are appealing for their structural designability, specific biological functionality, and stimuli-responsiveness. Here we present highlights in the field of protein-based hydrogels for tissue engineering applications including design requirements, components, and gel types. PMID:27677513

Near-Infrared Light-Sensitive Polyvinyl Alcohol Hydrogel Photoresist for Spatiotemporal Control of Cell-Instructive 3D Microenvironments.

PubMed

Qin, Xiao-Hua; Wang, Xiaopu; Rottmar, Markus; Nelson, Bradley J; Maniura-Weber, Katharina

2018-03-01

Advanced hydrogel systems that allow precise control of cells and their 3D microenvironments are needed in tissue engineering, disease modeling, and drug screening. Multiphoton lithography (MPL) allows true 3D microfabrication of complex objects, but its biological application requires a cell-compatible hydrogel resist that is sufficiently photosensitive, cell-degradable, and permissive to support 3D cell growth. Here, an extremely photosensitive cell-responsive hydrogel composed of peptide-crosslinked polyvinyl alcohol (PVA) is designed to expand the biological applications of MPL. PVA hydrogels are formed rapidly by ultraviolet light within 1 min in the presence of cells, providing fully synthetic matrices that are instructive for cell-matrix remodeling, multicellular morphogenesis, and protease-mediated cell invasion. By focusing a multiphoton laser into a cell-laden PVA hydrogel, cell-instructive extracellular cues are site-specifically attached to the PVA matrix. Cell invasion is thus precisely guided in 3D with micrometer-scale spatial resolution. This robust hydrogel enables, for the first time, ultrafast MPL of cell-responsive synthetic matrices at writing speeds up to 50 mm s -1 . This approach should enable facile photochemical construction and manipulation of 3D cellular microenvironments with unprecedented flexibility and precision. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Autonomic composite hydrogels by reactive printing: materials and oscillatory response.

PubMed

Kramb, R C; Buskohl, P R; Slone, C; Smith, M L; Vaia, R A

2014-03-07

Autonomic materials are those that automatically respond to a change in environmental conditions, such as temperature or chemical composition. While such materials hold incredible potential for a wide range of uses, their implementation is limited by the small number of fully-developed material systems. To broaden the number of available systems, we have developed a post-functionalization technique where a reactive Ru catalyst ink is printed onto a non-responsive polymer substrate. Using a succinimide-amine coupling reaction, patterns are printed onto co-polymer or biomacromolecular films containing primary amine functionality, such as polyacrylamide (PAAm) or poly-N-isopropyl acrylamide (PNIPAAm) copolymerized with poly-N-(3-Aminopropyl)methacrylamide (PAPMAAm). When the films are placed in the Belousov-Zhabotinsky (BZ) solution medium, the reaction takes place only inside the printed nodes. In comparison to alternative BZ systems, where Ru-containing monomers are copolymerized with base monomers, reactive printing provides facile tuning of a range of hydrogel compositions, as well as enabling the formation of mechanically robust composite monoliths. The autonomic response of the printed nodes is similar for all matrices in the BZ solution concentrations examined, where the period of oscillation decreases in response to increasing sodium bromate or nitric acid concentration. A temperature increase reduces the period of oscillations and temperature gradients are shown to function as pace-makers, dictating the direction of the autonomic response (chemical waves).

Hydrolytically Degradable Poly(Ethylene Glycol) Hydrogel Scaffolds as a Cell Delivery Vehicle: Characterization of PC12 Cell Response

PubMed Central

Zustiak, Silviya P.; Pubill, Stephanie; Ribeiro, Andreia; Leach, Jennie B.

2013-01-01

The central nervous system (CNS) has a low intrinsic potential for regeneration following injury and disease, yet neural stem/progenitor cell (NPC) transplants show promise to provide a dynamic therapeutic in this complex tissue environment. Moreover, biomaterial scaffolds may improve the success of NPC-based therapeutics by promoting cell viability and guiding cell response. We hypothesized that a hydrogel scaffold could provide a temporary neurogenic environment that supports cell survival during encapsulation, and degrades completely in a temporally controlled manner to allow progression of dynamic cellular processes such as neurite extension. We utilized PC12 cells as a model cell line with an inducible neuronal phenotype to define key properties of hydrolytically-degradable poly(ethylene glycol) hydrogel scaffolds that impact cell viability and differentiation following release from the degraded hydrogel. Adhesive peptide ligands (RGDS, IKVAV or YIGSR), were required to maintain cell viability during encapsulation; as compared to YIGSR, the RGDS and IKVAV ligands were associated with a higher percentage of PC12 cells that differentiated to the neuronal phenotype following release from the hydrogel. Moreover, among the hydrogel properties examined (e.g., ligand type, concentration), total polymer density within the hydrogel had the most prominent effect on cell viability, with densities above 15% w/v leading to decreased cell viability likely due to a higher shear modulus. Thus, by identifying key properties of degradable hydrogels that affect cell viability and differentiation following release from the hydrogel, we lay the foundation for application of this system towards future applications of the scaffold as a neural cell delivery vehicle. PMID:24474590

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.

Time-dependent chemo-electro-mechanical behavior of hydrogel-based structures

NASA Astrophysics Data System (ADS)

Leichsenring, Peter; Wallmersperger, Thomas

2018-03-01

Charged hydrogels are ionic polymer gels and belong to the class of smart materials. These gels are multiphasic materials which consist of a solid phase, a fluid phase and an ionic phase. Due to the presence of bound charges these materials are stimuli-responsive to electrical or chemical loads. The application of electrical or chemical stimuli as well as mechanical loads lead to a viscoelastic response. On the macroscopic scale, the response is governed by a local reversible release or absorption of water which, in turn, leads to a local decrease or increase of mass and a respective volume change. Furthermore, the chemo-electro-mechanical equilibrium of a hydrogel depends on the chemical composition of the gel and the surrounding solution bath. Due to the presence of bound charges in the hydrogel, this system can be understood as an osmotic cell where differences in the concentration of mobile ions in the gel and solution domain lead to an osmotic pressure difference. In the present work, a continuum-based numerical model is presented in order to describe the time-dependent swelling behavior of hydrogels. The numerical model is based on the Theory of Porous Media and captures the fluid-solid, fluid-ion and ion-ion interactions. As a direct consequence of the chemo-electro-mechanical equilibrium, the corresponding boundary conditions are defined following the equilibrium conditions. For the interaction of the hydrogel with surrounding mechanical structures, also respective jump condtions are formulated. Finaly, numerical results of the time-dependent behavior of a hydrogel-based chemo-sensor will be presented.

Fabrications and Applications of Stimulus-Responsive Polymer Films and Patterns on Surfaces: A Review

PubMed Central

Chen, Jem-Kun; Chang, Chi-Jung

2014-01-01

In the past two decades, we have witnessed significant progress in developing high performance stimuli-responsive polymeric materials. This review focuses on recent developments in the preparation and application of patterned stimuli-responsive polymers, including thermoresponsive layers, pH/ionic-responsive hydrogels, photo-responsive film, magnetically-responsive composites, electroactive composites, and solvent-responsive composites. Many important new applications for stimuli-responsive polymers lie in the field of nano- and micro-fabrication, where stimuli-responsive polymers are being established as important manipulation tools. Some techniques have been developed to selectively position organic molecules and then to obtain well-defined patterned substrates at the micrometer or submicrometer scale. Methods for patterning of stimuli-responsive hydrogels, including photolithography, electron beam lithography, scanning probe writing, and printing techniques (microcontact printing, ink-jet printing) were surveyed. We also surveyed the applications of nanostructured stimuli-responsive hydrogels, such as biotechnology (biological interfaces and purification of biomacromoles), switchable wettability, sensors (optical sensors, biosensors, chemical sensors), and actuators. PMID:28788489

Fabrication of hydrogels with elasticity changed by alkaline phosphatase for stem cell culture.

PubMed

Toda, Hiroyuki; Yamamoto, Masaya; Uyama, Hiroshi; Tabata, Yasuhiko

2016-01-01

The objective of this study is to design hydrogels whose elasticity can be changed by alkaline phosphatase (ALP) in cell culture and evaluate the effect of hydrogel elasticity on an osteogenic gene expression of cells. Hydrogels were prepared by the radical polymerization of acrylamide (AAm), N,N'-methylenebisacrylamide (BIS), and Phosmer™M containing phosphate groups (PE-PAAm hydrogels). The storage modulus of PE-PAAm hydrogels prepared was changed by the preparation conditions. When human mesenchymal stem cells (hMSC) were cultured on the ALP-responsive PE-PAAm hydrogels in the presence or absence of ALP, the morphology of hMSC was observed and one of the osteogenic differentiation markers, Runx2, was evaluated. By ALP addition into the culture medium, the morphology of hMSC was changed into an elongated shape without cell damage. ALP addition modified the level of Runx2 gene expression, which was influenced by the modulus of PE-PAAm hydrogels. It is concluded that the elasticity change of hydrogel substrates in cell culture had an influence on the Runx2 gene expression of hMSC. Stem cells sense the surface elasticity of culture substrates, and their differentiation fate is biologically modified by substrate properties. Most of experiments have been performed in static conditions during cell culture, while the in vivo microenvironment is dynamically changed. In this study, we established to design an enzyme-responsive hydrogel whose elasticity can be changed by alkaline phosphatase (ALP) in cell culture to mimic in vivo conditions. As a result, the cells were deformed and the gene expression level of an osteogenic maker, Runx2, was modified by ALP treatment. This is the novel report describing to demonstrate that the dynamic alteration of hydrogel substrate elasticity could modulate the osteoblastic gene expression of human MSC in vitro. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Metal nanoparticles triggered persistent negative photoconductivity in silk protein hydrogels

NASA Astrophysics Data System (ADS)

Gogurla, Narendar; Sinha, Arun K.; Naskar, Deboki; Kundu, Subhas C.; Ray, Samit K.

2016-03-01

Silk protein is a natural biopolymer with intriguing properties, which are attractive for next generation bio-integrated electronic and photonic devices. Here, we demonstrate the negative photoconductive response of Bombyx mori silk protein fibroin hydrogels, triggered by Au nanoparticles. The room temperature electrical conductivity of Au-silk hydrogels is found to be enhanced with the incorporation of Au nanoparticles over the control sample, due to the increased charge transporting networks within the hydrogel. Au-silk lateral photoconductor devices show a unique negative photoconductive response under an illumination of 325 nm, with excitation energy higher than the characteristic metal plasmon resonance band. The enhanced photoconductance yield in the hydrogels over the silk protein is attributed to the photo-oxidation of amino groups in the β-pleated sheets of the silk around the Au nanoparticles followed by the breaking of charge transport networks. The Au-silk nanocomposite does not show any photoresponse under visible illumination because of the localization of excited charges in Au nanoparticles. The negative photoconductive response of hybrid Au-silk under UV illumination may pave the way towards the utilization of silk for future bio-photonic devices using metal nanoparticle platforms.

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.

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.

Poly(N-isopropylacrylamide) hydrogel-based shape-adjustable polyimide films triggered by near-human-body temperature.

PubMed

Huanqing Cui; Xuemin Du; Juan Wang; Tianhong Tang; Tianzhun Wu

2016-08-01

Hydrogel-based shape-adjustable films were successfully fabricated via grafting poly(N-isopropylacrylamide) (PNIPAM) onto one side of polyimide (PI) films. The prepared PI-g-PNIPAM films exhibited rapid, reversible, and repeatable bending/unbending property by heating to near-human-body temperature (37 °C) or cooling to 25 °C. The excellent property of PI-g-PNIPAM films resulted from a lower critical solution temperature (LCST) of PNIPAM at about 32 °C. Varying the thickness of PNIPAM hydrogel layer regulated the thermo-responsive shape bending degree and response speed of PI-g-PNIPAM films. The thermo-induced shrinkage of hydrogel layers can tune the curvature of PI films, which have potential applications in the field of wearable and implantable devices.

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.

Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by Staphylococcus aureus and supports fracture healing

PubMed Central

Johnson, Christopher T.; Wroe, James A.; Agarwal, Rachit; Martin, Karen E.; Guldberg, Robert E.; Donlan, Rodney M.; Westblade, Lars F.; García, Andrés J.

2018-01-01

Orthopedic implant infections are a significant clinical problem, with current therapies limited to surgical debridement and systemic antibiotic regimens. Lysostaphin is a bacteriolytic enzyme with high antistaphylococcal activity. We engineered a lysostaphin-delivering injectable PEG hydrogel to treat Staphylococcus aureus infections in bone fractures. The injectable hydrogel formulation adheres to exposed tissue and fracture surfaces, ensuring efficient, local delivery of lysostaphin. Lysostaphin encapsulation within this synthetic hydrogel maintained enzyme stability and activity. Lysostaphin-delivering hydrogels exhibited enhanced antibiofilm activity compared with soluble lysostaphin. Lysostaphin-delivering hydrogels eradicated S. aureus infection and outperformed prophylactic antibiotic and soluble lysostaphin therapy in a murine model of femur fracture. Analysis of the local inflammatory response to infections treated with lysostaphin-delivering hydrogels revealed indistinguishable differences in cytokine secretion profiles compared with uninfected fractures, demonstrating clearance of bacteria and associated inflammation. Importantly, infected fractures treated with lysostaphin-delivering hydrogels fully healed by 5 wk with bone formation and mechanical properties equivalent to those of uninfected fractures, whereas fractures treated without the hydrogel carrier were equivalent to untreated infections. Finally, lysostaphin-delivering hydrogels eliminate methicillin-resistant S. aureus infections, supporting this therapy as an alternative to antibiotics. These results indicate that lysostaphin-delivering hydrogels effectively eliminate orthopedic S. aureus infections while simultaneously supporting fracture repair. PMID:29760099

Classification, processing and application of hydrogels: A review.

PubMed

Ullah, Faheem; Othman, Muhammad Bisyrul Hafi; Javed, Fatima; Ahmad, Zulkifli; Md Akil, Hazizan

2015-12-01

This article aims to review the literature concerning the choice of selectivity for hydrogels based on classification, application and processing. Super porous hydrogels (SPHs) and superabsorbent polymers (SAPs) represent an innovative category of recent generation highlighted as an ideal mould system for the study of solution-dependent phenomena. Hydrogels, also termed as smart and/or hungry networks, are currently subject of considerable scientific research due to their potential in hi-tech applications in the biomedical, pharmaceutical, biotechnology, bioseparation, biosensor, agriculture, oil recovery and cosmetics fields. Smart hydrogels display a significant physiochemical change in response to small changes in the surroundings. However, such changes are reversible; therefore, the hydrogels are capable of returning to its initial state after a reaction as soon as the trigger is removed. Copyright © 2015 Elsevier B.V. All rights reserved.

Smart and Fragrant Garment via Surface Modification of Cotton Fabric With Cinnamon Oil/Stimuli Responsive PNIPAAm/Chitosan Nano Hydrogels.

PubMed

Bashari, Azadeh; Hemmatinejad, Nahid; Pourjavadi, Ali

2017-09-01

This paper deals with obtaining aromatherapic textiles via applying stimuli-responsive poly N-isopropyl acryl amide (PNIPAAm) /chitosan (PNCS) nano hydrogels containing cinnamon oil on cotton fabric and looks into the treated fabric characteristics as an antibacterial and temperature/pH responsive fabric. The semi-batch surfactant-free dispersion polymerization method was proposed to the synthesis of PNCS nano particles. The incorporation of modified β -cyclodextrin ( β -CD) into the PNCS nanohydrogel was performed in order to prepare a hydrophobic(cinnamon oil) carrier embedded in stimuli-responsive nanohydrogel. The β -CD postloading process of cinnamon oil in to the hydrogel nano particles was performed via ultrasonic bath and exhaustion methods. The antibacterial activity of the treated fabrics at different temperatures demonstrated the preparing new functional bio-antibacterial fabrics with temperature responsiveness.

Iron-Based Redox Polymerization of Acrylic Acid for Direct Synthesis of Hydrogel/Membranes, and Metal Nanoparticles for Water Treatment

PubMed Central

Hernández, Sebastián; Papp, Joseph K.; Bhattacharyya, Dibakar

2014-01-01

Functionalized polymer materials with ion exchange groups and integration of nano-structured materials is an emerging area for catalytic and water pollution control applications. The polymerization of materials such as acrylic acid often requires persulfate initiator and a high temperature start. However, is generally known that metal ions accelerate such polymerizations starting from room temperature. If the metal is properly selected, it can be used in environmental applications adding two advantages simultaneously. This paper deals with this by polymerizing acrylic acid using iron as accelerant and its subsequent use for nanoparticle synthesis in hydrogel and PVDF membranes. Characterizations of hydrogel, membranes and nanoparticles were carried out with different techniques. Nanoparticles sizes of 30–60 nm were synthesized. Permeability and swelling measurements demonstrate an inverse relationship between hydrogel mesh size (6.30 to 8.34 nm) and membrane pores (222 to 110 nm). Quantitative reduction of trichloroethylene/chloride generation by Fe/Pd nanoparticles in hydrogel/membrane platforms was also performed. PMID:24954975

In Vivo Assessment of Mechanisms Controlling Corneal Hydration.

DTIC Science & Technology

1986-01-01

12 Chapter 3. CORNEAL RESPONSE TO HYPOXIA INDUCED WITH RIGID AND HYDROGEL LENSES WORN DURING EYE CLOSURE 3.1 Summary...thickness vs time (recovery) following lens removal ................................ 28 | ~,.4 3.3 Change in corneal thickness vs hydrogel lens oxygen...transmissibility for closed eye wear ......... 30 3.4 Change in corneal thickness and oxygen under the lens vs rigid and hydrogel lens oxygen

Robust multi-responsive supramolecular hydrogel based on a mono-component host-guest gelator.

PubMed

Cheng, Weinan; Zhao, Dongxu; Qiu, Yuan; Hu, Haisi; Wang, Hong; Wang, Qin; Liao, Yonggui; Peng, Haiyan; Xie, Xiaolin

2018-05-29

Supramolecular hydrogels have been widely investigated, but the construction of stimuli-responsive mono-component host-guest hydrogels remains a challenge in that it is still hard to balance the solubility and gelation ability of the gelator. In this work, three azobenzene-modified β-cyclodextrin derivatives with different alkyl lengths (β-CD-Azo-Cn) have been synthesized. The length of the alkyl chain dramatically influences the solubility and gelation ability of β-CD derivatives in water. Among these derivatives, β-CD-Azo-C8 possesses the lowest minimum gelation concentration (MGC). Based on the host-guest interaction between β-CD and azobenzene units in aqueous solution, which is confirmed by UV-visible and ROESY NMR spectra, the gelators self-assemble and further interwine into networks through the hydrogen bonds on the surface of β-CD cavities. Hydrogels formed by mono-component gelators can collapse under external stimuli such as heating, competition guests and hosts, and UV irradiation. When the concentration of the gelator is more than 8 wt%, the hydrogel exhibits good self-supporting ability with a storage modulus higher than 104 Pa. The gel-sol transition temperature of the hydrogel is near body temperature, indicating its potential applications in biological materials.

Hydrogel scaffolds promote neural gene expression and structural reorganization in human astrocyte cultures.

PubMed

Knight, V Bleu; Serrano, Elba E

2017-01-01

Biomaterial scaffolds have the potential to enhance neuronal development and regeneration. Understanding the genetic responses of astrocytes and neurons to biomaterials could facilitate the development of synthetic environments that enable the specification of neural tissue organization with engineered scaffolds. In this study, we used high throughput transcriptomic and imaging methods to determine the impact of a hydrogel, PuraMatrix™, on human glial cells in vitro . Parallel studies were undertaken with cells grown in a monolayer environment on tissue culture polystyrene. When the Normal Human Astrocyte (NHA) cell line is grown in a hydrogel matrix environment, the glial cells adopt a structural organization that resembles that of neuronal-glial cocultures, where neurons form clusters that are distinct from the surrounding glia. Statistical analysis of next generation RNA sequencing data uncovered a set of genes that are differentially expressed in the monolayer and matrix hydrogel environments. Functional analysis demonstrated that hydrogel-upregulated genes can be grouped into three broad categories: neuronal differentiation and/or neural plasticity, response to neural insult, and sensory perception. Our results demonstrate that hydrogel biomaterials have the potential to transform human glial cell identity, and may have applications in the repair of damaged brain tissue.

Thermoresponsive, in situ crosslinkable hydrogels based on N-isopropylacrylamide: Fabrication, characterization and mesenchymal stem cell encapsulation

PubMed Central

Klouda, Leda; Perkins, Kevin R.; Watson, Brendan M.; Hacker, Michael C.; Bryant, Stephanie J.; Raphael, Robert M.; Kasper, F. Kurtis; Mikos, Antonios G.

2011-01-01

Hydrogels that solidify in response to a dual, physical and chemical, mechanism upon temperature increase were fabricated and characterized. The hydrogels were based on N-isopropylacrylamide, which renders them thermoresponsive, and contained covalently crosslinkable moieties in the macromers. The effects of the macromer end group, namely acrylate or methacrylate, and the fabrication conditions were investigated on the degradative and swelling properties of the hydrogels. The hydrogels exhibited higher swelling below their lower critical solution temperature (LCST). When immersed in cell culture media at physiological temperature, which was above their LCST, hydrogels showed constant swelling and no degradation over eight weeks, with methacrylated hydrogels having higher swelling than their acrylated analogs. In addition, hydrogels immersed in cell culture media under the same conditions showed lower swelling as compared to phosphate buffered saline. The interplay between chemical crosslinking and thermally induced phase separation affected the swelling characteristics of hydrogels in different media. Mesenchymal stem cells encapsulated in the hydrogels in vitro were viable over three weeks and markers of osteogenic differentiation were detected when the cells were cultured with osteogenic supplements. Hydrogel mineralization in the absence of cells was observed in cell culture medium with the addition of fetal bovine serum and β-glycerol phosphate. The results suggest that these hydrogels may be suitable as carriers for cell delivery in tissue engineering. PMID:21187170

Rheological properties of a biological thermo-responsive hydrogel produced from soybean oil polymers

USDA-ARS?s Scientific Manuscript database

The rheological properties of a newly developed biological thermo-hydrogel made from vegetable oil were investigated. The material named HPSO-HG is a hydrolytic product of polymerized soybean oil (PSO). HPSO-HG is a thermo-responsive gel, and it exhibited viscoelastic behavior above 2% (wt.%) at roo...

Self-Healing and Thermo-Responsive Dual-Crosslinked Alginate Hydrogels based on Supramolecular Inclusion Complexes

PubMed Central

Miao, Tianxin; Fenn, Spencer L.; Charron, Patrick N.; Oldinski, Rachael A.

2015-01-01

β-cyclodextrin (β-CD), with a lipophilic inner cavity and hydrophilic outer surface, interacts with a large variety of non-polar guest molecules to form non-covalent inclusion complexes. Conjugation of β-CD onto biomacromolecules can form physically-crosslinked hydrogel networks upon mixing with a guest molecule. Herein describes the development and characterization of self-healing, thermo-responsive hydrogels, based on host-guest inclusion complexes between alginate-graft-β-CD and Pluronic® F108 (poly(ethylene glycol)-b-poly(propylene glycol)-b-poly(ethylene glycol)). The mechanics, flow characteristics, and thermal response were contingent on the polymer concentrations, and the host-guest molar ratio. Transient and reversible physical crosslinking between host and guest polymers governed self-assembly, allowing flow under shear stress, and facilitating complete recovery of the material properties within a few seconds of unloading. The mechanical properties of the dual-crosslinked, multi-stimuli responsive hydrogels were tuned as high as 30 kPa at body temperature, and are advantageous for biomedical applications such as drug delivery and cell transplantation. PMID:26509214

pH- and Temperature-Sensitive Hydrogel Nanoparticles with Dual Photoluminescence for Bioprobes.

PubMed

Zhao, Yue; Shi, Ce; Yang, Xudong; Shen, Bowen; Sun, Yuanqing; Chen, Yang; Xu, Xiaowei; Sun, Hongchen; Yu, Kui; Yang, Bai; Lin, Quan

2016-06-28

This study demonstrates high contrast and sensitivity by designing a dual-emissive hydrogel particle system, whose two emissions respond to pH and temperature strongly and independently. It describes the photoluminescence (PL) response of poly(N-isopropylacrylamide) (PNIPAM)-based core/shell hydrogel nanoparticles with dual emission, which is obtained by emulsion polymerization with potassium persulfate, consisting of the thermo- and pH-responsive copolymers of PNIPAM and poly(acrylic acid) (PAA). A red-emission rare-earth complex and a blue-emission quaternary ammonium tetraphenylethylene derivative (d-TPE) with similar excitation wavelengths are inserted into the core and shell of the hydrogel nanoparticles, respectively. The PL intensities of the nanoparticles exhibit a linear temperature response in the range from 10 to 80 °C with a change as large as a factor of 5. In addition, the blue emission from the shell exhibits a linear pH response between pH 6.5 and 7.6 with a resolution of 0.1 unit, while the red emission from the core is pH-independent. These stimuli-responsive PL nanoparticles have potential applications in biology and chemistry, including bio- and chemosensors, biological imaging, cancer diagnosis, and externally activated release of anticancer drugs.

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.

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.

Injectable nanoengineered stimuli-responsive hydrogels for on-demand and localized therapeutic delivery.

PubMed

Jalili, Nima A; Jaiswal, Manish K; Peak, Charles W; Cross, Lauren M; Gaharwar, Akhilesh K

2017-10-19

"Smart" hydrogels are an emerging class of biomaterials that respond to external stimuli and have been investigated for a range of biomedical applications, including therapeutic delivery and regenerative engineering. Stimuli-responsive nanogels constructed of thermoresponsive polymers such as poly(N-isopropylacrylamide-co-acrylamide) (poly(NIPAM-co-AM)) and magnetic nanoparticles (MNPs) have been developed as "smart carriers" for on-demand delivery of therapeutic biomolecules via magneto-thermal activation. However, due to their small size and systemic introduction, these poly(NIPAM-co-AM)/MNP nanogels result in limited control over long-term, localized therapeutic delivery. Here, we developed an injectable nanoengineered hydrogel loaded with poly(NIPAM-co-AM)/MNPs for localized, on-demand delivery of therapeutics (doxorubicin (DOX)). We have engineered shear-thinning and self-recoverable hydrogels by modulating the crosslinking density of a gelatin methacrylate (GelMA) network. Poly(NIPAM-co-AM)/MNP nanogels loaded with DOX were entrapped within a GelMA pre-polymer solution prior to crosslinking. The temperature and magnetic field dependent release of loaded DOX was observed from the nanoengineered hydrogels (GelMA/(poly(NIPAM-co-AM)/MNPs)). Finally, the in vitro efficacy of DOX released from injectable nanoengineered hydrogels was investigated using preosteoblast and osteosarcoma cells. Overall, these results demonstrated that the injectable nanoengineered hydrogels could be used for on-demand and localized therapeutic delivery for biomedical applications.

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.

Stimuli-Responsive Intelligent Nanomaterials Self-Assembled from Rigid Flexible Molecules

DTIC Science & Technology

2010-11-19

engineering, and controlled drug delivery . The hydrogels are formed through physical cross-links in a random way of flexible nanofibers . Here we...other to form hydrogels that have a variety of applications including tissue engineering, and controlled drug delivery . The hydrogels are formed through...opportunities in many biological applications including tissue regeneration and drug delivery vehicles. Molecular self-assembly into one-dimensional

Engineering three-dimensional cell mechanical microenvironment with hydrogels.

PubMed

Huang, Guoyou; Wang, Lin; Wang, Shuqi; Han, Yulong; Wu, Jinhui; Zhang, Qiancheng; Xu, Feng; Lu, Tian Jian

2012-12-01

Cell mechanical microenvironment (CMM) significantly affects cell behaviors such as spreading, migration, proliferation and differentiation. However, most studies on cell response to mechanical stimulation are based on two-dimensional (2D) planar substrates, which cannot mimic native three-dimensional (3D) CMM. Accumulating evidence has shown that there is a significant difference in cell behavior in 2D and 3D microenvironments. Among the materials used for engineering 3D CMM, hydrogels have gained increasing attention due to their tunable properties (e.g. chemical and mechanical properties). In this paper, we provide an overview of recent advances in engineering hydrogel-based 3D CMM. Effects of mechanical cues (e.g. hydrogel stiffness and externally induced stress/strain in hydrogels) on cell behaviors are described. A variety of approaches to load mechanical stimuli in 3D hydrogel-based constructs are also discussed.

Programmable hydrogels.

PubMed

Wang, Yong

2018-03-05

Programmable hydrogels are defined as hydrogels that are able to change their properties and functions periodically, reversibly and/or sequentially on demand. They are different from those responsive hydrogels whose changes are passive or cannot be stopped or reversed once started and vice versa. The purpose of this review is to summarize major progress in developing programmable hydrogels from the viewpoints of principles, functions and biomedical applications. The principles are first introduced in three categories including biological, chemical and physical stimulation. With the stimulation, programmable hydrogels can undergo functional changes in dimension, mechanical support, cell attachment and molecular sequestration, which are introduced in the middle of this review. The last section is focused on the introduction and discussion of four biomedical applications including mechanistic studies in mechanobiology, tissue engineering, cell separation and protein delivery. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mechano-responsive hydrogels crosslinked by reactive block copolymer micelles

NASA Astrophysics Data System (ADS)

Xiao, Longxi

Hydrogels are crosslinked polymeric networks that can swell in water without dissolution. Owing to their structural similarity to the native extracelluar matrices, hydrogels have been widely used in biomedical applications. Synthetic hydrogels have been designed to respond to various stimuli, but mechanical signals have not incorporated into hydrogel matrices. Because most tissues in the body are subjected to various types of mechanical forces, and cells within these tissues have sophisticated mechano-transduction machinery, this thesis is focused on developing hydrogel materials with built-in mechano-sensing mechanisms for use as tissue engineering scaffolds or drug release devices. Self-assembled block copolymer micelles (BCMs) with reactive handles were employed as the nanoscopic crosslinkers for the construction of covalently crosslinked networks. BCMs were assembled from amphiphilic diblock copolymers of poly(n-butyl acrylate) and poly(acrylic acid) partially modified with acrylate. Radical polymerization of acrylamide in the presence of micellar crosslinkers gave rise to elastomeric hydrogels whose mechanical properties can be tuned by varying the BCM composition and concentration. TEM imaging revealed that the covalently integrated BCMs underwent strain-dependent reversible deformation. A model hydrophobic drug, pyrene, loaded into the core of BCMs prior to the hydrogel formation, was dynamically released in response to externally applied mechanical forces, through force-induced reversible micelle deformation and the penetration of water molecules into the micelle core. The mechano-responsive hydrogel has been studied for tissue repair and regeneration purposes. Glycidyl methacrylate (GMA)-modified hyaluronic acid (HA) was photochemically crosslinked in the presence of dexamethasone (DEX)-loaded crosslinkable BCMs. The resultant HA gels (HAxBCM) contain covalently integrated micellar compartments with DEX being sequestered in the hydrophobic core. Compared to the traditional HA gels prepared by radical crosslinking of HAGMA, HAxBCM gels exhibited improved drug loading and release capacity. Moreover, compressive forces exerted on the gels were transmitted to the crosslinked BCMs, resulting in a force-modulated DEX release on demand. Micelle mobility in the crosslinked networks was analyzed by fluorescence correlation spectroscopy using nile red loaded BCMs. The anti-inflammatory activities of DEX-releasing HAxBCM gels were evaluated via the in vitro culture of lipopolysaccharide-activated macrophages.

LSPR and Interferometric Sensor Modalities Combined Using a Double-Clad Optical Fiber.

PubMed

Muri, Harald Ian; Bano, Andon; Hjelme, Dag Roar

2018-01-11

We report on characterization of an optical fiber-based multi-parameter sensor concept combining localized surface plasmon resonance (LSPR) signal and interferometric sensing using a double-clad optical fiber. The sensor consists of a micro-Fabry-Perot in the form of a hemispherical stimuli-responsive hydrogel with immobilized gold nanorods on the facet of a cleaved double-clad optical fiber. The swelling degree of the hydrogel is measured interferometrically using the single-mode inner core, while the LSPR signal is measured using the multi-mode inner cladding. The quality of the interferometric signal is comparable to previous work on hydrogel micro-Fabry-Perot sensors despite having gold nanorods immobilized in the hydrogel. We characterize the effect of hydrogel swelling and variation of bulk solution refractive index on the LSPR peak wavelength. The results show that pH-induced hydrogel swelling causes only weak redshifts of the longitudinal LSPR mode, while increased bulk refractive index using glycerol and sucrose causes large blueshifts. The redshifts are likely due to reduced plasmon coupling of the side-by-side configuration as the interparticle distance increases with increasing swelling. The blueshifts with increasing bulk refractive index are likely due to alteration of the surface electronic structure of the gold nanorods donated by the anionic polymer network and glycerol or sucrose solutions. The recombination of biotin-streptavidin on gold nanorods in hydrogel showed a 7.6 nm redshift of the longitudinal LSPR. The LSPR response of biotin-streptavidin recombination is due to the change in local refractive index (RI), which is possible to discriminate from the LSPR response due to changes in bulk RI. In spite of the large LSPR shifts due to bulk refractive index, we show, using biotin-functionalized gold nanorods binding to streptavidin, that LSPR signal from gold nanorods embedded in the anionic hydrogel can be used for label-free biosensing. These results demonstrate the utility of immobilizing gold nanorods in a hydrogel on a double-clad optical fiber-end facet to obtain multi-parameter sensing.

Bio-functionalized silk hydrogel microfluidic systems.

PubMed

Zhao, Siwei; Chen, Ying; Partlow, Benjamin P; Golding, Anne S; Tseng, Peter; Coburn, Jeannine; Applegate, Matthew B; Moreau, Jodie E; Omenetto, Fiorenzo G; Kaplan, David L

2016-07-01

Bio-functionalized microfluidic systems were developed based on a silk protein hydrogel elastomeric materials. A facile multilayer fabrication method using gelatin sacrificial molding and layer-by-layer assembly was implemented to construct interconnected, three dimensional (3D) microchannel networks in silk hydrogels at 100 μm minimum feature resolution. Mechanically activated valves were implemented to demonstrate pneumatic control of microflow. The silk hydrogel microfluidics exhibit controllable mechanical properties, long-term stability in various environmental conditions, tunable in vitro and in vivo degradability in addition to optical transparency, providing unique features for cell/tissue-related applications than conventional polydimethylsiloxane (PDMS) and existing hydrogel-based microfluidic options. As demonstrated in the work here, the all aqueous-based fabrication process at ambient conditions enabled the incorporation of active biological substances in the bulk phase of these new silk microfluidic systems during device fabrication, including enzymes and living cells, which are able to interact with the fluid flow in the microchannels. These silk hydrogel-based microfluidic systems offer new opportunities in engineering active diagnostic devices, tissues and organs that could be integrated in vivo, and for on-chip cell sensing systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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.

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.

Degradation prediction model and stem cell growth of gelatin-PEG composite hydrogel.

PubMed

Zhou, Nan; Liu, Chang; Lv, Shijie; Sun, Dongsheng; Qiao, Qinglong; Zhang, Rui; Liu, Yang; Xiao, Jing; Sun, Guangwei

2016-12-01

Gelatin hydrogel has great potential in regenerative medicine. The degradation of gelatin hydrogel is important to control the release profile of encapsulated biomolecules and regulate in vivo tissue repair process. As a plasticizer, PEG can significantly improve the mechanical property of gelatin hydrogel. However, how preparation parameters affect the degradation rate of gelatin-PEG composite hydrogel is still not clear. In this study, the significant effect factor, glutaraldehyde (GA) concentration, was confirmed by means of Plackett-Burman method. Then a mathematical model was built to predict the degradation rate of composite hydrogels under different preparation conditions using the response surface method (RSM), which was helpful to prepare the certain composite hydrogel with desired degradation rate. In addition, it was found that gelatin-PEG composite hydrogel surface well supported the adhesion and growth of human mesenchymal stem cells (MSCs). Moreover, PEG concentration not only could adjust hydrogel degradation more subtly, but also might increase the cross-linking degree and affect the cell migration. Therefore, these results would be useful to optimize the preparation of gelatin-PEG composite hydrogel for drug delivery or tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3149-3156, 2016. © 2016 Wiley Periodicals, Inc.

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.

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.

Neurofilaments Function as Shock Absorbers: Compression Response Arising from Disordered Proteins.

PubMed

Kornreich, Micha; Malka-Gibor, Eti; Zuker, Ben; Laser-Azogui, Adi; Beck, Roy

2016-09-30

What can cells gain by using disordered, rather than folded, proteins in the architecture of their skeleton? Disordered proteins take multiple coexisting conformations, and often contain segments which act as random-walk-shaped polymers. Using x-ray scattering we measure the compression response of disordered protein hydrogels, which are the main stress-responsive component of neuron cells. We find that at high compression their mechanics are dominated by gaslike steric and ionic repulsions. At low compression, specific attractive interactions dominate. This is demonstrated by the considerable hydrogel expansion induced by the truncation of critical short protein segments. Accordingly, the floppy disordered proteins form a weakly cross-bridged hydrogel, and act as shock absorbers that sustain large deformations without failure.

Neurofilaments Function as Shock Absorbers: Compression Response Arising from Disordered Proteins

NASA Astrophysics Data System (ADS)

Kornreich, Micha; Malka-Gibor, Eti; Zuker, Ben; Laser-Azogui, Adi; Beck, Roy

2016-09-01

What can cells gain by using disordered, rather than folded, proteins in the architecture of their skeleton? Disordered proteins take multiple coexisting conformations, and often contain segments which act as random-walk-shaped polymers. Using x-ray scattering we measure the compression response of disordered protein hydrogels, which are the main stress-responsive component of neuron cells. We find that at high compression their mechanics are dominated by gaslike steric and ionic repulsions. At low compression, specific attractive interactions dominate. This is demonstrated by the considerable hydrogel expansion induced by the truncation of critical short protein segments. Accordingly, the floppy disordered proteins form a weakly cross-bridged hydrogel, and act as shock absorbers that sustain large deformations without failure.

Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by Staphylococcus aureus and supports fracture healing.

PubMed

Johnson, Christopher T; Wroe, James A; Agarwal, Rachit; Martin, Karen E; Guldberg, Robert E; Donlan, Rodney M; Westblade, Lars F; García, Andrés J

2018-05-29

Orthopedic implant infections are a significant clinical problem, with current therapies limited to surgical debridement and systemic antibiotic regimens. Lysostaphin is a bacteriolytic enzyme with high antistaphylococcal activity. We engineered a lysostaphin-delivering injectable PEG hydrogel to treat Staphylococcus aureus infections in bone fractures. The injectable hydrogel formulation adheres to exposed tissue and fracture surfaces, ensuring efficient, local delivery of lysostaphin. Lysostaphin encapsulation within this synthetic hydrogel maintained enzyme stability and activity. Lysostaphin-delivering hydrogels exhibited enhanced antibiofilm activity compared with soluble lysostaphin. Lysostaphin-delivering hydrogels eradicated S. aureus infection and outperformed prophylactic antibiotic and soluble lysostaphin therapy in a murine model of femur fracture. Analysis of the local inflammatory response to infections treated with lysostaphin-delivering hydrogels revealed indistinguishable differences in cytokine secretion profiles compared with uninfected fractures, demonstrating clearance of bacteria and associated inflammation. Importantly, infected fractures treated with lysostaphin-delivering hydrogels fully healed by 5 wk with bone formation and mechanical properties equivalent to those of uninfected fractures, whereas fractures treated without the hydrogel carrier were equivalent to untreated infections. Finally, lysostaphin-delivering hydrogels eliminate methicillin-resistant S. aureus infections, supporting this therapy as an alternative to antibiotics. These results indicate that lysostaphin-delivering hydrogels effectively eliminate orthopedic S. aureus infections while simultaneously supporting fracture repair. Copyright © 2018 the Author(s). Published by PNAS.

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.

Development of gellan gum containing formulations for transdermal drug delivery: Component evaluation and controlled drug release using temperature responsive nanogels.

PubMed

Carmona-Moran, Carlos A; Zavgorodnya, Oleksandra; Penman, Andrew D; Kharlampieva, Eugenia; Bridges, S Louis; Hergenrother, Robert W; Singh, Jasvinder A; Wick, Timothy M

2016-07-25

Enhancing skin permeation is important for development of new transdermal drug delivery formulations. This is particularly relevant for non-steroidal anti-inflammatory drugs (NSAIDs). To address this, semisolid gel and solid hydrogel film formulations containing gellan gum as a gelling agent were developed and the effects of penetration enhancers (dimethyl sulfoxide, isopropyl alcohol and propylene glycol) on transport of the NSAID diclofenac sodium was quantified. A transwell diffusion system was used to accelerate formulation development. After 4h, diclofenac flux from a superior formulation of the semisolid gel or the solid hydrogel film was 130±11μg/cm(2)h and 108±7μg/cm(2)h, respectively, and significantly greater than that measured for a currently available diclofenac sodium topical gel (30±4μg/cm(2)h, p<0.05) or solution formulation (44±6μg/cm(2)h, p<0.05) under identical conditions. Over 24h diclofenac transport from the solid hydrogel film was greater than that measured for any new or commercial diclofenac formulation. Entrapment of temperature-responsive nanogels within the solid hydrogel film provides temperature-activated prolonged release of diclofenac. Diclofenac transport was minimal at 22°C, when diclofenac is entrapped within temperature-responsive nanogels incorporated into the solid hydrogel film, but increased 6-fold when the temperature was increased to skin surface temperature of 32°C. These results demonstrate the feasibility of the semisolid gel and solid hydrogel film formulations that can include thermo-responsive nanogels for development of transdermal drug formulations with adjustable drug transport kinetics. Copyright © 2016 Elsevier B.V. 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.

In situ gelable interpenetrating double network hydrogel formulated from binary components: thiolated chitosan and oxidized dextran.

PubMed

Zhang, Hanwei; Qadeer, Aisha; Chen, Weiliam

2011-05-09

In situ gelable interpenetrating double-network hydrogels composed of thiolated chitosan (Chitosan-NAC) and oxidized dextran (Odex), completely devoid of potentially cytotoxic small molecule cross-linkers and that do not require complex maneuvers or catalysis, have been formulated. The interpenetrating network structure is created by Schiff base formations and disulfide bond inter-cross-linkings through exploiting the disparity of their reaction times. Compared with the autogelable thiolated chitosan hydrogels that typically require a relatively long time span for gelation to occur, the Odex/Chitosan-NAC composition solidifies rapidly and forms a well-developed 3D network in a short time span. Compared with typical hydrogels derived from natural materials, the Odex/Chitosan-NAC hydrogels are mechanically strong and resist degradation. The cytotoxicity potential of the hydrogels was determined by an in vitro viability assay using fibroblast as a model cell, and the results reveal that the hydrogels are noncytotoxic. In parallel, in vivo results from subdermal implantation in mice models demonstrate that this hydrogel is not only highly resistant to degradation but also induces very mild tissue response.

In situ Gelable Interpenetrating Double Network Hydrogel Formulated from Binary Components: Thiolated Chitosan and Oxidized Dextran

PubMed Central

Zhang, Hanwei; Qadeer, Aisha; Chen, Weiliam

2011-01-01

In situ gelable interpenetrating double network hydrogels composed of thiolated chitosan (Chitosan-NAC) and oxidized dextran (Odex), completely devoid of potentially cytotoxic small molecule crosslinkers and do not require complex maneuvers or catalysis, have been formulated. The interpenetrating network structure is created by Schiff base formations and disulfide bond inter-crosslinkings through exploiting the disparity of their reaction times. Compare to the auto-gelable thiolated chitosan hydrogels that typically require a relatively long time span for gelation to occur, the Odex/Chitosan-NAC composition solidifies rapidly and forms a well-developed three-dimensional network in a short time span. Compare to typical hydrogels derived from natural materials, the Odex/Chitosan-NAC hydrogels are mechanically strong and resist degradation. The cytotoxicity potential of the hydrogels was determined by an in vitro viability assay using fibroblast as a model cell and the results reveal that the hydrogels are non-cytotoxic. In parallel, in vivo results from subdermal implantation in mice models demonstrate that this hydrogel is not only highly resistant to degradation but also induces very mild tissue response. PMID:21410248

Hydrogel Based Biosensors for In Vitro Diagnostics of Biochemicals, Proteins, and Genes.

PubMed

Jung, Il Young; Kim, Ji Su; Choi, Bo Ram; Lee, Kyuri; Lee, Hyukjin

2017-06-01

Hydrogel-based biosensors have drawn considerable attention due to their various advantages over conventional detection systems. Recent studies have shown that hydrogel biosensors can be excellent alternative systems to detect a wide range of biomolecules, including small biochemicals, pathogenic proteins, and disease specific genes. Due to the excellent physical properties of hydrogels such as the high water content and stimuli-responsive behavior of cross-linked network structures, this system can offer substantial improvement for the design of novel detection systems for various diagnostic applications. The other main advantage of hydrogels is the role of biomimetic three-dimensional (3D) matrix immobilizing enzymes and aptamers within the detection systems, which enhances their stability. This provides ideal reaction conditions for enzymes and aptamers to interact with substrates within the aqueous environment of the hydrogel. In this review, we have highlighted various novel detection approaches utilizing the outstanding properties of the hydrogel. This review summarizes the recent progress of hydrogel-based biosensors and discusses their future perspectives and clinical limitations to overcome. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

A novel honeycomb cell assay kit designed for evaluating horizontal cell migration in response to functionalized self-assembling peptide hydrogels

NASA Astrophysics Data System (ADS)

Guan, Fengyi; Lu, Jiaju; Wang, Xiumei

2017-03-01

A clear understanding on cell migration behaviors contributes to designing novel biomaterials in tissue engineering and elucidating related tissue regeneration processes. Many traditional evaluation methods on cell migration including scratch assay and transwell migration assay possess all kinds of limitations. In this study, a novel honeycomb cell assay kit was designed and made of photosensitive resin by 3D printing. This kit has seven hexagonal culture chambers so that it can evaluate the horizontal cell migration behavior in response to six surrounding environments simultaneously, eliminating the effect of gravity on cells. Here this cell assay kit was successfully applied to evaluate endothelial cell migration cultured on self-assembling peptide (SAP) RADA (AcN-RADARADARADARADA-CONH2) nanofiber hydrogel toward different functionalized SAP hydrogels. Our results indicated that the functionalized RADA hydrogels with different concentration of bioactive motifs of KLT or PRG could induce cell migration in a dose-dependent manner. The total number and migration distance of endothelial cells on functionalized SAP hydrogels significantly increased with increasing concentration of bioactive motif PRG or KLT. Therefore, the honeycomb cell assay kit provides a simple, efficient and convenient tool to investigate cell migration behavior in response to multi-environments simultaneously.

Synthesis and characterization of pH-responsive nanoscale hydrogels for oral delivery of hydrophobic therapeutics.

PubMed

Puranik, Amey S; Pao, Ludovic P; White, Vanessa M; Peppas, Nicholas A

2016-11-01

pH-responsive, polyanionic nanoscale hydrogels were developed for the oral delivery of hydrophobic therapeutics, such as common chemotherapeutic agents. Nanoscale hydrogels were designed to overcome physicochemical and biological barriers associated with oral delivery of hydrophobic therapeutics such as low solubility and poor permeability due to P-glycoprotein related drug efflux. Synthesis of these nanoscale materials was achieved by a robust photoemulsion polymerization method. By varying hydrophobic monomer components, four formulations were synthesized and screened for optimal physicochemical properties and in vitro biocompatibility. All of the responsive nanoscale hydrogels were capable of undergoing a pH-dependent transition in size. Depending on the selection of the hydrophobic monomer, the sizes of the nanoparticles vary widely from 120nm to about 500nm at pH 7.4. Polymer composition was verified using Fourier transform infrared spectroscopy and 1 H-nuclear magnetic resonance spectroscopy. Polymer biocompatibility was assessed in vitro with an intestinal epithelial cell model. All formulations were found to have no appreciable cytotoxicity, defined as greater than 80% viability after polymer incubation. We demonstrate that these nanoscale hydrogels possess desirable physicochemical properties and exhibit agreeable in vitro biocompatibility for oral delivery applications. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Glow discharge electrolysis plasma initiated preparation of temperature/pH dual sensitivity reed hemicellulose-based hydrogels.

PubMed

Zhang, Wenming; Zhu, Sha; Bai, Yunping; Xi, Ning; Wang, Shaoyang; Bian, Yang; Li, Xiaowei; Zhang, Yucang

2015-05-20

The temperature/pH dual sensitivity reed hemicellulose-based hydrogels have been prepared through glow discharge electrolysis plasma (GDEP). The effect of different discharge voltages on the temperature and pH response performance of reed hemicellulose-based hydrogels was inspected, and the formation mechanism, deswelling behaviors of reed hemicellulose-based hydrogels were also discussed. At the same time, infrared spectroscopy (FT-IR), scanning differential thermal analysis (DSC) and scanning electron microscope (SEM) were adopted to characterize the structure, phase transformation behaviors and microstructure of hydrogels. It turned out to be that all reed hemicellulose-based hydrogels had a double sensitivity to temperature and pH, and their phase transition temperatures were all approximately 33 °C, as well as the deswelling dynamics met the first model. In addition, the hydrogel (TPRH-3), under discharge voltage 600 V, was more sensitive to temperature and pH and had higher deswelling ratio. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of in vitro and in vivo biocompatibility of a myo-inositol hexakisphosphate gelated polyaniline hydrogel in a rat model

NASA Astrophysics Data System (ADS)

Sun, Kwang-Hsiao; Liu, Zhao; Liu, Changjian; Yu, Tong; Shang, Tao; Huang, Chen; Zhou, Min; Liu, Cheng; Ran, Feng; Li, Yun; Shi, Yi; Pan, Lijia

2016-04-01

Recent advances in understanding the interaction between electricity and cells/biomolecules have generated great interest in developing biocompatible electrically conductive materials. In this study, we investigated the biocompatibility of a myo-inositol hexakisphosphate gelated polyaniline hydrogel using in vitro and in vivo experiments in a rat model. The polyaniline hydrogel was used to coat a polycaprolactone scaffold and was cultured with rat endothelial progenitor cells differentiated from rat adipose-derived stem cells. Compared with the control sample on a pristine polycaprolactone scaffold, the treated polyaniline hydrogel had the same non-poisonous/cytotoxicity grade, enhanced cell adhesion, and a higher cell proliferation/growth rate. In implant studies, the polyaniline hydrogel sample induced milder inflammatory responses than did the control at the same time points. Combining the advantages of a biocompatible hydrogel and an organic conductor, the inositol phosphate-gelated polyaniline hydrogel could be used in bioelectronics applications such as biosensors, neural probes, cell stimulators, medical electrodes, tissue engineering, and electro-controlled drug delivery.

Development of biocompatible glycodynameric hydrogels joining two natural motifs by dynamic constitutional chemistry.

PubMed

Marin, Luminita; Ailincai, Daniela; Morariu, Simona; Tartau-Mititelu, Liliana

2017-08-15

The paper focusses on the synthesis of novel hydrogels by joining natural biodegradable compounds with the aim to achieve biocompatible materials for bio related applications. The hydrogels were prepared from chitosan and citral by constitutional dynamic chemistry, incorporating both molecular and supramolecular dynamic features. The hydrophobic flexible citral has been reversible immobilized onto the hydrophilic chitosan backbone via imine bonds to form amphiphilic glycodynamers, which further self-ordered through supramolecular interactions into a 3D-network of biodynameric hydrogel. The synthetic pathway has been demonstrated by NMR and FTIR spectroscopy, X-ray diffraction and polarized light microscopy. Studies of the hydrogel morphology revealed a 3D porous microstructure, whose pores size correlated with the crosslinking degree. Rheological investigations evidenced high elasticity, thermo-responsiveness and thixotropic behavior. As a proof of the concept, the hydrogels proved in vivo biocompatibility on laboratory mice. The paper successfully implements the constitutional dynamic chemistry in generation of chitosan high performance hydrogels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ocular response to environmental variations in contact lens wearers.

PubMed

López-de la Rosa, Alberto; Martín-Montañez, Vicente; López-Miguel, Alberto; Fernández, Itziar; Calonge, Margarita; González-Méijome, José M; González-García, María J

2017-01-01

To assess the influence of different indoor environments simulated in an environmental chamber on soft contact lens (CL) wearers. Fifty-four CL wearers were grouped based on their symptoms while wearing their CLs. Subjects were fitted with two different CL types, conventional hydrogel (Omafilcon A) and silicone hydrogel (comfilcon A), and exposed to two controlled indoor environmental conditions, standard [50% relative humidity (RH), 23°C, 930 mb of atmospheric pressure] and adverse (in-flight air cabin environment: 5% RH, localised air flow, 23°C, 750 mb atmospheric pressure), for 90 min in an environmental chamber, making a total of four visits. Symptoms, tear osmolarity, pre-lens tear breakup time (PLBUT), phenol red thread test, visual acuity, bulbar and limbal hyperaemia, corneal and limbal staining, and CL dehydration were assessed using repeated measures analysis of variance. A linear mixed model was used to analyse the effect of environment, CL type, discomfort-based grouping, and time on blink rate. Environment was found to significantly (p ≤ 0.018) affect limbal and bulbar hyperaemia, PLBUT, tear osmolarity, and CL dehydration. Likewise, CL type significantly (p ≤ 0.04) affected nasal and total corneal staining, limbal conjunctival staining, CL dehydration, comfort, and blurred vision. The environment, CL type, and time had significant effects (p ≤ 0.0001) on the blink rate. Ocular surface integrity and blink rate in CL wearers depend on the environment CL users are exposed to, as well as on the soft CL type that they are wearing. Tight control of environmental conditions can contribute to a better understanding of CL-related discomfort. © 2016 The Authors Ophthalmic & Physiological Optics © 2016 The College of Optometrists.

Aptamer-incorporated hydrogels for visual detection, controlled drug release, and targeted cancer therapy

PubMed Central

Liu, Jun; Kang, Huaizhi; Donovan, Michael; Zhu, Zhi

2017-01-01

Hydrogels are water-retainable materials, made from cross-linked polymers, that can be tailored to applications in bioanalysis and biomedicine. As technology advances, an increasing number of molecules have been used as the components of hydrogel systems. However, the shortcomings of these systems have prompted researchers to find new materials that can be incorporated into them. Among all of these emerging materials, aptamers have recently attracted substantial attention because of their unique properties, for example biocompatibility, selective binding, and molecular recognition, all of which make them promising candidates for target-responsive hydrogel engineering. In this work, we will review how aptamers have been incorporated into hydrogel systems to enable colorimetric detection, controlled drug release, and targeted cancer therapy. PMID:22052153

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.

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.

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.

Investigation of Magnetic Properties and Mechanical Responses on Hydrogel-TMAH-Magnetite

NASA Astrophysics Data System (ADS)

Sunaryono; Hidayat, M. F.; Insjaf, C.; Taufiq, A.; Mufti, N.; Munasir

2018-05-01

Hydrogel-TMAH-Magnetite (ferrogel) was fabricated by using polyvinyl alcohol (PVA) hydrogel and magnetite fluids with tetramethylammonium hydroxide (TMAH) surfactant. Iron sand as the raw material was used to synthesize magnetite nanoparticles by co-precipitation method. Magnetite nanoparticles and ferrogel were characterized using X-Ray Fluorescence (XRF) to determine the content of elements in it. To know the functional group network of magnetite nanoparticles, magnetite enclosed with TMAH and ferrogel; we investigated using Fourier Transform Infra-Red (FTIR). Meanwhile, the magnetic properties of the hydrogel-TMAH-magnetite were measured by using Vibrating Sample Magnetometer (VSM). Furthermore, the composition analysis of the ferrogels using FTIR showed that all the synthesis materials were inside the ferrogels. The saturation magnetization of the hydrogel-TMAH-magnetite with a composition of TMAH 1.2 mL (3.95 emu·g-1) was higher than that of TMAH 0.8 mL (0.85 emu·g-1). It exhibited that the composition of TMAH 1.2 mL was an optimum composition to produce nanoparticle magnetite-TMAH having a stable and high performance. Furthermore, the magneto-elasticity of hydrogel-TMAH-magnetite in the effect of the external magnetic field had a good response. However, the composition of the nanoparticle magnetite-TMAH in the ferrogel did not significantly affect the elongation of the gel.

Supramolecular nanofibers of triamcinolone acetonide for uveitis therapy

NASA Astrophysics Data System (ADS)

Li, Xingyi; Wang, Yuqin; Yang, Chengbiao; Shi, Shuai; Jin, Ling; Luo, Zichao; Yu, Jing; Zhang, Zhaoliang; Yang, Zhimou; Chen, Hao

2014-11-01

Supramolecular nanofibers of prodrugs hold advantages for drug release due to their high drug payload, sustained and constant drug release behavior, and stimuli responsiveness. In this study, we report on a supramolecular hydrogel mainly formed by a clinically used drug triamcinolone acetonide (TA). Such a hydrogel could only be prepared via an ester bond hydrolysis process from its prodrug of succinated triamcinolone acetonide (STA). The resulting hydrogel could constantly release TA in the in vitro release experiment. The TA hydrogel possessed an excellent transscleral penetration ability, as evaluated by the in vitro transscleral transport study. The developed TA hydrogel also exhibited a great ocular compatibility in rats, as indicated by the optical coherence tomography (OCT) images, HE observation, and glial fibrillary acidic protein (GFAP) and vimentin immuno-staining assays of the retinas. Our TA hydrogel showed a decreased efficacy to inhibit ocular inflammation in the rat's experiment autoimmune uveitis (EAU) model compared to the commercial TA suspension (Transton®), but without causing complications such as high intraocular pressure and cataracts. These promising properties of the hydrogel indicated its great potential for the treatment of eye diseases.Supramolecular nanofibers of prodrugs hold advantages for drug release due to their high drug payload, sustained and constant drug release behavior, and stimuli responsiveness. In this study, we report on a supramolecular hydrogel mainly formed by a clinically used drug triamcinolone acetonide (TA). Such a hydrogel could only be prepared via an ester bond hydrolysis process from its prodrug of succinated triamcinolone acetonide (STA). The resulting hydrogel could constantly release TA in the in vitro release experiment. The TA hydrogel possessed an excellent transscleral penetration ability, as evaluated by the in vitro transscleral transport study. The developed TA hydrogel also exhibited a great ocular compatibility in rats, as indicated by the optical coherence tomography (OCT) images, HE observation, and glial fibrillary acidic protein (GFAP) and vimentin immuno-staining assays of the retinas. Our TA hydrogel showed a decreased efficacy to inhibit ocular inflammation in the rat's experiment autoimmune uveitis (EAU) model compared to the commercial TA suspension (Transton®), but without causing complications such as high intraocular pressure and cataracts. These promising properties of the hydrogel indicated its great potential for the treatment of eye diseases. Electronic supplementary information (ESI) available: Synthesis and characterization of the STA agent. SEM image of TA suspension (Transton®). See DOI: 10.1039/c4nr04761c

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.

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.

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.

Effect of heterocyclic capping groups on the self-assembly of a dipeptide hydrogel.

PubMed

Martin, Adam D; Wojciechowski, Jonathan P; Warren, Holly; in het Panhuis, Marc; Thordarson, Pall

2016-03-14

The mechanism and design rules associated with the self-assembly of short peptides into hydrogels is currently not well understood. In this work, four diphenylalanine-based peptides have been synthesised, bearing heterocyclic capping groups which have different degrees of hydrogen bonding potential and nitrogen substitution. For these four peptides, zeta potential and electrical impedance spectroscopy measurements were undertaken to monitor gelation, with the impedance data showing different gelation times for each peptide hydrogel. Through a combination of atomic force microscopy and rheological measurmeents, including dynamic strain and frequency sweeps, and thixotropic tests, the relationship between the mechanism of self-assembly in these hydrogels and their macroscopic behaviour can be established. It is observed that the degree of nitrogen substitution affects the self-assembly mechanisms of the hydrogels and as such, that there is an interplay between branching and bundling self-assembly pathways that are responsible for the final properties of each hydrogel.

Smart Electrospun Nanofibers for Controlled Drug Release: Recent Advances and New Perspectives

PubMed Central

Weng, Lin; Xie, Jingwei

2017-01-01

In biological systems, chemical molecules or ions often release upon certain conditions, at a specific location, and over a desired period of time. Electrospun nanofibers that undergo alterations in the physicochemical characteristics corresponding to environmental changes have gained considerable interest for various applications. Inspired by biological systems, therapeutic molecules have been integrated with these smart electrospun nanofibers, presenting activation-modulated or feedback-regulated control of drug release. Compared to other materials like smart hydrogels, environment-responsive nanofiber-based drug delivery systems are relatively new but possess incomparable advantages due to their greater permeability, which allows shorter response time and more precise control over the release rate. In this article, we review the mechanisms of various environmental parameters functioning as stimuli to tailor the release rates of smart electrospun nanofibers. We also illustrate several typical examples in specific applications. We conclude this article with a discussion on perspectives and future possibilities in this field. PMID:25732665

Smart electrospun nanofibers for controlled drug release: recent advances and new perspectives.

PubMed

Weng, Lin; Xie, Jingwei

2015-01-01

In biological systems, chemical molecules or ions often release upon certain conditions, at a specific location, and over a desired period of time. Electrospun nanofibers that undergo alterations in the physicochemical characteristics corresponding to environmental changes have gained considerable interest for various applications. Inspired by biological systems, therapeutic molecules have been integrated with these smart electrospun nanofibers, presenting activation-modulated or feedback-regulated control of drug release. Compared to other materials like smart hydrogels, environment-responsive nanofiber-based drug delivery systems are relatively new but possess incomparable advantages due to their greater permeability, which allows shorter response time and more precise control over the release rate. In this article, we review the mechanisms of various environmental parameters functioning as stimuli to tailor the release rates of smart electrospun nanofibers. We also illustrate several typical examples in specific applications. We conclude this article with a discussion on perspectives and future possibilities in this field.

Nanoparticle-Hydrogel Composites: Concept, Design, and Applications of These Promising, Multi-Functional Materials.

PubMed

Thoniyot, Praveen; Tan, Mein Jin; Karim, Anis Abdul; Young, David James; Loh, Xian Jun

2015-02-01

New technologies rely on the development of new materials, and these may simply be the innovative combination of known components. The structural combination of a polymer hydrogel network with a nanoparticle (metals, non-metals, metal oxides, and polymeric moieties) holds the promise of providing superior functionality to the composite material with applications in diverse fields, including catalysis, electronics, bio-sensing, drug delivery, nano-medicine, and environmental remediation. This mixing may result in a synergistic property enhancement of each component: for example, the mechanical strength of the hydrogel and concomitantly decrease aggregation of the nanoparticles. These mutual benefits and the associated potential applications have seen a surge of interest in the past decade from multi-disciplinary research groups. Recent advances in nanoparticle-hydrogel composites are herein reviewed with a focus on their synthesis, design, potential applications, and the inherent challenges accompanying these exciting materials.

Nanoparticle–Hydrogel Composites: Concept, Design, and Applications of These Promising, Multi‐Functional Materials

PubMed Central

Thoniyot, Praveen; Tan, Mein Jin; Karim, Anis Abdul; Young, David James

2015-01-01

New technologies rely on the development of new materials, and these may simply be the innovative combination of known components. The structural combination of a polymer hydrogel network with a nanoparticle (metals, non‐metals, metal oxides, and polymeric moieties) holds the promise of providing superior functionality to the composite material with applications in diverse fields, including catalysis, electronics, bio‐sensing, drug delivery, nano‐medicine, and environmental remediation. This mixing may result in a synergistic property enhancement of each component: for example, the mechanical strength of the hydrogel and concomitantly decrease aggregation of the nanoparticles. These mutual benefits and the associated potential applications have seen a surge of interest in the past decade from multi‐disciplinary research groups. Recent advances in nanoparticle–hydrogel composites are herein reviewed with a focus on their synthesis, design, potential applications, and the inherent challenges accompanying these exciting materials. PMID:27980900

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.

Poly(Ionic Liquid) Semi-Interpenetrating Network Multi-Responsive Hydrogels

PubMed Central

Tudor, Alexandru; Florea, Larisa; Gallagher, Simon; Burns, John; Diamond, Dermot

2016-01-01

Herein we describe poly(ionic liquid) hydrogel actuators that are capable of responding to multiple stimuli, namely temperature, ionic strength and white light irradiation. Using two starting materials, a crosslinked poly ionic liquid (PIL) and a linear poly(N-isopropylacrylamide-co-spiropyran-co-acrylic acid), several semi-interpenetrating (sIPN) hydrogels were synthesised. The dimensions of hydrogels discs were measured before and after applying the stimuli, to quantify their response. Samples composed of 100% crosslinked PIL alone showed an average area reduction value of ~53% when the temperature was raised from 20 °C to 70 °C, ~24% when immersed in 1% w/w NaF salt solution and no observable photo-response. In comparison, sIPNs containing 300% w/w linear polymer showed an average area reduction of ~45% when the temperature was raised from 20 °C to 70 °C, ~36% when immersed in 1% NaF w/w salt solution and ~10% after 30 min exposure to white light irradiation, respectively. Moreover, by varying the content of the linear component, fine-control over the photo-, thermo- and salt response, swelling-deswelling rate and mechanical properties of the resulting sIPN was achieved. PMID:26861339

Enzyme actuated bioresponsive hydrogels

NASA Astrophysics Data System (ADS)

Wilson, Andrew Nolan

Bioresponsive hydrogels are emerging with technological significance in targeted drug delivery, biosensors and regenerative medicine. Conferred with the ability to respond to specific biologically derived stimuli, the design challenge is in effectively linking the conferred biospecificity with an engineered response tailored to the needs of a particular application. Moreover, the fundamental phenomena governing the response must support an appropriate dynamic range and limit of detection. The design of these systems is inherently complicated due to the high interdependency of the governing phenomena that guide the sensing, transduction, and the actuation response of hydrogels. To investigate the dynamics of these materials, model systems may be used which seek to interrogate the system dynamics by uni-variable experimentation and limit confounding phenomena such as: polymer-solute interactions, polymer swelling dynamics and biomolecular reaction-diffusion concerns. To this end, a model system, alpha-chymotrypsin (Cht) (a protease) and a cleavable peptide-chromogen (pro-drug) covalently incorporated into a hydrogel, was investigated to understand the mechanisms of covalent loading and release by enzymatic cleavage in bio-responsive delivery systems. Using EDC and Sulfo-NHS, terminal carboxyl groups of N-succinyl-Ala-Ala-Pro-Phe p-nitroanilide, a cleavable chromogen, were conjugated to primary amines of a hydrated poly(HEMA)-based hydrogel. Hydrogel discs were incubated in buffered Cht causing enzyme-mediated cleavage of the peptide and concomitant release of the chromophore for monitoring. To investigate substrate loading and the effects of hydrogel morphology on the system, the concentration of the amino groups (5, 10, 20, and 30 mol%) and the cross-linked density (1, 5, 7, 9 and 12 mol%) were independently varied. Loading-Release Efficiency of the chromogen was shown to exhibit a positive relation to increasing amino groups (AEMA). The release rates demonstrated a negative relation to increasing cross-linked density attributed to decreasing void fractions and increasing tortuosities. The diffusion coefficient of Cht, D0, Cht, was determined to be 6.9 +/- 0.5 x 10-7 cm2 s -1, and the range of Deff of Cht for 1 to 12 mol% TEGDA was determined to 6.9 x10-8 to 0.1 x 10 -8cm2 s-1. We show how these parameters may be optimized and used to achieve programmed release rates in engineered bio-responsive systems. The field of bioresponsive hydrogels is continuing to expand as the need for such materials persists. Future work will enable more control over the loading and release of therapeutic and diagnostic moieties. Continued research regarding in enzymatically actuated hydrogels will involve pre-polymerization loading methodologies; in silico diffusion-reaction multiphysics modeling; enzyme actuated degradation of the polymer; and substation of various mediating enzyme, cleavable peptides, and release molecules.

A Review of Injectable Polymeric Hydrogel Systems for Application in Bone Tissue Engineering.

PubMed

Kondiah, Pariksha J; Choonara, Yahya E; Kondiah, Pierre P D; Marimuthu, Thashree; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

2016-11-21

Biodegradable, stimuli-responsive polymers are essential platforms in the field of drug delivery and injectable biomaterials for application of bone tissue engineering. Various thermo-responsive hydrogels display water-based homogenous properties to encapsulate, manipulate and transfer its contents to the surrounding tissue, in the least invasive manner. The success of bioengineered injectable tissue modified delivery systems depends significantly on their chemical, physical and biological properties. Irrespective of shape and defect geometry, injectable therapy has an unparalleled advantage in which intricate therapy sites can be effortlessly targeted with minimally invasive procedures. Using material testing, it was found that properties of stimuli-responsive hydrogel systems enhance cellular responses and cell distribution at any site prior to the transitional phase leading to gelation. The substantially hydrated nature allows significant simulation of the extracellular matrix (ECM), due to its similar structural properties. Significant current research strategies have been identified and reported to date by various institutions, with particular attention to thermo-responsive hydrogel delivery systems, and their pertinent focus for bone tissue engineering. Research on future perspective studies which have been proposed for evaluation, have also been reported in this review, directing considerable attention to the modification of delivering natural and synthetic polymers, to improve their biocompatibility and mechanical properties.

High performance polymer chemical hydrogel-based electrode binder materials for direct borohydride fuel cells

NASA Astrophysics Data System (ADS)

Choudhury, Nurul A.; Ma, Jia; Sahai, Yogeshwar; Buchheit, Rudolph G.

Novel, cost-effective, high-performance, and environment-friendly electrode binders, comprising polyvinyl alcohol chemical hydrogel (PCH) and chitosan chemical hydrogel (CCH), are reported for direct borohydride fuel cells (DBFCs). PCH and CCH binders-based electrodes have been fabricated using a novel, simple, cost-effective, time-effective, and environmentally benign technique. Morphologies and electrochemical performance in DBFCs of the chemical hydrogel binder-based electrodes have been compared with those of Nafion ® binder-based electrodes. Relationships between the performance of binders in DBFCs with structural features of the polymers and the polymer-based chemical hydrogels are discussed. The CCH binder exhibited better performance than a Nafion ® binder whereas the PCH binder exhibited comparable performance to Nafion ® in DBFCs operating at elevated cell temperatures. The better performance of CCH binder at higher operating cell temperatures has been ascribed to the hydrophilic nature and water retention characteristics of chitosan. DBFCs employing CCH binder-based electrodes and a Nafion ®-117 membrane as an electrolyte exhibited a maximum peak power density of about 589 mW cm -2 at 70 °C.

Recent advances in green hydrogels from lignin: a review.

PubMed

Thakur, Vijay Kumar; Thakur, Manju Kumari

2015-01-01

Recently, biorenewable polymers from different natural resources have attracted a greater attention of the research community for different applications starting from biomedical to automotive. Lignin is the second most abundant non-food biomass next to cellulose in the category of biorenewable polymers and is abundantly available as byproduct of several industries involved in paper making, ethanol production, etc. The development of various green materials from lignin, which is most often considered as waste, is therefore of prime interest from environmental and economic points of view. Over the last few years, little studies have been made into the use of lignin as an indispensable component in the hydrogels. This article provides an overview of the research work carried out in the last few years on lignin based hydrogels. This article comprehensively reviews the potential efficacy of lignin in biopolymer based green hydrogels with particular emphasis on synthesis, characterization and applications. In this article, several examples of hydrogels synthesized using different types of lignin are discussed to illustrate the state of the art in the use of lignin.

Design and synthesis of target-responsive aptamer-cross-linked hydrogel for visual quantitative detection of ochratoxin A.

PubMed

Liu, Rudi; Huang, Yishun; Ma, Yanli; Jia, Shasha; Gao, Mingxuan; Li, Jiuxing; Zhang, Huimin; Xu, Dunming; Wu, Min; Chen, Yan; Zhu, Zhi; Yang, Chaoyong

2015-04-01

A target-responsive aptamer-cross-linked hydrogel was designed and synthesized for portable and visual quantitative detection of the toxin Ochratoxin A (OTA), which occurs in food and beverages. The hydrogel network forms by hybridization between one designed DNA strand containing the OTA aptamer and two complementary DNA strands grafting on linear polyacrylamide chains. Upon the introduction of OTA, the aptamer binds with OTA, leading to the dissociation of the hydrogel, followed by release of the preloaded gold nanoparticles (AuNPs), which can be observed by the naked eye. To enable sensitive visual and quantitative detection, we encapsulated Au@Pt core-shell nanoparticles (Au@PtNPs) in the hydrogel to generate quantitative readout in a volumetric bar-chart chip (V-Chip). In the V-Chip, Au@PtNPs catalyzes the oxidation of H2O2 to generate O2, which induces movement of an ink bar to a concentration-dependent distance for visual quantitative readout. Furthermore, to improve the detection limit in complex real samples, we introduced an immunoaffinity column (IAC) of OTA to enrich OTA from beer. After the enrichment, as low as 1.27 nM (0.51 ppb) OTA can be detected by the V-Chip, which satisfies the test requirement (2.0 ppb) by the European Commission. The integration of a target-responsive hydrogel with portable enrichment by IAC, as well as signal amplification and quantitative readout by a simple microfluidic device, offers a new method for portable detection of food safety hazard toxin OTA.

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.

Double network bacterial cellulose hydrogel to build a biology-device interface.

PubMed

Shi, Zhijun; Li, Ying; Chen, Xiuli; Han, Hongwei; Yang, Guang

2014-01-21

Establishing a biology-device interface might enable the interaction between microelectronics and biotechnology. In this study, electroactive hydrogels have been produced using bacterial cellulose (BC) and conducting polymer (CP) deposited on the BC hydrogel surface to cover the BC fibers. The structures of these composites thus have double networks, one of which is a layer of electroactive hydrogels combined with BC and CP. The electroconductivity provides the composites with capabilities for voltage and current response, and the BC hydrogel layer provides good biocompatibility, biodegradability, bioadhesion and mass transport properties. Such a system might allow selective biological functions such as molecular recognition and specific catalysis and also for probing the detailed genetic and molecular mechanisms of life. A BC-CP composite hydrogel could then lead to a biology-device interface. Cyclic voltammetry and electrochemical impedance spectroscopy (EIS) are used here to study the composite hydrogels' electroactive property. BC-PAni and BC-PPy respond to voltage changes. This provides a mechanism to amplify electrochemical signals for analysis or detection. BC hydrogels were found to be able to support the growth, spreading and migration of human normal skin fibroblasts without causing any cytotoxic effect on the cells in the cell culture. These double network BC-CP hydrogels are biphasic Janus hydrogels which integrate electroactivity with biocompatibility, and might provide a biology-device interface to produce implantable devices for personalized and regenerative medicine.

Double network bacterial cellulose hydrogel to build a biology-device interface

NASA Astrophysics Data System (ADS)

Shi, Zhijun; Li, Ying; Chen, Xiuli; Han, Hongwei; Yang, Guang

2013-12-01

Establishing a biology-device interface might enable the interaction between microelectronics and biotechnology. In this study, electroactive hydrogels have been produced using bacterial cellulose (BC) and conducting polymer (CP) deposited on the BC hydrogel surface to cover the BC fibers. The structures of these composites thus have double networks, one of which is a layer of electroactive hydrogels combined with BC and CP. The electroconductivity provides the composites with capabilities for voltage and current response, and the BC hydrogel layer provides good biocompatibility, biodegradability, bioadhesion and mass transport properties. Such a system might allow selective biological functions such as molecular recognition and specific catalysis and also for probing the detailed genetic and molecular mechanisms of life. A BC-CP composite hydrogel could then lead to a biology-device interface. Cyclic voltammetry and electrochemical impedance spectroscopy (EIS) are used here to study the composite hydrogels' electroactive property. BC-PAni and BC-PPy respond to voltage changes. This provides a mechanism to amplify electrochemical signals for analysis or detection. BC hydrogels were found to be able to support the growth, spreading and migration of human normal skin fibroblasts without causing any cytotoxic effect on the cells in the cell culture. These double network BC-CP hydrogels are biphasic Janus hydrogels which integrate electroactivity with biocompatibility, and might provide a biology-device interface to produce implantable devices for personalized and regenerative medicine.

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.

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.

Cell-Responsive Hydrogel for Encapsulation of Vascular Cells

PubMed Central

Kraehenbuehl, Thomas P.; Ferreira, Lino S.; Zammaretti, Prisca; Hubbell, Jeffrey A.; Langer, Robert

2014-01-01

The in vitro potential of a synthetic matrix metalloproteinase (MMP)-responsive polyethylene glycol) (PEG)-based hydrogel as a bioactive co-encapsulation system for vascular cells and a small bioactive peptide, thymosin β4 (Tp4), was examined. We show that the physical incorporation of Tβ4 in this bioactive matrix creates a three-dimensional (3D) environment conducive for human umbilical vein endothelial cell (HUVEC) adhesion, survival, migration and organization. Gels with entrapped Tβ4 increased the survival of HUVEC compared to gels without Tp4, and significantly up-regulated the endothelial genes vascular endothelial-cadherin and angiopoietin-2, whereas von Willebrand factor was significantly down-regulated. Incorporation of Tβ4 significantly increased MMP-2 and MMP-9 secretion of encapsulated HUVEC. The gel acts as a controlled Tβ4-release system, as MMP-2 and MMP-9 enzymes trigger the release. In addition, Tβ4 facilitated HUVEC attachment and induced vascular-like network formation upon the PEG-hydrogels. These MMP-responsive PEG-hydrogels may thus serve as controlled co-encapsulation system of vascular cells and bioactive factors for in situ regeneration of ischemic tissues. PMID:19500842

Nanoceria-loaded injectable hydrogels for potential age-related macular degeneration treatment.

PubMed

Wang, Kai; Mitra, Rajendra Narayan; Zheng, Min; Han, Zongchao

2018-05-12

The major purpose of this article is to evaluate oligochitosan coated cerium oxide nanoparticles (OCCNPs) alginate laden injectable hydrogels and their potential treatment for age-related macular degeneration (AMD). The water soluble OCCNPs were loaded within injectable hydrogels as antioxidative agents. The release of OCCNPs from hydrogel, radical scavenging properties, and biocompatibility were evaluated and calculated in vitro. The effects of OCCNP laden hydrogel downregulating expression of angiogenic proteins and pro-inflammatory cytokines were quantified in human retinal pigment epithlium-19 (ARPE-19) and umbilical endothelium cell lines. The hydrogels behaved with moderate swelling and controllable degradation. The laden OCCNPs were released in a controlled manner in vitro during two months of testing. The OCCNP loaded hydrogels exhibited robust antioxidative properties in oxygen radical absorbance capacity tests and reduced apoptosis in H 2 O 2 -induced ARPE-19 cells. Furthermore, OCCNP loaded injectable hydrogels are biocompatible and suppressed the LPS-induced inflammation response in ARPE-19 cells, and inhibited expression of vascular endothelium growth factor in human ARPE-19 and umbilical endothelium cell lines. The alginate-gelatin injectable hydrogel loaded OCCNPs are biocompatible and have high potential in protecting cells from apoptosis, angiogenesis, and production of pro-inflammatory cytokines in AMD cellular models. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Laser-ignited frontal polymerization of shape-controllable poly(VI-co-AM) hydrogels based on 3D templates toward adsorption of heavy metal ions

NASA Astrophysics Data System (ADS)

Fan, Suzhen; Liu, Sisi; Wang, Xiao-Qiao; Wang, Cai-Feng; Chen, Su

2016-06-01

Given the increasing heavy metal pollution issue, fast preparation of polymeric hydrogels with excellent adsorption property toward heavy metal ions is very attractive. In this work, a series of poly( N-vinylimidazole-co-acrylamide) (poly(VI-co-AM)) hydrogels were synthesized via laser-ignited frontal polymerization (LIFP) for the first time. The dependence of frontal velocity and temperature on two factors monomer ratios and initiator concentrations was systematically investigated. Poly(VI-co-AM) hydrogels with any self-supporting shapes can be synthesized by a one-step LIFP in seconds through the application of 3D templates. These shape-persistent hydrogels are pH-responsive and exhibit excellent adsorption/desorption characteristics toward Mn(II), Zn(II), Cd(II), Ni(II), Cu(II) and Co(II) ions, and the adsorption conformed to the pseudo-second-order kinetic model. The reusability of the hydrogels toward mental ions adsorption was further researched, which suggested that the hydrogels can be reused without serious decrease in adsorption capacity. This work might open a promising strategy to facilely prepare shape-controllable hydrogels and expand the application of LIFP.

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.

Exploiting Advanced Hydrogel Technologies to Address Key Challenges in Regenerative Medicine

PubMed Central

Gentleman, Eileen

2018-01-01

Regenerative medicine aims to tackle a panoply of challenges, from repairing focal damage to articular cartilage to preventing pathological tissue remodelling after myocardial infarction. Hydrogels are water-swollen networks formed from synthetic or naturally derived polymers, and are emerging as important tools to address these challenges. Recent advances in hydrogel chemistries are enabling researchers to create hydrogels that can act as 3D ex vivo tissue models, allowing them to explore fundamental questions in cell biology by replicating tissues’ dynamic and non-linear physical properties. Enabled by emerging techniques such as 3D bioprinting, cell-laden hydrogels are also being developed with highly controlled tissue-specific architectures, vasculature, and biological functions that together can direct tissue repair. Moreover, advanced in situ forming and acellular hydrogels are increasingly finding use as delivery vehicles for bioactive compounds and in mediating host cell response. Here, we review advances in the design and fabrication of hydrogels for regenerative medicine. We also address how controlled chemistries are allowing for precise engineering of spatial and time-dependent properties in hydrogels with a look to how these materials will eventually translate to clinical applications. PMID:29316363

Fabricating Degradable Thermoresponsive Hydrogels on Multiple Length Scales via Reactive Extrusion, Microfluidics, Self-assembly, and Electrospinning.

PubMed

Sivakumaran, Daryl; Bakaic, Emilia; Campbell, Scott B; Xu, Fei; Mueller, Eva; Hoare, Todd

2018-04-16

While various smart materials have been explored for a variety of biomedical applications (e.g., drug delivery, tissue engineering, bioimaging, etc.), their ultimate clinical use has been hampered by the lack of biologically-relevant degradation observed for most smart materials. This is particularly true for temperature-responsive hydrogels, which are almost uniformly based on polymers that are functionally non-degradable (e.g., poly(N-isopropylacrylamide) (PNIPAM) or poly(oligoethylene glycol methacrylate) (POEGMA)). As such, to effectively translate the potential of thermoresponsive hydrogels to the challenges of remote-controlled or metabolism-regulated drug delivery, cell scaffolds with tunable cell-material interactions, theranostic materials with the potential for both imaging and drug delivery, and other such applications, a method is required to render the hydrogels (if not fully degradable) at least capable of renal clearance following the required lifetime of the material. To that end, this protocol describes the preparation of hydrolytically-degradable hydrazone-crosslinked hydrogels on multiple length scales based on the reaction between hydrazide and aldehyde-functionalized PNIPAM or POEGMA oligomers with molecular weights below the renal filtration limit. Specifically, methods to fabricate degradable thermoresponsive bulk hydrogels (using a double barrel syringe technique), hydrogel particles (on both the microscale through the use of a microfluidics platform facilitating simultaneous mixing and emulsification of the precursor polymers and the nanoscale through the use of a thermally-driven self-assembly and cross-linking method), and hydrogel nanofibers (using a reactive electrospinning strategy) are described. In each case, hydrogels with temperature-responsive properties similar to those achieved via conventional free radical cross-linking processes can be achieved, but the hydrazone cross-linked network can be degraded over time to re-form the oligomeric precursor polymers and enable clearance. As such, we anticipate these methods (which may be generically applied to any synthetic water-soluble polymer, not just smart materials) will enable easier translation of synthetic smart materials to clinical applications.

Methods for Generating Hydrogel Particles for Protein Delivery

PubMed Central

Liu, Allen L.; García, Andrés J.

2016-01-01

Proteins represent a major class of therapeutic molecules with vast potential for the treatment of acute and chronic diseases and regenerative medicine applications. Hydrogels have long been investigated for their potential in carrying and delivering proteins. As compared to bulk hydrogels, hydrogel microparticles (microgels) hold promise in improving aspects of delivery owing to their less traumatic route of entry into the body and improved versatility. This review discusses common methods of fabricating microgels, including emulsion polymerization, microfluidic techniques, and lithographic techniques. Microgels synthesized from both natural and synthetic polymers are discussed, as are a series of microgels fashioned from environment-responsive materials. PMID:27160672

Target-responsive DNA hydrogel mediated "stop-flow" microfluidic paper-based analytic device for rapid, portable and visual detection of multiple targets.

PubMed

Wei, Xiaofeng; Tian, Tian; Jia, Shasha; Zhu, Zhi; Ma, Yanli; Sun, Jianjun; Lin, Zhenyu; Yang, Chaoyong James

2015-04-21

A versatile point-of-care assay platform was developed for simultaneous detection of multiple targets based on a microfluidic paper-based analytic device (μPAD) using a target-responsive hydrogel to mediate fluidic flow and signal readout. An aptamer-cross-linked hydrogel was used as a target-responsive flow regulator in the μPAD. In the absence of a target, the hydrogel is formed in the flow channel, stopping the flow in the μPAD and preventing the colored indicator from traveling to the final observation spot, thus yielding a "signal off" readout. In contrast, in the presence of a target, no hydrogel is formed because of the preferential interaction of target and aptamer. This allows free fluidic flow in the μPAD, carrying the indicator to the observation spot and producing a "signal on" readout. The device is inexpensive to fabricate, easy to use, and disposable after detection. Testing results can be obtained within 6 min by the naked eye via a simple loading operation without the need for any auxiliary equipment. Multiple targets, including cocaine, adenosine, and Pb(2+), can be detected simultaneously, even in complex biological matrices such as urine. The reported method offers simple, low cost, rapid, user-friendly, point-of-care testing, which will be useful in many applications.

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.

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).

Alginate-polyester comacromer based hydrogels as physiochemically and biologically favorable entities for cardiac tissue engineering.

PubMed

Thankam, Finosh G; Muthu, Jayabalan

2015-11-01

The physiochemical and biological responses of tissue engineering hydrogels are crucial in determining their desired performance. A hybrid comacromer was synthesized by copolymerizing alginate and poly(mannitol fumarate-co-sebacate) (pFMSA). Three bimodal hydrogels pFMSA-AA, pFMSA-MA and pFMSA-NMBA were synthesized by crosslinking with Ca(2+) and vinyl monomers acrylic acid (AA), methacrylic acid (MA) and N,N'-methylene bisacrylamide (NMBA), respectively. Though all the hydrogels were cytocompatible and exhibited a normal cell cycle profile, pFMSA-AA exhibited superior physiochemical properties viz non-freezable water content (58.34%) and water absorption per unit mass (0.97 g water/g gel) and pore length (19.92±3.91 μm) in comparing with other two hydrogels. The increased non-freezable water content and water absorption of pFMSA-AA hydrogels greatly influenced its biological performance, which was evident from long-term viability assay and cell cycle proliferation. The physiochemical and biological favorability of pFMSA-AA hydrogels signifies its suitability for cardiac tissue engineering. Copyright © 2015 Elsevier Inc. All rights reserved.

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

A wide range and highly sensitive optical fiber pH sensor using polyacrylamide hydrogel

NASA Astrophysics Data System (ADS)

Pathak, Akhilesh Kumar; Singh, Vinod Kumar

2017-12-01

In the present study we report the fabrication and characterization of no-core fiber sensor (NCFS) using smart hydrogel coating for pH measurement. The no-core fiber (NCF) is stubbed between two single-mode fibers with SMA connector before immobilizing of smart hydrogel. The wavelength interrogation technique is used to calculate the sensitivity of the proposed sensor. The result shows a high sensitivity of 1.94 nm/pH for a wide range of pH values varied from 3 to 10 with a good linear response. In addition to high sensitivity, the fabricated sensor provides a fast response time with a good stability, repeatability and reproducibility.

Microcontact printing of polydopamine on thermally expandable hydrogels for controlled cell adhesion and delivery of geometrically defined microtissues.

PubMed

Lee, Yu Bin; Kim, Se-Jeong; Kim, Eum Mi; Byun, Hayeon; Chang, Hyung-Kwan; Park, Jungyul; Choi, Yu Suk; Shin, Heungsoo

2017-10-01

Scaffold-free harvest of microtissue with a defined structure has received a great deal of interest in cell-based assay and regenerative medicine. In this study, we developed thermally expandable hydrogels with spatially controlled cell adhesive patterns for rapid harvest of geometrically controlled microtissue. We patterned polydopamine (PD) on to the hydrogel via microcontact printing (μCP), in linear shapes with widths of 50, 100 and 200μm. The hydrogels facilitated formation of spatially controlled strip-like microtissue of human dermal fibroblasts (HDFBs). It was possible to harvest and translocate microtissues with controlled widths of 61.4±14.7, 104.3±15.6, and 186.6±22.3μm from the hydrogel to glass substrates by conformal contact upon expansion of the hydrogel in response to a temperature change from 37 to 4°C, preserving high viability, extracellular matrix, and junction proteins. Microtissues were readily translocated in vivo to the subcutaneous tissue of mouse. The microtissues were further utilized as a simple assay model for monitoring of contraction in response to ROCK1 inhibitor. Collectively, micro-sized patterning of PD on the thermally expandable hydrogels via μCP holds promise for the development of microtissue harvesting systems that can be employed to ex vivo tissue assay and cell-based therapy. Harvest of artificial tissue with controlled cellular arrangement independently from external materials has been widely studied in cell-based assay and regenerative medicine. In this study, we developed scaffold-free harvest system of microtissues with anisotropic arrangement and controlled width by exploiting thermally expandable hydrogels with cell-adhesive patterns of polydopamine formed by simple microcontact printing. Cultured strips of human dermal fibroblasts on the hydrogels were rapidly delivered to various targets ranging from flat coverglass to mice subcutaneous tissue by thermal expansion of the hydrogel at 4°C for 10min. These were further utilized as a drug screening model responding to ROCK1 inhibitor, which imply its versatile applicability. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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.

The effects of cross-linked thermo-responsive PNIPAAm-based hydrogel injection on retinal function.

PubMed

Turturro, Sanja B; Guthrie, Micah J; Appel, Alyssa A; Drapala, Pawel W; Brey, Eric M; Pérez-Luna, Victor H; Mieler, William F; Kang-Mieler, Jennifer J

2011-05-01

There is significant interest in biomaterials that provide sustained release of therapeutic molecules to the retina. Poly(N-isopropylacrylamide) (PNIPAAm)-based materials have received significant attention as injectable drug delivery platforms due to PNIPAAm's thermo-responsive properties at approximately 32 °C. While the drug delivery properties of PNIPAAm materials have been studied extensively, there is a need to evaluate the safety effects of hydrogel injection on retinal function. The purpose of this study was to examine the effect of poly(ethylene glycol) diacrylate (PEG-DA) crosslinked PNIPAAm hydrogel injection on retinal function. Utilizing scanning laser ophthalmoscopy (SLO), optical coherent tomography (OCT), and electroretinography (ERG), retinal function was assessed following hydrogel injection. In region near the hydrogel, there was a significant decrease in arterial and venous diameters (∼4%) and an increase in venous blood velocity (∼8%) 1 week post-injection. Retinal thickness decreased (∼6%) at 1 week and the maximum a- and b-wave amplitudes of ERG decreased (∼15%). All data returned to baseline values after week 1. These data suggest that the injection of PEG-DA crosslinked PNIPAAm hydrogel results in a small transient effect on retinal function without any long-term effects. These results further support the potential of PNIPAAm-based materials as an ocular drug delivery platform. 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.

Biomaterials differentially regulate Src kinases and phosphoinositide 3-kinase-γ in polymorphonuclear leukocyte primary and tertiary granule release

PubMed Central

Cohen, Hannah Caitlin; Frost, Dustin C.; Lieberthal, Tyler Jacob; Li, Lingjun; Kao, W. John

2018-01-01

In the foreign body response, infiltrating PMNs exocytose granule subsets to influence subsequent downstream inflammatory and wound healing events. In previous studies, we found that PMNs cultured on poly(ethylene glycol) (PEG)-containing hydrogels (i.e., PEG and gelatin + PEG hydrogels) had enhanced primary granule release, yet similar tertiary granule release compared with PMNs cultured on polydimethylsiloxane or tissue culture polystyrene. PMN primary granules contain microbicidal proteins and proteases, which can potentially injure bystander cells, degrade the extracellular matrix, and promote inflammation. Here, we sought to understand the mechanism of the enhanced primary granule release from PMNs on PEG hydrogels. We found that primary granule release from PMNs on PEG hydrogels was adhesion mediated and involved Src family kinases and PI3K-γ. The addition of gelatin to PEG hydrogels did not further enhance PMN primary granule release. Using stable-isotope dimethyl labeling-based shotgun proteomics, we identified many serum proteins – including Ig gamma constant chain region proteins and alpha-1-acid glycoprotein 1 – that were absorbed/adsorbed in higher quantities on PEG hydrogels than on TCPS, and may be involved in mediating PMN primary granule release. Ultimately, this mechanistic knowledge can be used to direct inflammation and wound healing following biomaterial implantation to promote a more favorable healing response. PMID:25736495

Excited-state dynamics of the medicinal pigment curcumin in a hydrogel.

PubMed

Harada, Takaaki; Lincoln, Stephen F; Kee, Tak W

2016-10-12

Curcumin is a yellow polyphenol with multiple medicinal effects. These effects, however, are limited due to its poor aqueous stability and solubility. A hydrogel of 3% octadecyl randomly substituted polyacrylate (PAAC18) has been shown to provide high aqueous stability for curcumin under physiological conditions, offering a route for photodynamic therapy. In this study, the excited-state photophysics of curcumin in the PAAC18 hydrogel is investigated using a combination of femtosecond transient absorption and fluorescence upconversion spectroscopy. The transient absorption results reveal a multiexponential decay in the excited-state kinetics with fast (1 ps & 15 ps) and slow (110 ps & ≈5 ns) components. The fast decay component exhibits a deuterium isotope effect with D 2 O in the hydrogel, indicating that the 15 ps decay component is attributable to excited-state intramolecular hydrogen atom transfer of curcumin in the PAAC18 hydrogel. In addition, solvent reorganisation of excited-state curcumin is investigated using multiwavelength femtosecond fluorescence upconversion spectroscopy. The results show that the dominant solvation response (τ = 0.08 ps) is a fast inertial motion owing to the presence of bulk-like water in the vicinity of the hydrophobic octadecyl substituents of the PAAC18 hydrogel. The results also show an additional response with longer time constants of 1 and 6 ps, which is attributable to translational diffusion of confined water molecules in the three-dimensional, cross-linking network of the octadecyl substituents of PAAC18. Overall, we show that excited-state intramolecular hydrogen atom transfer and solvent reorganisation are major photophysical events for curcumin in the PAAC18 hydrogel.

Novel pH-sensitive photopolymer hydrogel and its holographic sensing response for solution characterization

NASA Astrophysics Data System (ADS)

Liu, Hongpeng; Yu, Dan; Zhou, Ke; Wang, Shichan; Luo, Suhua; Li, Li; Wang, Weibo; Song, Qinggong

2018-05-01

Optical sensor based on pH-sensitive hydrogel has important practical applications in medical diagnosis and bio-sensor areas. This report details the experimental and theoretical results from a novel photosensitive polymer hydrogel holographic sensor, which formed by thermal polymerization of 2-hydroxyethyl methacrylate, for the detection of pH in buffer. Volume grating recorded in the polymer hydrogel was employed in response to the performance of solution. Methacrylic acid with carboxyl groups was selected as the primary co-monomer to functionalize the matrix. Peak diffraction spectrum of holographic grating determined as a primary sensing parameter was characterized to reflect the change in pH. The extracted linear relation between peak wavelength and pH value provided a probability for the practical application of holographic sensor. To explore the sensing mechanism deeply, a theoretical model was used to describe the relevant holographic processes, including grating formation, dark diffusional enhancement, and final fringe swelling. Numerical result further showed all of the dynamic processes and internal sensing physical mechanism. These experimental and numerical results provided a significant foundation for the development of novel holographic sensor based on polymer hydrogel and improvement of its practical applicability.

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.

Cell recruiting chemokine-loaded sprayable gelatin hydrogel dressings for diabetic wound healing.

PubMed

Yoon, Dong Suk; Lee, Yunki; Ryu, Hyun Aae; Jang, Yeonsue; Lee, Kyoung-Mi; Choi, Yoorim; Choi, Woo Jin; Lee, Moses; Park, Kyung Min; Park, Ki Dong; Lee, Jin Woo

2016-07-01

In this study, we developed horseradish peroxidase (HRP)-catalyzed sprayable gelatin hydrogels (GH) as a bioactive wound dressing that can deliver cell-attracting chemotactic cytokines to the injured tissues for diabetic wound healing. We hypothesized that topical administration of chemokines using GH hydrogels might improve wound healing by inducing recruitment of the endogenous cells. Two types of chemokines (interleukin-8; IL-8, macrophage inflammatory protein-3α; MIP-3α) were simply loaded into GH hydrogels during in situ cross-linking, and then their wound-healing effects were evaluated in streptozotocin-induced diabetic mice. The incorporation of chemokines did not affect hydrogels properties including swelling ratio and mechanical stiffness, and the bioactivities of IL-8 and MIP-3α released from hydrogel matrices were stably maintained. In vivo transplantation of chemokine-loaded GH hydrogels facilitated cell infiltration into the wound area, and promoted wound healing with enhanced re-epithelialization/neovascularization and increased collagen deposition, compared with no treatment or the GH hydrogel alone. Based on our results, we suggest that cell-recruiting chemokine-loaded GH hydrogel dressing can serve as a delivery platform of various therapeutic proteins for wound healing applications. Despite development of materials combined with therapeutic agents for diabetic wound treatment, impaired wound healing by insufficient chemotactic responses still remain as a significant problem. In this study, we have developed enzyme-catalyzed gelatin (GH) hydrogels as a sprayable dressing material that can deliver cell-attracting chemokines for diabetic wound healing. The chemotactic cytokines (IL-8 and MIP-3α) were simply loaded within hydrogel during in situ gelling, and wound healing efficacy of chemokine-loaded GH hydrogels was investigated in STZ-induced diabetic mouse model. These hydrogels significantly promoted wound-healing efficacy with faster wound closure, neovascularization, and thicker granulation. Therefore, we expect that HRP-catalyzed in situ forming GH hydrogels can serve as an injectable/sprayable carrier of various therapeutic agents for wound healing applications. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The dynamic magnetoviscoelastic properties of biomineralized (Fe3O4) PVP-CMC hydrogel

NASA Astrophysics Data System (ADS)

Ray, Ayan; Saha, Nabanita; Saha, Petr

2017-05-01

The Polyvinylpyrrolidone (PVP) and carboxymethylcellulose (CMC) based polymer matrix was used as a template for the preparation of magnetic hydrogel. This freshly prepared PVP-CMC hydrogel template was successfully mineralized by in situ synthesis of magnetic nanoparticles (Fe3O4) via chemical co-precipitation reaction using liquid diffusion method. The present study emphasizes on the rheological behavior of non-mineralized and mineralized PVP-CMC hydrogels. Scanning Electron Microscopy (SEM), transmission electron microscopy (TEM), X-ray Diffraction (XRD) pattern, Fourier transform infrared spectroscopy (FT-TR), Vibrating sample magnetometer (VSM) and dynamic magneto rheometer were used to study the morphological, physical, chemical and magnetic properties of nanoparticle (Fe3O4) filled PVP-CMC hydrogel respectively in order to monitor how Fe3O4 magnetic nanoparticles affects the mechanical properties of the hydrogel network. The storage (G') and loss (G") moduli with a complex viscosity of the system was measured using a parallel plate rheometer. Frequency and amplitude sweep with temperature variation was performed to determine the frequency and amplitude dependent magneto viscoelastic moduli for both hydrogel samples. A strong shear thinning effect was observed in both (non-mineralized and mineralized) PVP-CMC hydrogels, which confirm that Fe3O4 filled magnetic hydrogels, are pseudoplastic in nature. This Fe3O4 filled PVP-CMC hydrogel can be considered as stimuli-responsive soft matter that may be used as an actuator in medical devices.

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

Self Assembled Bi-functional Peptide Hydrogels with Biomineralization-Directing Peptides

PubMed Central

Gungormus, Mustafa; Branco, Monica; Fong, Hanson; Schneider, Joel P.; Tamerler, Candan; Sarikaya, Mehmet

2014-01-01

A peptide-based hydrogel has been designed that directs the formation of hydroxyapatite. MDG1, a twenty-seven residue peptide, undergoes triggered folding to form an unsymmetrical β-hairpin that self-assembles in response to an increase in solution ionic strength to yield a mechanically rigid, self supporting hydrogel. The C-terminal portion of MDG1 contains a heptapeptide (MLPHHGA) capable of directing the mineralization process. Circular dichroism spectroscopy indicates that the peptide folds and assembles to form a hydrogel network rich in β-sheet secondary structure. Oscillatory rheology indicates that the hydrogel is mechanical rigid (G′ ∼ 2500 Pa) before mineralization. In separate experiments, mineralization was induced both biochemically and with cementoblast cells. Mineralization-domain had little effect on the mechanical rigidity of the gel. SEM and EDS show that MDG1 gels are capable of directing the formation of hydroxapatite. Control hydrogels, prepared by peptides either lacking the mineral-directing portion or reversing its sequence, indicated that the heptapeptide is necessary and its actions are sequence specific. PMID:20591477

Tough Al-alginate/poly(N-isopropylacrylamide) hydrogel with tunable LCST for soft robotics.

PubMed

Zheng, Wen Jiang; An, Ning; Yang, Jian Hai; Zhou, Jinxiong; Chen, Yong Mei

2015-01-28

Tough Al-alginate/poly(N-isopropylacrylamide) (PNIPAM) hydrogel has been synthesized by introducing an interpenetrating network with hybrid physically cross-linked alginate and chemically cross-linked PNIPAM. Varying the concentration of AlCl3 regulates the mechanical properties of the tough hydrogel and tunes its lower critical solution temperature (LCST) as well. The tough Al-alginate/PNIPAM exhibits 6.3 ± 0.3 MPa of compressive stress and 9.95 of uniaxial stretch. Tunability of LCST is also achieved in a wide range within 22.5-32 °C. A bending beam actuator and a four-arm gripper made of bilayer (Na-alginate/PNIPAM)/(Al-alginate/PNIPAM) hydrogel as prototype of all-hydrogel soft robotics are demonstrated. A finite element (FE) simulation model is developed to simulate the deformation of the soft robotics. The FE simulation not only reproduces the deformation process of performed experiments but also predicts more complicated devices that can be explored in the future. This work broadens the application of temperature-responsive PNIPAM-based hydrogels.

Cartilaginous extracellular matrix-modified chitosan hydrogels for cartilage tissue engineering.

PubMed

Choi, Bogyu; Kim, Soyon; Lin, Brian; Wu, Benjamin M; Lee, Min

2014-11-26

Cartilaginous extracellular matrix (ECM) components such as type-II collagen (Col II) and chondroitin sulfate (CS) play a crucial role in chondrogenesis. However, direct clinical use of natural Col II or CS as scaffolds for cartilage tissue engineering is limited by their instability and rapid enzymatic degradation. Here, we investigate the incorporation of Col II and CS into injectable chitosan hydrogels designed to gel upon initiation by exposure to visible blue light (VBL) in the presence of riboflavin. Unmodified chitosan hydrogel supported proliferation and deposition of cartilaginous ECM by encapsulated chondrocytes and mesenchymal stem cells. The incorporation of native Col II or CS into chitosan hydrogels further increased chondrogenesis. The incorporation of Col II, in particular, was found to be responsible for the enhanced cellular condensation and chondrogenesis observed in modified hydrogels. This was mediated by integrin α10 binding to Col II, increasing cell-matrix adhesion. These findings demonstrate the potential of cartilage ECM-modified chitosan hydrogels as biomaterials to promote cartilage regeneration.

Cross-linked β-cyclodextrin and carboxymethyl cellulose hydrogels for controlled drug delivery of acyclovir

PubMed Central

Malik, Nadia Shamshad; Ahmad, Mahmood; Minhas, Muhammad Usman

2017-01-01

To explore the potential role of polymers in the development of drug-delivery systems, this study investigated the use of β-cyclodextrin (β-CD), carboxymethyl cellulose (CMC), acrylic acid (AA) and N’ N’-methylenebis-acrylamide (MBA) in the synthesis of hydrogels for controlled drug delivery of acyclovir (ACV). Different proportions of β-CD, CMC, AA and MBA were blended with each other to fabricate hydrogels via free radical polymerization technique. Fourier transform infrared spectroscopy (FTIR) revealed successful grafting of components into the polymeric network. Thermal and morphological characterization confirmed the formation of thermodynamically stable hydrogels having porous structure. The pH-responsive behaviour of hydrogels has been documented by swelling dynamics and drug release behaviour in simulated gastrointestinal fluids. Drug release kinetics revealed controlled release behaviour of the antiviral drug acyclovir in developed polymeric network. Cross-linked β-cyclodextrin and carboxymethyl cellulose hydrogels can be used as promising candidates for the design and development of controlled drug-delivery systems. PMID:28245257

CRYOPRESERVATION EFFECTS ON RECOMBINANT MYOBLASTS ENCAPSULATED IN ADHESIVE ALGINATE HYDROGELS

PubMed Central

Ahmad, Hajira F.; Sambanis, Athanassios

2013-01-01

Cell encapsulation in hydrogels is widely used in tissue engineering applications, including encapsulation of islets or other insulin-secreting cells in pancreatic substitutes. Use of adhesive, bio-functionalized hydrogels is receiving increasing attention, as cell-matrix interactions in 3-D can be important for various cell processes. With pancreatic substitutes, studies have indicated benefits of 3-D adhesion on the viability and/or function of insulin-secreting cells. As long-term storage of microencapsulated cells is critical for their clinical translation, cryopreservation of cells in hydrogels is actively being investigated. Previous studies have examined the cryopreservation response of cells encapsulated in non-adhesive hydrogels using conventional freezing and/or vitrification (ice-free cryopreservation), however, none have systematically compared the two cryopreservation methods with cells encapsulated within an adhesive 3-D environment. The latter would be significant, as evidence suggests adhesion influences cellular response to cryopreservation. Thus, the objective of this study was to determine the response to conventional freezing and vitrification of insulin-secreting cells encapsulated in an adhesive biomimetic hydrogel. Recombinant insulin-secreting C2C12 myoblasts were encapsulated in oxidized RGD-alginate and cultured 1 or 4 days post-encapsulation, cryopreserved, and assessed up to 3 days post-warming for metabolic activity and insulin secretion, and one day post-warming for cell morphology. Besides certain transient differences of the vitrified group relative to the Fresh control, both conventional freezing and vitrification maintained metabolism, secretion and morphology of the recombinant C2C12 cells. Thus, due to a simpler procedure and slightly superior results, conventional freezing is recommended over vitrification for the cryopreservation of C2C12 cells in oxidized RGD-modified alginate. PMID:23499987

Novel Biocompatible Thermoresponsive Poly(N-vinyl Caprolactam)/Clay Nanocomposite Hydrogels with Macroporous Structure and Improved Mechanical Characteristics.

PubMed

Shi, Kun; Liu, Zhuang; Yang, Chao; Li, Xiao-Ying; Sun, Yi-Min; Deng, Yi; Wang, Wei; Ju, Xiao-Jie; Xie, Rui; Chu, Liang-Yin

2017-07-05

Poly(N-vinyl caprolactam) (PVCL) hydrogels usually suffer from the imporous structure and poor mechanical characteristics as well as the toxicity of cross-linkers, although PVCL itself is biocompatible. In this paper, novel biocompatible thermoresponsive poly(N-vinyl caprolactam)/clay nanocomposite (PVCL-Clay) hydrogels with macroporous structure and improved mechanical characteristics are developed for the first time. The macroporosity in the hydrogel is introduced by using Pickering emulsions as templates, which contain N-vinyl caprolactam (VCL) monomer as dispersed phase and clay sheets as stabilizers at the interface. After polymerization, macropores are formed inside the hydrogels with the residual unreacted VCL droplets as templates. The three-dimensional PVCL polymer networks are cross-linked by the clay nanosheets. Due to the nanocomposite structure, the hydrogel exhibits better mechanical characteristics in comparison to the conventional PVCL hydrogels cross-linked by N,N'-methylene diacrylamide (BIS). The prepared PVCL-Clay hydrogel possesses remarkable temperature-responsive characteristics with a volume phase transition temperature (VPTT) around 35 °C, and provides a feasible platform for cell culture. With macroporous structure and good mechanical characteristics as well as flexible assembly performance, the proposed biocompatible thermoresponsive PVCL-Clay nanocomposite hydrogels are ideal material candidates for biomedical, analytical, and other applications such as entrapment of enzymes, cell culture, tissue engineering, and affinity and displacement chromatography.

Inkjet-Spray Hybrid Printing for 3D Freeform Fabrication of Multilayered Hydrogel Structures.

PubMed

Yoon, Sejeong; Park, Ju An; Lee, Hwa-Rim; Yoon, Woong Hee; Hwang, Dong Soo; Jung, Sungjune

2018-04-30

Here, a new bioprinting process by combining drop-on-demand inkjet printing with a spray-coating technique, which enables the high-resolution, high-speed, and freeform fabrication of large-scale cell-laden hydrogel structures is reported. Hydrogel structures with various shapes and composed of different materials, including alginate, cellulose nanofiber, and fibrinogen, are fabricated using the inkjet-spray printing. To manufacture cell-friendly hydrogel structures with controllable stiffness, gelatine methacryloyl is saponified to stabilize jet formation and is subsequently mixed with sodium alginate to prepare blend inks. The hydrogels crosslinked from the blend inks are characterized by assessing physical properties including the microstructure and mechanical stiffness and cellular responses including the cell viability, metabolic activity, and functionality of human dermal fibroblasts within the hydrogel. Cell-laden hydrogel structures are generated on a large scale and collagen type I secretion and spreading of cells within the hydrogels are assessed. The results demonstrate that the inkjet-spray printing system will ensure the formation of a cell-laden hydrogel structure with high shape fidelity in a rapid and reliable manner. Ultimately, the proposed printing technique and the blend bioink to be used to fabricate 3D laminated large-scale tissue equivalents that potentially mimic the function of native tissues is expected. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

30 s Response Time of K+ Ion-Selective Hydrogels Functionalized with 18-Crown-6 Ether Based on QCM Sensor.

PubMed

Zhang, Zhenxiao; Dou, Qian; Gao, Hongkai; Bai, Bing; Zhang, Yongmei; Hu, Debo; Yetisen, Ali K; Butt, Haider; Yang, Xiaoxia; Li, Congju; Dai, Qing

2018-03-01

Potassium detection is critical in monitoring imbalances in electrolytes and physiological status. The development of rapid and robust potassium sensors is desirable in clinical chemistry and point-of-care applications. In this study, composite supramolecular hydrogels are investigated: polyethylene glycol methacrylate and acrylamide copolymer (P(PEGMA-co-AM)) are functionalized with 18-crown-6 ether by employing surface initiated polymerization. Real-time potassium ion monitoring is realized by combining these compounds with quartz crystal microbalance. The device demonstrates a rapid response time of ≈30 s and a concentration detection range from 0.5 to 7.0 × 10 -3 m. These hydrogels also exhibit high reusability and K + ion selectivity relative to other cations in biofluids such as Na + , NH 4 + , Mg 2+ , and Ca 2+ . These results provide a new approach for sensing alkali metal ions using P(PEGMA-co-AM) hydrogels. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Temperature-responsive copolymeric hydrogel systems synthetized by ionizing radiation

NASA Astrophysics Data System (ADS)

López-Barriguete, Jesús Eduardo; Bucio, Emilio

2017-06-01

Eight different systems of hydrogel copolymers with diverse temperature responsiveness were prepared to elaborate membranes for their biomedical application. The hydrogels were synthesized using poly(N-isopropylacrylamide) (PNIPAAm) and poly(N-vinylcaprolactam) (PNVCL), which have a low critical solution temperature (LCST) close to that of the human body temperature. The networks were synthesized using gamma radiation at a dose rate of 11.2 kGy h-1, and dose of 50 kGy. The LCST of each system was measured by differential scanning calorimetry (DSC). The effect of using hydrophilic monomers of acrylic acid (AAc), methacrylic acid (MAAc), dimethyl acrylamide (DMAAm), and hydroxyethyl methacrylate (HEMA) for the copolymerization on the critical point was evaluated. Five viable systems were obtained, with the best hydrogel being that of poly(NIPAAm-co-DMAAm), which an LCST at 39.8 °C. All the samples were characterized by FTIR-ATR, DSC, TGA, X-Ray Diffraction, and SEM. The proportion of monomers during the formation of the copolymers was decisive in the displacement of the LCST.

Supramolecular peptide hydrogel adjuvanted subunit vaccine elicits protective antibody responses against West Nile virus.

PubMed

Friedrich, Brian M; Beasley, David W C; Rudra, Jai S

2016-11-04

A crucial issue in vaccine development is to balance safety with immunogenicity. The low immunogenicity of most subunit antigens warrants a search for adjuvants able to stimulate both cell-mediated and humoral immunity. In recent years, successful applications of nanotechnology and bioengineering in the field of vaccine development have enabled the production of novel adjuvant technologies. In this work, we investigated totally synthetic and supramolecular peptide hydrogels as novel vaccine adjuvants in conjunction with the immunoprotective envelope protein domain III (EIII) of West Nile virus as an immunogen in a mouse model. Our results indicate that, compared to the clinically approved adjuvant alum, peptide hydrogel adjuvanted antigen elicited stronger antibody responses and conferred significant protection against mortality after virus challenge. The high chemical definition and biocompatibility of self-assembling peptide hydrogels makes them attractive as immune adjuvants for the production of subunit vaccines against viral and bacterial infections where antibody-mediated protection is desirable. Copyright © 2016 Elsevier Ltd. All rights reserved.

Retention of Human-Induced Pluripotent Stem Cells (hiPS) With Injectable HA Hydrogels for Vocal Fold Engineering.

PubMed

Imaizumi, Mitsuyoshi; Li-Jessen, Nicole Y K; Sato, Yuka; Yang, David T; Thibeault, Susan L

2017-04-01

One prospective treatment option for vocal fold scarring is regeneration with an engineered scaffold containing induced pluripotent stem cells (iPS). In the present study, we investigated the feasibility of utilizing an injectable hyaluronic acid (HA) scaffold encapsulated with human-iPS cell (hiPS) for regeneration of vocal folds. Thirty athymic nude rats underwent unilateral vocal fold injury. Contralateral vocal folds served as uninjured controls. Hyaluronic acid hydrogel scaffold, HA hydrogel scaffold containing hiPS, and HA hydrogel scaffold containing hiPS with epidermal growth factor (EGF) were injected in both vocal folds immediately after surgery. One and 2 weeks after injection, larynges were excised for histology, immunohistochemistry, and fluorescence in situ hybridization (FISH). Presence of HA hydrogel was confirmed in vocal folds 1 and 2 weeks post injection. The FISH analysis confirmed the presence and viability of hiPS in the injected vocal folds. Histological results demonstrated that vocal folds injected with HA hydrogel scaffold containing EGF demonstrated less fibrosis than those with HA hydrogel only. Human-iPS survived in injured rat vocal folds. The HA hydrogel with hiPS and EGF ameliorated the fibrotic response. Additional work is necessary to optimize hiPS differentiation and further confirm the safety of hiPS for clinical applications.

Advances in hydrogel delivery systems for tissue regeneration.

PubMed

Toh, Wei Seong; Loh, Xian Jun

2014-12-01

Hydrogels are natural or synthetic polymer networks that have high water-absorbing capacity and closely mimic native extracellular matrices. As hydrogel-based cell delivery systems are being increasingly employed in regenerative medicine, several advances have been made in the hydrogel chemistry and modification for enhanced control of cell fate and functions, and modulation of cell and tissue responses against oxidative stress and inflammation in the tissue environment. This review aims to provide the state-of-the-art overview of the recent advances in field, discusses new perspectives and challenges in the regeneration of specific tissues, and highlights some of the limitations of current systems for possible future advancements. Copyright © 2014 Elsevier B.V. All rights reserved.

Synthesis of stiffness-tunable and cell-responsive Gelatin-poly(ethylene glycol) hydrogel for three-dimensional cell encapsulation.

PubMed

Cao, Ye; Lee, Bae Hoon; Peled, Havazelet Bianco; Venkatraman, Subbu S

2016-10-01

Biosynthetic poly(ethylene glycol) (PEG)-based hydrogels have been extensively investigated as extracellular matrix (ECM) mimicking gels as they retain the benefits of both ECM (biological cues) and synthetic hydrogels (tunable mechanical properties). In this article, we developed and characterized a new gelatin-PEG (GP) hydrogel that retains the benefits of gelatin and synthetic hydrogels. In this strategy, the thiolation of gelatin was accomplished by reacting with Traut's reagent; the thiolated gelatin was then conjugated to one end of PEG diacrylate (PEGDA) by Michael-type addition reaction. Two kinds of GP precursors, GP30 and GP60, were synthesized by changing the amount of Traut's reagent, while the weight ratio between thiolated-gelatin and PEGDA of GP30 and GP60 was 1.451:1 and 0.785:1, respectively. Finally, neonatal human dermal fibroblasts were encapsulated into the hydrogel by cross-linking the remaining double bonds of precursor under ultraviolet light. These GP hydrogels can encapsulate the fibroblasts in situ with high cell viability. Moreover, the behaviors of cells within the GP hydrogels can be modulated by varying the cross-linking density of GP hydrogel (storage modulus from 40 to 2000 Pa). In particular, this article showed that a minimum amount of cell-binding motifs (gelatin >2.30 wt/vol % and 44.0% dry weight percentage) are required for attachment; and appropriate initial rheological and structural properties (storage modulus <∼100 Pa and mesh size >∼150 nm) can accelerate the attachment of cells and improve cell viability. Hence, this mixed-hydrogel platform allows an easily control hydrogel structure and modulates cell behavior to reconstruct new tissue in the three-dimensional microenvironments. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2401-2411, 2016. © 2016 Wiley Periodicals, Inc.

Extracellular-Matrix-Based and Arg-Gly-Asp–Modified Photopolymerizing Hydrogels for Cartilage Tissue Engineering

PubMed Central

Kim, Hwan D.; Heo, Jiseung; Hwang, Yongsung; Kwak, Seon-Yeong; Park, Ok Kyu; Kim, Hyunbum; Varghese, Shyni

2015-01-01

Articular cartilage damage is a persistent and increasing problem with the aging population. Strategies to achieve complete repair or functional restoration remain a challenge. Photopolymerizing-based hydrogels have long received an attention in the cartilage tissue engineering, due to their unique bioactivities, flexible method of synthesis, range of constituents, and desirable physical characteristics. In the present study, we have introduced unique bioactivity within the photopolymerizing-based hydrogels by copolymerizing polyethylene glycol (PEG) macromers with methacrylated extracellular matrix (ECM) molecules (hyaluronic acid and chondroitin sulfate [CS]) and integrin binding peptides (RGD peptide). Results indicate that cellular morphology, as observed by the actin cytoskeleton structures, was strongly dependent on the type of ECM component as well as the presence of integrin binding moieties. Further, CS-based hydrogel with integrin binding RGD moieties increased the lubricin (or known as superficial zone protein [SZP]) gene expression of the encapsulated chondrocytes. Additionally, CS-based hydrogel displayed cell-responsive degradation and resulted in increased DNA, GAG, and collagen accumulation compared with other hydrogels. This study demonstrates that integrin-mediated interactions within CS microenvironment provide an optimal hydrogel scaffold for cartilage tissue engineering application. PMID:25266634

Case Studies

PubMed Central

Danielson, John R.; Walter, Robert J.

2005-01-01

Objective: The purpose of this report is to present the results of a preliminary treatment regimen for hypertrophic scars combining topical 2% salicylic acid cream (Avosil) with an overlay of hydrogel dressing (Avogel). Methods: The study group consisted of 3 patients with symptomatic hypertrophic scars: 2 presternal and 1 on the inner thigh. Scars were divided into 3 equal-size areas: (1) untreated control, (2) hydrogel alone, and (3) 2% salicylic acid with hydrogel cover. Treatments were applied every 8 to 12 hours and a Velcro appliance was employed to cover the area during treatment. The total length of treatment was 60 days. Results: At the end of the 60-day treatment protocol, the area treated with 2% salicylic acid and hydrogel was asymptomatic. In contrast, the hydrogel-treated and untreated control areas remained erythematous and symptomatic for burning pain and pruritis. Conclusion: This small study suggests the efficacy of combined salicylic acid and hydrogel therapy in the treatment of hypertrophic scars. More extensive studies of scar treatment with salicylic acid and hydrogel are needed. These studies must be larger in scope to carefully document the spectrum of patient responses and should include methods for evaluating alterations in the levels of different inflammatory mediators. PMID:16921411

Super-tough, ultra-stretchable and strongly compressive hydrogels with core-shell latex particles inducing efficient aggregation of hydrophobic chains.

PubMed

Ren, Xiuyan; Huang, Chang; Duan, Lijie; Liu, Baijun; Bu, Lvjun; Guan, Shuang; Hou, Jiliang; Zhang, Huixuan; Gao, Guanghui

2017-05-14

Toughness, strechability and compressibility for hydrogels were ordinarily balanced for their use as mechanically responsive materials. For example, macromolecular microsphere composite hydrogels with chemical crosslinking exhibited excellent compression strength and strechability, but poor tensile stress. Here, a novel strategy for the preparation of a super-tough, ultra-stretchable and strongly compressive hydrogel was proposed by introducing core-shell latex particles (LPs) as crosslinking centers for inducing efficient aggregation of hydrophobic chains. The core-shell LPs always maintained a spherical shape due to the presence of a hard core even by an external force and the soft shell could interact with hydrophobic chains due to hydrophobic interactions. As a result, the hydrogels reinforced by core-shell LPs exhibited not only a high tensile strength of 1.8 MPa and dramatic elongation of over 20 times, but also an excellent compressive performance of 13.5 MPa at a strain of 90%. The Mullins effect was verified for the validity of core-shell LP-reinforced hydrogels by inducing aggregation of hydrophobic chains. The novel strategy strives to provide a better avenue for designing and developing a new generation of hydrophobic association tough hydrogels with excellent mechanical properties.

Contact lens induced papillary conjunctivitis with silicone hydrogel lenses.

PubMed

Sorbara, L; Jones, L; Williams-Lyn, D

2009-04-01

To describe the refitting of a soft lens wearer into a silicone hydrogel lens due to neovascularization. This change, in turn, caused contact lens induced papillary conjunctivitis (CLPC) and a further refitting was necessary. The patient was refit into a high Dk surface treated silicone hydrogel with a high modulus value. A second refitting was undertaken into a lower Dk silicone hydrogel contact lens with a lower modulus value which had no surface treatment but incorporated an internal wetting agent. A high Dk/t lens was used to resolve existing neovascularization and chronic hyperaemia. Subsequently, CLPC response occurred, possibly due to a combination of factors, resulting in irritation of the palpebral conjunctiva. This resulted in temporary lens discontinuation. A second silicone hydrogel lens was fit, along with the use of a non-preserved care system, which led to improvement and eventual resolution of the condition. High Dk silicone hydrogel lenses have shown excellent efficacy in resolving hypoxic complications such as neovascularization and hyperaemia. However, attention needs to be paid to their potential effect on the upper tarsal plate. More than one silicone hydrogel lens may be needed to help resolve these issues.

Supramolecular hydrogel formation between chitosan and hydroxypropyl β-cyclodextrin via Diels-Alder reaction and its drug delivery.

PubMed

Zhang, Mengke; Wang, Jinpeng; Jin, Zhengyu

2018-07-15

Chitosan-cyclodextrin hydrogel (CFCD) was prepared via Diels-Alder reaction between furfural functionalized chitosan (CF) and N-maleoyl alanine functionalized hydroxypropyl β-cyclodextrin (HPCD-AMI) in aqueous media without any catalyst or initiator. The CF and HPCD-AMI were confirmed by Fourier transform infrared spectroscopy and 1 H nuclear magnetic resonance spectroscopy. The resultant CFCD hydrogel was characterized in terms of thermal peripteries, microstructure, rheology behavior, and swelling capacity. The rheology analysis found that the storage modulus G' ranged from 1pa to 1200pa as the degree of furfural substitute on chitosan increased from 2.6% to 28.3%, indicating the hydrogel strength can be tuned readily by reaction stoichiometry. The swelling behaviors proved that CFCD hydrogel was pH-responsive with low swelling capacity, which would be preferable for drug delivery. Drug adsorption analysis showed the introduction of cyclodextrin into CFCD hydrogels promoted drug adsorption capacity. In addition, methyl orange cumulative release in PBS buffer was only 48.85% after 24h, suggesting CFCD hydrogel had good sustained release capacity on the loaded drug. Copyright © 2018 Elsevier B.V. All rights reserved.

3D Printing of Thermo-Responsive Methylcellulose Hydrogels for Cell-Sheet Engineering.

PubMed

Cochis, Andrea; Bonetti, Lorenzo; Sorrentino, Rita; Contessi Negrini, Nicola; Grassi, Federico; Leigheb, Massimiliano; Rimondini, Lia; Farè, Silvia

2018-04-10

A possible strategy in regenerative medicine is cell-sheet engineering (CSE), i.e., developing smart cell culture surfaces from which to obtain intact cell sheets (CS). The main goal of this study was to develop 3D printing via extrusion-based bioprinting of methylcellulose (MC)-based hydrogels. Hydrogels were prepared by mixing MC powder in saline solutions (Na₂SO₄ and PBS). MC-based hydrogels were analyzed to investigate the rheological behavior and thus optimize the printing process parameters. Cells were tested in vitro on ring-shaped printed hydrogels; bulk MC hydrogels were used for comparison. In vitro tests used murine embryonic fibroblasts (NIH/3T3) and endothelial murine cells (MS1), and the resulting cell sheets were characterized analyzing cell viability and immunofluorescence. In terms of CS preparation, 3D printing proved to be an optimal approach to obtain ring-shaped CS. Cell orientation was observed for the ring-shaped CS and was confirmed by the degree of circularity of their nuclei: cell nuclei in ring-shaped CS were more elongated than those in sheets detached from bulk hydrogels. The 3D printing process appears adequate for the preparation of cell sheets of different shapes for the regeneration of complex tissues.

Super strong dopamine hydrogels with shape memory and bioinspired actuating behaviours modulated by solvent exchange.

PubMed

Huang, Jiahe; Liao, Jiexin; Wang, Tao; Sun, Weixiang; Tong, Zhen

2018-03-28

Dopamine-containing hydrogels were synthesized by copolymerization of dopamine methacrylamide (DMA), N,N-dimethylacrylamide (DMAA), and an N,N'-methylenebisacrylamide (BIS) crosslinker in a mixed solvent of water and DMSO. The association of DMA was formed by simply immersing in water to facilely reinforce the hydrogel due to the introduction of the second physical crosslinking. The tensile strength of the hydrogels was increased greatly and regulated in a wide range from 200 kPa to over 2 MPa. The association of DMA was destroyed upon immersing in DMSO. This reversible formation and dissociation of the association structure endowed the hydrogel with shape memory and actuating capabilities. Rapid shape fixing in water and complete shape recovery in DMSO was realized within several minutes. Bioinspired functional soft actuators were designed based on the reversible association and metal ion coordination of DMA, including fast responsive hydrogel tentacles, programable multiple shape change, reversible and versatile painting and writing "hydrogel paper". The facile preparation and strength regulation provide a new way to design novel soft actuators through solvent exchange, and will inspire more complex applications upon combining the association with other properties of mussel inspired dopamine derivatives.

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 dopamine-modified poly(α,β-aspartic acid) nanocomposite hydrogel as bioadhesive drug delivery system.

PubMed

Gong, Chu; Lu, Caicai; Li, Bingqiang; Shan, Meng; Wu, Guolin

2017-04-01

Hydrogel systems based on cross-linked polymeric materials with adhesive properties in wet environments have been considered as promising candidates for tissue adhesives. The 3,4-dihydroxyphenylalanine (DOPA) is believed to be responsible for the water-resistant adhesive characteristics of mussel adhesive proteins. Under the inspiration of DOPA containing adhesive proteins, a dopamine-modified poly(α,β-aspartic acid) derivative (PDAEA) was successfully synthesized by successive ring-opening reactions of polysuccinimide (PSI) with dopamine and ethanolamine, and an injectable bioadhesive hydrogel was prepared via simply mixing PDAEA and FeCl 3 solutions. The formation mechanism of the hydrogel was investigated by ultraviolet-visible (UV-vis) spectroscopic, Fourier transformation infrared (FT-IR) spectroscopic, visual colorimetric measurements and EDTA immersion methods. The study demonstrated that the PDAEA-Fe 3+ hydrogel is a dual cross-linking system composed of covalent and coordination crosslinks. The PDAEA-Fe 3+ hydrogel is suitable to serve as a bioadhesive agent according to the rheological behaviors and the observed significant shear adhesive strength. The slow and sustained release of the model drug curcumin from the hydrogel in vitro demonstrated the hydrogel could also be potentially used for drug delivery. Moreover, the cytotoxicity tests in vitro suggested the prepared polymer and hydrogel possessed excellent cytocompatibility. All the results indicated that the dopamine modified poly(α,β-aspartic acid) derivative based hydrogel was a promising candidate for bioadhesive drug delivery system. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1000-1008, 2017. © 2017 Wiley Periodicals, Inc.

On the structural stability of guanosine-based supramolecular hydrogels.

PubMed

Carducci, Federica; Yoneda, Juliana S; Itri, Rosangela; Mariani, Paolo

2018-04-18

Supramolecular hydrogels formed from the self-assembly of low molecular weight derivatives are very attractive systems, because of their potential applications in nano- and bio-technology. In this paper, the stable and transparent hydrogels observed in binary mixtures of guanosine derivatives (G), namely guanosine 5'-monophosphate (GMP) and guanosine (Gua), dissolved in water (at volume fractions larger than 0.95), were investigated by microscopy techniques and Small Angle X-ray Scattering (SAXS). The results confirm the presence of G-quadruplexes, chiral cylindrical rods obtained by the regular stacking of self-assembled planar cyclic guanosine quartets. However, the addition of Gua determines the formation of very stable hydrogels able to trap large amounts of water (up to a volume fraction of 0.99) and characterised by an unusual anisotropic order. A modified lateral helix-to-helix interaction pattern, tuned by Gua, is suggested to be responsible for the supramolecular gelation and the stability of the hydrogels during swelling.

Silk Hydrogels of Tunable Structure and Viscoelastic Properties Using Different Chronological Orders of Genipin and Physical Cross-Linking.

PubMed

Elliott, Winston H; Bonani, Walter; Maniglio, Devid; Motta, Antonella; Tan, Wei; Migliaresi, Claudio

2015-06-10

Catering the hydrogel manufacturing process toward defined viscoelastic properties for intended biomedical use is important to hydrogel scaffolding function and cell differentiation. Silk fibroin hydrogels may undergo "physical" cross-linking through β-sheet crystallization during high pressure carbon dioxide treatment, or covalent "chemical" cross-linking by genipin. We demonstrate here that time-dependent mechanical properties are tunable in silk fibroin hydrogels by altering the chronological order of genipin cross-linking with β-sheet formation. Genipin cross-linking before β-sheet formation affects gelation mechanics through increased molecular weight, affecting gel morphology, and decreasing stiffness response. Alternately, genipin cross-linking after gelation anchored amorphous regions of the protein chain, and increasing stiffness. These differences are highlighted and validated through large amplitude oscillatory strain near physiologic levels, after incorporation of material characterization at molecular and micron length scales.

Functionalized core-shell hydrogel microsprings by anisotropic gelation with bevel-tip capillary

PubMed Central

Yoshida, Koki; Onoe, Hiroaki

2017-01-01

This study describes a novel microfluidic-based method for the synthesis of hydrogel microsprings that are capable of encapsulating various functional materials. A continuous flow of alginate pre-gel solution can spontaneously form a hydrogel microspring by anisotropic gelation around the bevel-tip of the capillary. This technique allows fabrication of hydrogel microsprings using only simple capillaries and syringe pumps, while their complex compartmentalization characterized by a laminar flow inside the capillary can contribute to the optimization of the microspring internal structure and functionality. Encapsulation of several functional materials including magnetic-responsive nanoparticles or cell dispersed collagen for tissue scaffold was demonstrated to functionalize the microsprings. Our core-shell hydrogel microsprings have immense potential for application in a number of fields, including biological/chemical microsensors, biocompatible soft robots/microactuators, drug release, self-assembly of 3D structures and tissue engineering. PMID:28378803

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.

Optimum design for effective water transport through a double-layered porous hydrogel inspired by plant leaves

NASA Astrophysics Data System (ADS)

Kim, Hyejeong; Kim, Hyeonjeong; Huh, Hyungkyu; Hwang, Hyung Ju; Lee, Sang Joon

2014-11-01

Plant leaves are generally known to have optimized morphological structure in response to environmental changes for efficient water usage. However, the advantageous features of plant leaves are not fully utilized in engineering fields yet, since the optimum design in internal structure of plant leaves is unclear. In this study, the tissue organization of the hydraulic pathways inside plant leaves was investigated. Water transport through double-layered porous hydrogel models analogous to mesophyll cells was experimentally observed. In addition, computational experiment and theoretical analysis were applied to the model systems to find the optimal design for efficient water transport. As a result, the models with lower porosity or with pores distributed widely in the structure exhibit efficient mass transport. Our theoretical prediction supports that structural features of plant leaves guarantee sufficient water supply as survival strategy. This study may provide a new framework for investigating the biophysical principles governing the morphological optimization of plant leaves and for designing microfluidic devices to enhance mass transport ability. This study was supported by the National Research Foundation of Korea and funded by the Korean government.

Hybrid Elastin-like Polypeptide–Polyethylene Glycol (ELP-PEG) Hydrogels with Improved Transparency and Independent Control of Matrix Mechanics and Cell Ligand Density

PubMed Central

2015-01-01

Hydrogels have been developed as extracellular matrix (ECM) mimics both for therapeutic applications and basic biological studies. In particular, elastin-like polypeptide (ELP) hydrogels, which can be tuned to mimic several biochemical and physical characteristics of native ECM, have been constructed to encapsulate various types of cells to create in vitro mimics of in vivo tissues. However, ELP hydrogels become opaque at body temperature because of ELP’s lower critical solution temperature behavior. This opacity obstructs light-based observation of the morphology and behavior of encapsulated cells. In order to improve the transparency of ELP hydrogels for better imaging, we have designed a hybrid ELP-polyethylene glycol (PEG) hydrogel system that rapidly cross-links with tris(hydroxymethyl) phosphine (THP) in aqueous solution via Mannich-type condensation. As expected, addition of the hydrophilic PEG component significantly improves the light transmittance. Coherent anti-Stokes Raman scattering (CARS) microscopy reveals that the hybrid ELP-PEG hydrogels have smaller hydrophobic ELP aggregates at 37 °C. Importantly, this hydrogel platform enables independent tuning of adhesion ligand density and matrix stiffness, which is desirable for studies of cell–matrix interactions. Human fibroblasts encapsulated in these hydrogels show high viability (>98%) after 7 days of culture. High-resolution confocal microscopy of encapsulated fibroblasts reveals that the cells adopt a more spread morphology in response to higher RGD ligand concentrations and softer gel mechanics. PMID:25111283

Hybrid elastin-like polypeptide-polyethylene glycol (ELP-PEG) hydrogels with improved transparency and independent control of matrix mechanics and cell ligand density.

PubMed

Wang, Huiyuan; Cai, Lei; Paul, Alexandra; Enejder, Annika; Heilshorn, Sarah C

2014-09-08

Hydrogels have been developed as extracellular matrix (ECM) mimics both for therapeutic applications and basic biological studies. In particular, elastin-like polypeptide (ELP) hydrogels, which can be tuned to mimic several biochemical and physical characteristics of native ECM, have been constructed to encapsulate various types of cells to create in vitro mimics of in vivo tissues. However, ELP hydrogels become opaque at body temperature because of ELP's lower critical solution temperature behavior. This opacity obstructs light-based observation of the morphology and behavior of encapsulated cells. In order to improve the transparency of ELP hydrogels for better imaging, we have designed a hybrid ELP-polyethylene glycol (PEG) hydrogel system that rapidly cross-links with tris(hydroxymethyl) phosphine (THP) in aqueous solution via Mannich-type condensation. As expected, addition of the hydrophilic PEG component significantly improves the light transmittance. Coherent anti-Stokes Raman scattering (CARS) microscopy reveals that the hybrid ELP-PEG hydrogels have smaller hydrophobic ELP aggregates at 37 °C. Importantly, this hydrogel platform enables independent tuning of adhesion ligand density and matrix stiffness, which is desirable for studies of cell-matrix interactions. Human fibroblasts encapsulated in these hydrogels show high viability (>98%) after 7 days of culture. High-resolution confocal microscopy of encapsulated fibroblasts reveals that the cells adopt a more spread morphology in response to higher RGD ligand concentrations and softer gel mechanics.

Synthesis and Properties of pH-, Thermo-, and Salt-Sensitive Modified Poly(aspartic acid)/Poly(vinyl alcohol) IPN Hydrogel and Its Drug Controlled Release.

PubMed

Lu, Jingqiong; Li, Yinhui; Hu, Deng; Chen, Xiaoling; Liu, Yongmei; Wang, Liping; Zhao, Yansheng

2015-01-01

Modified poly(aspartic acid)/poly(vinyl alcohol) interpenetrating polymer network (KPAsp/PVA IPN) hydrogel for drug controlled release was synthesized by a simple one-step method in aqueous system using poly(aspartic acid) grafting 3-aminopropyltriethoxysilane (KH-550) and poly(vinyl alcohol) (PVA) as materials. The hydrogel surface morphology and composition were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The thermal stability was analyzed by thermogravimetric analysis (TGA). The swelling properties and pH, temperature, and salt sensitivities of KPAsp, KPAsp/PVA semi-interpenetrating polymer network (semi-IPN), and KPAsp/PVA IPN hydrogels were also investigated. All of the three hydrogels showed ampholytic pH-responsive properties, and swelling behavior was also extremely sensitive to the temperature, ionic strength, and cationic species. Finally, the drug controlled release properties of the three hydrogels were evaluated and results indicated that three hydrogels could control drug release by external surroundings stimuli. The drug controlled release properties of KPAsp/PVA IPN hydrogel are the most outstanding, and the correlative measured release profiles of salicylic acid at 37°C were 32.6 wt% at pH = 1.2 (simulated gastric fluid) and 62.5 wt% at pH = 7.4 (simulated intestinal fluid), respectively. These results indicated that KPAsp/PVA IPN hydrogels are a promising carrier system for controlled drug delivery.

Rheological properties of a biological thermo-responsive hydrogel produced from soybean oil polymers

USDA-ARS?s Scientific Manuscript database

The rheological properties of a newly developed biological thermo-hydrogel made from vegetable oil were investigated. The material named HPSO-VI is a hydrolytic product of polymerized soybean oil (PSO). HPSO-VI exhibited viscoelastic behavior above 2% (wt. %) at room temperature and viscous fluid ...

Characterization and manipulation of the in vivo host response and in vitro macrophage response to synthetic hydrogels

NASA Astrophysics Data System (ADS)

Lynn, Aaron David

Tissue engineering hope to fill the donor gap between patient needing transplantation and donors able to provide organs. Many challenges exist in the engineering of replacement tissues such as cell sourcing and scaffold design. A particularly promising group of scaffolds used extensively in tissue engineering research are based on cross-linked poly(ethylene glycol) (PEG) hydrogels. Materials based on these gels have been selected for their tissue-like high water content, low cell toxicty, mild polymerization conditions and the ease with which their mechanical and chemical properties can be tuned. However, all materials which will ultimately be implanted into will elicit a host response. This reaction is initiated when a wound is created. It leads to bathing of the material in proteins from the blood, recruitment, attachment and interrogation of the material by macrophages, attempted degradation and phagocytosis, macrophage fusion into foreign body giant cells (FBGCs) and ultimately the "walling off" of the implant as a dense collagenous capsule surrounds the material restricting further interactions with the host. This foreign body response (FBR) is well studied and contributes significantly to premature failure of implanted medical devices. The research presented in this thesis aims to characterize the FBR to PEG-based tissue engineering scaffolds with the intention of uncovering mechanisms by which the response can be attenuated. To this end, implantation studies have been performed to gauge the severity of the foreign body response to these hydrogels and to establish to what degree modifications with the cell adhesion peptide alter this reaction in vivo. Additionally, in vitro models were established to study characteristics of the the early (< 1 week), middle (1-2 weeks) and late phases (> 2 weeks) of the FBR. Studies were performed to determine the potentially detrimental effects of macrophage interrogation of a PEG-based skin tissue engineering system containing encapsulated fibroblasts. Finally, preliminary work has been done on a strategy for manipulating macrophage interactions with tissue engineering hydrogels utilizing a novel hydrogel coating system. This provides some of the first correlations between in vivo host responses and in vitro macrophage responses to PEG-based tissue engineering materials.

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.

RAFT polymerization of temperature- and salt-responsive block copolymers as reversible hydrogels.

PubMed

Hemp, Sean T; Smith, Adam E; Bunyard, W Clayton; Rubinstein, Michael H; Long, Timothy E

2014-05-13

Reversible-addition fragmentation chain transfer (RAFT) polymerization enabled the synthesis of novel, stimuli-responsive, AB and ABA block copolymers. The B block contained oligo(ethylene glycol) methyl ether methacrylate (OEG) and was permanently hydrophilic in the conditions examined. The A block consisted of diethylene glycol methyl ether methacrylate (DEG) and [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMA). The A block displayed both salt- and temperature-response with lower critical solution temperatures (LCSTs) dependent on the molar content of TMA and the presence of salt. Higher TMA content in the AB diblock copolymers increased the critical micelle temperatures (CMT) in HPLC-grade water due to an increased hydrophilicity of the A block. Upon addition of 0.9 wt% NaCl, the CMTs of poly(OEG- b -DEG 95 TMA 5 ) decreased from 50 °C to 36 °C due to screening of electrostatic repulsion between the TMA units. ABA triblock copolymers displayed excellent hydrogel properties with salt- and temperature-dependent gel points. TMA incorporation in the A block increased the gel points for all triblock copolymers, and salt-response increased with higher TMA composition in the A block. For example, poly(DEG 98 TMA 2 - b -OEG- b -DEG 98 TMA 2 ) formed a hydrogel at 40 °C in HPLC-grade water and 26 °C in 0.9 wt% NaCl aqueous solution. These salt- and temperature-responsive AB diblock and ABA triblock copolymers find applications as drug delivery vehicles, adhesives, and hydrogels.

On-Demand Dissolution of Chemically Cross-Linked Hydrogels.

PubMed

Konieczynska, Marlena D; Grinstaff, Mark W

2017-02-21

The formation and subsequent on-demand dissolution of chemically cross-linked hydrogels is of keen interest to chemists, engineers, and clinicians. In this Account, we summarize our recent advances in the area of dissolvable chemically cross-linked hydrogels and provide a comparative discussion of other recent hydrogel systems. Using biocompatible macromonomers, we developed a library of cross-linked dendritic hydrogels that possess favorable properties, including biocompatibility, tissue adhesion, and swelling. Additionally, these hydrogels possess the unique ability to dissolve on-demand via application of a biocompatible aqueous solution. Each of the three hydrogel systems described employs a thiol-thioester exchange reaction as the mechanism of dissolution. These new materials successfully decrease bleeding in in vivo models of hepatic and aortic hemorrhage and dissolve on-demand, providing easy removal. In addition, we evaluated these hydrogels as dressings for second-degree burn wounds and performed proof-of-concept in vivo studies. These hydrogel wound dressings provide a means of repeatedly changing the dressing in a minimally invasive and atraumatic manner while also serving as a protective barrier against bacterial infection. Finally, we highlight the seminal work of other researchers in the field of dissolvable chemically cross-linked hydrogels using thiol-disulfide exchange, retro-Michael-type, and retro-Diels-Alder reactions. These chemistries provide a versatile synthetic toolbox to dissolve hydrogels in a controlled manner on time scales from minutes to weeks. Continued investigation of these dissolution approaches as well as the development of new chemical reactions will open doors to other avenues of on-demand dissolution and expand the application space for these materials. In summary, the management and closure of wounds after traumatic injury or surgical intervention are of significant clinical importance. Stimuli-responsive hydrogels that function as sealants, adhesives, or dressings are emerging as vital alternatives to current standards of care that rely upon conventional sutures, staples, or dressings.

Performance and biocompatibility of extremely tough alginate/polyacrylamide hydrogels.

PubMed

Darnell, Max C; Sun, Jeong-Yun; Mehta, Manav; Johnson, Christopher; Arany, Praveen R; Suo, Zhigang; Mooney, David J

2013-11-01

Although hydrogels now see widespread use in a host of applications, low fracture toughness and brittleness have limited their more broad use. As a recently described interpenetrating network (IPN) of alginate and polyacrylamide demonstrated a fracture toughness of ≈ 9000 J/m(2), we sought to explore the biocompatibility and maintenance of mechanical properties of these hydrogels in cell culture and in vivo conditions. These hydrogels can sustain a compressive strain of over 90% with minimal loss of Young's Modulus as well as minimal swelling for up to 50 days of soaking in culture conditions. Mouse mesenchymal stem cells exposed to the IPN gel-conditioned media maintain high viability, and although cells exposed to conditioned media demonstrate slight reductions in proliferation and metabolic activity (WST assay), these effects are abrogated in a dose-dependent manner. Implantation of these IPN hydrogels into subcutaneous tissue of rats for 8 weeks led to mild fibrotic encapsulation and minimal inflammatory response. These results suggest the further exploration of extremely tough alginate/PAAM IPN hydrogels as biomaterials. © 2013 Elsevier Ltd. All rights reserved.

Extracellular matrix-derived hydrogels for dental stem cell delivery.

PubMed

Viswanath, Aiswarya; Vanacker, Julie; Germain, Loïc; Leprince, Julian G; Diogenes, Anibal; Shakesheff, Kevin M; White, Lisa J; des Rieux, Anne

2017-01-01

Decellularized mammalian extracellular matrices (ECM) have been widely accepted as an ideal substrate for repair and remodelling of numerous tissues in clinical and pre-clinical studies. Recent studies have demonstrated the ability of ECM scaffolds derived from site-specific homologous tissues to direct cell differentiation. The present study investigated the suitability of hydrogels derived from different source tissues: bone, spinal cord and dentine, as suitable carriers to deliver human apical papilla derived mesenchymal stem cells (SCAP) for spinal cord regeneration. Bone, spinal cord, and dentine ECM hydrogels exhibited distinct structural, mechanical, and biological characteristics. All three hydrogels supported SCAP viability and proliferation. However, only spinal cord and bone derived hydrogels promoted the expression of neural lineage markers. The specific environment of ECM scaffolds significantly affected the differentiation of SCAP to a neural lineage, with stronger responses observed with spinal cord ECM hydrogels, suggesting that site-specific tissues are more likely to facilitate optimal stem cell behavior for constructive spinal cord regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 319-328, 2017. © 2016 Wiley Periodicals, Inc.

A novel bio electro active alginate-aniline tetramer/ agarose scaffold for tissue engineering: synthesis, characterization, drug release and cell culture study.

PubMed

Atoufi, Zhale; Zarrintaj, Payam; Motlagh, Ghodratollah Hashemi; Amiri, Anahita; Bagher, Zohreh; Kamrava, Seyed Kamran

2017-10-01

In this study, synthesis of a novel biocompatible stimuli-responsive conducting hydrogel based on agarose/alginate-aniline tetramer with the capability of a tailored electrically controlled drug-release for neuroregeneration is investigated. First, aniline tetramer is synthesized and grafted onto sodium alginate. Then, this material is added to agarose as an electrical conductivity modifier to obtain Agarose/alginate-aniline tetramer hydrogel. The synthesized materials are characterized by H NMR and FTIR. The hydrogels are prepared with varying content of aniline tetramer and their swelling-deswelling and shape memory behavior is evaluated. The electroactivity and ionic conductivity of hydrogels against temperature is measured. The sample with 10% aniline tetramer (AT10) reveals the highest ionic conductivity. In MTT and SEM assays, AT10 shows the best cell viability and cell proliferation due to its highest ionic conductivity highlighting the fact that electrical stimuli cell signaling. Hydrogels also represent great potentials for passive and electro-stimulated dexamethasone release. These results demonstrate that the newly developed conducting hydrogels are promising materials for neuroregenerative medicine.

Synthesis and evaluation of functional alginate hydrogels based on click chemistry for drug delivery applications.

PubMed

García-Astrain, Clara; Avérous, Luc

2018-06-15

Environment-sensitive alginate-based hydrogels for drug delivery applications are receiving increasing attention. However, most work in this field involves traditional cross-linking strategies which led to hydrogels with poor long-term stability. Herein, a series of chemically cross-linked alginate hydrogels was synthesized via click chemistry using Diels-Alder reaction by reacting furan-modified alginate and bifunctional cross-linkers. Alginate was successfully functionalized with furfurylamine. Then, 3D architectures were synthesized with water-soluble bismaleimides. Different substitution degrees were achieved in order to study the effect of alginate modification and the cross-linking extent over the behaviour of the hydrogels. The ensuing hydrogels were analysed in terms of microstructure, swelling, structure modification and rheological behaviour. The materials response to external stimuli such as pH was also investigated, revealing a pulsatile behaviour in a large pH range (1-13) and a clear pH-dependent swelling. Finally, vanillin release studies were conducted to demonstrate the potential of these biobased materials for drug delivery applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mechanomimetic hydrogels for vocal fold lamina propria regeneration.

PubMed

Kutty, Jaishankar K; Webb, Ken

2009-01-01

Vocal fold injury commonly leads to reduced vocal quality due to scarring-induced alterations in matrix composition and tissue biomechanics. The long-term hypothesis motivating our work is that rapid restoration of phonation and the associated dynamic mechanical environment will reduce scarring and promote regenerative healing. Toward this end, the objective of this study was to develop mechanomimetic, degradable hydrogels approximating the viscoelastic properties of the vocal ligament and mucosa that may be photopolymerized in situ to restore structural integrity to vocal fold tissues. The tensile and rheological properties of hydrogels (targeting the vocal ligament and mucosa, respectively) were varied as a function of macromer concentration. PEG diacrylate-based hydrogels exhibited linear stress-strain response and elastic modulus consistent with the properties of the vocal ligament at low strains (0-15%), but did not replicate the non-linear behavior observed in native tissue at higher strains. Methacrylated hyaluronic acid hydrogels displayed dynamic viscosity consistent with native vocal mucosa, while elastic shear moduli values were several-fold higher. Cell culture studies indicated that both hydrogels supported spreading, proliferation and collagen/proteoglycan matrix deposition by encapsulated fibroblasts throughout the 3D network.

Colorimetric photonic hydrogel aptasensor for the screening of heavy metal ions.

PubMed

Ye, Bao-Fen; Zhao, Yuan-Jin; Cheng, Yao; Li, Ting-Ting; Xie, Zhuo-Ying; Zhao, Xiang-Wei; Gu, Zhong-Ze

2012-09-28

We have developed a robust method for the visual detection of heavy metal ions (such as Hg(2+) and Pb(2+)) by using aptamer-functionalized colloidal photonic crystal hydrogel (CPCH) films. The CPCHs were derived from a colloidal crystal array of monodisperse silica nanoparticles, which were polymerized within the polyacrylamide hydrogel. The heavy metal ion-responsive aptamers were then cross-linked in the hydrogel network. During detection, the specific binding of heavy metal ions and cross-linked single-stranded aptamers in the hydrogel network caused the hydrogel to shrink, which was detected as a corresponding blue shift in the Bragg diffraction peak position of the CPCHs. The shift value could be used to estimate, quantitatively, the amount of the target ion. It was demonstrated that our CPCH aptasensor could screen a wide concentration range of heavy metal ions with high selectivity and reversibility. In addition, these aptasensors could be rehydrated from dried gels for storage and aptamer protection. It is anticipated that our technology may also be used in the screening of a broad range of metal ions in food, drugs and the environment.

PEG-chitosan hydrogel with tunable stiffness for study of drug response of breast cancer cells

PubMed Central

Chang, Fei-Chien; Tsao, Ching-Ting; Lin, Anqi; Zhang, Mengying; Levengood, Sheeny Lan; Zhang, Miqin

2016-01-01

Mechanical properties of the extracellular matrix have a profound effect on the behavior of anchorage-dependent cells. However, the mechanisms that define the effects of matrix stiffness on cell behavior remains unclear. Therefore, the development and fabrication of synthetic matrices with well-defined stiffness is invaluable for studying the interactions of cells with their biophysical microenvironment in vitro. We demonstrate a methoxypolyethylene glycol (mPEG)-modified chitosan hydrogel network where hydrogel stiffness can be easily modulated under physiological conditions by adjusting the degree of mPEG grafting onto chitosan (PEGylation). We show that the storage modulus of the hydrogel increases as PEGylation decreases and the gels exhibit instant self-recovery after deformation. Breast cancer cells cultured on the stiffest hydrogels adopt a more malignant phenotype with increased resistance to doxorubicin as compared with cells cultured on tissue culture polystyrene or Matrigel. This work demonstrates the utility of mPEG-modified chitosan hydrogel, with tunable mechanical properties, as an improved replacement of conventional culture system for in vitro characterization of breast cancer cell phenotype and evaluation of cancer therapies. PMID:27595012

Tensile Properties of a Cellulose Ether Hydrogel

NASA Technical Reports Server (NTRS)

Hinkley, Jeffrey A.; Gehrke, Stevin H.

2003-01-01

Poly(hydroxycellulose) solutions were molded into dumbell-shaped specimens crosslinked with divinyl sulfone. The resulting hydrogels were tested in tension at room temperature and also at a temperature above the 40 C shrinkage transition. In contrast to behavior seen in some other responsive gels, apparent initial tangent moduli were lower in the shrunken state; breaking elongations were significantly higher. Possible molecular mechanisms are suggested, and implications for the design of temperature-responsive actuators ("artificial muscles") from this material are discussed.

Hygroscopic Metamorphic 4D Pleats

NASA Astrophysics Data System (ADS)

Yang, Shu

There have been significant interests in morphing 2D sheets into 3D structures via programmed out-of-plane distortion, including bending, tilting, rotating, and folding as seen in recent origami and kirigami strategies. Hydrogel is one of the unique soft materials that can swell and shrink, thereby enabling real-time 4D motions in response to external stimuli, such as pH, temperature, and moisture. To achieve reliable folding behaviors, it often requires a large amount of water molecules or ions diffusing in and out of the hydrogel sheet, thus the entire sheet is immersed in an aqueous solution. Here, we demonstrate the design and folding of hierarchical pleats patterned from a combination of hydrophobic and hygroscopic materials, allowing us to spatially and locally control the water condensation induced by environmental humidity. In turn, we show out-of-plane deformation of the 2D sheets only in the patterned hygroscopic regions, much like the folding behaviors of many plants. By designing the dimension, geometry, and density of hygroscopic microstructures (as pixels) in the hydrophobic materials, we can display the enhanced water condensation together with the spatial guidance of obtained droplets as unified water-harvesting systems. When the water droplets become large enough, they roll off from the hierarchical sheet along the inclined plane that is programmed by the hygroscopic motion of hydrogel, and eventually wrapped by the folded sheet to keep them from evaporation. We acknowledge support from NSF/EFRI-ODISSEI, EFRI 13-31583.

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.

A biohybrid hydrogel for the urate-responsive release of urate oxidase.

PubMed

Geraths, Christian; Daoud-El Baba, Marie; Charpin-El Hamri, Ghislaine; Weber, Wilfried

2013-10-10

Functional biomaterials that detect and correct pathological parameters hold high promises for biomedical application. In this study we describe a biohybrid hydrogel that detects elevated concentrations of uric acid and responds by dissolution and the release of uric acid-degrading urate oxidase. This material was synthesized by incorporating PEG-stabilized urate oxidase into a polyacrylamide hydrogel that was crosslinked by the uric acid-sensitive interaction between the uric acid transcription factor HucR and its operator hucO. We characterize the uric acid responsiveness of the material and demonstrate that it can effectively be applied to counteract flares of uric acid in a mouse model. This approach might be a first step towards a biomedical device autonomously managing uric acid burst associated to gouty arthritis and the tumor lysis syndrome. © 2013.

Dual Thermosensitive Hydrogels Assembled from the Conserved C-Terminal Domain of Spider Dragline Silk.

PubMed

Qian, Zhi-Gang; Zhou, Ming-Liang; Song, Wen-Wen; Xia, Xiao-Xia

2015-11-09

Stimuli-responsive hydrogels have great potentials in biomedical and biotechnological applications. Due to the advantages of precise control over molecular weight and being biodegradable, protein-based hydrogels and their applications have been extensively studied. However, protein hydrogels with dual thermosensitive properties are rarely reported. Here we present the first report of dual thermosensitive hydrogels assembled from the conserved C-terminal domain of spider dragline silk. First, we found that recombinant C-terminal domain of major ampullate spidroin 1 (MaSp1) of the spider Nephila clavipes formed hydrogels when cooled to approximately 2 °C or heated to 65 °C. The conformational changes and self-assembly of the recombinant protein were studied to understand the mechanism of the gelation processes using multiple methods. It was proposed that the gelation in the low-temperature regime was dominated by hydrogen bonding and hydrophobic interaction between folded protein molecules, whereas the gelation in the high-temperature regime was due to cross-linking of the exposed hydrophobic patches resulting from partial unfolding of the protein upon heating. More interestingly, genetic fusion of the C-terminal domain to a short repetitive region of N. clavipes MaSp1 resulted in a chimeric protein that formed a hydrogel with significantly improved mechanical properties at low temperatures between 2 and 10 °C. Furthermore, the formation of similar hydrogels was observed for the recombinant C-terminal domains of dragline silk of different spider species, thus demonstrating the conserved ability to form dual thermosensitive hydrogels. These findings may be useful in the design and construction of novel protein hydrogels with tunable multiple thermosensitivity for applications in the future.

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

3D Printing of Thermo-Responsive Methylcellulose Hydrogels for Cell-Sheet Engineering

PubMed Central

Cochis, Andrea; Sorrentino, Rita; Grassi, Federico; Leigheb, Massimiliano; Farè, Silvia

2018-01-01

A possible strategy in regenerative medicine is cell-sheet engineering (CSE), i.e., developing smart cell culture surfaces from which to obtain intact cell sheets (CS). The main goal of this study was to develop 3D printing via extrusion-based bioprinting of methylcellulose (MC)-based hydrogels. Hydrogels were prepared by mixing MC powder in saline solutions (Na2SO4 and PBS). MC-based hydrogels were analyzed to investigate the rheological behavior and thus optimize the printing process parameters. Cells were tested in vitro on ring-shaped printed hydrogels; bulk MC hydrogels were used for comparison. In vitro tests used murine embryonic fibroblasts (NIH/3T3) and endothelial murine cells (MS1), and the resulting cell sheets were characterized analyzing cell viability and immunofluorescence. In terms of CS preparation, 3D printing proved to be an optimal approach to obtain ring-shaped CS. Cell orientation was observed for the ring-shaped CS and was confirmed by the degree of circularity of their nuclei: cell nuclei in ring-shaped CS were more elongated than those in sheets detached from bulk hydrogels. The 3D printing process appears adequate for the preparation of cell sheets of different shapes for the regeneration of complex tissues. PMID:29642573

Development of pre-implantation porcine blastocysts cultured within alginate hydrogel systems either supplemented with secreted phosphoprotein 1 or conjugated with Arg-Gly-Asp Peptide.

PubMed

Laughlin, Taylor D; Miles, Jeremy R; Wright-Johnson, Elane C; Rempel, Lea A; Lents, Clay A; Pannier, Angela K

2017-11-01

Although deficiencies in porcine blastocyst elongation play a significant role in early embryonic mortality and establishment of within-litter developmental variation, the exact mechanisms of elongation are poorly understood. Secreted phosphoprotein 1 (SPP1) is increased within the uterine milieu during early porcine pregnancy and contains an Arg-Gly-Asp (RGD) peptide sequence that binds to cell surface integrins on the uterine endometrium and trophectoderm, promoting cell adhesion and migration. The aim of the present study was to evaluate the development of preimplantation porcine blastocysts encapsulated and cultured within alginate hydrogels either supplemented with SPP1 or conjugated with RGD. Blastocysts encapsulated within alginate hydrogels supplemented with SPP1 or conjugated with RGD had increased survival compared with non-encapsulated control blastocysts. In addition, the percentage of blastocysts encapsulated within RGD hydrogels that underwent morphological changes was greater than that of blastocysts encapsulated within standard alginate hydrogels or SPP1-supplemented hydrogels. Finally, only blastocysts encapsulated within RGD hydrogels had both increased expression of steroidogenic and immune responsiveness transcripts and increased 17β-oestradiol production, consistent with blastocysts undergoing elongation in vivo. These results illustrate the importance of the integrin-binding RGD peptide sequence for stimulating the initiation of blastocyst elongation.

Synergistically enhanced selective intracellular uptake of anticancer drug carrier comprising folic acid-conjugated hydrogels containing magnetite nanoparticles

NASA Astrophysics Data System (ADS)

Kim, Haneul; Jo, Ara; Baek, Seulgi; Lim, Daeun; Park, Soon-Yong; Cho, Soo Kyung; Chung, Jin Woong; Yoon, Jinhwan

2017-01-01

Targeted drug delivery has long been extensively researched since drug delivery and release at the diseased site with minimum dosage realizes the effective therapy without adverse side effects. In this work, to achieve enhanced intracellular uptake of anticancer drug carriers for efficient chemo-therapy, we have designed targeted multifunctional anticancer drug carrier hydrogels. Temperature-responsive poly(N-isopropylacrylamide) (PNIPAm) hydrogel core containing superparamagnetic magnetite nanoparticles (MNP) were prepared using precipitation polymerization, and further polymerized with amine-functionalized copolymer shell to facilitate the conjugation of targeting ligand. Then, folic acid, specific targeting ligand for cervical cancer cell line (HeLa), was conjugated on the hydrogel surface, yielding the ligand conjugated hybrid hydrogels. We revealed that enhanced intracellular uptake by HeLa cells in vitro was enabled by both magnetic attraction and receptor-mediated endocytosis, which were contributed by MNP and folic acid, respectively. Furthermore, site-specific uptake of the developed carrier was confirmed by incubating with several other cell lines. Based on synergistically enhanced intracellular uptake, efficient cytotoxicity and apoptotic activity of HeLa cells incubated with anticancer drug loaded hybrid hydrogels were successfully achieved. The developed dual-targeted hybrid hydrogels are expected to provide a platform for the next generation intelligent drug delivery systems.

Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels

PubMed Central

Yue, Kan; Santiago, Grissel Trujillo-de; Alvarez, Mario Moisés; Tamayol, Ali; Annabi, Nasim; Khademhosseini, Ali

2015-01-01

Gelatin methacryloyl (GelMA) hydrogels have been widely used for various biomedical applications due to their suitable biological properties and tunable physical characteristics. Three dimensional (3D) GelMA hydrogels closely resemble some essential properties of native extracellular matrix (ECM) due to the presence of cell-attaching and matrix metalloproteinase responsive peptide motifs, which allow cells to proliferate and spread in GelMA-based scaffolds. GelMA is also versatile from a processing perspective. It crosslinks when exposed to light irradiation to form hydrogels with tunable mechanical properties which mimic the native ECM. It can also be microfabricated using different methodologies including micromolding, photomasking, bioprinting, self-assembly, and microfluidic techniques to generate constructs with controlled architectures. Hybrid hydrogel systems can also be formed by mixing GelMA with nanoparticles such as carbon nanotubes and graphene oxide, and other polymers to form networks with desired combined properties and characteristics for specific biological applications. Recent research has demonstrated the proficiency of GelMA-based hydrogels in a wide range of applications including engineering of bone, cartilage, cardiac, and vascular tissues, among others. Other applications of GelMA hydrogels, besides tissue engineering, include fundamental single-single cell research, cell signaling, drug and gene delivery, and bio-sensing. PMID:26414409

Automation of 3D cell culture using chemically defined hydrogels.

PubMed

Rimann, Markus; Angres, Brigitte; Patocchi-Tenzer, Isabel; Braum, Susanne; Graf-Hausner, Ursula

2014-04-01

Drug development relies on high-throughput screening involving cell-based assays. Most of the assays are still based on cells grown in monolayer rather than in three-dimensional (3D) formats, although cells behave more in vivo-like in 3D. To exemplify the adoption of 3D techniques in drug development, this project investigated the automation of a hydrogel-based 3D cell culture system using a liquid-handling robot. The hydrogel technology used offers high flexibility of gel design due to a modular composition of a polymer network and bioactive components. The cell inert degradation of the gel at the end of the culture period guaranteed the harmless isolation of live cells for further downstream processing. Human colon carcinoma cells HCT-116 were encapsulated and grown in these dextran-based hydrogels, thereby forming 3D multicellular spheroids. Viability and DNA content of the cells were shown to be similar in automated and manually produced hydrogels. Furthermore, cell treatment with toxic Taxol concentrations (100 nM) had the same effect on HCT-116 cell viability in manually and automated hydrogel preparations. Finally, a fully automated dose-response curve with the reference compound Taxol showed the potential of this hydrogel-based 3D cell culture system in advanced drug development.

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.

Touch Locating and Stretch Sensing Studies of Conductive Hydrogels with Applications to Soft Robots.

PubMed

Zhou, Yanmin; He, Bin; Yan, Zhe; Shang, Yinghui; Wang, Qigang; Wang, Zhipeng

2018-02-13

Soft robots possess great potential in environmental adaptations, while their environmental sensing abilities are critical. Conductive hydrogels have been suggested to possess sensing abilities. However, their application in soft robots is lacking. In this work, we fabricated a soft and stretchable gel material, introduced its sensing mechanisms, and developed a measurement setup. Both experimental and simulation studies indicate strong nonlinearity of touch locating on a square touch panel with Cartesian coordinates. To simplify the touch locating, we proposed a touch locating system based on round touch panels with polar coordinates. Mathematical calculations and finite element method (FEM) simulations showed that in this system the locating of a touch point was only determined by its polar radius. This was verified by experimental studies. As a resistor, a gel strip's resistance increases with stretching. To demonstrate their applications on soft robots, a 3D printed three-fingered soft gripper was employed with gel strips attached. During finger bending for rod grasping, the resistances of the gel strips increased, indicating stretching of the soft material. Furthermore, the strain and stress of a gel strip increased with a decrease of the rod diameter. These studies advance the application of conductive hydrogels on soft robots.

Artificial phototropism based on a photo-thermo-responsive hydrogel

NASA Astrophysics Data System (ADS)

Gopalakrishna, Hamsini

Solar energy is leading in renewable energy sources and the aspects surrounding the efforts to harvest light are gaining importance. One such aspect is increasing the light absorption, where heliotropism comes into play. Heliotropism, the ability to track the sun across the sky, can be integrated with solar cells for more efficient photon collection and other optoelectronic systems. Inspired by plants, which optimize incident sunlight in nature, several researchers have made artificial heliotropic and phototropic systems. This project aims to design, synthesize and characterize a material system and evaluate its application in a phototropic system. A gold nanoparticle (Au NP) incorporated poly(N-isopropylacrylamide) (PNIPAAm) hydrogel was synthesized as a photo-thermo-responsive material in our phototropic system. The Au NPs generate heat from the incident via plasmonic resonance to induce a volume phase change of the thermo-responsive hydrogel PNIPAAm. PNIPAAm shrinks or swells at temperature above or below 32°C. Upon irradiation, the Au NP-PNIPAAm micropillar actuates, specifically bending toward the incident light and precisely following the varying incident angle. Swelling ratio tests, bending angle tests with a static incident light and bending tests with varying angles were carried out on hydrogel samples with varying Au NP concentrations. Swelling ratios ranging from 1.45 to 2.9 were recorded for pure hydrogel samples and samples with very low Au NP concentrations. Swelling ratios of 2.41 and 3.37 were calculated for samples with low and high concentrations of Au NPs, respectively. A bending of up to 88° was observed in Au NP-hydrogel pillars with a low Au NP concentration with a 90° incident angle. The light tracking performance was assessed by the slope of the pillar Bending angle (response angle) vs. Incident light angle plot. A slope of 1 indicates ideal tracking with top of the pillar being normal to the incident light, maximizing the photon absorption. Slopes of 0.82 and 0.56 were observed for the low and high Au NP concentration samples. The rapid and precise incident light tracking of our system has shown the promise in phototropic applications.

Engineered 3D-scaffolds of photocrosslinked chitosan-gelatin hydrogel hybrids for chronic wound dressings and regeneration.

PubMed

Carvalho, Isadora C; Mansur, Herman S

2017-09-01

Wound repair is one of the most complex biological processes in human life. To date, no ideal biomaterial solution has been identified, which that encompasses all functions and properties of real skin tissue. Thus, this study focused on the synthesis of new biocompatible hybrid hydrogel scaffolds based on methacrylate-functionalized high molecular mass chitosan with gelatin-A photocrosslinked with UV radiation to tailor matrix network properties. These hybrid hydrogels were produced via freeze-drying and were extensively characterized by swelling and degradation measurements, Fourier transform infrared spectroscopy (FTIR), UV-visible spectroscopy (UV-Vis), scanning electron microscopy (SEM-EDS), and micro-computed tomography (micro-CT). The results demonstrated that hydrogels were produced with broadly designed swelling degrees typically ranging from 500% to 2000%, which were significantly dependent on the relative concentration of polymers and irradiation time for crosslinking. Analogously, degradation was reduced with increased photocrosslinking of the network. Moreover, insights into the mechanism of photochemical crosslinking were suggested based on FTIR and UV-Vis analyses of the characteristic functional groups involved in the reactions. SEM analysis associated with micro-CT imaging of the hybrid scaffolds showed uniformly interconnected 3D porous structures, with architectural features affected by the crosslinking of the network. These hydrogels were biocompatible, with live cell viability responses of human embryonic kidney (HEK293T) cells being above 95%. Hence, novel hybrid hydrogels were designed and produced with tunable properties through photocrosslinking and with a biocompatible response suitable for use in wound dressing and skin tissue repair applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Design of a Coupled Thermoresponsive Hydrogel and Robotic System for Postinfarct Biomaterial Injection Therapy

PubMed Central

Fok, Kevin; Yoshizumi, Tomo; Park, Daewoo; Jiang, Hongbin; Schwartzman, David S.; Zenati, Marco A.; Uchibori, Takafumi

2016-01-01

Background In preclinical testing, ventricular wall injection of hydrogels has been shown to be effective in modulating ventricular remodeling and preserving cardiac function. For some approaches, early-stage clinical trials are under way. The hydrogel delivery method varies, with minimally invasive approaches being preferred. Endocardial injections carry a risk of hydrogel regurgitation into the circulation, and precise injection patterning is a challenge. An epicardial approach with a thermally gelling hydrogel through the subxiphoid pathway overcomes these disadvantages. Methods A relatively stiff, thermally responsive, injectable hydrogel based on N-isopropylacrylamide and N-vinylpyrrolidone (VP gel) was synthesized and characterized. VP gel thermal behavior was tuned to couple with a transepicardial injection robot, incorporating a cooling feature to achieve injectability. Ventricular wall injections of the optimized VP gel have been performed ex vivo and on beating porcine hearts. Results Thermal transition temperature, viscosity, and gelling time for the VP gel were manipulated by altering N-vinylpyrrolidone content. The target parameters for cooling in the robotic system were chosen by thermal modeling to support smooth, repeated injections on an ex vivo heart. Injections at predefined locations and depth were confirmed in an infarcted porcine model. Conclusions A coupled thermoresponsive hydrogel and robotic injection system incorporating a temperature-controlled injectate line was capable of targeted injections and amenable to use with a subxiphoid transepicardial approach for hydrogel injection after myocardial infarction. The confirmation of precise location and depth injections would facilitate a patient-specific planning strategy to optimize injection patterning to maximize the mechanical benefits of hydrogel placement. PMID:27154150

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.

Shape-Morphing Materials from Stimuli-Responsive Hydrogel Hybrids.

PubMed

Jeon, Seog-Jin; Hauser, Adam W; Hayward, Ryan C

2017-02-21

The formation of well-defined and functional three-dimensional (3D) structures by buckling of thin sheets subjected to spatially nonuniform stresses is common in biological morphogenesis and has become a subject of great interest in synthetic systems, as such programmable shape-morphing materials hold promise in areas including drug delivery, biomedical devices, soft robotics, and biomimetic systems. Given their ability to undergo large changes in swelling in response to a wide variety of stimuli, hydrogels have naturally emerged as a key type of material in this field. Of particular interest are hybrid systems containing rigid inclusions that can define both the anisotropy and spatial nonuniformity of swelling as well as nanoparticulate additives that can enhance the responsiveness and functionality of the material. In this Account, we discuss recent progress in approaches to achieve well-defined shape morphing in hydrogel hybrids. First, we provide an overview of materials and methods that facilitate fabrication of such systems and outline the geometry and mechanics behind shape morphing of thin sheets. We then discuss how patterning of stiff inclusions within soft responsive hydrogels can be used to program both bending and swelling, thereby providing access to a wide array of complex 3D forms. The use of discretely patterned stiff regions to provide an effective composite response offers distinct advantages in terms of scalability and ease of fabrication compared with approaches based on smooth gradients within a single layer of responsive material. We discuss a number of recent advances wherein control of the mechanical properties and geometric characteristics of patterned stiff elements enables the formation of 3D shapes, including origami-inspired structures, concatenated helical frameworks, and surfaces with nonzero Gaussian curvature. Next, we outline how the inclusion of functional elements such as nanoparticles can enable unique pathways to programmable and even reprogrammable shape-morphing materials. We focus to a large extent on photothermally reprogrammable systems that include one of a variety of additives that serve to efficiently absorb light and convert it into heat, thereby driving the response of a temperature-sensitive hydrogel. Such systems are advantageous in that patterns of light can be defined with very high spatial and temporal resolution in addition to offering the potential for wavelength-selective addressability of multiple different inclusions. We highlight recent advances in the preparation of light-responsive hybrid systems capable of undergoing reprogrammable bending and buckling into well-defined 3D shapes. In addition, we describe several examples where shape tuning of hybrid systems enables control over the motion of responsive hydrogel-based materials. Finally, we offer our perspective on open challenges and future areas of interest for the field.

On the Interaction between Superabsorbent Hydrogels and Cementitious Materials

NASA Astrophysics Data System (ADS)

Farzanian, Khashayar

Autogenous shrinkage induced cracking is a major concern in high performance concretes (HPC), which are produced with low water to cement ratios. Internal curing to maintain high relative humidity in HPC with the use of an internal water reservoir has proven effective in mitigating autogenous shrinkage in HPC. Superabsorbent polymers (SAP) or hydrogels have received increasing attention as an internal curing agent in recent years. A key advantage of SAP is its versatility in size distribution and absorption/desorption characteristics, which allow it to be adapted to specific mix designs. Understanding the behavior of superabsorbent hydrogels in cementitious materials is critical for accurate design of internal curing. The primary goal of this study is to fundamentally understand the interaction between superabsorbent hydrogels and cementitious materials. In the first step, the effect of chemical and mechanical conditions on the absorption of hydrogels is investigated. In the second step, the desorption of hydrogels in contact with porous cementitious materials is examined to aid in understanding the mechanisms of water release from superabsorbent hydrogels (SAP) into cementitious materials. The dependence of hydrogel desorption on the microstructure of cementitious materials and relative humidity is studied. It is shown that the capillary forces developed at the interface between the hydrogel and cementitious materials increased the desorption of the hydrogels. The size of hydrogels is shown to influence desorption, beyond the known size dependence of bulk diffusion, through debonding from the cementitious matrix, thereby decreasing the effect of the Laplace pressure on desorption. In the third step, the desorption of hydrogels synthesized with varied chemical compositions in cementitious materials are investigated. The absorption, chemical structure and mechanical response of hydrogels swollen in a cement mixture are studied. The effect of the capillary forces on the desorption of hydrogels is investigated in relation to the chemical composition of the hydrogels. In the second set of experiments of this part, the behavior of the hydrogels in a hydrating cement paste is monitored by tracking the size and morphology evolution of hydrogels interacting with the cement paste matrix. It is shown that the changes on the surface characteristics of hydrogels as a result of interactions with the pore solution and cement particles can affect the desorption rate of hydrogels in contact with a porous cementitious material. Scanning electron microscopic (SEM) examination demonstrates two different desorption modes with distinct morphologies of hydrogels depending on the chemical composition of hydrogels. The effect of the interfacial bonding between the hydrogels and the cementitious matrix and its relation to the desorption is illustrated. The desorption of hydrogels with different chemical compositions in blended cement mixture containing different supplementary cementitious materials (SCMs) such as slag, fly ash, silica fume and two types of glass powders, are examined. The absorption/desorption kinetics of hydrogels in different hydrating blended cement mixtures are monitored by freeze drying the samples at different times. The surface characteristics of different hydrogels after interaction with pore solution, cement particles and SCMs particles are examined and their relation to interfacial bonding is illustrated. It is shown that different SCMs can cause distinct changes on interfacial bonding. The understanding of hydrogel behavior in cementitious materials helps with accurate mixture design for internal curing. The kinetics of desorption is crucial for the purpose of internal curing. The understanding of release mechanisms and the change in the hydrogel morphology is important for the self-healing and self-sealing applications. Two major contributions of this research are (1) to show the effect of capillary forces developed at the interface between cementitious matrix and hydrogel which can increase the rate of desorption dramatically and (2) to illustrate the chemo-physical interaction between cement pore solution and hydrating particles with hydrogels which can affect the interfacial bonding between hydrogel and cement. These two main contributions will be useful to understand the absorption and desorption behavior of hydrogel in cementitious materials. Two main strengths of experimental procedures of this research are (1) use of in-house synthesis of hydrogels that permits establishing a link between the chemical composition of hydrogels and their behavior in cementitious materials and (2) use of freeze drying for the first time to monitor the behavior of hydrogels interacting with a hydrating cementitious matrix.

'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.

Supramolecular gelation of a polymeric prodrug for its encapsulation and sustained release.

PubMed

Ma, Dong; Zhang, Li-Ming

2011-09-12

A polymeric prodrug, PEGylated indomethacin (MPEG-indo), was prepared and then used to interact with α-cyclodextrin (α-CD) in their aqueous mixed system. This process could lead to the formation of supramolecular hydrogel under mild conditions and simultaneous encapsulation of MPEG-indo in the hydrogel matrix. For the formed supramolecular hydrogel, its gelation kinetics, mechanical strength, shear-thinning behavior and thixotropic response were investigated with respect to the effects of MPEG-indo and α-CD amounts by dynamic and steady rheological tests. Meanwhile, the possibility of using this hydrogel matrix as injectable drug delivery system was also explored. By in vitro release and cell viability tests, it was found that the encapsulated MPEG-indo could exhibit a controlled and sustained release behavior as well as maintain its biological activity.

Mechanical reinforcement of gellan gum polyelectrolyte hydrogels by cationic polyurethane soft nanoparticles.

PubMed

Sahraro, Maryam; Barikani, Mehdi; Daemi, Hamed

2018-05-01

Novel mechanically reinforced nanocomposite hydrogels (NCHs) were developed based on methacrylated gellan gum (MGG) and cationic polyurethane nanoparticles (CPUNs) through a green chemical approach. A series of NCHs were synthesized by the incorporation of CPUNs with weight ratios of 0, 10, 30 and 50 w/w% into the MGG solution, with two different methacrylation degrees (1.2, 5.6%). The chemical structure, morphology, mechanical properties, stimuli-responsivity and cytotoxicity of synthesized NCHs were investigated. Analysis of the hydrogels mechanical testing demonstrated that the addition of CPUNs affords the significant increase in compressive properties. Meanwhile, the formulation of NCH containing the MGG with lower methacrylation degree and 30 w/w% CPUNs showed the highest mechanical properties. Furthermore, equilibrium swelling ratio of the hydrogels decreased by CPUNs addition. Finally, it is worth mentioning that NCHs showed no significant toxicity to human dermal fibroblast cells (HDFs) which idealize them as the suitable hydrogels for biomedical applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical Sintering Generates Uniform Porous Hyaluronic Acid Hydrogels

PubMed Central

Cam, Cynthia; Segura, Tatiana

2014-01-01

Implantation of scaffolds for tissue repair has been met with limited success primarily due to the inability to achieve vascularization within the construct. Many strategies have shifted to incorporate pores into these scaffolds to encourage rapid cellular infiltration and subsequent vascular ingrowth. We utilized an efficient chemical sintering technique to create a uniform network of polymethyl methacrylate (PMMA) microspheres for porous hyaluronic acid hydrogel formation. The porous hydrogels generated from chemical sintering possessed comparable pore uniformity and interconnectivity as the commonly used non- and heat sintering techniques. Moreover, similar cell response to the porous hydrogels generated from each sintering approach was observed in cell viability, spreading, proliferation in vitro, as well as, cellular invasion in vivo. We propose chemical sintering of PMMA microspheres using a dilute acetone solution as an alternative method to generating porous hyaluronic acid hydrogels since it requires equal or ten-fold less processing time as the currently used non-sintering or heat sintering technique, respectively. PMID:24120847

Photoactive Self-Shaping Hydrogels as Noncontact 3D Macro/Microscopic Photoprinting Platforms.

PubMed

Liao, Yue; An, Ning; Wang, Ning; Zhang, Yinyu; Song, Junfei; Zhou, Jinxiong; Liu, Wenguang

2015-12-01

A photocleavable terpolymer hydrogel cross-linked with o-nitrobenzyl derivative cross-linker is shown to be capable of self-shaping without losing its physical integrity and robustness due to spontaneous asymmetric swelling of network caused by UV-light-induced gradient cleavage of chemical cross-linkages. The continuum model and finite element method are used to elucidate the curling mechanism underlying. Remarkably, based on the self-changing principle, the photosensitive hydrogels can be developed as photoprinting soft and wet platforms onto which specific 3D characters and images are faithfully duplicated in macro/microscale without contact by UV light irradiation under the cover of customized photomasks. Importantly, a quick response (QR) code is accurately printed on the photoactive hydrogel for the first time. Scanning QR code with a smartphone can quickly connect to a web page. This photoactive hydrogel is promising to be a new printing or recording material. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

3D hydrogel scaffold doped with 2D graphene materials for biosensors and bioelectronics.

PubMed

Song, Hyun Seok; Kwon, Oh Seok; Kim, Jae-Hong; Conde, João; Artzi, Natalie

2017-03-15

Hydrogels consisting of three-dimensional (3D) polymeric networks have found a wide range of applications in biotechnology due to their large water capacity, high biocompatibility, and facile functional versatility. The hydrogels with stimulus-responsive swelling properties have been particularly instrumental to realizing signal transduction in biosensors and bioelectronics. Graphenes are two-dimensional (2D) nanomaterials with unprecedented physical, optical, and electronic properties and have also found many applications in biosensors and bioelectronics. These two classes of materials present complementary strengths and limitations which, when effectively coupled, can result in significant synergism in their electrical, mechanical, and biocompatible properties. This report reviews recent advances made with hydrogel and graphene materials for the development of high-performance bioelectronics devices. The report focuses on the interesting intersection of these materials wherein 2D graphenes are hybridized with 3D hydrogels to develop the next generation biosensors and bioelectronics. Copyright © 2016 Elsevier B.V. All rights reserved.

Bio-inspired metal-coordinate hydrogels with programmable viscoelastic material functions controlled by longwave UV light.

PubMed

Grindy, Scott C; Holten-Andersen, Niels

2017-06-07

Control over the viscoelastic mechanical properties of hydrogels intended for use as biomedical materials has long been a goal of soft matter scientists. Recent research has shown that materials made from polymers with reversibly associating transient crosslinks are a promising strategy for controlling viscoelasticity in hydrogels, for example leading to systems with precisely tunable mechanical energy-dissipation. We and others have shown that bio-inspired histidine:transition metal ion complexes allow highly precise and tunable control over the viscoelastic properties of transient network hydrogels. In this paper, we extend the design of these hydrogels such that their viscoelastic properties respond to longwave UV radiation. We show that careful selection of the histidine:transition metal ion crosslink mixtures allows unique control over pre- and post-UV viscoelastic properties. We anticipate that our strategy for controlling stimuli-responsive viscoelastic properties will aid biomedical materials scientists in the development of soft materials with specific stress-relaxing or energy-dissipating properties.

Carbohydrate hydrogels with stabilized phage particles for bacterial biosensing: bacterium diffusion studies.

PubMed

Balcão, Victor M; Barreira, Sérgio V P; Nunes, Thiago M; Chaud, Marco V; Tubino, Matthieu; Vila, Marta M D C

2014-02-01

Bacteriophage particles have been reported as potentially useful in the development of diagnosis tools for pathogenic bacteria as they specifically recognize and lyse bacterial isolates thus confirming the presence of viable cells. One of the most representative microorganisms associated with health care services is the bacterium Pseudomonas aeruginosa, which alone is responsible for nearly 15% of all nosocomial infections. In this context, structural and functional stabilization of phage particles within biopolymeric hydrogels, aiming at producing cheap (chromogenic) bacterial biosensing devices, has been the goal of a previous research effort. For this, a detailed knowledge of the bacterial diffusion profile into the hydrogel core, where the phage particles lie, is of utmost importance. In the present research effort, the bacterial diffusion process into the biopolymeric hydrogel core was mathematically described and the theoretical simulations duly compared with experimental results, allowing determination of the effective diffusion coefficients of P. aeruginosa in the agar and calcium alginate hydrogels tested.

Biocompatibility and in vivo degradation of chitosan based hydrogels as potential drug carrier.

PubMed

Su, Feng; Wang, Yuandou; Liu, Xue; Shen, Xin; Zhang, Xingjian; Xing, Quansheng; Wang, Lihong; Chen, Yangsheng

2018-06-07

Carboxymethyl chitosan-graft-polylactide (CMCS-PLA) and carboxymethyl chitosan (CMCS) hydrogels were prepared by using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) as crosslinking agent and catalyst at room temperature. The biocompatibility of the hydrogels was evaluated with the aim of assessing their potential as drug carrier. Various aspects of biocompatibility were considered, including MTT assay, agar diffusion test, release of lactate dehydrogenase (LDH), hemolytic test, plasma recalcification time (PRT), and dynamic clotting time. MTT assay showed that the cytotoxicity level of both hydrogels to L-929 cells was 0 or 1. The LDH release of CMCS and CMCS-PLA was 26 and 29%, respectively, which is slightly higher than that of the negative control (21%) and much lower than that of the negative control (87%). The hemolysis ratio of CMCS and CMCS-PLA was 1.4 and 1.7%, respectively, suggesting outstanding anti-hemolysis properties of both materials. The PRT value of CMCS and CMCS-PLA was higher by 77 and 99% than the value of the positive control. All the results revealed that the hydrogels present good cytocompatibility and hemocompatibility in vitro. In vivo degradation and tissue compatibility were evaluated by subcutaneous injection in the dorsal area of rats. CMCS and CMCS-PLA hydrogels were completely degraded and the inflammatory response also completely disappeared around hydrogels after 19 days in vivo. It is thus concluded that hydrogels formed of CMCS and CMCS-PLA with outstanding biocompatibility are promising as potential drug carrier.

Pore Interconnectivity Influences Growth Factor-Mediated Vascularization in Sphere-Templated Hydrogels

PubMed Central

Somo, Sami I.; Akar, Banu; Bayrak, Elif S.; Larson, Jeffery C.; Appel, Alyssa A.; Mehdizadeh, Hamidreza; Cinar, Ali

2015-01-01

Rapid and controlled vascularization within biomaterials is essential for many applications in regenerative medicine. The extent of vascularization is influenced by a number of factors, including scaffold architecture. While properties such as pore size and total porosity have been studied extensively, the importance of controlling the interconnectivity of pores has received less attention. A sintering method was used to generate hydrogel scaffolds with controlled pore interconnectivity. Poly(methyl methacrylate) microspheres were used as a sacrificial agent to generate porous poly(ethylene glycol) diacrylate hydrogels with interconnectivity varying based on microsphere sintering conditions. Interconnectivity levels increased with sintering time and temperature with resultant hydrogel structure showing agreement with template structure. Porous hydrogels with a narrow pore size distribution (130–150 μm) and varying interconnectivity were investigated for their ability to influence vascularization in response to gradients of platelet-derived growth factor-BB (PDGF-BB). A rodent subcutaneous model was used to evaluate vascularized tissue formation in the hydrogels in vivo. Vascularized tissue invasion varied with interconnectivity. At week 3, higher interconnectivity hydrogels had completely vascularized with twice as much invasion. Interconnectivity also influenced PDGF-BB transport within the scaffolds. An agent-based model was used to explore the relative roles of steric and transport effects on the observed results. In conclusion, a technique for the preparation of hydrogels with controlled pore interconnectivity has been developed and evaluated. This method has been used to show that pore interconnectivity can independently influence vascularization of biomaterials. PMID:25603533

Biocompatibility in the development of silicone-hydrogel lenses.

PubMed

Jacob, Jean T

2013-01-01

In response to patient demands for extended contact lens wearing times, the contact lens industry has developed novel silicone-hydrogel (SiHy) lens materials that combine the enhanced oxygen permeability of silicone polymers with the water-based comfort of conventional hydrogels. In the past 12 years since the successful launch of these SiHy lenses, much has been learned about their ability to provide the biocompatibility necessary to sustain ocular health and comfort. A review of the unique physiologic requirements for a successful extended wear lens and how the first and current SiHy lenses address them is provided.

Preparation of SMART wound dressings based on colloidal microgels and textile fibres

NASA Astrophysics Data System (ADS)

Cornelius, Victoria J.; Majcen, Natasa; Snowden, Martin J.; Mitchell, John C.; Voncina, Bojana

2007-01-01

Wound dressings and other types of wound healing technologies are experiencing fast-paced development and rapid growth. As the population ages, demand will continue to rise for advanced dressings used to treat chronic wounds, such as pressure ulcers, venous stasis ulcers, and diabetic ulcers. Moist wound dressings, which facilitate natural wound healing in a cost-effective manner, will be increasingly important. In commercially available hydrogel / gauze wound dressings the gel swells to adsorb wound excreta and provide an efficient non adhesive particle barrier. An alternative to hydrogels are microgels. Essentially discrete colloidal gel particles, as a result of their very high surface area to volume ratio compared to bulk gels, they have a much faster response to external stimuli such as temperature or pH. In response to either an increase or decrease in solvent quality these porous networks shrink and swell reversibly. When swollen the interstitial regions within the polymer matrix are available for further chemistry; such as the incorporation of small molecules. The reversible shrinking and swelling as a function of external stimuli provides a novel drug release system. As the environmental conditions of a wound change over its lifetime, tending to increase in pH if there is an infection combining these discrete polymeric particles with a substrate such as cotton, results in a smart wound dressing.

X-ray Phase Contrast Allows Three Dimensional, Quantitative Imaging of Hydrogel Implants

PubMed Central

Appel, Alyssa A.; Larson, Jeffery C.; Jiang, Bin; Zhong, Zhong; Anastasio, Mark A.; Brey, Eric M.

2015-01-01

Three dimensional imaging techniques are needed for the evaluation and assessment of biomaterials used for tissue engineering and drug delivery applications. Hydrogels are a particularly popular class of materials for medical applications but are difficult to image in tissue using most available imaging modalities. Imaging techniques based on X-ray Phase Contrast (XPC) have shown promise for tissue engineering applications due to their ability to provide image contrast based on multiple X-ray properties. In this manuscript, we investigate the use of XPC for imaging a model hydrogel and soft tissue structure. Porous fibrin loaded poly(ethylene glycol) hydrogels were synthesized and implanted in a rodent subcutaneous model. Samples were explanted and imaged with an analyzer-based XPC technique and processed and stained for histology for comparison. Both hydrogel and soft tissues structures could be identified in XPC images. Structure in skeletal muscle adjacent could be visualized and invading fibrovascular tissue could be quantified. There were no differences between invading tissue measurements from XPC and the gold-standard histology. These results provide evidence of the significant potential of techniques based on XPC for 3D imaging of hydrogel structure and local tissue response. PMID:26487123

Frequency-Dependent Magnetic Susceptibility of Magnetite and Cobalt Ferrite Nanoparticles Embedded in PAA Hydrogel

PubMed Central

van Berkum, Susanne; Dee, Joris T.; Philipse, Albert P.; Erné, Ben H.

2013-01-01

Chemically responsive hydrogels with embedded magnetic nanoparticles are of interest for biosensors that magnetically detect chemical changes. A crucial point is the irreversible linkage of nanoparticles to the hydrogel network, preventing loss of nanoparticles upon repeated swelling and shrinking of the gel. Here, acrylic acid monomers are adsorbed onto ferrite nanoparticles, which subsequently participate in polymerization during synthesis of poly(acrylic acid)-based hydrogels (PAA). To demonstrate the fixation of the nanoparticles to the polymer, our original approach is to measure low-field AC magnetic susceptibility spectra in the 0.1 Hz to 1 MHz range. In the hydrogel, the magnetization dynamics of small iron oxide nanoparticles are comparable to those of the particles dispersed in a liquid, due to fast Néel relaxation inside the particles; this renders the ferrogel useful for chemical sensing at frequencies of several kHz. However, ferrogels holding thermally blocked iron oxide or cobalt ferrite nanoparticles show significant decrease of the magnetic susceptibility resulting from a frozen magnetic structure. This confirms that the nanoparticles are unable to rotate thermally inside the hydrogel, in agreement with their irreversible fixation to the polymer network. PMID:23673482

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.

X-ray Phase Contrast Allows Three Dimensional, Quantitative Imaging of Hydrogel Implants

DOE PAGES

Appel, Alyssa A.; Larson, Jeffrey C.; Jiang, Bin; ...

2015-10-20

Three dimensional imaging techniques are needed for the evaluation and assessment of biomaterials used for tissue engineering and drug delivery applications. Hydrogels are a particularly popular class of materials for medical applications but are difficult to image in tissue using most available imaging modalities. Imaging techniques based on X-ray Phase Contrast (XPC) have shown promise for tissue engineering applications due to their ability to provide image contrast based on multiple X-ray properties. In this manuscript we describe results using XPC to image a model hydrogel and soft tissue structure. Porous fibrin loaded poly(ethylene glycol) hydrogels were synthesized and implanted inmore » a rodent subcutaneous model. Samples were explanted and imaged with an analyzer-based XPC technique and processed and stained for histology for comparison. Both hydrogel and soft tissues structures could be identified in XPC images. Structure in skeletal muscle adjacent could be visualized and invading fibrovascular tissue could be quantified. In quantitative results, there were no differences between XPC and the gold-standard histological measurements. These results provide evidence of the significant potential of techniques based on XPC for 3D imaging of hydrogel structure and local tissue response.« less

Heparin-based hydrogels induce human renal tubulogenesis in vitro.

PubMed

Weber, Heather M; Tsurkan, Mikhail V; Magno, Valentina; Freudenberg, Uwe; Werner, Carsten

2017-07-15

Dialysis or kidney transplantation is the only therapeutic option for end stage renal disease. Accordingly, there is a large unmet clinical need for new causative therapeutic treatments. Obtaining robust models that mimic the complex nature of the human kidney is a critical step in the development of new therapeutic strategies. Here we establish a synthetic in vitro human renal tubulogenesis model based on a tunable glycosaminoglycan-hydrogel platform. In this system, renal tubulogenesis can be modulated by the adjustment of hydrogel mechanics and degradability, growth factor signaling, and the presence of insoluble adhesion cues, potentially providing new insights for regenerative therapy. Different hydrogel properties were systematically investigated for their ability to regulate renal tubulogenesis. Hydrogels based on heparin and matrix metalloproteinase cleavable peptide linker units were found to induce the morphogenesis of single human proximal tubule epithelial cells into physiologically sized tubule structures. The generated tubules display polarization markers, extracellular matrix components, and organic anion transport functions of the in vivo renal proximal tubule and respond to nephrotoxins comparable to the human clinical response. The established hydrogel-based human renal tubulogenesis model is thus considered highly valuable for renal regenerative medicine and personalized nephrotoxicity studies. The only cure for end stage kidney disease is kidney transplantation. Hence, there is a huge need for reliable human kidney models to study renal regeneration and establish alternative treatments. Here we show the development and application of an in vitro human renal tubulogenesis model using heparin-based hydrogels. To the best of our knowledge, this is the first system where human renal tubulogenesis can be monitored from single cells to physiologically sized tubule structures in a tunable hydrogel system. To validate the efficacy of our model as a drug toxicity platform, a chemotherapy drug was incubated with the model, resulting in a drug response similar to human clinical pathology. The established model could have wide applications in the field of nephrotoxicity and renal regenerative medicine and offer a reliable alternative to animal models. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Temperature and magnetic field responsive hyaluronic acid particles with tunable physical and chemical properties

NASA Astrophysics Data System (ADS)

Ekici, Sema; Ilgin, Pinar; Yilmaz, Selahattin; Aktas, Nahit; Sahiner, Nurettin

2011-01-01

We report the preparation and characterization of thiolated-temperature-responsive hyaluronic acid-cysteamine-N-isopropyl acrylamide (HA-CYs-NIPAm) particles and thiolated-magnetic-responsive hyaluronic acid (HA-Fe-CYs) particles. Linear hyaluronic acid (HA) crosslinked with divinyl sulfone as HA particles was prepared using a water-in-oil micro emulsion system which were then oxidized HA-O with NaIO4 to develop aldehyde groups on the particle surface. HA-O hydrogel particles were then reacted with cysteamine (CYs) which interacted with aldehydes on the HA surface to form HA particles with cysteamine (HA-CYs) functionality on the surface. HA-CYs particles were further exposed to radical polymerization with NIPAm to obtain temperature responsive HA-CYs-NIPAm hydrogel particles. To acquire magnetic field responsive HA composites, magnetic iron particles were included in HA to form HA-Fe during HA particle preparation. HA-Fe hydrogel particles were also chemically modified. The prepared HA-CYs-NIPAm demonstrated temperature dependent size variations and phase transition temperature. HA-CYs-NIPAm and HA-Fe-CYs particles can be used as drug delivery vehicles. Sulfamethoxazole (SMZ), an antibacterial drug, was used as a model drug for temperature-induced release studies from these particles.

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

An injectable thermosensitive polymeric hydrogel for sustained release of Avastin® to treat posterior segment disease.

PubMed

Xie, Binbin; Jin, Ling; Luo, Zichao; Yu, Jing; Shi, Shuai; Zhang, Zhaoliang; Shen, Meixiao; Chen, Hao; Li, Xingyi; Song, Zongming

2015-07-25

Delivery of drugs, especially bioactive macromolecules such as proteins and nucleic acids, to the posterior segment is still a significant challenge for pharmaceutical scientists. In the present study, we developed an injectable thermosensitive polymeric hydrogel for sustained release of Avastin(®) to treat posterior segment disorders. The payload of Avastin(®) to poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) hydrogel did not influence its inherent sol-gel transition behavior, but shifted the sol-gel transition to a lower temperature. The resulting Avastin(®)/PLGA-PEG-PLGA hydrogels had a porous structure (pore size, 100 ∼ 150 μm) as determined by scanning electron microcopy (SEM), facilitating sustained Avastin(®) release over a period of up to 14 days in vitro. The PLGA-PEG-PLGA hydrogel was immediately formed in the vitreous humor after intravitreal injection, followed by slow clearance over an 8 week study period. The PLGA-PEG-PLGA hydrogel exhibited no apparent toxicity against retinal tissue, as indicated by the absence of inflammation, retinal necrosis, and stress responses, using optical coherence tomography (OCT) and histological/immunochemical analyses. Electrophysiology (ERG) examination also showed that the PLGA-PEG-PLGA hydrogel did not affect retinal function. In vivo pharmacokinetic studies indicated that the use of the PLGA-PEG-PLGA hydrogel greatly extended the release of Avastin(®) over time in the vitreous humor and retina after intravitreal injection. Together, these results demonstrated that the PLGA-PEG-PLGA hydrogel was a promising candidate for ocular drug delivery of Avastin(®)via intravitreal injection. Copyright © 2015 Elsevier B.V. All rights reserved.

Design of a Coupled Thermoresponsive Hydrogel and Robotic System for Postinfarct Biomaterial Injection Therapy.

PubMed

Zhu, Yang; Wood, Nathan A; Fok, Kevin; Yoshizumi, Tomo; Park, Dae Woo; Jiang, Hongbin; Schwartzman, David S; Zenati, Marco A; Uchibori, Takafumi; Wagner, William R; Riviere, Cameron N

2016-09-01

In preclinical testing, ventricular wall injection of hydrogels has been shown to be effective in modulating ventricular remodeling and preserving cardiac function. For some approaches, early-stage clinical trials are under way. The hydrogel delivery method varies, with minimally invasive approaches being preferred. Endocardial injections carry a risk of hydrogel regurgitation into the circulation, and precise injection patterning is a challenge. An epicardial approach with a thermally gelling hydrogel through the subxiphoid pathway overcomes these disadvantages. A relatively stiff, thermally responsive, injectable hydrogel based on N-isopropylacrylamide and N-vinylpyrrolidone (VP gel) was synthesized and characterized. VP gel thermal behavior was tuned to couple with a transepicardial injection robot, incorporating a cooling feature to achieve injectability. Ventricular wall injections of the optimized VP gel have been performed ex vivo and on beating porcine hearts. Thermal transition temperature, viscosity, and gelling time for the VP gel were manipulated by altering N-vinylpyrrolidone content. The target parameters for cooling in the robotic system were chosen by thermal modeling to support smooth, repeated injections on an ex vivo heart. Injections at predefined locations and depth were confirmed in an infarcted porcine model. A coupled thermoresponsive hydrogel and robotic injection system incorporating a temperature-controlled injectate line was capable of targeted injections and amenable to use with a subxiphoid transepicardial approach for hydrogel injection after myocardial infarction. The confirmation of precise location and depth injections would facilitate a patient-specific planning strategy to optimize injection patterning to maximize the mechanical benefits of hydrogel placement. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

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.

Internalization of Red Blood Cell-Mimicking Hydrogel Capsules with pH-Triggered Shape Responses

PubMed Central

2015-01-01

We report on naturally inspired hydrogel capsules with pH-induced transitions from discoids to oblate ellipsoids and their interactions with cells. We integrate characteristics of erythrocytes such as discoidal shape, hollow structure, and elasticity with reversible pH-responsiveness of poly(methacrylic acid) (PMAA) to design a new type of drug delivery carrier to be potentially triggered by chemical stimuli in the tumor lesion. The capsules are fabricated from cross-linked PMAA multilayers using sacrificial discoid silicon templates. The degree of capsule shape transition is controlled by the pH-tuned volume change, which in turn is regulated by the capsule wall composition. The (PMAA)15 capsules undergo a dramatic 24-fold volume change, while a moderate 2.3-fold volume variation is observed for more rigid PMAA–(poly(N-vinylpyrrolidone) (PMAA–PVPON)5 capsules when solution pH is varied between 7.4 and 4. Despite that both types of capsules exhibit discoid-to-oblate ellipsoid transitions, a 3-fold greater swelling in radial dimensions is found for one-component systems due to a greater degree of the circular face bulging. We also show that (PMAA–PVPON)5 discoidal capsules interact differently with J774A.1 macrophages, HMVEC endothelial cells, and 4T1 breast cancer cells. The discoidal capsules show 60% lower internalization as compared to spherical capsules. Finally, hydrogel capsules demonstrate a 2-fold decrease in size upon internalization. These capsules represent a unique example of elastic hydrogel discoids capable of pH-induced drastic and reversible variations in aspect ratios. Considering the RBC-mimicking shape, their dimensions, and their capability to undergo pH-triggered intracellular responses, the hydrogel capsules demonstrate considerable potential as novel carriers in shape-regulated transport and cellular uptake. PMID:24848786

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.

Designing injectable beta-hairpin peptide hydrogels for cartilage tissue engineering application

NASA Astrophysics Data System (ADS)

Sinthuvanich, Chomdao

In this work, it was demonstrated that peptide-based gels having different electrostatic network character but similar mechanical properties can be designed by modulating the primary sequence of the peptides used for self-assembly. As a result, HLT2 and HET1 peptides, having formal charge states of +5 per monomer, were designed using MAX8, a peptide with a charge state of +7 per monomer, as a template. Using gels prepared from all three peptides (MAX8, HLT2, and HET1), it was shown that the electropositive character of the network influences chondrocyte behavior. Specifically, the less electropositive gel (HLT2) is able to maintain chondrocyte viability and phenotype. In contrast, chondrocytes encapsulated in the more positively charged gel (MAX8) are more prone to dedifferentiation, resulting in tissue constructs with inferior mechanical properties. Gels prepared from peptides having the same net charge but differing only in their primary sequences (HLT2 and HET1) were also shown to influence cell behavior, but only during the early period of culturing. If constructs derived from these two different peptide gels are allowed to culture for extended times, their mechanical properties become similar. This suggests that the amino acid composition and sequence of the peptides used to make the gels also influences cell behavior, but perhaps not to the extent that network electrostatics plays. Supplementation of bioactive factors in the culturing media, as opposed to being encapsulated directly in the network, was shown to adversely affect the cellular response resulting in tissue constructs where extracellular matrix (ECM) components are non-uniformly distributed. When bioactive factors were encapsulated and co-delivered with cells, positive results were observed, particularly when cells were co-encapsulated with the growth factor, TGF-β1. The effect of TGF-β1 on cellular response and the mechanical properties of the tissue-engineered constructs is largely governed by the ability of the growth factor to be retained within the hydrogels and made available to the cells, which in turn, dictate the quality of the engineered tissue. Rational peptide design was also employed to generate negatively charged peptides capable of folding and self-assembling under physiological conditions to afford electronegative gel. Initial designs resulted in peptides that undergo gelation in response to a change in environmental pH and temperature. Modification of these initially designed peptides led to the design of VE3 and VEQ1, two negatively charged peptides that can be used to directly encapsulate chondrocytes providing gel-cell constructs with homogeneous cellular distribution. Finally, the positively charged peptide gel (HET1) and negatively charged peptide gel (VE3) were compared to investigate the influence of vastly different network electrostatics on the response of encapsulated primary chondrocytes. In these gels, a majority of cells were able to retain their chondrocyte phenotype within the scaffold regardless of which gel was used for encapsulation and delivery. However, the positively charge hydrogel is better at supporting cell proliferation and ECM accumulation. On the other hand, the cells encapsulated in the negatively charged hydrogel were less proliferative and the negatively charged hydrogel had a limited ability to retain ECM produced by the cells. In contrast, when culturing in the presence of TGF-β1, constructs derived from the negatively charged gel showed greater compressive moduli than those derived from the positively charged hydrogel. This difference is largely due to the amount of TGF-β1 made available to the encapsulated cells as a function of time, which was found to be governed by the electrostatic character of the hydrogel network. This work indicates that network electrostatics influence the response of encapsulated chondrocytes, retention of secreted ECM, and the diffusion of bioactive factors necessary for the generation of engineered cartilage. During the course of these studies, I have a serendipitous discovery that a derivative of one of the material forming β-hairpin peptides displays anticancer activity. Chapter 8 describes this peptide, SVS-1, and its mechanism of action. (Abstract shortened by UMI.).

Bioprinting Organotypic Hydrogels with Improved Mesenchymal Stem Cell Remodeling and Mineralization Properties for Bone Tissue Engineering.

PubMed

Duarte Campos, Daniela Filipa; Blaeser, Andreas; Buellesbach, Kate; Sen, Kshama Shree; Xun, Weiwei; Tillmann, Walter; Fischer, Horst

2016-06-01

3D-manufactured hydrogels with precise contours and biological adhesion motifs are interesting candidates in the regenerative medicine field for the culture and differentiation of human bone-marrow-derived mesenchymal stem cells (MSCs). 3D-bioprinting is a powerful technique to approach one step closer the native organization of cells. This study investigates the effect of the incorporation of collagen type I in 3D-bioprinted polysaccharide-based hydrogels to the modulation of cell morphology, osteogenic remodeling potential, and mineralization. By combining thermo-responsive agarose hydrogels with collagen type I, the mechanical stiffness and printing contours of printed constructs can be improved compared to pure collagen hydrogels which are typically used as standard materials for MSC osteogenic differentiation. The results presented here show that MSC not only survive the 3D-bioprinting process but also maintain the mesenchymal phenotype, as proved by live/dead staining and immunocytochemistry (vimentin positive, CD34 negative). Increased solids concentrations of collagen in the hydrogel blend induce changes in cell morphology, namely, by enhancing cell spreading, that ultimately contribute to enhanced and directed MSC osteogenic differentiation. 3D-bioprinted agarose-collagen hydrogels with high-collagen ratio are therefore feasible for MSC osteogenic differentiation, contrarily to low-collagen blends, as proved by two-photon microscopy, Alizarin Red staining, and real-time polymerase chain reaction. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Microfluidic bioassay system based on microarrays of hydrogel sensing elements entrapping quantum dot-enzyme conjugates.

PubMed

Jang, Eunji; Kim, Sinyoung; Koh, Won-Gun

2012-01-15

This paper presents a simple method to fabricate a microfluidic biosensor that is able to detect substrates for H(2)O(2)-generating oxidase. The biosensor consists of three components (quantum dot-enzyme conjugates, hydrogel microstructures, and a set of microchannels) that were hierarchically integrated into a microfluidic device. The quantum dot (QD)-enzyme conjugates were entrapped within the poly(ethylene glycol) (PEG)-based hydrogel microstructures that were fabricated within the microchannels by a photopatterning process. Glucose oxidase (GOX) and alcohol oxidase (AOX) were chosen as the model oxidase enzymes, conjugated to carboxyl-terminated CdSe/ZnS QDs, and entrapped within the hydrogel microstructures, which resulted in a fluorescent hydrogel microarray that was responsive to glucose or alcohol. The hydrogel-entrapped GOX and AOX were able to perform enzyme-catalyzed oxidation of glucose and alcohol, respectively, to produce H(2)O(2), which subsequently quenched the fluorescence of the conjugated QDs. The fluorescence intensity of the hydrogel microstructures decreased as the glucose and alcohol concentrations increased, and the detection limits of this system were found to be 50 μM of glucose and 70 μM of alcohol. Because each microchannel was able to carry out different assays independently, the simultaneous detection of glucose and alcohol was possible using our novel microfluidic device composed of multiple microchannels. Copyright © 2011 Elsevier B.V. All rights reserved.

Synthesis, characterization, and application of reversible PDLLA-PEG-PDLLA copolymer thermogels in vitro and in vivo

PubMed Central

Shi, Kun; Wang, Ya-Li; Qu, Ying; Liao, Jin-Feng; Chu, Bing-Yang; Zhang, Hua-Ping; Luo, Feng; Qian, Zhi-Yong

2016-01-01

In this study, a series of injectable thermoreversible and thermogelling PDLLA-PEG-PDLLA copolymers were developed and a systematic evaluation of the thermogelling system both in vitro and in vivo was performed. The aqueous PDLLA-PEG-PDLLA solutions above a critical gel concentration could transform into hydrogel spontaneously within 2 minutes around the body temperature in vitro or in vivo. Modulating the molecular weight, block length and polymer concentration could adjust the sol-gel transition behavior and the mechanical properties of the hydrogels. The gelation was thermally reversible due to the physical interaction of copolymer micelles and no crystallization formed during the gelation. Little cytotoxicity and hemolysis of this polymer was found, and the inflammatory response after injecting the hydrogel to small-animal was acceptable. In vitro and in vivo degradation experiments illustrated that the physical hydrogel could retain its integrity as long as several weeks and eventually be degraded by hydrolysis. A rat model of sidewall defect-bowel abrasion was employed, and a significant reduction of post-operative adhesion has been found in the group of PDLLA-PEG-PDLLA hydrogel-treated, compared with untreated control group and commercial hyaluronic acid (HA) anti-adhesion hydrogel group. As such, this PDLLA-PEG-PDLLA hydrogel might be a promising candidate of injectable biomaterial for medical applications. PMID:26752008

Temporal and spatial distribution of macrophage phenotype markers in the foreign body response to glutaraldehyde-crosslinked gelatin hydrogels.

PubMed

Yu, Tony; Wang, Wenbo; Nassiri, Sina; Kwan, Thomas; Dang, Chau; Liu, Wei; Spiller, Kara L

2016-01-01

Currently, it is not well understood how changes in biomaterial properties affect the foreign body response (FBR) or macrophage behavior. Because failed attempts at biomaterial degradation by macrophages have been linked to frustrated phagocytosis, a defining feature of the FBR, we hypothesized that increased hydrogel crosslinking density (and decreased degradability) would exacerbate the FBR. Gelatin hydrogels were crosslinked with glutaraldehyde (0.05, 0.1, and 0.3%) and implanted subcutaneously in C57BL/6 mice over the course of 3 weeks. Interestingly, changes in hydrogel crosslinking did not affect the thickness of the fibrous capsule surrounding the hydrogels, expression of the pan-macrophage marker F480, expression of three macrophage phenotype markers (iNOS, Arg1, CD163), or expression of the myofibroblast marker aSMA, determined using semi-quantitative immunohistochemical analysis. With respect to temporal changes, the level of expression of the M1 marker (iNOS) remained relatively constant throughout the study, while the M2 markers Arg1 and CD163 increased over time. Expression of these M2 markers was highly correlated with fibrous capsule thickness. Differences in spatial distribution of staining also were noted, with the strongest staining for iNOS at the hydrogel surface and increasing expression of the myofibroblast marker aSMA toward the outer edge of the fibrous capsule. These results confirm previous reports that macrophages in the FBR exhibit characteristics of both M1 and M2 phenotypes. Understanding the effects (or lack of effects) of biomaterial properties on the FBR and macrophage phenotype may aid in the rational design of biomaterials to integrate with surrounding tissue.

Nanoparticle-Hydrogel: A Hybrid Biomaterial System for Localized Drug Delivery

PubMed Central

Gao, Weiwei; Zhang, Yue; Zhang, Qiangzhe; Zhang, Liangfang

2016-01-01

Nanoparticles have offered a unique set of properties for drug delivery including high drug loading capacity, combinatorial delivery, controlled and sustained drug release, prolonged stability and lifetime, and targeted delivery. To further enhance therapeutic index, especially for localized application, nanoparticles have been increasingly combined with hydrogels to form a hybrid biomaterial system for controlled drug delivery. Herein, we review recent progresses in engineering such nanoparticle-hydrogel hybrid system (namely ‘NP-gel’) with a particular focus on its application for localized drug delivery. Specifically, we highlight four research areas where NP-gel has shown great promises, including (1) passively controlled drug release, (2) stimuli-responsive drug delivery, (3) site-specific drug delivery, and (4) detoxification. Overall, integrating therapeutic nanoparticles with hydrogel technologies creates a unique and robust hybrid biomaterial system that enables effective localized drug delivery. PMID:26951462

Energy Efficient Glazing for Adaptive Solar Control Fabricated with Photothermotropic Hydrogels Containing Graphene Oxide

PubMed Central

Kim, Dowan; Lee, Eunsu; Lee, Heon Sang; Yoon, Jinhwan

2015-01-01

Glazing for adaptive solar control is the most promising for energy efficient development, because the use of this technology in buildings can be expected to significantly impact energy use and efficiency by screening sunlight that enters a building in summer. To achieve autonomous adjustable transparency, we have developed photothermotropic material system by combining photothermal materials with thermotropic hydrogels. We found that graphene oxide dispersed within a hydrogel matrix effectively converts the photo energy of sunlight into thermal energy, providing the efficient means to trigger transparency of thermotropic hydrogels. Therefore, we could develop switchable glazing of novel photothermotropic mechanism that screen strong sunlight and heat radiation in response to the sunlight intensity, as well as the temperature. Furthermore, in this study, a prototype device was manufactured with developed materials and successfully operated in outdoor testing. PMID:25561372

Eco-friendly and biocompatible cross-linked carboxymethylcellulose hydrogels as adsorbents for the removal of organic dye pollutants for environmental applications.

PubMed

Capanema, Nádia S V; Mansur, Alexandra A P; Mansur, Herman S; de Jesus, Anderson C; Carvalho, Sandhra M; Chagas, Poliane; de Oliveira, Luiz C

2017-08-28

In this study, new eco-friendly hydrogel adsorbents were synthesized based on carboxymethylcellulose (CMC, degree of substitution [DS] = 0.7) chemically cross-linked with citric acid (CA) using a green process in aqueous solution and applied for the adsorption of methylene blue (MB). Spectroscopic analyses demonstrated the mechanism of cross-linking through the reaction of hydroxyl functional groups from CMC with CA. These CMC hydrogels showed very distinct morphological features dependent on the extension of cross-linking and their nanomechanical properties were drastically increased by approximately 300% after cross-linking with 20% CA (e.g. elastic moduli from 80 ± 15 to 270 ± 50 MPa). Moreover, they were biocompatible using an in vitro cell viability assay in contact with human osteosarcoma-derived cells (SAOS) for 24 h. These CMC-based hydrogels exhibited adsorption efficiency above 90% (24 h) and maximum removal capacity of MB from 5 to 25 mg g -1 depending on the dye concentration (from 100 to 500 mg L -1 ), which was used as the model cationic organic pollutant. The adsorption of process of MB was well-fit to the pseudo-second-order kinetics model. The desorption of MB by immersion in KCl solution (3 mol L -1 , 24 h) showed a typical recovery efficiency of over 60% with conceivable reuse of these CMC-based hydrogels. Conversely, CMC hydrogels repelled methyl orange dye used as model anionic pollutant, proving the mechanism of adsorption by the formation of charged polyelectrolyte/dye complexes.

Self-rolling up micro 3D structures using temperature-responsive hydrogel sheet

NASA Astrophysics Data System (ADS)

Iwata, Y.; Miyashita, S.; Iwase, E.

2017-12-01

This paper proposes a micro self-folding using a self-rolling up deformation. In the fabrication method at micro scale, self-folding is an especially useful method of easily fabricating complex three-dimensional (3D) structures from engineered two-dimensional (2D) sheets. However, most self-folded structures are limited to 3D structures with a hollow region. Therefore, we made 3D structures with a small hollow region by self-rolling up a 2D sheet consisting of SU-8 and a temperature-responsive hybrid hydrogel of poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAM-AAc). The temperature-responsive hydrogel can provide repetitive deformation, which is a good feature for micro soft robots or actuators, using hydrogel shrinking and swelling. Our micro self-rolling up method is a self-folding method for a 3D structure performed by rolling up a 2D flat sheet, like making a croissant, through continuous self-folding. We used our method to fabricate 3D structures with a small hollow region, such as cylindrical, conical, and croissant-like ellipsoidal structures, and 3D structures with a hollow region, such as spiral shapes. All the structures showed repetitive deformation, forward rolling up in 20 °C cold water and backward rolling up in 40 °C hot water. The results demonstrate that self-rolling up deformation can be useful in the field of micro soft devices.

Biocompatibility and intradiscal application of a thermoreversible celecoxib-loaded poly-N-isopropylacrylamide MgFe-layered double hydroxide hydrogel in a canine model.

PubMed

Willems, Nicole; Yang, Hsiao-Yin; Langelaan, Marloes L P; Tellegen, Anna R; Grinwis, Guy C M; Kranenburg, Hendrik-Jan C; Riemers, Frank M; Plomp, Saskia G M; Craenmehr, Eric G M; Dhert, Wouter J A; Papen-Botterhuis, Nicole E; Meij, Björn P; Creemers, Laura B; Tryfonidou, Marianna A

2015-08-20

Chronic low back pain due to intervertebral disc (IVD) degeneration is associated with increased levels of inflammatory mediators. Current medical treatment consists of oral anti-inflammatory drugs to alleviate pain. In this study, the efficacy and safety of a novel thermoreversible poly-N-isopropylacrylamide MgFe-layered double hydroxide (pNIPAAM MgFe-LDH) hydrogel was evaluated for intradiscal controlled delivery of the selective cyclooxygenase (COX) 2 inhibitor and anti-inflammatory drug celecoxib (CXB). Degradation, release behavior, and the ability of a CXB-loaded pNIPAAM MgFe-LDH hydrogel to suppress prostaglandin E2 (PGE2) levels in a controlled manner in the presence of a proinflammatory stimulus (TNF-α) were evaluated in vitro. Biocompatibility was evaluated histologically after subcutaneous injection in mice. Safety of intradiscal application of the loaded and unloaded hydrogels was studied in a canine model of spontaneous mild IVD degeneration by histological, biomolecular, and biochemical evaluation. After the hydrogel was shown to be biocompatible and safe, an in vivo dose-response study was performed in order to determine safety and efficacy of the pNIPAAM MgFe-LDH hydrogel for intradiscal controlled delivery of CXB. CXB release correlated to hydrogel degradation in vitro. Furthermore, controlled release from CXB-loaded hydrogels was demonstrated to suppress PGE2 levels in the presence of TNF-α. The hydrogel was shown to exhibit a good biocompatibility upon subcutaneous injection in mice. Upon intradiscal injection in a canine model, the hydrogel exhibited excellent biocompatibility based on histological evaluation of the treated IVDs. Gene expression and biochemical analyses supported the finding that no substantial negative effects of the hydrogel were observed. Safety of application was further confirmed by the absence of clinical symptoms, IVD herniation or progression of degeneration. Controlled release of CXB resulted in a nonsignificant maximal inhibition (approximately 35 %) of PGE2 levels in the mildly degenerated canine IVDs. In conclusion, this study showed biocompatibility and safe intradiscal application of an MgFe LDH-pNIPAAM hydrogel. Controlled release of CXB resulted in only limited inhibition of PGE2 in this model with mild IVD degeneration, and further studies should concentrate on application of controlled release from this type of hydrogel in animal models with more severe IVD degeneration.

Dynamic behavior of acrylic acid clusters as quasi-mobile nodes in a model of hydrogel network

NASA Astrophysics Data System (ADS)

Zidek, Jan; Milchev, Andrey; Vilgis, Thomas A.

2012-12-01

Using a molecular dynamics simulation, we study the thermo-mechanical behavior of a model hydrogel subject to deformation and change in temperature. The model is found to describe qualitatively poly-lactide-glycolide hydrogels in which acrylic acid (AA)-groups are believed to play the role of quasi-mobile nodes in the formation of a network. From our extensive analysis of the structure, formation, and disintegration of the AA-groups, we are able to elucidate the relationship between structure and viscous-elastic behavior of the model hydrogel. Thus, in qualitative agreement with observations, we find a softening of the mechanical response at large deformations, which is enhanced by growing temperature. Several observables as the non-affinity parameter A and the network rearrangement parameter V indicate the existence of a (temperature-dependent) threshold degree of deformation beyond which the quasi-elastic response of the model system turns over into plastic (ductile) one. The critical stretching when the affinity of the deformation is lost can be clearly located in terms of A and V as well as by analysis of the energy density of the system. The observed stress-strain relationship matches that of known experimental systems.

Rapid Fabrication of Cell-Laden Alginate Hydrogel 3D Structures by Micro Dip-Coating.

PubMed

Ghanizadeh Tabriz, Atabak; Mills, Christopher G; Mullins, John J; Davies, Jamie A; Shu, Wenmiao

2017-01-01

Development of a simple, straightforward 3D fabrication method to culture cells in 3D, without relying on any complex fabrication methods, remains a challenge. In this paper, we describe a new technique that allows fabrication of scalable 3D cell-laden hydrogel structures easily, without complex machinery: the technique can be done using only apparatus already available in a typical cell biology laboratory. The fabrication method involves micro dip-coating of cell-laden hydrogels covering the surface of a metal bar, into the cross-linking reagents calcium chloride or barium chloride to form hollow tubular structures. This method can be used to form single layers with thickness ranging from 126 to 220 µm or multilayered tubular structures. This fabrication method uses alginate hydrogel as the primary biomaterial and a secondary biomaterial can be added depending on the desired application. We demonstrate the feasibility of this method, with survival rate over 75% immediately after fabrication and normal responsiveness of cells within these tubular structures using mouse dermal embryonic fibroblast cells and human embryonic kidney 293 cells containing a tetracycline-responsive, red fluorescent protein (tHEK cells).

Hydrogels Containing Prussian Blue Nanoparticles Toward Removal of Radioactive Cesium Ions.

PubMed

Kamachi, Yuichiro; Zakaria, Mohamed B; Torad, Nagy L; Nakato, Teruyuki; Ahamad, Tansir; Alshehri, Saad M; Malgras, Victor; Yamauchil, Yusuke

2016-04-01

Recent reports have demonstrated the practical application of Prussian blue (PB) nanoparticles toward environmental clean-up of radionuclide 173Cs. Herein, we prepared a large amount of PB nanoparticles by mixing both iron(III) chloride and sodium ferrocyanide hydrate as starting precursors. The obtained PB nanoparticles show a high surface area (440 m2. g-1) and consequently an excellent uptake ability of Cs ions from aqueous solutions. The uptake ability of Cs ions into poly(N-isopropylacrylamide (PNIPA) hydrogel is drastically increased up to 156.7 m2. g-1 after incorporating our PB nanoparticles, compared to 30.2 m2 . g-1 after using commercially available PB. Thus, our PB-containing PNIPA hydrogel can be considered as an excellent candidate for the removal of Cs ions from aqueous solutions, which will be useful for the remediation of the nuclear waste.

P25-graphene hydrogels: room-temperature synthesis and application for removal of methylene blue from aqueous solution.

PubMed

Hou, Chengyi; Zhang, Qinghong; Li, Yaogang; Wang, Hongzhi

2012-02-29

Herein we report a room-temperature synthesis of chemically bonded TiO2 (P25)-graphene composite hydrogels and their use as high performance visible light photocatalysts. The three-dimensional (3D) TiO2-carbon composite exhibits a significant enhancement in the reaction rate in the decontamination of methylene blue, compared to the bare P25. The 3D P25-graphene hydrogel is much easier to prepare and apply as a macroscopic device, compared to the 2D P25-graphene sheets. This work could provide new insights into the room-temperature synthesis of graphene-based materials. As a kind of the novel 3D graphene-based composite, the obtained high performance P25-graphene gel could be widely used in the environmental protection issues. Copyright © 2012. Published by Elsevier B.V.

pH-responsive poly(aspartic acid) hydrogel-coated magnetite nanoparticles for biomedical applications.

PubMed

Vega-Chacón, Jaime; Arbeláez, María Isabel Amaya; Jorge, Janaina Habib; Marques, Rodrigo Fernando C; Jafelicci, Miguel

2017-08-01

A novel multifunctional nanosystem formed by magnetite nanoparticles coated with pH-responsive poly(aspartic acid) hydrogel was developed. Magnetite nanoparticles (Fe 3 O 4 ) have been intensively investigated for biomedical applications due to their magnetic properties and dimensions similar to the biostructures. Poly(aspartic acid) is a water-soluble, biodegradable and biocompatible polymer, which features makes it a potential candidate for biomedical applications. The nanoparticles surface modification was carried out by crosslinking polysuccinimide on the magnetite nanoparticles surface and hydrolyzing the succinimide units in mild alkaline medium to obtain the magnetic poly(aspartic acid) hydrogel. The surface modification in each step was confirmed by DRIFTS, TEM and zeta potential measurements. The hydrodynamic diameter of the nanosystems decreases as the pH value decreases. The nanosystems showed high colloidal stability in water and no cytotoxicity was detected, which make these nanosystems suitable for biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Experimental evaluation of photocrosslinkable chitosan as a biologic adhesive with surgical applications.

PubMed

Ono, K; Ishihara, M; Ozeki, Y; Deguchi, H; Sato, M; Saito, Y; Yura, H; Sato, M; Kikuchi, M; Kurita, A; Maehara, T

2001-11-01

In various surgical cases, effective tissue adhesives are required for both hemostasis (eg, intraoperative bleeding) and air sealing (eg, thoracic surgery). We have designed a chitosan molecule (Az-CH-LA) that can be photocrosslinked by ultraviolet (UV) light irradiation, thereby forming a hydrogel. The purpose of this work was to evaluate the effectiveness and safety of the photocrosslinkable chitosan hydrogel as an adhesive with surgical applications. The sealing ability of the chitosan hydrogel, determined as a bursting pressure, was assessed with removed thoracic aorta, trachea, and lung of farm pigs and in a rabbit model. The carotid artery and lung of rabbits were punctured with a needle, and the chitosan hydrogel was applied to, respectively, stop the bleeding and the air leakage. In vivo chitosan degradability and biologic responses were histologically assessed in animal models. The bursting pressure of chitosan hydrogel (30 mg/mL) and fibrin glue, respectively, was 225 +/- 25 mm Hg (mean +/- SD) and 80 +/- 20 mm Hg in the thoracic aorta; 77 +/- 29 mm Hg and 48 +/- 21 mm Hg in the trachea; and in the lung, 51 +/- 11 mm Hg (chitosan hydrogel), 62 +/- 4 mm Hg (fibrin glue, rubbing method), and 12 +/- 2 mm Hg (fibrin glue, layer method). The sealing ability of the chitosan hydrogel was stronger than that of fibrin glue. All rabbits with a carotid artery (n = 8) or lung (n = 8) that was punctured with a needle and then sealed with chitosan hydrogel survived the 1-month observation period without any bleeding or air leakage from the puncture sites. Histologic examinations demonstrated that 30 days after application, a fraction of the chitosan hydrogel was phagocytosed by macrophages, had partially degraded, and had induced the formation of fibrous tissues around the hydrogel. A newly developed photocrosslinkable chitosan has demonstrated strong sealing ability and a great potential for use as an adhesive in surgical operations.

A High-Performance and Recyclable Al-Air Coin Cell Based on Eco-Friendly Chitosan Hydrogel Membranes.

PubMed

Liu, Yisi; Sun, Qian; Yang, Xiaofei; Liang, Jianneng; Wang, Biqiong; Koo, Alicia; Li, Ruying; Li, Jie; Sun, Xueliang

2018-05-18

Aluminum-air batteries are a promising power supply for electronics due to its low cost and high energy density. However, portable coin-type Al-air batteries operating under ambient air condition for small electronic appliances have rarely been reported. Herein, coin cell-type Al-air batteries using cost-effective and eco-friendly chitosan hydrogel membranes modified by SiO2, SnO2, and ZnO have been prepared and assembled. The Al-air coin cell employing chitosan hydrogel membrane containing 10 wt.% SiO2 as a separator exhibits better discharge performance with a higher flat voltage plateau, longer discharge duration, and higher power density than the cells using a chitosan hydrogel membrane containing SnO2 or ZnO. Moreover, we also demonstrate that the presented Al-air coin cell can be recycled by a series of eco-friendly procedures using food grade ingredients, resulting in recycled products that are environmentally safe and ready for reuse. The Al-air coin cell adopting a recycled cathode from a fully discharged Al-air coin cell using the above-mentioned procedure has shown comparable performance to cells assembled with a new cathode. With these merits of enhanced electrochemical performance and recyclability, this new Al-air coin cell with modified chitosan hydrogel membrane can find wide applications for powering portable and small-size electronics.

Graphene oxide-dependent growth and self-aggregation into a hydrogel complex of exoelectrogenic bacteria

PubMed Central

Yoshida, Naoko; Miyata, Yasushi; Doi, Kasumi; Goto, Yuko; Nagao, Yuji; Tero, Ryugo; Hiraishi, Akira

2016-01-01

Graphene oxide (GO) is reduced by certain exoelectrogenic bacteria, but its effects on bacterial growth and metabolism are a controversial issue. This study aimed to determine whether GO functions as the terminal electron acceptor to allow specific growth of and electricity production by exoelectrogenic bacteria. Cultivation of environmental samples with GO and acetate as the sole substrate could specifically enrich exoelectrogenic bacteria with Geobacter species predominating (51–68% of the total populations). Interestingly, bacteria in these cultures self-aggregated into a conductive hydrogel complex together with biologically reduced GO (rGO). A novel GO-respiring bacterium designated Geobacter sp. strain R4 was isolated from this hydrogel complex. This organism exhibited stable electricity production at >1000 μA/cm3 (at 200 mV vs Ag/AgCl) for more than 60 d via rGO while temporary electricity production using graphite felt. The better electricity production depends upon the characteristics of rGO such as a large surface area for biofilm growth, greater capacitance, and smaller internal resistance. This is the first report to demonstrate GO-dependent growth of exoelectrogenic bacteria while forming a conductive hydrogel complex with rGO. The simple put-and-wait process leading to the formation of hydrogel complexes of rGO and exoelectrogens will enable wider applications of GO to bioelectrochemical systems. PMID:26899353

Macroporous Double-Network Hydrogel for High-Efficiency Solar Steam Generation Under 1 sun Illumination.

PubMed

Yin, Xiangyu; Zhang, Yue; Guo, Qiuquan; Cai, Xiaobing; Xiao, Junfeng; Ding, Zhifeng; Yang, Jun

2018-04-04

Solar steam generation is one of the most promising solar-energy-harvesting technologies to address the issue of water shortage. Despite intensive efforts to develop high-efficiency solar steam generation devices, challenges remain in terms of the relatively low solar thermal efficiency, complicated fabrications, high cost, and difficulty in scaling up. Herein, a double-network hydrogel with a porous structure (p-PEGDA-PANi) is demonstrated for the first time as a flexible, recyclable, and efficient photothermal platform for low-cost and scalable solar steam generation. As a novel photothermal platform, the p-PEGDA-PANi involves all necessary properties of efficient broadband solar absorption, exceptional hydrophilicity, low heat conductivity, and porous structure for high-efficiency solar steam generation. As a result, the hydrogel-based solar steam generator exhibits a maximum solar thermal efficiency of 91.5% with an evaporation rate of 1.40 kg m -2 h -1 under 1 sun illumination, which is comparable to state-of-the-art solar steam generation devices. Furthermore, the good durability and environmental stability of the p-PEGDA-PANi hydrogel enables a convenient recycling and reusing process toward real-life applications. The present research not only provides a novel photothermal platform for solar energy harvest but also opens a new avenue for the application of the hydrogel materials in solar steam generation.

Drug delivery systems based on biocompatible imino-chitosan hydrogels for local anticancer therapy.

PubMed

Ailincai, Daniela; Tartau Mititelu, Liliana; Marin, Luminita

2018-11-01

A series of drug delivery systems were prepared by chitosan hydrogelation with citral in the presence of an antineoplastic drug: 5-fluorouracil. The dynamic covalent chemistry of the imine linkage allowed the obtaining of supramolecular tridimensional architectures in which the drug has been homogenously dispersed. Fourier-transform infrared spectroscopy (FTIR), wide-angle X-ray diffraction (WXRD) and polarized light microscopy (POM) measurements were used in order to follow the hydrogelation and drug encapsulation processes. The ability of the prepared systems to release the drug has been investigated by UV-Vis spectroscopy using a calibration curve and by fitting the results with different mathematic models. To mimic the behavior of the hydrogel matrix in bio-environmental conditions in view of applications, their enzymatic degradability was monitored in the presence of lysozyme. The in vivo side effects of the systems, in terms of their influence on the blood elements, biochemical and immune parameters were monitored on white Swiss mice by intraperitoneal administration of the injectable obtained hydrogels. All the characteristics of the obtained systems, such as micro-porous morphology, uniform drug encapsulation, enzymatic degradability, lack of side effects, other than the one of the drug itself, along with their ability to release the drug in a sustained manner proved that these material meet the requirements for the development of drug delivery systems, making them suitable for being applied in intraperitoneal chemotherapy.

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.

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

Biomimetic poly(amidoamine) hydrogels as synthetic materials for cell culture

PubMed Central

Jacchetti, Emanuela; Emilitri, Elisa; Rodighiero, Simona; Indrieri, Marco; Gianfelice, Antonella; Lenardi, Cristina; Podestà, Alessandro; Ranucci, Elisabetta; Ferruti, Paolo; Milani, Paolo

2008-01-01

Background Poly(amidoamine)s (PAAs) are synthetic polymers endowed with many biologically interesting properties, being highly biocompatible, non toxic and biodegradable. Hydrogels based on PAAs can be easily modified during the synthesis by the introduction of functional co-monomers. Aim of this work is the development and testing of novel amphoteric nanosized poly(amidoamine) hydrogel film incorporating 4-aminobutylguanidine (agmatine) moieties to create RGD-mimicking repeating units for promoting cell adhesion. Results A systematic comparative study of the response of an epithelial cell line was performed on hydrogels with agmatine and on non-functionalized amphoteric poly(amidoamine) hydrogels and tissue culture plastic substrates. The cell adhesion on the agmatine containing substrates was comparable to that on plastic substrates and significantly enhanced with respect to the non-functionalized controls. Interestingly, spreading and proliferation on the functionalized supports are slower than on plastic exhibiting the possibility of an easier control of the cell growth kinetics. In order to favor the handling of the samples, a procedure for the production of bi-layered constructs was also developed by means the deposition via spin coating of a thin layer of hydrogel on a pre-treated cover slip. Conclusion The obtained results reveal that PAAs hydrogels can be profitably functionalized and, in general, undergo physical and chemical modifications to meet specific requirements. In particular the incorporation of agmatine warrants good potential in the field of cell culturing and the development of supported functionalized hydrogels on cover glass are very promising substrates for applications in cell screening devices. PMID:19014710

Hierarchical structures based on self-assembling beta-hairpin peptides and their application as biomaterials and hybrid materials

NASA Astrophysics Data System (ADS)

Altunbas, Aysegul

Self-assembly represents a robust and powerful paradigm for the bottom-up construction of nanostructures. Self-assembled peptide hydrogels are emerging as promising routes to novel multifunctional materials. The 20 amino acid MAX1and MAX8 peptides self-assemble into a three dimensional network of entangled, branched fibrils rich in beta-sheet secondary structure with a high density of lysine groups exposed on the fibril-surfaces. These hydrogels form self-supporting structures that shear thin upon application of shear and then immediately recover to a solid hydrogel upon cessation of shear which facilitates the local delivery of the hydrogel into a site in vivo. Templated condensation of silica precursors on self-assembled nanoscale peptide fibrils with various surface functionalities can be used to mimic biosilicification. This template-defined approach towards biomineralization was utilized for the controlled fabrication of 3D hybrid nanostructures. We report a study on the structure-property relationship of self-assembled peptide hydrogels where mineralization of individual fibrils through sol-gel chemistry was achieved. The nanostructure and consequent mechanical characteristics of these hybrid networks can be modulated by changing the stoichiometric parameters of the sol-gel process. Construction of such organic-inorganic hybrid networks by sol-gel processing of self-assembled peptide hydrogels has improved mechanical properties and resulted in materials with ˜ 3 orders of magnitude higher stiffness. The physical characterization of the hybrid networks via electron microscopy and small angle scattering is detailed and correlated with changes in the network mechanical behavior. The resultant high fidelity templating process suggests that the peptide substrate can be used to template the coating of other functional inorganic materials. Self-assembling peptide hydrogels encapsulating an anti-tumorigenic drug, curcumin, have been prepared and demonstrated to be an effective vehicle for the localized delivery of curcumin over sustained periods of time in vitro. The curcumin-hydrogel is prepared in-situ where curcumin encapsulation within the hydrogel network is accomplished concurrently with peptide self-assembly. Physical characterization methods and in vitro biological studies were used to demonstrate the effectiveness of curcumin-loaded beta-hairpin hydrogels as injectable agents for localized curcumin delivery. Notably, rheological characterization of the curcumin loaded hydrogel before and after shear flow have indicated solid-like properties even at high curcumin payloads. In vitro experiments with a medulloblastoma cell line confirm that the encapsulation of the curcumin within the hydrogel does not have an adverse effect on its bioactivity. Most importantly, the rate of curcumin release and its consequent therapeutic efficacy can be conveniently modulated by changing the morphological characteristics of the peptide hydrogel network. Lastly, MAX8 hydrogel cytocompatibility and biocompatibility was assessed with the future aim of utilizing this hydrogel as a scaffold in liver regeneration studies in rats. MAX8 hydrogel cytotoxity was evaluated using MC3T3-E1 and MG63 cell lines. Encapsulation, syringe delivery and subsequent viability of MG63 cells in hydrogels was also assessed to study the feasibility of using hydrogel/cell constructs as minimally invasive cell delivery vehicles. Biocompatibility was evaluated by monitoring inflammatory response induced by the MAX8 hydrogel via a subcutaneous mice model. Biocompatibility of MAX8 hydrogels at sites other than the subcutaneous region was also investigated using a cylindrical punch resection model in rat liver. The preliminary biocompatibility studies provide an elemental understanding of MAX8 hydrogel behavior in vivo.

Touch Locating and Stretch Sensing Studies of Conductive Hydrogels with Applications to Soft Robots

PubMed Central

He, Bin; Yan, Zhe; Shang, Yinghui; Wang, Qigang; Wang, Zhipeng

2018-01-01

Soft robots possess great potential in environmental adaptations, while their environmental sensing abilities are critical. Conductive hydrogels have been suggested to possess sensing abilities. However, their application in soft robots is lacking. In this work, we fabricated a soft and stretchable gel material, introduced its sensing mechanisms, and developed a measurement setup. Both experimental and simulation studies indicate strong nonlinearity of touch locating on a square touch panel with Cartesian coordinates. To simplify the touch locating, we proposed a touch locating system based on round touch panels with polar coordinates. Mathematical calculations and finite element method (FEM) simulations showed that in this system the locating of a touch point was only determined by its polar radius. This was verified by experimental studies. As a resistor, a gel strip’s resistance increases with stretching. To demonstrate their applications on soft robots, a 3D printed three-fingered soft gripper was employed with gel strips attached. During finger bending for rod grasping, the resistances of the gel strips increased, indicating stretching of the soft material. Furthermore, the strain and stress of a gel strip increased with a decrease of the rod diameter. These studies advance the application of conductive hydrogels on soft robots. PMID:29438318

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.

DNA nanotechnology-based composite-type gold nanoparticle-immunostimulatory DNA hydrogel for tumor photothermal immunotherapy.

PubMed

Yata, Tomoya; Takahashi, Yuki; Tan, Mengmeng; Nakatsuji, Hirotaka; Ohtsuki, Shozo; Murakami, Tatsuya; Imahori, Hiroshi; Umeki, Yuka; Shiomi, Tomoki; Takakura, Yoshinobu; Nishikawa, Makiya

2017-11-01

Success of tumor photothermal immunotherapy requires a system that induces heat stress in cancer cells and enhances strong anti-tumor immune responses. Here, we designed a composite-type immunostimulatory DNA hydrogel consisting of a hexapod-like structured DNA (hexapodna) with CpG sequences and gold nanoparticles. Mixing of the properly designed hexapodna and oligodeoxynucleotide-modified gold nanoparticles resulted in the formation of composite-type gold nanoparticle-DNA hydrogels. Laser irradiation of the hydrogel resulted in the release of hexapodna, which efficiently stimulated immune cells to release proinflammatory cytokines. Then, EG7-OVA tumor-bearing mice received an intratumoral injection of a gold nanoparticle-DNA hydrogel, followed by laser irradiation at 780 nm. This treatment increased the local temperature and the mRNA expression of heat shock protein 70 in the tumor tissue, increased tumor-associated antigen-specific IgG levels in the serum, and induced tumor-associated antigen-specific interferon-γ production from splenocytes. Moreover, the treatment significantly retarded the tumor growth and extended the survival of the tumor-bearing mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hydrogel-based electrochemical sensor for non-invasive and continuous glucose monitoring

NASA Astrophysics Data System (ADS)

Park, Habeen; Lee, Ji-Young; Kim, Dong-Chul; Koh, Younggook; Cha, Junhoe

2017-07-01

Monitoring blood glucose level of diabetic patients is crucial in diabetes care from life threating complications. Selfmonitoring blood glucose (SMBG) that involves finger prick to draw blood samples into the measurement system is a widely-used method of routine measurement of blood glucose levels to date. SMBG includes, however, unavoidable pain problems resulting from the repetitive measurements. We hereby present a hydrogel-based electrochemical (H-EC) sensor to monitor the glucose level, non-invasively. Glucose oxidase (GOx) was immobilized in the disc-type hydroxyethyl methacrylate (HEMA) based hydrogel and kept intact in the hydrogel. Fast electron transfer mediated by Prussian blue (PB, hexacyanoferrate) generated efficient signal amplifications to facilitate the detection of the extracted glucose from the interstitial fluid. The linear response and the selectivity against glucose of the H-EC sensor were validated by chronoamperometry. For the practical use, the outcomes from the correlation of the extracted glucose concentration and the blood glucose value by on-body extraction, as well as the validation of the hydrogel-based electrochemical (H-EC) device, were applied to the on-body glucose monitoring.

Encapsulation optimization of lemon balm antioxidants in calcium alginate hydrogels.

PubMed

Najafi-Soulari, Samira; Shekarchizadeh, Hajar; Kadivar, Mahdi

2016-11-01

Calcium alginate hydrogel beads were used to encapsulate lemon balm extract. Chitosan layer was used to investigate the effect of hydrogel coating. To determine the interactions of antioxidant compounds of extract with encapsulation materials and its stability, microstructure of hydrogel beads was thoroughly monitored using scanning electron microscopy and Fourier transform infrared (FTIR). Total polyphenols content and antiradical activity of lemon balm extract were also evaluated before and after encapsulation. Three significant parameters (lemon balm extract, sodium alginate, and calcium chloride concentrations) were optimized by response surface methodology to obtain maximum encapsulation efficiency. The FTIR spectra showed no interactions between extract and polymers as there were no new band in spectra of alginate hydrogel after encapsulation of active compounds of lemon balm extract. The antioxidant activity of lemon balm extract did not change after encapsulation. Therefore, it was found that alginate is a suitable material for encapsulation of natural antioxidants. Sodium alginate solution concentration, 1.84%, lemon balm extract concentration, 0.4%, and calcium chloride concentration, 0.2% was determined to be the optimum condition to reach maximum encapsulation efficiency.

Silk ionomers for encapsulation and differentiation of human MSCs

PubMed Central

Calabrese, Rossella; Kaplan, David L.

2012-01-01

The response of human bone marrow derived human mesenchymal stem cells (hMSCs) encapsulated in silk ionomer hydrogels was studied. Silk aqueous solutions with silk-poly-L-lysine or silk-poly-L-glutamate were formed into hydrogels via ultrasonication in situ with different net charges. hMSCs were encapsulated within the hydrogels and the impact of matrix charge was assessed over weeks in osteogenic, adipogenic and maintenance growth media. These modified silk charged polymers supported cell viability and proliferative potential, and the hMSCs were able to differentiate toward osteogenic or adipogenic lineages in the corresponding differentiation media. The silk/silk-poly-L-lysine hydrogels exhibited a positive effect on selective osteogenesis of hMSCs, inducing differentiation toward an osteogenic lineage even in the absence of osteogenic supplements, while also inhibiting adipogenesis. In contrast, silk/silk fibroin-poly-L-glutamate hydrogels supported both osteogenic and adipogenic differentiation of hMSCs when cultured under induction conditions. The results demonstrate the potential utility of silk-based ionomers in gel formats for hMSCs encapsulation and for directing hMSCs long term functional differentiation toward specific lineages. PMID:22824008

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.

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.

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.

Self-cleaned electrochemical protein imprinting biosensor basing on a thermo-responsive memory hydrogel.

PubMed

Wei, Yubo; Zeng, Qiang; Hu, Qiong; Wang, Min; Tao, Jia; Wang, Lishi

2018-01-15

Herein, the self-cleaned electrochemical protein imprinting biosensor basing on a thermo-responsive memory hydrogel was constructed on a glassy carbon electrode (GCE) with a free radical polymerization method. Combining the advantages of thermo-responsive molecular imprinted polymers and electrochemistry, the resulted biosensor presents a novel self-cleaned ability for bovine serum albumin (BSA) in aqueous media. As a temperature controlled gate, the hydrogel film undergoes the adsorption and desorption of BSA basing on a reversible structure change with the external temperature stimuli. In particular, these processes have been revealed by the response of cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) of electroactive [Fe(CN) 6 ] 3-/4- . The results have been supported by the evidences of scanning electron microscopy (SEM) and contact angles measurements. Under the optimal conditions, a wide detection range from 0.02μmolL -1 to 10μmolL -1 with a detection limit of 0.012 μmolL -1 (S/N = 3) was obtained for BSA. This proposed BSA sensor also possesses high selectivity, excellent stability, acceptable recovery and good reproducibility in its practical applications. Copyright © 2017. Published by Elsevier B.V.

Rational design and application of responsive alpha-helical peptide hydrogels.

PubMed

Banwell, Eleanor F; Abelardo, Edgardo S; Adams, Dave J; Birchall, Martin A; Corrigan, Adam; Donald, Athene M; Kirkland, Mark; Serpell, Louise C; Butler, Michael F; Woolfson, Derek N

2009-07-01

Biocompatible hydrogels have a wide variety of potential applications in biotechnology and medicine, such as the controlled delivery and release of cells, cosmetics and drugs, and as supports for cell growth and tissue engineering. Rational peptide design and engineering are emerging as promising new routes to such functional biomaterials. Here, we present the first examples of rationally designed and fully characterized self-assembling hydrogels based on standard linear peptides with purely alpha-helical structures, which we call hydrogelating self-assembling fibres (hSAFs). These form spanning networks of alpha-helical fibrils that interact to give self-supporting physical hydrogels of >99% water content. The peptide sequences can be engineered to alter the underlying mechanism of gelation and, consequently, the hydrogel properties. Interestingly, for example, those with hydrogen-bonded networks of fibrils melt on heating, whereas those formed through hydrophobic fibril-fibril interactions strengthen when warmed. The hSAFs are dual-peptide systems that gel only on mixing, which gives tight control over assembly. These properties raise possibilities for using the hSAFs as substrates in cell culture. We have tested this in comparison with the widely used Matrigel substrate, and demonstrate that, like Matrigel, hSAFs support both growth and differentiation of rat adrenal pheochromocytoma cells for sustained periods in culture.

Rational design and application of responsive α-helical peptide hydrogels

PubMed Central

Banwell, Eleanor F.; Abelardo, Edgardo S.; Adams, Dave J.; Birchall, Martin A.; Corrigan, Adam; Donald, Athene M.; Kirkland, Mark; Serpell, Louise C.; Butler, Michael F.; Woolfson, Derek N.

2009-01-01

Biocompatible hydrogels have a wide variety of potential applications in biotechnology and medicine, such as the controlled delivery and release of cells, cosmetics and drugs; and as supports for cell growth and tissue engineering1. Rational peptide design and engineering are emerging as promising new routes to such functional biomaterials2-4. Here we present the first examples of rationally designed and fully characterized self-assembling hydrogels based on standard linear peptides with purely α-helical structures, which we call hydrogelating self-assembling fibres (hSAFs). These form spanning networks of α-helical fibrils that interact to give self-supporting physical hydrogels of >99% water content. The peptide sequences can be engineered to alter the underlying mechanism of gelation and, consequently, the hydrogel properties. Interestingly, for example, those with hydrogen-bonded networks melt upon heating, whereas those formed via hydrophobic interactions strengthen when warmed. The hSAFs are dual-peptide systems that only gel on mixing, which gives tight control over assembly5. These properties raise possibilities for using the hSAFs as substrates in cell culture. We have tested this in comparison with the widely used Matrigel substrate, and demonstrate that, like Matrigel, hSAFs support both growth and differentiation of rat adrenal pheochromocytoma cells for sustained periods in culture. PMID:19543314

Rational design and application of responsive α-helical peptide hydrogels

NASA Astrophysics Data System (ADS)

Banwell, Eleanor F.; Abelardo, Edgardo S.; Adams, Dave J.; Birchall, Martin A.; Corrigan, Adam; Donald, Athene M.; Kirkland, Mark; Serpell, Louise C.; Butler, Michael F.; Woolfson, Derek N.

2009-07-01

Biocompatible hydrogels have a wide variety of potential applications in biotechnology and medicine, such as the controlled delivery and release of cells, cosmetics and drugs, and as supports for cell growth and tissue engineering. Rational peptide design and engineering are emerging as promising new routes to such functional biomaterials. Here, we present the first examples of rationally designed and fully characterized self-assembling hydrogels based on standard linear peptides with purely α-helical structures, which we call hydrogelating self-assembling fibres (hSAFs). These form spanning networks of α-helical fibrils that interact to give self-supporting physical hydrogels of >99% water content. The peptide sequences can be engineered to alter the underlying mechanism of gelation and, consequently, the hydrogel properties. Interestingly, for example, those with hydrogen-bonded networks of fibrils melt on heating, whereas those formed through hydrophobic fibril-fibril interactions strengthen when warmed. The hSAFs are dual-peptide systems that gel only on mixing, which gives tight control over assembly. These properties raise possibilities for using the hSAFs as substrates in cell culture. We have tested this in comparison with the widely used Matrigel substrate, and demonstrate that, like Matrigel, hSAFs support both growth and differentiation of rat adrenal pheochromocytoma cells for sustained periods in culture.

pH/NIR Light-Controlled Multidrug Release via a Mussel-Inspired Nanocomposite Hydrogel for Chemo-Photothermal Cancer Therapy

NASA Astrophysics Data System (ADS)

Ghavaminejad, Amin; Samarikhalaj, Melisa; Aguilar, Ludwig Erik; Park, Chan Hee; Kim, Cheol Sang

2016-09-01

This study reports on an intelligent composite hydrogel with both pH-dependent drug release in a cancer environment and heat generation based on NIR laser exposure, for the combined application of photothermal therapy (PTT) and multidrug chemotherapy. For the first time in the literature, Dopamine nanoparticle (DP) was incorporated as a highly effective photothermal agent as well as anticancer drug, bortezomib (BTZ) carrier inside a stimuli responsive pNIPAAm-co-pAAm hydrogel. When light is applied to the composite hydrogel, DP nanoparticle absorbs the light, which is dissipated locally as heat to impact cancer cells via hyperthermia. On the other hand, facile release of the anticancer drug BTZ from the surface of DP encapsulated hydrogel could be achieved due to the dissociation between catechol groups of DP and the boronic acid functionality of BTZ in typical acidic cancer environment. In order to increase the synergistic effect by dual drug delivery, Doxorubicin (DOXO) were also loaded to pNIPAAm-co-pAAm/DP-BTZ hydrogel and the effect of monotherapy as well as combined therapy were detailed by a complete characterization. Our results suggest that these mussel inspired nanocomposite with excellent heating property and controllable multidrug release can be considered as a potential material for cancer therapy.

In vivo evaluation of the bone integration of coated poly(vinyl-alcohol) hydrogel fiber implants.

PubMed

Moreau, David; Villain, Arthur; Bachy, Manon; Proudhon, Henry; Ku, David N; Hannouche, Didier; Petite, Hervé; Corté, Laurent

2017-08-01

Recently, it has been shown that constructs of poly(vinyl alcohol) (PVA) hydrogel fibers reproduce closely the tensile behavior of ligaments. However, the biological response to these systems has not been explored yet. Here, we report the first in vivo evaluation of these implants and focus on the integration in bone, using a rabbit model of bone tunnel healing. Implants consisted in bundles of PVA hydrogel fibers embedded in a PVA hydrogel matrix. Half of the samples were coated with a composite coating of hydroxyapatite (HA) particles embedded in PVA hydrogel. The biological integration was evaluated at 6 weeks using histology and micro-CT imaging. For all implants, a good biological tolerance and growth of new bone tissue are reported. All the implants were surrounded by a fibrous layer comparable to what was previously observed for poly(ethylene terephthalate) (PET) fibers currently used in humans for ligament reconstruction. An image analysis method is proposed to quantify the thickness of this fibrous capsule. Implants coated with HA were not significantly osteoconductive, which can be attributed to the slow dissolution of the selected hydroxyapatite. Overall, these results confirm the relevance of PVA hydrogel fibers for ligament reconstruction and adjustments are proposed to enhance its osseointegration.

Biocompatibility and inflammatory response in vitro and in vivo to gelatin-based biomaterials with tailorable elastic properties.

PubMed

Ullm, Sandra; Krüger, Anne; Tondera, Christoph; Gebauer, Tim P; Neffe, Axel T; Lendlein, Andreas; Jung, Friedrich; Pietzsch, Jens

2014-12-01

Hydrogels prepared from gelatin and lysine diisocyanate ethyl ester provide tailorable elastic properties and degradation behavior. Their interaction with human aortic endothelial cells (HAEC) as well as human macrophages (Mɸ) and granulocytes (Gɸ) were explored. The experiments revealed a good biocompatibility, appropriate cell adhesion, and cell infiltration. Direct contact to hydrogels, but not contact to hydrolytic or enzymatic hydrogel degradation products, resulted in enhanced cyclooxygenase-2 (COX-2) expression in all cell types, indicating a weak inflammatory activation in vitro. Only Mɸ altered their cytokine secretion profile after direct hydrogel contact, indicating a comparably pronounced inflammatory activation. On the other hand, in HAEC the expression of tight junction proteins, as well as cytokine and matrix metalloproteinase secretion were not influenced by the hydrogels, suggesting a maintained endothelial cell function. This was in line with the finding that in HAEC increased thrombomodulin synthesis but no thrombomodulin membrane shedding occurred. First in vivo data obtained after subcutaneous implantation of the materials in immunocompetent mice revealed good integration of implants in the surrounding tissue, no progredient fibrous capsule formation, and no inflammatory tissue reaction in vivo. Overall, the study demonstrates the potential of gelatin-based hydrogels for temporal replacement and functional regeneration of damaged soft tissue. Copyright © 2014 Elsevier Ltd. All rights reserved.

In Situ Gelation-Induced Death of Cancer Cells Based on Proteinosomes.

PubMed

Zhou, Yuting; Song, Jianmin; Wang, Lei; Xue, Xuting; Liu, Xiaoman; Xie, Hui; Huang, Xin

2017-08-14

Hydrogels are an excellent type of material that can be utilized as a platform for cell culture. However, when a bulky hydrogel forms on the inside of cancer cells, the result would be different. In this study, we demonstrate a method for in situ gelation inside cancer cells that can efficiently induce cell death. Glutathione-responsive proteinosomes with good biocompatibility were prepared as carriers for sodium alginate to be endocytosed by cancer cells, where the chelation between sodium alginate and free calcium ions in the culture medium occurs during the diffusion process. The uptake of the hydrogel-loaded proteinosomes into the cancer cells, and then the triggered release of hydrogel with concomitant aggregation, was well-confirmed by monitoring the change of the Young's modulus of the cells based on AFM force measurements. Accordingly, when a large amount of hydrogel formed in cells, the cell viability would be inhibited by ∼90% by MTT assay at a concentration of 5.0 μM of hydrogel-loaded proteinosomes after 48 h incubation, which clearly proves the feasibility of the demonstrated method for killing cancer cells. Although more details regarding the mechanism of cell death should be conducted in the near future, such a demonstrated method of in situ gelation inside cells provides another choice for killing cancer cells.

Micro-Mechanical Viscoelastic Properties of Crosslinked Hydrogels Using the Nano-Epsilon Dot Method.

PubMed

Mattei, Giorgio; Cacopardo, Ludovica; Ahluwalia, Arti

2017-08-02

Engineering materials that recapitulate pathophysiological mechanical properties of native tissues in vitro is of interest for the development of biomimetic organ models. To date, the majority of studies have focused on designing hydrogels for cell cultures which mimic native tissue stiffness or quasi-static elastic moduli through a variety of crosslinking strategies, while their viscoelastic (time-dependent) behavior has been largely ignored. To provide a more complete description of the biomechanical environment felt by cells, we focused on characterizing the micro-mechanical viscoelastic properties of crosslinked hydrogels at typical cell length scales. In particular, gelatin hydrogels crosslinked with different glutaraldehyde (GTA) concentrations were analyzed via nano-indentation tests using the nano-epsilon dot method. The experimental data were fitted to a Maxwell Standard Linear Solid model, showing that increasing GTA concentration results in increased instantaneous and equilibrium elastic moduli and in a higher characteristic relaxation time. Therefore, not only do gelatin hydrogels become stiffer with increasing crosslinker concentration (as reported in the literature), but there is also a concomitant change in their viscoelastic behavior towards a more elastic one. As the degree of crosslinking alters both the elastic and viscous behavior of hydrogels, caution should be taken when attributing cell response merely to substrate stiffness, as the two effects cannot be decoupled.

Moisture-driven actuators inspired by motility of plants

NASA Astrophysics Data System (ADS)

Shin, Beomjune; Lee, Minhee; Kim, Ho-Young

2015-11-01

We report design and fabrication of moisture-driven actuators mimicking pine cones, wild wheats and seeds of Erodium cicutarium, which can bend and even helically coil with variation of environmental humidity. The actuators adopt a bilayer configuration, one of whose layers is hygroscopically active while the other is inactive. In order to enhance the degree and speed of deformation which critically depends on moisture-responsivity of the active layer, nanofibers of hydrogel are directionally deposited on the inactive layer via electrospinning. As a result, several designs of soft robots are demonstrated which are capable of locomotion by harvesting environmental humidity energy. The dynamics of the robots are analyzed by coupling moisture diffusion kinetics and elastic theory of multi-layer bending. The theoretical predictions are compared with the experimental results, to lead to the optimal design to maximize the locomotion speed measured by travel distance normalized by body length per unit time.

Injectable Hydrogel Scaffold from Decellularized Human Lipoaspirate

PubMed Central

Young, D. Adam; Ibrahim, Dina O.; Hu, Diane; Christman, Karen L.

2010-01-01

Soft tissue fillers are rapidly gaining popularity for aesthetic improvements or repair of adipose tissue deficits. Several injectable biopolymers have been investigated for this purpose but often face rapid resorption or limited adipogenesis, and do not mimic the native adipose extracellular matrix (ECM). We have generated an injectable adipose matrix scaffold by efficiently removing both the cellular and lipid contents of human lipoaspirate. The decellularized material retained a complex composition of peptides and glycosaminoglycans found in native adipose ECM. This matrix can be further processed by solubilizing the extracted ECM to generate a thermally-responsive hydrogel that self-assembles upon subcutaneous injection. This hydrogel also supports the growth and survival of patient matched adipose - derived stem cells in vitro. The development of an injectable hydrogel from human lipoaspirate represents a minimally-invasive option for adipose tissue engineering in terms of both the collection of source material and delivery of the scaffold. PMID:20932943

Polyurethane/poly(vinyl alcohol) hydrogel coating improves the cytocompatibility of neural electrodes

PubMed Central

Li, Mei; Zhou, Hai-han; Li, Tao; Li, Cheng-yan; Xia, Zhong-yuan; Duan, Yanwen Y.

2015-01-01

Neural electrodes, the core component of neural prostheses, are usually encapsulated in polydimethylsiloxane (PDMS). However, PDMS can generate a tissue response after implantation. Based on the physicochemical properties and excellent biocompatibility of polyurethane (PU) and poly(vinyl alcohol) (PVA) when used as coating materials, we synthesized PU/PVA hydrogel coatings and coated the surface of PDMS using plasma treatment, and the cytocompatibility to rat pheochromocytoma (PC12) cells was assessed. Protein adsorption tests indicated that the amount of protein adsorption onto the PDMS substrate was reduced by 92% after coating with the hydrogel. Moreover, the PC12 cells on the PU/PVA-coated PDMS showed higher cell density and longer and more numerous neurites than those on the uncoated PDMS. These results indicate that the PU/PVA hydrogel is cytocompatible and a promising coating material for neural electrodes to improve their biocompatibility. PMID:26889197

N-(furfural) chitosan hydrogels based on Diels-Alder cycloadditions and application as microspheres for controlled drug release.

PubMed

Montiel-Herrera, Marcelino; Gandini, Alessandro; Goycoolea, Francisco M; Jacobsen, Neil E; Lizardi-Mendoza, Jaime; Recillas-Mota, Maricarmen; Argüelles-Monal, Waldo M

2015-09-05

In this study, chitosan was chemically modified by reductive amination in a two-step process. The synthesis of N-(furfural) chitosan (FC) was confirmed by FT-IR and (1)H NMR analysis, and the degrees of substitution were estimated as 8.3 and 23.8%. The cross-linkable system of bismaleimide (BM) and FC shows that FC shared properties of furan-maleimide chemistry. This system produced non-reversible hydrogel networks by Diels-Alder cycloadditions at 85 °C. The system composed of BM and FC (23.8% substitution) generated stronger hydrogel networks than those of FC with an 8.3% degree of substitution. Moreover, the FC-BM system was able to produce hydrogel microspheres. Environmental scanning electron microscopy revealed the surface of the microspheres to be non-porous with small protuberances. In water, the microspheres swelled, increasing their volume by 30%. Finally, microspheres loaded with methylene blue were able to release the dye gradually, obeying second-order kinetics for times less than 600 min. This behavior suggests that diffusion is governed by the relaxation of polymer chains in the swelled state, thus facilitating drug release outside the microspheres. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hydrogel brushes grafted from stainless steel via surface-initiated atom transfer radical polymerization for marine antifouling

NASA Astrophysics Data System (ADS)

Wang, Jingjing; Wei, Jun

2016-09-01

Crosslinked hydrogel brushes were grafted from stainless steel (SS) surfaces for marine antifouling. The brushes were prepared by surface-initiated atom transfer radical polymerization (SI-ATRP) of 2-methacryloyloxyethyl phosphorylcholine (MPC) and poly(ethylene glycol) methyl ether methacrylate (PEGMA) respectively with different fractions of crosslinker in the feed. The grafted layers prepared with different thickness were characterized by X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), ellipsometry and water contact angle measurements. With the increase in the fraction of crosslinker in the feed, the thickness of the grafted layer increased and the surface became smooth. All the brush-coated SS surfaces could effectively reduce the adhesion of bacteria and microalgae and settlement of barnacle cyprids, as compared to the pristine SS surface. The antifouling efficacy of the PEGMA polymer (PPEGMA)-grafted surface was higher than that of the MPC polymer (PMPC)-grafted surfaces. Furthermore, the crosslinked hydrogel brush-grafted surfaces exhibited better fouling resistance than the non-crosslinked polymer brush-grafted surfaces, and the antifouling efficacy increased with the crosslinking density. These hydrogel coatings of low toxicity and excellent anti-adhesive characteristics suggested their useful applications as environmentally friendly antifouling coatings.

Root desiccation and drought stress responses of bareroot Quercus rubra seedlings treated with a hydrophilic polymer root dip

Treesearch

Kent G. Apostol; Douglass F. Jacobs; R. Kasten Dumroese

2009-01-01

Root hydrogel, a hydrophilic polymer, has been used to improve transplanting success of bareroot conifer seedlings through effects on water holding capacity. We examined mechanisms by which Terra-sorb Fine Hydrogel reduces damage that occurs when roots of 1-year old, dormant northern red oak (Quercus rubra L.) were subjected to shortterm (1, 3, and 5...

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

Recent advances in clay mineral-containing nanocomposite hydrogels.

PubMed

Zhao, Li Zhi; Zhou, Chun Hui; Wang, Jing; Tong, Dong Shen; Yu, Wei Hua; Wang, Hao

2015-12-28

Clay mineral-containing nanocomposite hydrogels have been proven to have exceptional composition, properties, and applications, and consequently have attracted a significant amount of research effort over the past few years. The objective of this paper is to summarize and evaluate scientific advances in clay mineral-containing nanocomposite hydrogels in terms of their specific preparation, formation mechanisms, properties, and applications, and to identify the prevailing challenges and future directions in the field. The state-of-the-art of existing technologies and insights into the exfoliation of layered clay minerals, in particular montmorillonite and LAPONITE®, are discussed first. The formation and structural characteristics of polymer/clay nanocomposite hydrogels made from in situ free radical polymerization, supramolecular assembly, and freezing-thawing cycles are then examined. Studies indicate that additional hydrogen bonding, electrostatic interactions, coordination bonds, hydrophobic interaction, and even covalent bonds could occur between the clay mineral nanoplatelets and polymer chains, thereby leading to the formation of unique three-dimensional networks. Accordingly, the hydrogels exhibit exceptional optical and mechanical properties, swelling-deswelling behavior, and stimuli-responsiveness, reflecting the remarkable effects of clay minerals. With the pivotal roles of clay minerals in clay mineral-containing nanocomposite hydrogels, the nanocomposite hydrogels possess great potential as superabsorbents, drug vehicles, tissue scaffolds, wound dressing, and biosensors. Future studies should lay emphasis on the formation mechanisms with in-depth insights into interfacial interactions, the tactical functionalization of clay minerals and polymers for desired properties, and expanding of their applications.

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.

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.

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.

Biomimetic hydrogel with tunable mechanical properties for vitreous substitutes.

PubMed

Santhanam, Sruthi; Liang, Jue; Struckhoff, Jessica; Hamilton, Paul D; Ravi, Nathan

2016-10-01

The vitreous humor of the eye is a biological hydrogel principally composed of collagen fibers interspersed with hyaluronic acid. Certain pathological conditions necessitate its removal and replacement. Current substitutes, like silicone oils and perfluorocarbons, are not biomimetic and have known complications. In this study, we have developed an in situ forming two-component biomimetic hydrogel with tunable mechanical and osmotic properties. The components are gellan, an analogue of collagen, and poly(methacrylamide-co-methacrylate), an analogue of hyaluronic acid; both endowed with thiol side groups. We used response surface methodology to consider seventeen possible hydrogels to determine how each component affects the optical, mechanical, sol-gel transition temperature and swelling properties. The optical and physical properties of the hydrogels were similar to vitreous. The shear storage moduli ranged from 3 to 358Pa at 1Hz and sol-gel transition temperatures from 35.5 to 43°C. The hydrogel had the ability to remain swollen without degradation for four weeks in vitro. Three hydrogels were tested for biocompatibility on primary porcine retinal pigment epithelial cells, human retinal pigment epithelial cells, and fibroblast (3T3/NIH) cells, by electric cell-substrate impedance sensing system. The two-component hydrogels allowed for the tuning and optimizing of mechanical, swelling, and transition temperature to obtain three biocompatible hydrogels with properties similar to the vitreous. Future studies include testing of the optimized hydrogels in animal models for use as a long-term substitute, whose preliminary results are mentioned. Although hydrogels are researched as long-term vitreous substitute, none have advanced sufficiently to reach clinical application. Our work focuses on the development of a novel two component in situ forming hydrogel that bio-mimic the natural vitreous. Our thiol-containing copolymers can be injected as an aqueous solution into the vitreous cavity wherein, at physiological temperature, the rigid component will instantaneously form a physical gel imbedding the random coil copolymer. Upon subsequent oxidation, the two components will form disulfide cross-links and a stable reversible hydrogel capable of providing osmotic pressure to reattach the retina. It may be left in the eye permanently or easily removed by injection of a simple reducing agent to cleave the disulfide bonds, rather than surgery. This contribution is significant because it is expected to provide patients with a much better quality of life by improving surgical outcomes, creating much less post-operative burden, and reducing the need for secondary surgeries. Published by Elsevier Ltd.

PNIPAAm-based biohybrid injectable hydrogel for cardiac tissue engineering.

PubMed

Navaei, Ali; Truong, Danh; Heffernan, John; Cutts, Josh; Brafman, David; Sirianni, Rachael W; Vernon, Brent; Nikkhah, Mehdi

2016-03-01

Injectable biomaterials offer a non-invasive approach to deliver cells into the myocardial infarct region to maintain a high level of cell retention and viability and initiate the regeneration process. However, previously developed injectable matrices often suffer from low bioactivity or poor mechanical properties. To address this need, we introduced a biohybrid temperature-responsive poly(N-isopropylacrylamide) PNIPAAm-Gelatin-based injectable hydrogel with excellent bioactivity as well as mechanical robustness for cardiac tissue engineering. A unique feature of our work was that we performed extensive in vitro biological analyses to assess the functionalities of cardiomyocytes (CMs) alone and in co-culture with cardiac fibroblasts (CFs) (2:1 ratio) within the hydrogel matrix. The synthesized hydrogel exhibited viscoelastic behavior (storage modulus: 1260 Pa) and necessary water content (75%) to properly accommodate the cardiac cells. The encapsulated cells demonstrated a high level of cell survival (90% for co-culture condition, day 7) and spreading throughout the hydrogel matrix in both culture conditions. A dense network of stained F-actin fibers (∼ 6 × 10(4) μm(2) area coverage, co-culture condition) illustrated the formation of an intact and three dimensional (3D) cell-embedded matrix. Furthermore, immunostaining and gene expression analyses revealed mature phenotypic characteristics of cardiac cells. Notably, the co-culture group exhibited superior structural organization and cell-cell coupling, as well as beating behavior (average ∼ 45 beats per min, co-culture condition, day 7). The outcome of this study is envisioned to open a new avenue for extensive in vitro characterization of injectable matrices embedded with 3D mono- and co-culture of cardiac cells prior to in vivo experiments. In this work, we synthesized a new class of biohybrid temperature-responsive poly(N-isopropylacrylamide) PNIPAAm-Gelatin-based injectable hydrogel with suitable bioactivity and mechanical properties for cardiac tissue engineering. A significant aspect of our work was that we performed extensive in vitro biological analyses to assess the functionality of cardiomyocytes alone and in co-culture with cardiac fibroblasts encapsulated within the 3D hydrogel matrix. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

RISK FACTORS FOR CONTACT LENS INDUCED PAPILLARY CONJUNCTIVITIS ASSOCIATED WITH SILICONE HYDROGEL CONTACT LENS WEAR

PubMed Central

Tagliaferri, Angela; Love, Thomas E.; Szczotka-Flynn, Loretta

2014-01-01

BACKGROUND Contact lens induced papillary conjunctivitis (CLPC) continues to be a major cause of dropout during contact lens extended wear. This retrospective study explores risk factors for the development of CLPC during silicone hydrogel lens extended wear. METHODS Data from 205 subjects enrolled in the Longitudinal Analysis of Silicone Hydrogel Contact Lens (LASH) study wearing lotrafilcon A silicone hydrogel lenses for up to 30 days of continuous wear were used to determine risk factors for CLPC in this secondary analysis of the main cohort. The main covariates of interest included substantial lens-associated bacterial bioburden, and topographically determined lens base curve-to-cornea fitting relationships. Additional covariates of interest included history of prior adverse events, time of year, race, education level, gender and other subject demographics. Statistical analyses included univariate logistic regression to assess the impact of potential risk factors on the binary CLPC outcome, and Cox proportional hazards regression to describe the impact of those factors on time-to-CLPC diagnosis. RESULTS Across 12 months of follow-up, 52 subjects (25%) experienced CLPC. No associations were found between CLPC development and the presence of bacterial bioburden, lens-to-cornea fitting relationships, history of prior adverse events, gender or race. CLPC development followed the same seasonal trends as the local peaks in environmental allergans. CONCLUSIONS Lens fit and biodeposits, in the form of lens associated bacterial bioburden, were not associated with the development of CLPC during extended wear with lotrafilcon A silicone hydrogel lenses. PMID:24681609

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.

Elastic, silk-cardiac extracellular matrix hydrogels exhibit time-dependent stiffening that modulates cardiac fibroblast response

PubMed Central

Stoppel, Whitney L.; Gao, Albert E.; Greaney, Allison M.; Partlow, Benjamin P.; Bretherton, Ross C.; Kaplan, David L.; Black, Lauren D.

2018-01-01

Heart failure is the leading cause of death in the United States and rapidly becoming the leading cause of death worldwide. While pharmacological treatments can reduce progression to heart failure following myocardial infarction, there still exists a need for new therapies that promote better healing post injury for a more functional cardiac repair and methods to understand how the changes to tissue mechanical properties influence cell phenotype and function following injury. To address this need, we have optimized a silk-based hydrogel platform containing cardiac tissue-derived extracellular matrix (cECM). These silk-cECM hydrogels have tunable mechanical properties, as well as rate-controllable hydrogel stiffening over time. In vitro, silk-cECM scaffolds led to enhanced cardiac fibroblast (CF) cell growth and viability with culture time. cECM incorporation improved expression of integrin an focal adhesion proteins, suggesting that CFs were able to interact with the cECM in the hydrogel. Subcutaneous injection of silk hydrogels in rats demonstrated that addition of the cECM led to endogenous cell infiltration and promoted endothelial cell ingrowth after 4 weeks in vivo. This naturally derived silk fibroin platform is applicable to the development of more physiologically relevant constructs that replicate healthy and diseased tissue in vitro and has the potential to be used as an injectable therapeutic for cardiac repair. PMID:27480328

PAMAM dendrimer hydrogel film—biocompatible material to an efficient dermal delivery of drugs

NASA Astrophysics Data System (ADS)

Magalhães, Thamiris Machado; Guerra, Rodrigo Cinti; San Gil, Rosane Aguiar da Silva; Valente, Ana Paula; Simão, Renata Antoun; Soares, Bluma Guenther; Mendes, Thamara de Carvalho; Pyrrho, Alexandre dos Santos; Sousa, Valeria Pereira de; Rodrigues-Furtado, Vanessa Lúcia

2017-08-01

We report the preparation, characterization, and drug release kinetics of a pH-responsive hydrogel film from a dendrimer megamer. The megamer (GP32) is a three-dimensional reticulated structure with a mean diameter of 71.16 nm (PDI 0.150) and was prepared by the reaction between Poly(amidoamine) generation4 (PAMAM G4) dendrimer and glutaraldehyde (G:P molar ratio 32). The crosslinking units in the megamer are provided mainly by the bicyclic dimer 2-hydroxy-3,4,4a,7,8,8a-hexahydro-2 H-chromene-6-carbaldehyde as determined by high-resolution (800 MHz) 1H NMR and FTIR. The hydrogel film (F[GP32]) is formed upon evaporation of a methanolic solution of the megamer and has a high degree of organization and homogeneity. Further crosslinking with glutaraldehyde (CLF[GP32]) enhanced the mechanical properties of the hydrogel film. The chemical constitution and unique megamer architecture enable the hydrogel film to carry both lipophilic and hydrophilic substances. The film did not cause any dermal irritation or clinical signs of toxicity in tests on rabbits, allowed for a sustained release of ketoprofen and played an important role in the process of drug delivery into the receptor medium. This performance taken together with the absence of toxicity makes this hydrogel film a good choice for dermal sustained drug release. [Figure not available: see fulltext.

Neovascularization Induced by the Hyaluronic Acid-Based Spongy-Like Hydrogels Degradation Products.

PubMed

Silva, Lucília P da; Pirraco, Rogério P; Santos, Tírcia C; Novoa-Carballal, Ramon; Cerqueira, Mariana T; Reis, Rui L; Correlo, Vitor M; Marques, Alexandra P

2016-12-14

Neovascularization has been a major challenge in many tissue regeneration strategies. Hyaluronic acid (HA) of 3-25 disaccharides is known to be angiogenic due to its interaction with endothelial cell receptors. This effect has been explored with HA-based structures but a transitory response is observed due to HA burst biodegradation. Herein we developed gellan gum (GG)-HA spongy-like hydrogels from semi-interpenetrating network hydrogels with different HA amounts. Enzymatic degradation was more evident in the GG-HA with high HA amount due to their lower mechanical stability, also resulting from the degradation itself, which facilitated the access of the enzyme to the HA in the bulk. GG-HA spongy-like hydrogels hyaluronidase-mediated degradation lead to the release of HA oligosaccharides of different amounts and sizes in a HA content-dependent manner which promoted in vitro proliferation of human umbilical cord vein endothelial cells (HUVECs) but not their migration. Although no effect was observed in human dermal microvascular endothelial cells (hDMECs) in vitro, the implantation of GG-HA spongy-like hydrogels in an ischemic hind limb mice model promoted neovascularization in a material-dependent manner, consistent with the in vitro degradation profile. Overall, GG-HA spongy-like hydrogels with a sustained release of HA oligomers are valuable options to improve tissue vascularization, a critical issue in several applications in the tissue engineering and regenerative medicine field.

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.

Can UV radiation-blocking soft contact lenses attenuate UV radiation to safe levels during summer months in the southern United States?

PubMed

Walsh, James E; Bergmanson, Jan P G; Saldana, Gerardo; Gaume, Amber

2003-01-01

Peak solar UV radiation (UVR) intensities are typically experienced in summer months. People living in the southern states of the United States, where the UVR frequently exceeds the recommended minimum erythema dose (MED), are at particular risk, especially outdoor workers. The present study analyzed summertime MED readings in Houston, TX, to assess the frequency of intensities regarded as unhealthy. The study also sought to assess whether UV-blocking hydrogel contact lenses provide ocular protection from these high doses. Readings, taken at midday using a UVR biometer, were analyzed to assess the potential UVR risk. The spectral response of the meter, modified by the spectral transmission curves of the contact lenses, allowed us to mathematically assess the ocular protection provided. In addition, ambient UVR measurements were taken at midday, using a portable UVR radiometer. The detector was adapted so that a standard diameter hydrogel contact lens could be placed over it to quantify the UV-blocking capabilities of the lens. The MED readings showed that the recommended safety standards were exceeded approximately at local midday 90% of the time. Model calculations and empirical data demonstrated that contact lenses attenuated the MED readings by up to 90%, bringing them well within the recommended Environmental Protection Agency safety standards. The efficacy of the model used in this study was verified through direct comparison of the modeled and measured data. UV-blocking hydrogel soft contact lenses reduce the MED to the human eye and therefore limit the lifetime ocular dose. These lenses are highly recommended to prevent the development of UVR-related ocular pathologic conditions.

Long period grating-based fiber-optic PH sensor for ocean monitoring

NASA Astrophysics Data System (ADS)

Wang, Ke; Klimov, Denis; Kolber, Zbigniew

2007-09-01

A fiber-optic PH sensor is developed based-on the long period grating (LPG). The LPG is fabricated by using CO II laser with a point-by-point technique. Then the grating portion is coated with PH sensitive hydrogel. The hydrogel, made of PVA/PAA, swells its volume in response to the PH change in the surrounding environment and results in a change in the refractive index. As a result, the LPG can response to the refractive index change in the coating by shifting its wavelength. Therefore, change in refractive index can be measured by tracking the wavelength shift using an optical spectrum analyzer (OSA). In this research, the LPG is dip-coated by the hydrogel. A chemostat is designed to simulate the marine environment. The PH in the chemostat is varied by controlling the CO II concentration in the sea water. A PH resolution 0.046/nm using the OSA has been obtained. This sensor is designed to monitor the sea water PH change in a long term basis.

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.

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.

Gelatin-based Hydrogel Degradation and Tissue Interaction in vivo: Insights from Multimodal Preclinical Imaging in Immunocompetent Nude Mice.

PubMed

Tondera, Christoph; Hauser, Sandra; Krüger-Genge, Anne; Jung, Friedrich; Neffe, Axel T; Lendlein, Andreas; Klopfleisch, Robert; Steinbach, Jörg; Neuber, Christin; Pietzsch, Jens

2016-01-01

Hydrogels based on gelatin have evolved as promising multifunctional biomaterials. Gelatin is crosslinked with lysine diisocyanate ethyl ester (LDI) and the molar ratio of gelatin and LDI in the starting material mixture determines elastic properties of the resulting hydrogel. In order to investigate the clinical potential of these biopolymers, hydrogels with different ratios of gelatin and diisocyanate (3-fold (G10_LNCO3) and 8-fold (G10_LNCO8) molar excess of isocyanate groups) were subcutaneously implanted in mice (uni- or bilateral implantation). Degradation and biomaterial-tissue-interaction were investigated in vivo (MRI, optical imaging, PET) and ex vivo (autoradiography, histology, serum analysis). Multimodal imaging revealed that the number of covalent net points correlates well with degradation time, which allows for targeted modification of hydrogels based on properties of the tissue to be replaced. Importantly, the degradation time was also dependent on the number of implants per animal. Despite local mechanisms of tissue remodeling no adverse tissue responses could be observed neither locally nor systemically. Finally, this preclinical investigation in immunocompetent mice clearly demonstrated a complete restoration of the original healthy tissue.

Supramolecular Hydrogels Based on Minimalist Amphiphilic Squaramide-Squaramates for Controlled Release of Zwitterionic Biomolecules.

PubMed

López, Carlos; Ximenis, Marta; Orvay, Francisca; Rotger, Carmen; Costa, Antonio

2017-06-01

Supramolecular hydrogels with tunable properties have innovative applications in biomedicine, catalysis, and materials chemistry. Minimalist low-molecular-weight hydrogelators based on squaramide and squaramic acid motifs have been designed. This approach benefits from the high acidity of squaramic acids and the aromaticity of squaramides. Moreover, substituents on the aryl ring tune the π density of the arylsquaramide motif. Thus, materials featuring distinct thermal and mechanical properties have been successfully prepared. The hydrogel (G'≈400 Pa, G''≈57 Pa; at 1.0 % w/v; 1 Hz) obtained from 4-nitrophenylsquaramide motif 1 is thermoreversible (T=57 °C at 0.2 % w/v), thixotropic, self-healable, and undergoes irreversible shrinking in response to saline stress. Furthermore, the hydrogel is injectable and can be loaded with substantial amounts (5:1 excess molar ratio) of zwitterionic biomolecules, such as l-carnitine, γ-aminobutyric acid (GABA), or d,l-Ala-d,l-Ala, without any loss of structural integrity. Then, the release of these molecules can be modulated by saline solutions. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phenotypic Characterization of Prostate Cancer LNCaP Cells Cultured within a Bioengineered Microenvironment

PubMed Central

Sieh, Shirly; Taubenberger, Anna V.; Rizzi, Simone C.; Sadowski, Martin; Lehman, Melanie L.; Rockstroh, Anja; An, Jiyuan; Clements, Judith A.; Nelson, Colleen C.; Hutmacher, Dietmar W.

2012-01-01

Biophysical and biochemical properties of the microenvironment regulate cellular responses such as growth, differentiation, morphogenesis and migration in normal and cancer cells. Since two-dimensional (2D) cultures lack the essential characteristics of the native cellular microenvironment, three-dimensional (3D) cultures have been developed to better mimic the natural extracellular matrix. To date, 3D culture systems have relied mostly on collagen and Matrigel™ hydrogels, allowing only limited control over matrix stiffness, proteolytic degradability, and ligand density. In contrast, bioengineered hydrogels allow us to independently tune and systematically investigate the influence of these parameters on cell growth and differentiation. In this study, polyethylene glycol (PEG) hydrogels, functionalized with the Arginine-glycine-aspartic acid (RGD) motifs, common cell-binding motifs in extracellular matrix proteins, and matrix metalloproteinase (MMP) cleavage sites, were characterized regarding their stiffness, diffusive properties, and ability to support growth of androgen-dependent LNCaP prostate cancer cells. We found that the mechanical properties modulated the growth kinetics of LNCaP cells in the PEG hydrogel. At culture periods of 28 days, LNCaP cells underwent morphogenic changes, forming tumor-like structures in 3D culture, with hypoxic and apoptotic cores. We further compared protein and gene expression levels between 3D and 2D cultures upon stimulation with the synthetic androgen R1881. Interestingly, the kinetics of R1881 stimulated androgen receptor (AR) nuclear translocation differed between 2D and 3D cultures when observed by immunofluorescent staining. Furthermore, microarray studies revealed that changes in expression levels of androgen responsive genes upon R1881 treatment differed greatly between 2D and 3D cultures. Taken together, culturing LNCaP cells in the tunable PEG hydrogels reveals differences in the cellular responses to androgen stimulation between the 2D and 3D environments. Therefore, we suggest that the presented 3D culture system represents a powerful tool for high throughput prostate cancer drug testing that recapitulates tumor microenvironment. PMID:22957009

Mechanical stabilization of proteolytically degradable polyethylene glycol dimethacrylate hydrogels through peptide interaction.

PubMed

Lim, Hyun Ju; Khan, Zara; Lu, Xi; Perera, T Hiran; Wilems, Thomas S; Ravivarapu, Krishna T; Smith Callahan, Laura A

2018-04-15

Balancing enhancement of neurite extension against loss of matrix support in synthetic hydrogels containing proteolytically degradable and bioactive signaling peptides to optimize tissue formation is difficult. Using a systematic approach, polyethylene glycol hydrogels containing concurrent continuous concentration gradients of the laminin derived bioactive signaling peptide, Ile-Lys-Val-Ala-Val (IKVAV), and collagen derived matrix metalloprotease degradable peptide, GPQGIWGQ, were fabricated and characterized. During proteolytic degradation of the concentration gradient hydrogels, the IKVAV and IWGQ cleavage fragment from GPQGIWGQ were found to interact and stabilize the bulk Young's Modulus of the hydrogel. Further testing of discrete samples containing GPQGIWGQ or its cleavage fragments, GPQG and IWGQ, indicates hydrophobic interactions between the peptides are not necessary for mechanical stabilization of the hydrogel, but changes in the concentration ratio between the peptides tethered in the hydrogel and salts and ions in the swelling solution can affect the stabilization. Encapsulation of human induced pluripotent stem cell derived neural stem cells did not reduce the mechanical properties of the hydrogel over a 14 day neural differentiation culture period, and IKVAV was found to maintain concentration dependent effects on neurite extension and mRNA gene expression of neural cytoskeletal markers, similar to previous studies. As a result, this work has significant implications for the analysis of biological studies in matrices, as the material and mechanical properties of the hydrogel may be unexpectedly temporally changing during culture due to interactions between peptide signaling elements, underscoring the need for greater matrix characterization during the degradation and cell culture. Greater emulation of the native extracellular matrix is necessary for tissue formation. To achieve this, matrices are becoming more complex, often including multiple bioactive signaling elements. However, peptide signaling in polyethylene glycol matrices and amino acids interactions between peptides can affect hydrogel material and mechanical properties, but are rarely studied. The current study identifies such an interaction between laminin derived peptide, IKVAV, and collagen derived matrix metalloprotease degradable peptide, GPQGIWGQ. Previous studies using these peptides did not identify their interactions' ability to mechanically stabilize the hydrogel during degradation. This work underscores the need for greater matrix characterization and consideration of bioactive signaling element effects temporally on the matrix's material and mechanical properties, as they can contribute to cellular response. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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.

One-step assembly of Fe(III)-CMC chelate hydrogel onto nanoneedle-like CuO@Cu membrane with superhydrophilicity for oil-water separation

NASA Astrophysics Data System (ADS)

Dai, Jiangdong; Chang, Zhongshuai; Xie, Atian; Zhang, Ruilong; Tian, Sujun; Ge, Wenna; Yan, Yongsheng; Li, Chunxiang; Xu, Wei; Shao, Rong

2018-05-01

The research of superhydrophilic interface is developing rapidly, but the preparations of superhydrophilic surfaces through simple methods are still challenging. Herein, we reported a facile, rapid and environmentally-friendly approach for preparing a novel superhydrophilic and underwater superoleophobic membrane via the thermal oxidation of Cu mesh and one-step coordinated assembly of Fe(III)-CMC chelate hydrogel. Superhydrophilicity was attributed to the hydrophilicity of Fe(III)-CMC chelate hydrogel and nanoneedle-like rough structure of CuO@Cu membrane. The membrane was used to separate a variety of oil/water mixtures and exhibited excellent separation performance. Moreover, the membrane exhibited the excellent durability and superior stability against corrosion conditions. We envision that the Fe(III)-CMC@CuO@Cu membrane with good underwater superoleophobicity could provide a candidate not only for oil/water separation but also many other potential applications such as underwater oil manipulation, self-clean, and bio-adhesion control.

pH-responsive hydrogel coated fiber Bragg grating-based chemo mechanical sensor bioreactor applications

NASA Astrophysics Data System (ADS)

Kishore, P. V. N.; Sai Shankar, M.

2017-04-01

This paper describes a fiber optics based pH sensor by using wavelength modulated techniques. Fiber Bragg grating (FBG) is functionalized with a stimulus responsive hydrogel which 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 which is monitored by an interrogator. The sensor system shows a good linearity in acidic pH range of 3 to 7 with a sensitivity of 12.16pm/pH. Besides that it shows good repeatability which proves it to be fit for pH sensing applications.

Scalable manufacturing of biomimetic moldable hydrogels for industrial applications.

PubMed

Yu, Anthony C; Chen, Haoxuan; Chan, Doreen; Agmon, Gillie; Stapleton, Lyndsay M; Sevit, Alex M; Tibbitt, Mark W; Acosta, Jesse D; Zhang, Tony; Franzia, Paul W; Langer, Robert; Appel, Eric A

2016-12-13

Hydrogels are a class of soft material that is exploited in many, often completely disparate, industrial applications, on account of their unique and tunable properties. Advances in soft material design are yielding next-generation moldable hydrogels that address engineering criteria in several industrial settings such as complex viscosity modifiers, hydraulic or injection fluids, and sprayable carriers. Industrial implementation of these viscoelastic materials requires extreme volumes of material, upwards of several hundred million gallons per year. Here, we demonstrate a paradigm for the scalable fabrication of self-assembled moldable hydrogels using rationally engineered, biomimetic polymer-nanoparticle interactions. Cellulose derivatives are linked together by selective adsorption to silica nanoparticles via dynamic and multivalent interactions. We show that the self-assembly process for gel formation is easily scaled in a linear fashion from 0.5 mL to over 15 L without alteration of the mechanical properties of the resultant materials. The facile and scalable preparation of these materials leveraging self-assembly of inexpensive, renewable, and environmentally benign starting materials, coupled with the tunability of their properties, make them amenable to a range of industrial applications. In particular, we demonstrate their utility as injectable materials for pipeline maintenance and product recovery in industrial food manufacturing as well as their use as sprayable carriers for robust application of fire retardants in preventing wildland fires.

Scalable manufacturing of biomimetic moldable hydrogels for industrial applications

NASA Astrophysics Data System (ADS)

Yu, Anthony C.; Chen, Haoxuan; Chan, Doreen; Agmon, Gillie; Stapleton, Lyndsay M.; Sevit, Alex M.; Tibbitt, Mark W.; Acosta, Jesse D.; Zhang, Tony; Franzia, Paul W.; Langer, Robert; Appel, Eric A.

2016-12-01

Hydrogels are a class of soft material that is exploited in many, often completely disparate, industrial applications, on account of their unique and tunable properties. Advances in soft material design are yielding next-generation moldable hydrogels that address engineering criteria in several industrial settings such as complex viscosity modifiers, hydraulic or injection fluids, and sprayable carriers. Industrial implementation of these viscoelastic materials requires extreme volumes of material, upwards of several hundred million gallons per year. Here, we demonstrate a paradigm for the scalable fabrication of self-assembled moldable hydrogels using rationally engineered, biomimetic polymer-nanoparticle interactions. Cellulose derivatives are linked together by selective adsorption to silica nanoparticles via dynamic and multivalent interactions. We show that the self-assembly process for gel formation is easily scaled in a linear fashion from 0.5 mL to over 15 L without alteration of the mechanical properties of the resultant materials. The facile and scalable preparation of these materials leveraging self-assembly of inexpensive, renewable, and environmentally benign starting materials, coupled with the tunability of their properties, make them amenable to a range of industrial applications. In particular, we demonstrate their utility as injectable materials for pipeline maintenance and product recovery in industrial food manufacturing as well as their use as sprayable carriers for robust application of fire retardants in preventing wildland fires.

Scalable manufacturing of biomimetic moldable hydrogels for industrial applications

PubMed Central

Yu, Anthony C.; Chen, Haoxuan; Chan, Doreen; Agmon, Gillie; Stapleton, Lyndsay M.; Sevit, Alex M.; Tibbitt, Mark W.; Acosta, Jesse D.; Zhang, Tony; Franzia, Paul W.; Langer, Robert

2016-01-01

Hydrogels are a class of soft material that is exploited in many, often completely disparate, industrial applications, on account of their unique and tunable properties. Advances in soft material design are yielding next-generation moldable hydrogels that address engineering criteria in several industrial settings such as complex viscosity modifiers, hydraulic or injection fluids, and sprayable carriers. Industrial implementation of these viscoelastic materials requires extreme volumes of material, upwards of several hundred million gallons per year. Here, we demonstrate a paradigm for the scalable fabrication of self-assembled moldable hydrogels using rationally engineered, biomimetic polymer–nanoparticle interactions. Cellulose derivatives are linked together by selective adsorption to silica nanoparticles via dynamic and multivalent interactions. We show that the self-assembly process for gel formation is easily scaled in a linear fashion from 0.5 mL to over 15 L without alteration of the mechanical properties of the resultant materials. The facile and scalable preparation of these materials leveraging self-assembly of inexpensive, renewable, and environmentally benign starting materials, coupled with the tunability of their properties, make them amenable to a range of industrial applications. In particular, we demonstrate their utility as injectable materials for pipeline maintenance and product recovery in industrial food manufacturing as well as their use as sprayable carriers for robust application of fire retardants in preventing wildland fires. PMID:27911849

Self-assembled Nanofibrils for Immunomodulation

NASA Astrophysics Data System (ADS)

Zhao, Fan

This thesis has been mainly focused on applying self-assembled nanofibrils as unique depots for controlled release to modulate immune system, with two major chapters on modulation of innate immunity in chapter 2 and adaptive immunity in chapter 3, respectively. There are 5 chapters in the thesis. Chapter 1 gives a detailed review on the discovery, synthesis and application of self-assembled nanofibrils of therapeutic agents (termed as "self-delivery drugs"), including bioactive molecules; Chapter 2 demonstrates the supramolecular hydrogel of chemotactic peptides as a prolonged inflammation model through proper molecular engineering; Chapter 3 reports a suppressive antibody response achieved by encapsulation of antigens by supramolecular hydrogel of glycopeptide; Chapter 4 illustrates an example of supramolecular hydrogel formation of molecules with extremely low solubility, based on the fact that many small organic drugs have poor solubility. Chapter 5 used beta-galatosidase as a model to study glycosidase-instructed supramolecular hydrogel formation, with potential to target cancer cells due to their distinct metabolic profile.

Comparing goblet cell densities in patients wearing disposable hydrogel contact lenses versus silicone hydrogel contact lenses in an extended-wear modality.

PubMed

Lievens, Christopher W; Connor, Charles G; Murphy, Heather

2003-10-01

The current study evaluates the response of the ocular surface to extended contact lens wear by comparing a new silicone hydrogel lens to an ACUVUE 2 lens. Twenty subjects with an average age of 28 years were randomly assigned to a fitting with ACUVUE 2 or PureVision lenses. Ocular surface assessment by impression cytology was performed at baseline and for the 6 months after initiation of lens wear. Although goblet cell density significantly increased with wear time, no statistically significant difference was observed between the contact lens groups. The average baseline goblet cell percentages were as follows: ACUVUE 2 group, 1.44; PureVision group, 1.11. The 6-month averages were as follows: ACUVUE 2 group, 3.16; PureVision group, 2.22. It appears that silicone hydrogel lenses may be slightly less irritating to the ocular surface than lenses not containing silicone. This could be a promising indicator for successful 30-day continuous wear.

Supermacroporous chemically cross-linked poly(aspartic acid) hydrogels.

PubMed

Gyarmati, Benjámin; Mészár, E Zsuzsanna; Kiss, Lóránd; Deli, Mária A; László, Krisztina; Szilágyi, András

2015-08-01

Chemically cross-linked poly(aspartic acid) (PASP) gels were prepared by a solid-liquid phase separation technique, cryogelation, to achieve a supermacroporous interconnected pore structure. The precursor polymer of PASP, polysuccinimide (PSI) was cross-linked below the freezing point of the solvent and the forming crystals acted as templates for the pores. Dimethyl sulfoxide was chosen as solvent instead of the more commonly used water. Thus larger temperatures could be utilized for the preparation and the drawback of increase in specific volume of water upon freezing could be eliminated. The morphology of the hydrogels was characterized by scanning electron microscopy and interconnectivity of the pores was proven by the small flow resistance of the gels. Compression tests also confirmed the interconnected porous structure and the complete re-swelling and shape recovery of the supermacroporous PASP hydrogels. The prepared hydrogels are of interest for several biomedical applications as scaffolding materials because of their cytocompatibility, controllable morphology and pH-responsive character. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Tunable thermo-responsive hydrogels: synthesis, structural analysis and drug release studies.

PubMed

Cirillo, Giuseppe; Spataro, Tania; Curcio, Manuela; Spizzirri, U Gianfranco; Nicoletta, Fiore Pasquale; Picci, Nevio; Iemma, Francesca

2015-03-01

Thermo-responsive hydrogel films, synthesized by UV-initiated radical polymerization, are proposed as delivery devices for non-steroidal anti-inflammatory drugs (Diclofenac sodium and Naproxen). N-isopropylacrylamide and N,N'-ethylenebisacrylamide were chosen as thermo-sensitive monomer and crosslinker, respectively. Infrared spectroscopy was used to assess the incorporation of monomers into the network, and the network density of hydrogel films was found to strictly depend on both feed composition and film thickness. Calorimetric analyses showed negative thermo-responsive behaviour with shrinking/swelling transition values in the range 32.8-36.1°C. Equilibrium swelling studies around the LCST allowed the correlation between the structural changes and the temperature variations. The mesh size, indeed, rapidly changed from a collapsed to a swollen state, with beneficial effects in applications such as size-selective permeation or controlled drug delivery, while the crosslinking degree, the film thickness, and the loading method deeply influenced the drug release profiles at 25 and 40°C. The analysis of both 3D-network structure, release kinetics and diffusional constraints at different temperatures was evaluated by mathematical modelling. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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

Preparation of fast response superabsorbent hydrogels by radiation polymerization and crosslinking of N-isopropylacrylamide in solution

NASA Astrophysics Data System (ADS)

Abd El-Mohdy, H. L.; Safrany, Agnes

2008-03-01

Macroporous temperature-responsive poly( N-isopropylacrylamide) (PNIPAAm) hydrogels with high equilibrium swelling and fast response rates were obtained by a 60Co γ- and electron beam (EB) irradiation of aqueous N-isopropylacrylamide (NIPAAm) monomer solutions. The effect of irradiation temperatures, the dose, the addition of a pore-forming agent on the swelling ratio, and the kinetics of swelling and shrinking of the PNIPAAm gels was studied. The gels synthesized above the LCST exhibited the highest equilibrium swelling (300-400) and fastest response rate measured by minutes. Scanning electron microscope (SEM) pictures revealed that the gels synthesized above the LCST have larger pores than those prepared at temperatures below the LCST. The gels showed a reversible response to cyclical changes in temperature and might be used in a pulsed drug delivery device. The gels synthesized above the LCST exhibited the highest testosterone propionate release.

Thermo-responsive gels that absorb moisture and ooze water.

PubMed

Matsumoto, Kazuya; Sakikawa, Nobuki; Miyata, Takashi

2018-06-13

The water content of thermo-responsive hydrogels can be drastically altered by small changes in temperature because their polymer chains change from hydrophilic to hydrophobic above their low critical solution temperature (LCST). In general, such smart hydrogels have been utilized in aqueous solutions or in their wet state, and no attempt has been made to determine the phase-transition behavior of the gels in their dried states. Here we demonstrate an application of the thermo-responsive behavior of an interpenetrating polymer network (IPN) gel comprising thermo-responsive poly(N-isopropylacrylamide) and hydrophilic sodium alginate networks in their dried states. The dried IPN gel absorbs considerable moisture from air at temperatures below its LCST and oozes the absorbed moisture as liquid water above its LCST. These phenomena provide energy exchange systems in which moisture from air can be condensed to liquid water using the controllable hydrophilic/hydrophobic properties of thermo-responsive gels with a small temperature change.

Transient rheology of stimuli responsive hydrogels: Integrating microrheology and microfluidics

NASA Astrophysics Data System (ADS)

Sato, Jun

Stimuli-responsive hydrogels have diverse potential applications in the field of drug delivery, tissue engineering, agriculture, cosmetics, gene therapy, and as sensors and actuators due to their unique responsiveness to external signals, such as pH, temperature, and ionic strength. Understanding the responsiveness of hydrogel structure and rheology to these stimuli is essential for designing materials with desirable performance. However, no instrumentation and well-defined methodology are available to characterize the structural and rheological responses to rapid solvent changes. In this thesis, a new microrheology set-up is described, which allows us to quantitatively measure the transient rheological properties and microstructure of a variety of solvent-responsive complex fluids. The device was constructed by integrating particle tracking microrheology and microfluidics and offers unique experimental capabilities for performing solvent-reponse measurements on soft fragile materials without applying external shear forces. Transient analysis methods to quantitatively obtain rheological properties were also constructed, and guidelines for the trade-off between statistical validity and temporal resolution were developed to accurately capture physical transitions. Employing the new device and methodology, we successfully quantified the transient rheological and microstructural responses during gel formation and break-up, and viscosity changes of solvent-responsive complex fluids. The analysis method was expanded for heterogeneous samples, incorporating methods to quantify the microrheology of samples with broad distributions of individual particle dynamics. Transient microrheology measurements of fragile, heterogeneous, self-assembled block copolypeptide hydrogels revealed that solvent exchange via convective mixing and dialysis can lead to significantly different gel properties and that commonly applied sample preparation protocols for the characterization of soft biomaterials could lead to erroneous conclusions about microstructural dynamics. Systematic investigations by varying key parameters, like molecular structure, gel concentration, salt concentration, and tracer particle size for microrheology, revealed that subtle variations in molecular architecture can cause major changes in response dynamics. Moreover, the results showed that the method can be applied for studying gel formation and breakup kinetics. The research in this thesis facilitates the design of solvent-responsive soft materials with appropriate microstructural dynamics for in vivo applications like tissue engineering and drug delivery, and can also be applied to study the effect of solvents on self-assembly mechanisms in other responsive soft materials, such as polymer solutions and colloidal dispersions.

Concentration dependent survival and neural differentiation of murine embryonic stem cells cultured on polyethylene glycol dimethacrylate hydrogels possessing a continuous concentration gradient of n-cadherin derived peptide His-Ala-Val-Asp-Lle.

PubMed

Lim, Hyun Ju; Mosley, Matthew C; Kurosu, Yuki; Smith Callahan, Laura A

2017-07-01

N-cadherin cell-cell signaling plays a key role in the structure and function of the nervous system. However, few studies have incorporated bioactive signaling from n-cadherin into tissue engineering matrices. The present study uses a continuous gradient approach in polyethylene glycol dimethacrylate hydrogels to identify concentration dependent effects of n-cadherin peptide, His-Ala-Val-Asp-Lle (HAVDI), on murine embryonic stem cell survival and neural differentiation. The n-cadherin peptide was found to affect the expression of pluripotency marker, alkaline phosphatase, in murine embryonic stem cells cultured on n-cadherin peptide containing hydrogels in a concentration dependent manner. Increasing n-cadherin peptide concentrations in the hydrogels elicited a biphasic response in neurite extension length and mRNA expression of neural differentiation marker, neuron-specific class III β-tubulin, in murine embryonic stem cells cultured on the hydrogels. High concentrations of n-cadherin peptide in the hydrogels were found to increase the expression of apoptotic marker, caspase 3/7, in murine embryonic stem cells compared to that of murine embryonic stem cell cultures on hydrogels containing lower concentrations of n-cadherin peptide. Increasing the n-cadherin peptide concentration in the hydrogels facilitated greater survival of murine embryonic stem cells exposed to increasing oxidative stress caused by hydrogen peroxide exposure. The combinatorial approach presented in this work demonstrates concentration dependent effects of n-cadherin signaling on mouse embryonic stem cell behavior, underscoring the need for the greater use of systematic approaches in tissue engineering matrix design in order to understand and optimize bioactive signaling in the matrix for tissue formation. Single cell encapsulation is common in tissue engineering matrices. This eliminates cellular access to cell-cell signaling. N-cadherin, a cell-cell signaling molecule, plays a vital role in the development of neural tissues, but has not been well studied as a bioactive signaling element in neural tissue engineering matrices. The present study uses a systematic continuous gradient approach to identify concentration dependent effects of n-cadherin derived peptide, HAVDI, on the survival and neural differentiation of murine embryonic stem cells. This work underscores the need for greater use to combinatorial strategies to understand the effect complex bioactive signaling, such as n-cadherin, and the need to optimize the concentration of such bioactive signaling within tissue engineering matrices for maximal cellular response. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Cytocompatibility, antibacterial activity and biodegradability of self-assembling beta-hairpin peptide-based hydrogels for tissue regenerative applications

NASA Astrophysics Data System (ADS)

Salick, Daphne Ann

Every year, millions of people suffer from tissue loss or failure. One approach to repair damaged or diseased tissue is through tissue/organ transplantation. However, one of the major problems which exist with this approach is that there are more people in need of a transplant than there are donors. Over the past several decades, scientists and doctors have come together to find a way to overcome this challenge. This collaboration has led to the development of biomimetic scaffolds, which closely mimic the desired tissue of interest to act as a substitute for the unfunctional tissue, with hopes to improve the quality of life. The Schneider and Pochan labs have developed a biomimetic scaffold using self-assembling beta-hairpin peptides. The self-assembly event can be triggered in response to physiological conditions, which is dictated by the monomer, to form non covalently crosslinked mechanically rigid hydrogels. In vitro studies showed that hydrogels were cytocompatible and may not elicit a pro-inflammatory response from murine macrophages. These material properties show promise for the use of these hydrogels in tissue engineering. When implanting a material into a host, a major concern is the introduction of infection. Infection, if not prevented or halted, results in poor tissue integration and function, ultimately leading to implant removal from the host. Interestingly, the beta-hairpin hydrogels were shown to exhibit antibacterial properties against pathogens commonly found in hospital environments. This inherently antibacterial hydrogel is advantageous because it may help decrease or diminish bacterial contamination when implanted in vivo, which may help to increase the success of implants. Also, a unique and exciting feature of these peptide-based hydrogels is their ability to shear-thin and self-heal. Hydrogels can be directly formed in a syringe and be subsequently delivered to a tissue defect in a minimally invasive manner where they will recover to their original mechanical rigidity. The resultant syringe-delivered gel was also shown to possess antibacterial properties. Aside from the material's inherent antibacterial activity, these peptide-based scaffolds display degradation that can be controlled using an exogenously added enzyme. This suggests that by using peptide design, the gel network degradation can be controlled to allow for the proper formation of functional tissue. The work described in this thesis shows these described attributes, as well as, the potential of these peptide-based gels for use as tissue substitutes.

A stimuli responsive liposome loaded hydrogel provides flexible on-demand release of therapeutic agents.

PubMed

O'Neill, Hugh S; Herron, Caroline C; Hastings, Conn L; Deckers, Roel; Lopez Noriega, Adolfo; Kelly, Helena M; Hennink, Wim E; McDonnell, Ciarán O; O'Brien, Fergal J; Ruiz-Hernández, Eduardo; Duffy, Garry P

2017-01-15

Lysolipid-based thermosensitive liposomes (LTSL) embedded in a chitosan-based thermoresponsive hydrogel matrix (denoted Lipogel) represents a novel approach for the spatiotemporal release of therapeutic agents. The entrapment of drug-loaded liposomes in an injectable hydrogel permits local liposome retention, thus providing a prolonged release in target tissues. Moreover, release can be controlled through the use of a minimally invasive external hyperthermic stimulus. Temporal control of release is particularly important for complex multi-step physiological processes, such as angiogenesis, in which different signals are required at different times in order to produce a robust vasculature. In the present work, we demonstrate the ability of Lipogel to provide a flexible, easily modifiable release platform. It is possible to tune the release kinetics of different drugs providing a passive release of one therapeutic agent loaded within the gel and activating the release of a second LTSL encapsulated agent via a hyperthermic stimulus. In addition, it was possible to modify the drug dosage within Lipogel by varying the duration of hyperthermia. This can allow for adaption of drug dosing in real time. As an in vitro proof of concept with this system, we investigated Lipogels ability to recruit stem cells and then elevate their production of vascular endothelial growth factor (VEGF) by controlling the release of a pro-angiogenic drug, desferroxamine (DFO) with an external hyperthermic stimulus. Initial cell recruitment was accomplished by the passive release of hepatocyte growth factor (HGF) from the hydrogel, inducing a migratory response in cells, followed by the delayed release of DFO from thermosensitive liposomes, resulting in a significant increase in VEGF expression. This delayed release could be controlled up to 14days. Moreover, by changing the duration of the hyperthermic pulse, a fine control over the amount of DFO released was achieved. The ability to trigger the release of therapeutic agents at a specific timepoint and control dosing level through changes in duration of hyperthermia enables sequential multi-dose profiles. This paper details the development of a heat responsive liposome loaded hydrogel for the controlled release of pro-angiogenic therapeutics. Lysolipid-based thermosensitive liposomes (LTSLs) embedded in a chitosan-based thermoresponsive hydrogel matrix represents a novel approach for the spatiotemporal release of therapeutic agents. This hydrogel platform demonstrates remarkable flexibility in terms of drug scheduling and sequencing, enabling the release of multiple agents and the ability to control drug dosing in a minimally invasive fashion. The possibility to tune the release kinetics of different drugs independently represents an innovative platform to utilise for a variety of treatments. This approach allows a significant degree of flexibility in achieving a desired release profile via a minimally invasive stimulus, enabling treatments to be tuned in response to changing symptoms and complications. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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.

3D Printed Reversible Shape Changing Components with Stimuli Responsive Materials

PubMed Central

Mao, Yiqi; Ding, Zhen; Yuan, Chao; Ai, Shigang; Isakov, Michael; Wu, Jiangtao; Wang, Tiejun; Dunn, Martin L.; Qi, H. Jerry

2016-01-01

The creation of reversibly-actuating components that alter their shapes in a controllable manner in response to environmental stimuli is a grand challenge in active materials, structures, and robotics. Here we demonstrate a new reversible shape-changing component design concept enabled by 3D printing two stimuli responsive polymers—shape memory polymers and hydrogels—in prescribed 3D architectures. This approach uses the swelling of a hydrogel as the driving force for the shape change, and the temperature-dependent modulus of a shape memory polymer to regulate the time of such shape change. Controlling the temperature and aqueous environment allows switching between two stable configurations – the structures are relatively stiff and can carry load in each – without any mechanical loading and unloading. Specific shape changing scenarios, e.g., based on bending, or twisting in prescribed directions, are enabled via the controlled interplay between the active materials and the 3D printed architectures. The physical phenomena are complex and nonintuitive, and so to help understand the interplay of geometric, material, and environmental stimuli parameters we develop 3D nonlinear finite element models. Finally, we create several 2D and 3D shape changing components that demonstrate the role of key parameters and illustrate the broad application potential of the proposed approach. PMID:27109063

3D Printed Reversible Shape Changing Components with Stimuli Responsive Materials

NASA Astrophysics Data System (ADS)

Mao, Yiqi; Ding, Zhen; Yuan, Chao; Ai, Shigang; Isakov, Michael; Wu, Jiangtao; Wang, Tiejun; Dunn, Martin L.; Qi, H. Jerry

2016-04-01

The creation of reversibly-actuating components that alter their shapes in a controllable manner in response to environmental stimuli is a grand challenge in active materials, structures, and robotics. Here we demonstrate a new reversible shape-changing component design concept enabled by 3D printing two stimuli responsive polymers—shape memory polymers and hydrogels—in prescribed 3D architectures. This approach uses the swelling of a hydrogel as the driving force for the shape change, and the temperature-dependent modulus of a shape memory polymer to regulate the time of such shape change. Controlling the temperature and aqueous environment allows switching between two stable configurations - the structures are relatively stiff and can carry load in each - without any mechanical loading and unloading. Specific shape changing scenarios, e.g., based on bending, or twisting in prescribed directions, are enabled via the controlled interplay between the active materials and the 3D printed architectures. The physical phenomena are complex and nonintuitive, and so to help understand the interplay of geometric, material, and environmental stimuli parameters we develop 3D nonlinear finite element models. Finally, we create several 2D and 3D shape changing components that demonstrate the role of key parameters and illustrate the broad application potential of the proposed approach.

Programmable Matter Creating Systems that Can Think, Talk, and Morph Autonomously. Phase 2

DTIC Science & Technology

2011-09-13

irradiation. SWNTs have a well-defined near-IR optical absorption, specifically ideal for biocompatible devices such as drug delivery mediums or biological...investigated as follows: • Lower Critical Transition Temperature(LCST) of the CNT-pNIPAM composites. • Strain change of CNT-pNIPAM hydrogel at LCST...loading at concentrations of 0.75mg/mL, we demonstrate up to 5 times enhancement to the thermal response time of the nanotube- pNIPAM hydrogel

Edge-Hydroxylated Boron Nitride Nanosheets as an Effective Additive to Improve the Thermal Response of Hydrogels.

PubMed

Xiao, Feng; Naficy, Sina; Casillas, Gilberto; Khan, Majharul H; Katkus, Tomas; Jiang, Lei; Liu, Huakun; Li, Huijun; Huang, Zhenguo

2015-11-25

Upon flowing hot steam over hexagonal boron nitride (h-BN) bulk powder, efficient exfoliation and hydroxylation of BN occur simultaneously. Through effective hydrogen bonding with water and N-isopropylacrylamide, edge-hydroxylated BN nanosheets dramatically improve the dimensional change and dye release of this temperature-sensitive hydrogel and thereby enhance its efficacy in bionic, soft robotic, and drug-delivery applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Characterisation of cell-substrate interactions between Schwann cells and three-dimensional fibrin hydrogels containing orientated nanofibre topographical cues.

PubMed

Hodde, Dorothee; Gerardo-Nava, José; Wöhlk, Vanessa; Weinandy, Stefan; Jockenhövel, Stefan; Kriebel, Andreas; Altinova, Haktan; Steinbusch, Harry W M; Möller, Martin; Weis, Joachim; Mey, Jörg; Brook, Gary A

2016-02-01

The generation of complex three-dimensional bioengineered scaffolds that are capable of mimicking the molecular and topographical cues of the extracellular matrix found in native tissues is a field of expanding research. The systematic development of such scaffolds requires the characterisation of cell behaviour in response to the individual components of the scaffold. In the present investigation, we studied cell-substrate interactions between purified populations of Schwann cells and three-dimensional fibrin hydrogel scaffolds, in the presence or absence of multiple layers of highly orientated electrospun polycaprolactone nanofibres. Embedded Schwann cells remained viable within the fibrin hydrogel for up to 7 days (the longest time studied); however, cell behaviour in the hydrogel was somewhat different to that observed on the two-dimensional fibrin substrate: Schwann cells failed to proliferate in the fibrin hydrogel, whereas cell numbers increased steadily on the two-dimensional fibrin substrate. Schwann cells within the fibrin hydrogel developed complex process branching patterns, but, when presented with orientated nanofibres, showed a strong tendency to redistribute themselves onto the nanofibres, where they extended long processes that followed the longitudinal orientation of the nanofibres. The process length along nanofibre-containing fibrin hydrogel reached near-maximal levels (for the present experimental conditions) as early as 1 day after culturing. The ability of this three-dimensional, extracellular matrix-mimicking scaffold to support Schwann cell survival and provide topographical cues for rapid process extension suggest that it may be an appropriate device design for the bridging of experimental lesions of the peripheral nervous system. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Physicochemical characteristics of Fe3O4 magnetic nanocomposites based on Poly(N-isopropylacrylamide) for anti-cancer drug delivery.

PubMed

Davaran, Soodabeh; Alimirzalu, Samira; Nejati-Koshki, Kazem; Nasrabadi, Hamid Tayef; Akbarzadeh, Abolfazl; Khandaghi, Amir Ahmad; Abbasian, Mojtaba; Alimohammadi, Somayeh

2014-01-01

Hydrogels are a class of polymers that can absorb water or biological fluids and swell to several times their dry volume, dependent on changes in the external environment. In recent years, hydrogels and hydrogel nanocomposites have found a variety of biomedical applications, including drug delivery and cancer treatment. The incorporation of nanoparticulates into a hydrogel matrix can result in unique material characteristics such as enhanced mechanical properties, swelling response, and capability of remote controlled actuation. In this work, synthesis of hydrogel nanocomposites containing magnetic nanoparticles are studied. At first, magnetic nanoparticles (Fe3O4) with an average size 10 nm were prepared. At second approach, thermo and pH-sensitive poly (N-isopropylacrylamide -co-methacrylic acid-co-vinyl pyrrolidone) (NIPAAm-MAA- VP) were prepared. Swelling behavior of co-polymer was studied in buffer solutions with different pH values (pH=5.8, pH=7.4) at 37 °C. Magnetic iron oxide nanoparticles (Fe3O4) and doxorubicin were incorporated into copolymer and drug loading was studied. The release of drug, carried out at different pH and temperatures. Finally, chemical composition, magnetic properties and morphology of doxorubicin-loaded magnetic hydrogel nanocomposites were analyzed by FT- IR, vibrating sample magnetometry (VSM), scanning electron microscopy (SEM). The results indicated that drug loading efficiency was increased by increasing the drug ratio to polymer. Doxorubicin was released more at 40 °C and in acidic pH compared to that 37 °C and basic pH. This study suggested that the poly (NIPAAm-MAA-VP) magnetic hydrogel nanocomposite could be an effective carrier for targeting drug delivery systems of anti-cancer drugs due to its temperature sensitive properties.

Superporous hybrid hydrogels based on polyacrylamide and chitosan: Characterization and in vitro drug release

PubMed Central

Nagpal, Manju; Singh, Shailendra Kumar; Mishra, Dinanath

2013-01-01

Objective: Current research was aimed at the development of the drug delivery systems based on the superporous hydrogels (SPH) with the desired swelling and the mechanical properties. Materials and Methods: Superporous hydrogel composites (SPHCs) and superporous hybrid hydrogels (SPHHs) based on the chitosan and the polyacrylamide were synthesized using the gas blowing technique. The prepared hydrogels were evaluated for swelling studies, mechanical strength and scanning electron microscopy. The selected hydrogels were loaded with the drug (verapamil hydrochloride) by aqueous loading method. Drug integrity with in polymeric network was evaluated via fourier transform infrared spectroscopy (FTIR), X-ray diffraction (X-RD), differential scanning calorimetry (DSC), proton nuclear magnetic resonance (1HNMR) studies. In vitro drug release studies were carried out using the united state pharmacopoeial (USP) dissolution apparatus (type II). Results and Discussion: The mechanical strength was observed to be higher in SPH hybrids in comparison to that in SPHCs while no significant difference was observed in swelling behavior. In situ crosslinking of chitosan with glutaraldehyde (GA) may be responsible for high mechanical strength. The equilibrium swelling time was slight higher in SPHH than in SPHCs. The integrity of pores was maintained in ethanol treated hydrogels as observed in scanning electron micrographs. Whereas, freeze dried SPH samples showed non-uniform pores. No drug polymer interaction was observed as indicated by DSC, FTIR, X-RD and NMR studies. However, the crosslinking of chitosan with GA was clearly indicated by these studies. The in vitro drug release studies from SPH hybrids indicated initial fast release (65%) with in first 2 h and then sustained release at the end of 24 h (95%). The addition of hydroxypropyl methyl cellulose with drug; however, leads to a significant decrease in drug release (56% at the end of 24 h). Conclusion: Superporous hybrid hydrogels can be promising devices for the sustained delivery of drug candidates to the gastrointestinal region. PMID:24015380

Spatially localized recruitment of anti-inflammatory monocytes by SDF-1α-releasing hydrogels enhances microvascular network remodeling.

PubMed

Krieger, J R; Ogle, M E; McFaline-Figueroa, J; Segar, C E; Temenoff, J S; Botchwey, E A

2016-01-01

Tissue repair processes are characterized by the biphasic recruitment of distinct subpopulations of blood monocytes, including classical ("inflammatory") monocytes (IMs, Ly6C(hi)Gr1(+)CX3CR1(lo)) and non-classical anti-inflammatory monocytes (AMs, Ly6C(lo)Gr1(-)CX3CR1(hi)). Drug-eluting biomaterial implants can be used to tune the endogenous repair process by the preferential recruitment of pro-regenerative cells. To enhance recruitment of AMs during inflammatory injury, a novel N-desulfated heparin-containing poly(ethylene glycol) diacrylate (PEG-DA) hydrogel was engineered to deliver exogenous stromal derived factor-1α (SDF-1α), utilizing the natural capacity of heparin to sequester and release growth factors. SDF-1α released from the hydrogels maintained its bioactivity and stimulated chemotaxis of bone marrow cells in vitro. Intravital microscopy and flow cytometry demonstrated that SDF-1α hydrogels implanted in a murine dorsal skinfold window chamber promoted spatially-localized recruitment of AMs relative to unloaded internal control hydrogels. SDF-1α delivery stimulated arteriolar remodeling that was correlated with AM enrichment in the injury niche. SDF-1α, but not unloaded control hydrogels, supported sustained arteriogenesis and microvascular network growth through 7 days. The recruitment of AMs correlated with parameters of vascular remodeling suggesting that tuning the innate immune response by biomaterial SDF-1α release is a promising strategy for promoting vascular remodeling in a spatially controlled manner. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hydrogels for engineering: normalization of swelling due to arbitrary stimulus

NASA Astrophysics Data System (ADS)

Ehrenhofer, Adrian; Wallmersperger, Thomas

2017-04-01

In engineering, materials are chosen from databases: Engineers orient on specific parameters such as Young's modulus, yield stress or thermal expansion coefficients for a desired application. For hydrogels, the choice of materials is rather tedious since no generalized material parameters are currently available to quantify the swelling behavior. The normalization of swelling, which we present in the current work, allows an easy comparison of different hydrogel materials. Thus, for a specific application like a sensor or an actuator, an adequate material can be chosen. In the current work, we present the process of normalization and provide a course of action for the data analysis. Special challenges for hydrogels like hysteresis, conditional multi-sensitivity and anisotropic swelling are addressed. Then, the Temperature Expansion Model is shortly described and applied. Using the derived normalized swelling curves, a nonlinear expansion coefficient ß(F) is derived. The derived material behavior is used in an analytical model to predict the bending behavior of a beam made of thermo-responsive hydrogel material under an anisotropic temperature load. A bending behavior of the beam can be observed and the impact of other geometry and material parameters can be investigated. To overcome the limitations of the one-dimensional beam theory, the material behavior and geometry can be implemented in Finite Element analysis tools. Thus, novel applications for hydrogels in various fields can be envisioned, designed and tested. This can lead to a wider use of smart materials in sensor or actuator devices even by engineers without chemical background.

Process Extension from Embryonic Stem Cell-Derived Motor Neurons through Synthetic Extracellular Matrix Mimics

NASA Astrophysics Data System (ADS)

McKinnon, Daniel Devaud

This thesis focuses on studying the extension of motor axons through synthetic poly(ethylene glycol) PEG hydrogels that have been modified with biochemical functionalities to render them more biologically relevant. Specifically, the research strategy is to encapsulate embryonic stem cell-derived motor neurons (ESMNs) in synthetic PEG hydrogels crosslinked through three different chemistries providing three mechanisms for dynamically tuning material properties. First, a covalently crosslinked, enzymatically degradable hydrogel is developed and exploited to study the biophysical dynamics of axon extension and matrix remodeling. It is demonstrated that dispersed motor neurons require a battery of adhesive peptides and growth factors to maintain viability and extend axons while those in contact with supportive neuroglial cells do not. Additionally, cell-degradable crosslinker peptides and a soft modulus mimicking that of the spinal cord are requirements for axon extension. However, because local degradation of the hydrogel results in a cellular environment significantly different than that of the bulk, enzymatically degradable peptide crosslinkers were replaced with reversible covalent hydrazone bonds to study the effect of hydrogel modulus on axon extension. This material is characterized in detail and used to measure forces involved in axon extension. Finally, a hydrogel with photocleavable linkers incorporated into the network structure is exploited to explore motor axon response to physical channels. This system is used to direct the growth of motor axons towards co-cultured myotubes, resulting in the formation of an in vitro neural circuit.

Design of beta-domain swapping, alpha/beta-protein, environmentally sensitive coiled coil and peptide functionalized titania materials

NASA Astrophysics Data System (ADS)

Nagarkar, Radhika P.

2009-12-01

The objective of this dissertation is to apply rational peptide design to fabricate nanomaterials via self-assembly. This has been demonstrated in structurally diverse systems with an aim of deciphering the underlying principles governing how sequence affects the peptide's ability to adopt a specific secondary structure and ultimate material properties that are realized from the association of these secondary structural elements. Several amyloidogenic proteins have been shown to self-assemble into fibrils using a mechanism known as domain swapping. Here, discreet units of secondary structure are exchanged among discreet proteins during self-assembly to form extended networks with precise three dimensional organization. The possibility of using these mechanisms to design peptides capable of controlled assembly and fibril formation leading to materials with targeted properties is explored. By altering the placement of a beta-turn sequence that varies the size and location of the exchanged strand, twisting, non-twisting and laminated fibrillar nanostructures are obtained. Hydrogels prepared from these strand swapping beta-hairpins have varied rheological properties due to differences in their fibrillar nanostructures. In a second distinct design, alpha/beta-proteins are used to prepare environmentally sensitive hydrogels. Here, multiple distinct motifs for structural integrity and dynamic response within a single self-assembling peptide allow the amyloid-like fibrils formed to controllably alter their nano-topography in response to an external stimulus such as temperature. The development of these self-assembling alpha/beta-protein motifs also necessitated the design of pH sensitive antiparallel coiled coils. Exploring the basic principles responsible for pH dependent conformational changes in coiled coils can lead to new insights in the control of protein structure and function. Lastly, this dissertation discusses the interface between biomolecules and inorganic materials. Here, a new methodology of functionalizing titania nanoparticles with peptides is developed. In all of these different material forming systems, extensive biophysical characterization by circular dichroism spectroscopy, fourier transform infrared spectroscopy, X-ray diffraction and analytical ultracentrifugation is performed to understand peptide folding and self-assembly. Careful nanostructural characterization by electron and force microscopies is performed to elucidate self-assembly mechanisms and has proved to be vital in applying the iterative design process to develop responsive nanomaterials.

Spatially Assembled Bilayer Cell Sheets of Stem Cells and Endothelial Cells Using Thermosensitive Hydrogels for Therapeutic Angiogenesis.

PubMed

Jun, Indong; Ahmad, Taufiq; Bak, Seongwoo; Lee, Joong-Yup; Kim, Eun Mi; Lee, Jinkyu; Lee, Yu Bin; Jeong, Hongsoo; Jeon, Hojeong; Shin, Heungsoo

2017-05-01

Although the coculture of multiple cell types has been widely employed in regenerative medicine, in vivo transplantation of cocultured cells while maintaining the hierarchical structure remains challenging. Here, a spatially assembled bilayer cell sheet of human mesenchymal stem cells and human umbilical vein endothelial cells on a thermally expandable hydrogel containing fibronectin is prepared and its effect on in vitro proangiogenic functions and in vivo ischemic injury is investigated. The expansion of hydrogels in response to a temperature change from 37 to 4 °C allows rapid harvest and delivery of the bilayer cell sheet to two different targets (an in vitro model glass surface and in vivo tissue). The in vitro study confirms that the bilayer sheet significantly increases proangiogenic functions such as the release of nitric oxide and expression of vascular endothelial cell genes. In addition, transplantation of the cell sheet from the hydrogels into a hindlimb ischemia mice model demonstrates significant retardation of necrosis particularly in the group transplated with the bilayer sheet. Collectively, the bilayer cell sheet is readily transferrable from the thermally expandable hydrogel and represents an alternative approach for recovery from ischemic injury, potentially via improved cell-cell communication. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hydrogels for precision meniscus tissue engineering: a comprehensive review.

PubMed

Rey-Rico, Ana; Cucchiarini, Magali; Madry, Henning

The meniscus plays a pivotal role to preserve the knee joint homeostasis. Lesions to the meniscus are frequent, have a reduced ability to heal, and may induce tibiofemoral osteoarthritis. Current reconstructive therapeutic options mainly focus on the treatment of lesions in the peripheral vascularized region. In contrast, few approaches are capable of stimulating repair of damaged meniscal tissue in the central, avascular portion. Tissue engineering approaches are of high interest to repair or replace damaged meniscus tissue in this area. Hydrogel-based biomaterials are of special interest for meniscus repair as its inner part contains relatively high proportions of proteoglycans which are responsible for the viscoelastic compressive properties and hydration grade. Hydrogels exhibiting high water content and providing a specific three-dimensional (3D) microenvironment may be engineered to precisely resemble this topographical composition of the meniscal tissue. Different polymers of both natural and synthetic origins have been manipulated to produce hydrogels hosting relevant cell populations for meniscus regeneration and provide platforms for meniscus tissue replacement. So far, these compounds have been employed to design controlled delivery systems of bioactive molecules involved in meniscal reparative processes or to host genetically modified cells as a means to enhance meniscus repair. This review describes the most recent advances on the use of hydrogels as platforms for precision meniscus tissue engineering.

Retardation of Antigen Release from DNA Hydrogel Using Cholesterol-Modified DNA for Increased Antigen-Specific Immune Response.

PubMed

Umeki, Yuka; Saito, Masaaki; Takahashi, Yuki; Takakura, Yoshinobu; Nishikawa, Makiya

2017-10-01

Our previous study indicates that cationization of an antigen is effective for sustained release of both immunostimulatory DNA containing unmethylated cytosine-phosphate-guanine (CpG) dinucleotides, or CpG DNA, and antigen from a DNA hydrogel. Another approach to sustained antigen release would increase the applicability and versatility of the system. In this study, a hydrophobic interaction-based sustained release system of ovalbumin (OVA), a model antigen, from immunostimulatory CpG DNA hydrogel is developed by the use of cholesterol-modified DNA and urea-denatured OVA (udOVA). Cholesterol-modified DNA forms a hydrogel, Dgel(chol), and induces IL-6 mRNA expression in mouse skin after intradermal injection, as DNA without cholesterol does. Cholesterol-modified DNA associated with OVA and denaturation of OVA using urea increases the interaction. The release of udOVA from Dgel(chol) is significantly slower than that from DNA hydrogel with no cholesterol, Dgel. Moreover, intratumoral injections of udOVA/Dgel(chol) significantly inhibit the growth of EG7-OVA tumors in mice. These results indicate that sustained release of antigen from Dgel can be achieved by the combination of urea denaturation and cholesterol modification, and retardation of antigen release is effective to induce antigen-specific cancer immunity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lightweight armor system

DOEpatents

Chu, Henry S; Langhorst, Benjamin R; Bakas, Michael P; Thinnes, Gary L

2013-02-26

The disclosure provides a shock absorbing layer comprised of one or more shock absorbing cells, where a shock absorbing cell is comprised of a cell interior volume containing a plurality of hydrogel particles and a free volume, and where the cell interior volume is surrounded by a containing layer. The containing layer has a permeability such that the hydrogel particles when swollen remain at least partially within the cell interior volume when subjected to a design shock pressure wave, allowing for force relaxation through hydrogel compression response. Additionally, the permeability allows for the flow of exuded free water, further dissipating wave energy. In an embodiment, a plurality of shock absorbing cells is combined with a penetration resistant material to mitigate the transmitted shock wave generated by an elastic precursor wave in the penetration resistant material.

Preparation and characterization of a novel micro- and nanocomposite hydrogels containing cellulosic fibrils

USDA-ARS?s Scientific Manuscript database

In recent years, the preparation of cellulosic composites and nanocomposites has become an important approach because of the wide abundance of cellulose, its biodegradability, renewability, and the ability to effectively reinforce a polymer matrix in an environmentally benign nature. The main object...

Additive Manufacturing of Catalytically Active Living Materials.

PubMed

Saha, Abhijit; Johnston, Trevor G; Shafranek, Ryan T; Goodman, Cassandra J; Zalatan, Jesse G; Storti, Duane W; Ganter, Mark A; Nelson, Alshakim

2018-04-25

Living materials, which are composites of living cells residing in a polymeric matrix, are designed to utilize the innate functionalities of the cells to address a broad range of applications such as fermentation and biosensing. Herein, we demonstrate the additive manufacturing of catalytically active living materials (AMCALM) for continuous fermentation. A multi-stimuli-responsive yeast-laden hydrogel ink, based on F127-dimethacrylate, was developed and printed using a direct-write 3D printer. The reversible stimuli-responsive behaviors of the polymer hydrogel inks to temperature and pressure are critical, as they enabled the facile incorporation of yeast cells and subsequent fabrication of 3D lattice constructs. Subsequent photo-cross-linking of the printed polymer hydrogel afforded a robust elastic material. These yeast-laden living materials were metabolically active in the fermentation of glucose into ethanol for 2 weeks in a continuous batch process without significant reduction in efficiency (∼90% yield of ethanol). This cell immobilization platform may potentially be applicable toward other genetically modified yeast strains to produce other high-value chemicals in a continuous biofermentation process.

Bioprinting 3D cell-laden hydrogel microarray for screening human periodontal ligament stem cell response to extracellular matrix.

PubMed

Ma, Yufei; Ji, Yuan; Huang, Guoyou; Ling, Kai; Zhang, Xiaohui; Xu, Feng

2015-12-22

Periodontitis is an inflammatory disease negatively affecting up to 15% of adults worldwide. Periodontal ligament stem cells (PDLSCs) hold great promises for periodontal tissue regeneration, where it is necessary to find proper extracellular matrix (ECM) materials (e.g., composition, concentration). In this study, we proposed a bioprinting-based approach to generate nano-liter sized three-dimensional (3D) cell-laden hydrogel array with gradient of ECM components, through controlling the volume ratio of two hydrogels, such as gelatin methacrylate (GelMA) and poly(ethylene glycol) (PEG) dimethacrylate. The resulting cell-laden array with a gradient of GelMA/PEG composition was used to screen human PDLSC response to ECM. The behavior (e.g., cell viability, spreading) of human PDLSCs in GelMA/PEG array were found to be depended on the volume ratios of GelMA/PEG, with cell viability and spreading area decreased along with increasing the ratio of PEG. The developed approach would be useful for screening cell-biomaterial interaction in 3D and promoting regeneration of functional tissue.

Production of bioinspired and rationally designed polymer hydrogels for controlled delivery of therapeutic proteins

NASA Astrophysics Data System (ADS)

Kim, Sung Hye

Hydrogel systems for controlled delivery therapeutic growth factors have been developed in a wide spectrum of strategies: these systems aim for the release of growth factors via a passive diffusion, electrostatic interaction, degradation of hydrogels, and responsiveness to external stimuli. Heparin, a highly sulfated glycosaminoglycan (GAG), was employed for a targeted delivery system of vascular endothelial growth factor (VEGF) to endothelial cells overexpressing a relevant receptor VEGFR-2. Addition of dimeric VEGF to 4-arm star-shaped poly(ethylene glycol) (PEG) immobilized with low-molecular weight heparin (LMWH) afforded a non-covalently assembled hydrogel via interaction between heparin and VEGF, with storage modulus 10 Pa. The release of VEGF and hydrogel erosion reached maximum 100 % at day 4 in the presence of VEGFR-2 overexpressing pocine aortic endothelial cell (PAE/KDR), while those of 80% were achieved via passive release at day 5 in the presence of PAE cell lacking VEGFR-2 or in the absence of cell, indicating that the release of VEGF was in targeted manner toward cell receptor. The proliferation of PAE/KDR in the presence of [PEG-LMWH/VEGF] hydrogel was greater by ca. 30% at day 4 compared to that of PAE, confirming that the release of VEGF was in response to the cellular demand. The phosphorylation fraction of VEGFR-2 on PAE/KDR was greater in the presence of [PEG-LMWH/VEGF] hydrogel, increasing from 0.568 at day 1 to 0.790 at day 4, whereas it was maintained at 0.230 at day 4 in the presence of [PEG-LMWH] hydrogel. This study has proven that this hydrogel, assembled via bio-inspired non-covalent interaction, liberating VEGFon celluar demand to target cell, eroding upon VEGF release, and triggering endothelial cell proliferation, could be used in multiple applications including targeted delivery and angiogenesis. Heparin has been widely exploited in growth factor delivery systems owing to its ability to bind many growth factors through the flexible patterns of functional groups. However, heterogeneity in the composition and in the polydispersity of heparin has been problematic in controlled delivery system and thus motivated the development of homogeneous heparin mimics. Peptides of appropriate sequence and chemical function have therefore recently emerged as potential replacements for heparin in select applications. Studied was the assessment of the binding affinities of multiple sulfated peptides (SPs) for a set of heparin-binding peptides (HBPs) and for VEGF; these binding partners have application in the selective immobilization of proteins and in hydrogel formation through non-covalent interactions. Sulfated peptides were produced via solid-phase methods, and their affinity for the HBPs and VEGF was assessed via affinity liquid chromatography (ALC), surface plasmon resonance (SPR), and in select cases, isothermal titration calorimetry (ITC). The shortest peptide, SPa, showed the highest affinity binding of HBPs and VEGF165 in both ALC and SPR measurements, with slight exceptions. Of the investigated HBPs, a peptide based on the heparin-binding domain of human platelet factor 4 showed greatest binding affinities toward all of the SPs, consistent with its stronger binding to heparin. The affinity between SPa and PF4ZIP was indicated via SPR ( KD = 5.27 muM) and confirmed via ITC (KD = 8.09 muM). The binding by SPa of both VEGF and HBPs suggests its use as a binding partner to multiple species, and the use of these interactions in assembly of materials. Given that the peptide sequences can be varied to control binding affinity and selectivity, opportunities are also suggested for the production of a wider array of matrices with selective binding and release properties useful for biomaterials applications. Hydrogel consisting of SPa was formed via a covalent Michael Addition reaction between maleimide- and thiol-terminated multi-arm PEGs and Cys-SPa. The mechanical property of hydrogel was tunable from ca. 186 to 1940 Pa. by varing the cross-linking density, suggesting its flexible applications depending on matrix needs. The non-anti-coagulative property of SPa, assessed via activated partial thromboplastin time (APTT) and HeptestRTM in comparison to LMWH, implied its usefulness in applications without excessive bleeding. The VEGF released from [PEG-SPa] hydrogel showed up to ca. 400% greater bioactivity on proliferation of human umbilical vein endothelical cell (HUVEC) compared to the VEGF incubated in solution for the same period: this was significantly higher than that of [PEG] hydrogel (ca. 280%), suggesting the SPa may protect the bioactivity of VEGF when bound. The release of dual growth factor, i.e. VEGF and fibroblast growth factor-2 (FGF-2), were investigated on [PEG-SPa] hydrogel: the release of bFGF was lower than that of VEGF due to weaker binding affinity to matrix-bound SPa. The HUVEC culture on dual growth factor loaded [PEG-SPa] showed that the synergistic effects of dual system in select concentrations, suggesting the opportunity of manipulating cell responses. Given that sulfated peptides for various binding targets with desired affinity can be identified, applications are suggested in multiple growth factors delivery where an integrated action of multiple growth factors is required, such as angiogenesis.

Ophthalmic gels: Past, present and future.

PubMed

Al-Kinani, Ali A; Zidan, Ghada; Elsaid, Naba; Seyfoddin, Ali; Alani, Adam W G; Alany, Raid G

2018-02-15

Aqueous gels formulated using hydrophilic polymers (hydrogels) along with those based on stimuli responsive polymers (in situ gelling or gel forming systems) continue to attract increasing interest for various eye health-related applications. They allow the incorporation of a variety of ophthalmic pharmaceuticals to achieve therapeutic levels of drugs and bioactives at target ocular sites. The integration of sophisticated drug delivery technologies such as nanotechnology-based ones with intelligent and environment responsive systems can extend current treatment duration to provide more clinically relevant time courses (weeks and months instead of hours and days) which will inevitably reduce dose frequency, increase patient compliance and improve clinical outcomes. Novel applications and design of contact lenses and intracanalicular delivery devices along with the move towards integrating gels into various drug delivery devices like intraocular pumps, injections and implants has the potential to reduce comorbidities caused by glaucoma, corneal keratopathy, cataract, diabetic retinopathies and age-related macular degeneration. This review describes ophthalmic gelling systems with emphasis on mechanism of gel formation and application in ophthalmology. It provides a critical appraisal of the techniques and methods used in the characterization of ophthalmic preformed gels and in situ gelling systems along with a thorough insight into the safety and biocompatibility of these systems. Newly developed ophthalmic gels, hydrogels, preformed gels and in situ gelling systems including the latest in the area of stimuli responsive gels, molecularly imprinted gels, nanogels, 3D printed hydrogels; 3D printed devices comprising ophthalmic gels are covered. Finally, new applications of gels in the production of artificial corneas, corneal wound healing and hydrogel contact lenses are described. Copyright © 2017 Elsevier B.V. All rights reserved.

Bio-inspired Self-healing Composite Hydrogel with Iron Oxide Nanoparticle as Coordination Crosslinker

NASA Astrophysics Data System (ADS)

Li, Qiaochu; Barret, Devin G.; Messersmith, Phillip B.; Holten-Andersen, Niels

2014-03-01

Polymer-nanoparticle (NP) composites have attracted renewed attention due to enhanced mechanical strength combined with various functionalities, but controlling the interfacial chemistry between NPs and polymer matrix, which is crucial for the composite's mechanical behavior, remains a major challenge. Inspired by the adhesion chemistry of mussel fibers, we investigated a novel approach to incorporate Fe3O4 NPs into hydrogel matrix. A polyethylene glycol polymer is designed with both ends conjugated by catechol groups, which have strong coordination affinity to Fe. The polymer network is crosslinked via coordination bonding at the surface of Fe3O4 NPs, yielding a stiff nanocomposite hydrogel. Due to the reversible nature of coordination bonding, the hydrogel presents self-healing behavior. Oscillatory rheology allows comparative kinetic studies of self-healing driven by catechol bonding at Fe3O4 NP interfaces and by catechol-Fe3+ coordination complexes. Furthermore, the superparamagnetic property of Fe3O4 NP is preserved after gelation, allowing for response to external stimuli. This gelation motif can serve as a versatile platform for tuning functional and mechanical properties for future polymer nanocomposite materials.

Effects of alginate hydrogel cross-linking density on mechanical and biological behaviors for tissue engineering.

PubMed

Jang, Jinah; Seol, Young-Joon; Kim, Hyeon Ji; Kundu, Joydip; Kim, Sung Won; Cho, Dong-Woo

2014-09-01

An effective cross-linking of alginate gel was made through reaction with calcium carbonate (CaCO3). We used human chondrocytes as a model cell to study the effects of cross-linking density. Three different pore size ranges of cross-linked alginate hydrogels were fabricated. The morphological, mechanical, and rheological properties of various alginate hydrogels were characterized and responses of biosynthesis of cells encapsulated in each gel to the variation in cross-linking density were investigated. Desired outer shape of structure was maintained when the alginate solution was cross-linked with the applied method. The properties of alginate hydrogel could be tailored through applying various concentrations of CaCO3. The rate of synthesized GAGs and collagens was significantly higher in human chondrocytes encapsulated in the smaller pore structure than that in the larger pore structure. The expression of chondrogenic markers, including collagen type II and aggrecan, was enhanced in the smaller pore structure. It was found that proper structural morphology is a critical factor to enhance the performance and tissue regeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

A simple strategy for in situ fabrication of a smart hydrogel microvalve within microchannels for thermostatic control.

PubMed

Lin, Shuo; Wang, Wei; Ju, Xiao-Jie; Xie, Rui; Chu, Liang-Yin

2014-08-07

Self-regulation of temperature in microchip systems is crucial for their applications in biomedical fields such as cell culture and biomolecule synthesis as well as those cases that require constant temperature conditions. Here we report on a simple and versatile approach for in situ fabrication of a smart hydrogel microvalve within a microchip for thermostatic control. The thermo-responsive hydrogel microvalve enables the "on-off" switch by sensing temperature fluctuations to control the fluid flux as well as the fluid heat exchange for self-regulation of the temperature at a constant range. Such temperature self-regulation is demonstrated by integrating the microvalve-incorporated microchip into the flow circulation loop of a micro-heat-exchanging system for thermostatic control. Moreover, the microvalve-incorporated microchip is employed for culturing cells under temperature self-regulation. The smart microvalve shows great potential as a temperature controller for applications that require thermostatic conditions. This approach offers a facile and flexible strategy for in situ fabricating hydrogel microvalves within microchips as chemostats and microreactors for biomedical applications.

A pure magnetite hydrogel: synthesis, properties and possible applications.

PubMed

Anastasova, Elizaveta I; Ivanovski, Vladimir; Fakhardo, Anna F; Lepeshkin, Artem I; Omar, Suheir; Drozdov, Andrey S; Vinogradov, Vladimir V

2017-11-22

A magnetite-only hydrogel was prepared for the first time by weak base mediated gelation of stable magnetite hydrosols at room temperature. The hydrogel consists of 10 nm magnetite nanoparticles linked by interparticle Fe-O-Fe bonds and has the appearance of a dark-brown viscous thixotropic material. The water content in the hydrogel could be up to 93.6% by mass while volume fraction reaches 99%. The material shows excellent biocompatibility and minor cytotoxic effects at concentrations up to 207 μg mL -1 . The gel shows excellent sorption capacity for heavy metal adsorption such as chrome and lead ions, which is 225% more than the adsorption capacity of magnetite nanoparticles. Due to thixotropic nature, the gel demonstrates mechanical stimuli-responsive release behavior with up to 98% release triggered by ultrasound irradiation. The material shows superparamagnetic behavior with a coercivity of 65 emu g -1 at 6000 Oe. The magnetite gels prepared could be used for the production of magnetite aerogels, magnetic drug delivery systems with controlled release and highly efficient sorbents for hydrometallurgy.

Fabrication of the novel hydrogel based on waste corn stalk for removal of methylene blue dye from aqueous solution

NASA Astrophysics Data System (ADS)

Ma, Dongzhuo; Zhu, Baodong; Cao, Bo; Wang, Jian; Zhang, Jianwei

2017-11-01

The novel hydrogel based on waste corn stalk was synthetized by aqueous solution polymerization technique with functional monomers in the presence of organic montmorillonite (OMMT) under ultrasonic. In this study, batch adsorption experiments were carried out to research the effect of initial dye concentration, the dosage of hydrogel, stirring speed, contact time and temperature on the adsorption of methylene blue (MB) dye. The adsorption process was best described by the pseudo-second-order kinetic model, which confirmed that it should be a chemical process. Furthermore, we ascertained the rate controlling step by establishing the intraparticle diffusion model and the liquid film diffusion model. The adsorption and synthesis mechanisms were vividly depicted in our work as well. Structural and morphological characterizations by virtue of FTIR, FESEM, and Biomicroscope supported the relationship between the adsorption performance and material's microstructure. This research is a valuable contribution for the environmental protection, which not only converts waste corn stalks into functional materials, but improves the removal of organic dye from sewage water.

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

Surface plasmon resonance based fiber optic pH sensor utilizing Ag/ITO/Al/hydrogel layers.

PubMed

Mishra, Satyendra K; Gupta, Banshi D

2013-05-07

The fabrication and characterization of a surface plasmon resonance based pH sensor using coatings of silver, ITO (In2O3:SnO2), aluminium and smart hydrogel layers over an unclad core of an optical fiber have been reported. The silver, aluminium and ITO layers were coated using a thermal evaporation technique, while the hydrogel layer was prepared using a dip-coating method. The sensor works on the principle of detecting changes in the refractive index of the hydrogel layer due to its swelling and shrinkage caused by changes in the pH of the fluid surrounding the hydrogel layer. The sensor utilizes a wavelength interrogation technique and operates in a particular window of low and high pH values. Increasing the pH value of the fluid causes swelling of the hydrogel layer, which decreases its refractive index and results in a shift of the resonance wavelength towards blue in the transmitted spectra. The thicknesses of the ITO and aluminium layers have been optimized to achieve the best performance of the sensor. The ITO layer increases the sensitivity while the aluminium layer increases the detection accuracy of the sensor. The proposed sensor possesses maximum sensitivity in comparison to the sensors reported in the literature. A negligible effect of ambient temperature in the range 25 °C to 45 °C on the performance of the sensor has been observed. The additional advantages of the sensor are short response time, low cost, probe miniaturization, probe re-usability and the capability of remote sensing.

The influence of hyaluronic acid hydrogel crosslinking density and macromolecular diffusivity on human MSC chondrogenesis and hypertrophy.

PubMed

Bian, Liming; Hou, Chieh; Tous, Elena; Rai, Reena; Mauck, Robert L; Burdick, Jason A

2013-01-01

Hyaluronic acid (HA) hydrogels formed via photocrosslinking provide stable 3D hydrogel environments that support the chondrogenesis of mesenchymal stem cells (MSCs). Crosslinking density has a significant impact on the physical properties of hydrogels, including their mechanical stiffness and macromolecular diffusivity. Variations in the HA hydrogel crosslinking density can be obtained by either changes in the HA macromer concentration (1, 3, or 5% w/v at 15 min exposure) or the extent of reaction through light exposure time (5% w/v at 5, 10, or 15 min). In this work, increased crosslinking by either method resulted in an overall decrease in cartilage matrix content and more restricted matrix distribution. Increased crosslinking also promoted hypertrophic differentiation of the chondrogenically induced MSCs, resulting in more matrix calcification in vitro. For example, type X collagen expression in the high crosslinking density 5% 15 min group was ~156 and 285% higher when compared to the low crosslinking density 1% 15 min and 5% 5 min groups on day 42, respectively. Supplementation with inhibitors of the small GTPase pathway involved in cytoskeletal tension or myosin II had no effect on hypertrophic differentiation and matrix calcification, indicating that the differential response is unlikely to be related to force-sensing mechanotransduction mechanisms. When implanted subcutaneously in nude mice, higher crosslinking density again resulted in reduced cartilage matrix content, restricted matrix distribution, and increased matrix calcification. This study demonstrates that hydrogel properties mediated through alterations in crosslinking density must be considered in the context of the hypertrophic differentiation of chondrogenically induced MSCs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Biomimetic hydrogels direct spinal progenitor cell differentiation and promote functional recovery after spinal cord injury.

PubMed

Geissler, Sydney A; Sabin, Alexandra L; Besser, Rachel R; Gooden, Olivia M; Shirk, Bryce D; Nguyen, Quan M; Khaing, Zin Z; Schmidt, Christine E

2018-04-01

Demyelination that results from disease or traumatic injury, such as spinal cord injury (SCI), can have a devastating effect on neural function and recovery. Many researchers are examining treatments to minimize demyelination by improving oligodendrocyte availability in vivo. Transplantation of stem and oligodendrocyte progenitor cells is a promising option, however, trials are plagued by undirected differentiation. Here we introduce a biomaterial that has been optimized to direct the differentiation of neural progenitor cells (NPCs) toward oligodendrocytes as a cell delivery vehicle after SCI. A collagen-based hydrogel was modified to mimic the mechanical properties of the neonatal spinal cord, and components present in the developing extracellular matrix were included to provide appropriate chemical cues to the NPCs to direct their differentiation toward oligodendrocytes. The hydrogel with cells was then transplanted into a unilateral cervical contusion model of SCI to examine the functional recovery with this treatment. Six behavioral tests and histological assessment were performed to examine the in vivo response to this treatment. Our results demonstrate that we can achieve a significant increase in oligodendrocyte differentiation of NPCs compared to standard culture conditions using a three-component biomaterial composed of collagen, hyaluronic acid, and laminin that has mechanical properties matched to those of neonatal neural tissue. Additionally, SCI rats with hydrogel transplants, with and without NPCs, showed functional recovery. Animals transplanted with hydrogels with NPCs showed significantly increased functional recovery over six weeks compared to the media control group. The three-component hydrogel presented here has the potential to provide cues to direct differentiation in vivo to encourage regeneration of the central nervous system.

Perylene bisimide hydrogels and lyotropic liquid crystals with temperature-responsive color change.

PubMed

Görl, Daniel; Soberats, Bartolome; Herbst, Stefanie; Stepanenko, Vladimir; Würthner, Frank

2016-11-01

The self-assembly of perylene bisimide (PBI) dyes bearing oligo ethylene glycol (OEG) units in water affords responsive functional nanostructures characterized by their lower critical solution temperature (LCST). Tuning of the LCST is realized by a supramolecular approach that relies on two structurally closely related PBI-OEG molecules. The two PBIs socially co-assemble in water and the resulting nanostructures exhibit a single LCST in between the transition temperatures of the aggregates formed by single components. This permits to precisely tune the transition from a hydrogel to a lyotropic liquid crystal state at temperatures between 26 and 51 °C by adjusting the molar fraction of the two PBIs. Owing to concomitant changes in PBI-PBI interactions this phase transition affords a pronounced color change with "fluorescence-on" response that can be utilized as a smart temperature sensory system.

Visualizing hydrophobic domains in silicone hydrogel lenses with Sudan IV.

PubMed

Jacob, Jean T; Levet, Jacques; Edwards, Tamika A; Dassanayake, Nissanke; Ketelson, Howard

2012-06-08

A lipophilic dye is used to investigate the degree to which the surface and bulk hydrophobic domains of the lenses can be imaged and to identify specific changes in the availability of those domains after in vitro wear and cleaning conditions. The effect of a multipurpose solution (MPS), OPTI-FREE RepleniSH, on lens hydrophobic domains was also investigated. Hydrophobic domains were determined using a saturated solution of Sudan IV. Staining periods of 30 minutes and 16 hours were used to determine surface versus bulk hydrophobic domains. Four types of silicone hydrogel lens materials were tested. The degree of staining was visually documented by photography and quantitatively determined by extraction and analysis of the total amount of dye adsorbed. Specific differences in staining were found for all control lenses. Exposure to in vitro wear conditions significantly decreased the staining response for all lens types as compared with unworn lenses (P = 0.001). However, the trend of staining remained the same: balafilcon A > galyfilcon A > senofilcon A > lotrafilcon B. MPS decreased the extent of staining; the degree of its effect varied with lens type. Hydrophobic staining with Sudan IV visualized domains on and within silicone hydrogel lenses. Differences in staining response after exposure to wear and cleaning conditions indicate the potential for protein and lipid deposition on the different lens types and the ability of MPS to affect that deposition. Hydrophobic staining may be useful for determining differences in surface modification and lipophilicity of silicone hydrogel lenses.

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.

Recent Advances in the Synthesis and Biomedical Applications of Nanocomposite Hydrogels

PubMed Central

Spizzirri, Umile Gianfranco; Curcio, Manuela; Cirillo, Giuseppe; Spataro, Tania; Vittorio, Orazio; Picci, Nevio; Hampel, Silke; Iemma, Francesca; Nicoletta, Fiore Pasquale

2015-01-01

Hydrogels sensitive to electric current are usually made of polyelectrolytes and undergo erosion, swelling, de-swelling or bending in the presence of an applied electric field. The electrical conductivity of many polymeric materials used for the fabrication of biomedical devices is not high enough to achieve an effective modulation of the functional properties, and thus, the incorporation of conducting materials (e.g., carbon nanotubes and nanographene oxide) was proposed as a valuable approach to overcome this limitation. By coupling the biological and chemical features of both natural and synthetic polymers with the favourable properties of carbon nanostructures (e.g., cellular uptake, electromagnetic and magnetic behaviour), it is possible to produce highly versatile and effective nanocomposite materials. In the present review, the recent advances in the synthesis and biomedical applications of electro-responsive nanocomposite hydrogels are discussed. PMID:26473915

Recent Advances in the Synthesis and Biomedical Applications of Nanocomposite Hydrogels.

PubMed

Spizzirri, Umile Gianfranco; Curcio, Manuela; Cirillo, Giuseppe; Spataro, Tania; Vittorio, Orazio; Picci, Nevio; Hampel, Silke; Iemma, Francesca; Nicoletta, Fiore Pasquale

2015-10-13

Hydrogels sensitive to electric current are usually made of polyelectrolytes and undergo erosion, swelling, de-swelling or bending in the presence of an applied electric field. The electrical conductivity of many polymeric materials used for the fabrication of biomedical devices is not high enough to achieve an effective modulation of the functional properties, and thus, the incorporation of conducting materials (e.g., carbon nanotubes and nanographene oxide) was proposed as a valuable approach to overcome this limitation. By coupling the biological and chemical features of both natural and synthetic polymers with the favourable properties of carbon nanostructures (e.g., cellular uptake, electromagnetic and magnetic behaviour), it is possible to produce highly versatile and effective nanocomposite materials. In the present review, the recent advances in the synthesis and biomedical applications of electro-responsive nanocomposite hydrogels are discussed.

The effect of bacterial cellulose on the shape memory behavior of polyvinyl alcohol nanocomposite hydrogel

NASA Astrophysics Data System (ADS)

Pirahmadi, Pegah; Kokabi, Mehrdad

2018-01-01

Most research on shape memory polymers has been confined to neat polymers in their dry state, while, some hydrogel networks are known for their shape memory properties. Hydrogels have low glass transition temperatures which are below 100°C depend on the content of water. But they are usually weak and brittle, and not suitable for structural applications due to their low mechanical strengths because of these materials have large amount of water (>50%), so they could not remember original shape perfectly. Bacterial cellulose nanofibers with perfect properties such as high water holding capacity, high crystallinity, high tensile strength and good biocompatibility can dismiss all the drawbacks. In the present study, polyvinyl alcohol/bacterial cellulose nanocomposite hydrogel prepared by repetitive freezing-thawing method. The bacterial cellulose was used as reinforcement to improve the mechanical properties and stimuli response. Differential scanning calorimetry was employed to obtain the glass transition temperature. Nanocomposite morphology was characterized by field-emission scanning electron microscopy and mechanical properties were investigated by standard tensile test. Finally, the effect of bacterial cellulose nanofiber on shape memory behavior of polyvinyl alcohol/bacterial cellulose nanocomposite hydrogel was investigated. It is found that switching temperature of this system is the glass transition temperature of the nano domains formed within the system. The results also show increase of shape recovery, and shape recovery speed due to presence of bacterial cellulose.

Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction

PubMed Central

Yoshizumi, Tomo; Zhu, Yang; Jiang, Hongbin; D’Amore, Antonio; Sakaguchi, Hirokazu; Tchao, Jason; Tobita, Kimimasa; Wagner, William R.

2016-01-01

Intramyocardial injection of various injectable hydrogel materials has shown benefit in positively impacting the course of left ventricular (LV) remodeling after myocardial infarction (MI). However, since LV remodeling is a complex, time dependent process, the most efficacious time of hydrogel injection is not clear. In this study, we injected a relatively stiff, thermoresponsive and bioabsorbable hydrogel in rat hearts at 3 different time points - immediately after MI (IM), 3 d post-MI (3D), and 2 w post-MI (2W), corresponding to the beginnings of the necrotic, fibrotic and chronic remodeling phases. The employed left anterior descending coronary artery ligation model showed expected infarction responses including functional loss, inflammation and fibrosis with distinct time dependent patterns. Changes in LV geometry and contractile function were followed by longitudinal echocardiography for 10 w post-MI. While all injection times positively affected LV function and wall thickness, the 3D group gave better functional outcomes than the other injection times and also exhibited more local vascularization and less inflammatory markers than the earlier injection time. The results indicate an important role for injection timing in the increasingly explored concept of post-MI biomaterial injection therapy and suggest that for hydrogels with mechanical support as primary function, injection at the beginning of the fibrotic phase may provide improved outcomes. PMID:26774561

Controlled intramyocardial release of engineered chemokines by biodegradable hydrogels as a treatment approach of myocardial infarction

PubMed Central

Projahn, Delia; Simsekyilmaz, Sakine; Singh, Smriti; Kanzler, Isabella; Kramp, Birgit K; Langer, Marcella; Burlacu, Alexandrina; Bernhagen, Jürgen; Klee, Doris; Zernecke, Alma; Hackeng, Tilman M; Groll, Jürgen; Weber, Christian; Liehn, Elisa A; Koenen, Rory R

2014-01-01

Myocardial infarction (MI) induces a complex inflammatory immune response, followed by the remodelling of the heart muscle and scar formation. The rapid regeneration of the blood vessel network system by the attraction of hematopoietic stem cells is beneficial for heart function. Despite the important role of chemokines in these processes, their use in clinical practice has so far been limited by their limited availability over a long time-span in vivo. Here, a method is presented to increase physiological availability of chemokines at the site of injury over a defined time-span and simultaneously control their release using biodegradable hydrogels. Two different biodegradable hydrogels were implemented, a fast degradable hydrogel (FDH) for delivering Met-CCL5 over 24 hrs and a slow degradable hydrogel (SDH) for a gradual release of protease-resistant CXCL12 (S4V) over 4 weeks. We demonstrate that the time-controlled release using Met-CCL5-FDH and CXCL12 (S4V)-SDH suppressed initial neutrophil infiltration, promoted neovascularization and reduced apoptosis in the infarcted myocardium. Thus, we were able to significantly preserve the cardiac function after MI. This study demonstrates that time-controlled, biopolymer-mediated delivery of chemokines represents a novel and feasible strategy to support the endogenous reparatory mechanisms after MI and may compliment cell-based therapies. PMID:24512349

Stem Cell-Containing Hyaluronic Acid-Based Spongy Hydrogels for Integrated Diabetic Wound Healing.

PubMed

da Silva, Lucília Pereira; Santos, Tírcia Carlos; Rodrigues, Daniel Barreira; Pirraco, Rogério Pedro; Cerqueira, Mariana Teixeira; Reis, Rui Luís; Correlo, Vitor Manuel; Marques, Alexandra Pinto

2017-07-01

The detailed pathophysiology of diabetic foot ulcers is yet to be established and improved treatments are still required. We propose a strategy that directs inflammation, neovascularization, and neoinnervation of diabetic wounds. Aiming to potentiate a relevant secretome for nerve regeneration, stem cells were precultured in hyaluronic acid-based spongy hydrogels under neurogenic/standard media before transplantation into diabetic mice full-thickness wounds. Acellular spongy hydrogels and empty wounds were used as controls. Re-epithelialization was attained 4 weeks after transplantation independently of the test groups, whereas a thicker and more differentiated epidermis was observed for the cellular spongy hydrogels. A switch from the inflammatory to the proliferative phase of wound healing was revealed for all the experimental groups 2 weeks after injury, but a significantly higher M2(CD163 + )/M1(CD86 + ) subtype ratio was observed in the neurogenic preconditioned group that also failed to promote neoinnervation. A higher number of intraepidermal nerve fibers were observed for the unconditioned group probably due to a more controlled transition from the inflammatory to the proliferative phase. Overall, stem cell-containing spongy hydrogels represent a promising approach to enhance diabetic wound healing by positively impacting re-epithelialization and by modulating the inflammatory response to promote a successful neoinnervation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction.

PubMed

Yoshizumi, Tomo; Zhu, Yang; Jiang, Hongbin; D'Amore, Antonio; Sakaguchi, Hirokazu; Tchao, Jason; Tobita, Kimimasa; Wagner, William R

2016-03-01

Intramyocardial injection of various injectable hydrogel materials has shown benefit in positively impacting the course of left ventricular (LV) remodeling after myocardial infarction (MI). However, since LV remodeling is a complex, time dependent process, the most efficacious time of hydrogel injection is not clear. In this study, we injected a relatively stiff, thermoresponsive and bioabsorbable hydrogel in rat hearts at 3 different time points - immediately after MI (IM), 3 d post-MI (3D), and 2 w post-MI (2W), corresponding to the beginnings of the necrotic, fibrotic and chronic remodeling phases. The employed left anterior descending coronary artery ligation model showed expected infarction responses including functional loss, inflammation and fibrosis with distinct time dependent patterns. Changes in LV geometry and contractile function were followed by longitudinal echocardiography for 10 w post-MI. While all injection times positively affected LV function and wall thickness, the 3D group gave better functional outcomes than the other injection times and also exhibited more local vascularization and less inflammatory markers than the earlier injection time. The results indicate an important role for injection timing in the increasingly explored concept of post-MI biomaterial injection therapy and suggest that for hydrogels with mechanical support as primary function, injection at the beginning of the fibrotic phase may provide improved outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Analgesic Effect of Intra-Articular Injection of Temperature-Responsive Hydrogel Containing Bupivacaine on Osteoarthritic Pain in Rats

PubMed Central

Kim, Taemin; Seol, Dong Rim; Hahm, Suk-Chan; Ko, Cheolwoong; Kim, Eun-Hye; Chun, Keyoungjin; Kim, Junesun; Lim, Tae-Hong

2015-01-01

The present study examined the analgesic effects of slow-releasing bupivacaine from hydrogel on chronic arthritic pain in rats. Osteoarthritis (OA) was induced by monosodium iodoacetate (MIA) injection into the right knee joint. Hydrogel (HG: 20, 30, and 50 μL) and temperature-sensitive hydrogel containing bupivacaine (T-gel: 20, 30, and 50 μL) were injected intra-articularly 14 days after MIA injection. Behavioral tests were conducted. The rats showed a significant decrease in weight load and paw withdrawal threshold (PWT). Intra-articular 0.5% bupivacaine (10 and 20 μL) significantly reversed MIA-induced decreased PWT, with no effect on weight load. In normal rats, hydrogel did not produce significant changes in PWT but at 30 and 50 μL slightly decreased weight bearing; T-gel did not cause any changes in both the weight load and PWT. In OA rats, T-gel at 20 μL had a significant analgesic effect for 2 days, even though T-gel at 50 μL further reduced the weight load, demonstrating that intra-articular T-gel (20 μL) has long-lasting analgesic effects in OA rats. Thus, T-gel designed to deliver analgesics into the joint cavity could be an effective therapeutic tool in the clinical setting. PMID:26881207

Thiol functionalized polymethacrylic acid-based hydrogel microparticles for oral insulin delivery.

PubMed

Sajeesh, S; Vauthier, C; Gueutin, C; Ponchel, G; Sharma, Chandra P

2010-08-01

In the present study thiol functionalized polymethacrylic acid-polyethylene glycol-chitosan (PCP)-based hydrogel microparticles were utilized to develop an oral insulin delivery system. Thiol modification was achieved by grafting cysteine to the activated surface carboxyl groups of PCP hydrogels (Cys-PCP). Swelling and insulin loading/release experiments were conducted on these particles. The ability of these particles to inhibit protease enzymes was evaluated under in vitro experimental conditions. Insulin transport experiments were performed on Caco-2 cell monolayers and excised intestinal tissue with an Ussing chamber set-up. Finally, the efficacy of insulin-loaded particles in reducing the blood glucose level in streptozotocin-induced diabetic rats was investigated. Thiolated hydrogel microparticles showed less swelling and had a lower insulin encapsulation efficiency as compared with unmodified PCP particles. PCP and Cys-PCP microparticles were able to inhibit protease enzymes under in vitro conditions. Thiolation was an effective strategy to improve insulin absorption across Caco-2 cell monolayers, however, the effect was reduced in the experiments using excised rat intestinal tissue. Nevertheless, functionalized microparticles were more effective in eliciting a pharmacological response in diabetic animal, as compared with unmodified PCP microparticles. From these studies thiolation of hydrogel microparticles seems to be a promising approach to improve oral delivery of proteins/peptides. Copyright 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Drug-Triggered and Cross-Linked Self-Assembling Nanofibrous Hydrogels

PubMed Central

Kumar, Vivek A.; Shi, Siyu; Wang, Benjamin K.; Li, I-Che; Jalan, Abhishek A.; Sarkar, Biplab; Wickremasinghe, Navindee C.; Hartgerink, Jeffrey D.

2015-01-01

Self-assembly of multidomain peptides (MDP) can be tailored to carry payloads that modulate the extracellular environment. Controlled release of growth factors, cytokines, and small-molecule drugs allows for unique control of in vitro and in vivo responses. In this study, we demonstrate this process of ionic cross-linking of peptides using multivalent drugs to create hydrogels for sustained long-term delivery of drugs. Using phosphate, heparin, clodronate, trypan, and suramin, we demonstrate the utility of this strategy. Although all multivalent anions result in good hydrogel formation, demonstrating the generality of this approach, suramin led to the formation of the best hydrogels per unit concentration and was studied in greater detail. Suramin ionically cross-linked MDP into a fibrous meshwork as determined by scanning and transmission electron microscopy. We measured material storage and loss modulus using rheometry and showed a distinct increase in G′ and G″ as a function of suramin concentration. Release of suramin from scaffolds was determined using UV spectroscopy and showed prolonged release over a 30 day period. Suramin bioavailability and function were demonstrated by attenuated M1 polarization of THP-1 cells compared to positive control. Overall, this design strategy has allowed for the development of a novel class of polymeric delivery vehicles with generally long-term release and, in the case of suramin, cross-linked hydrogels that can modulate cellular phenotype. PMID:25831137

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.

Mitigating Scarring and Inflammation during Corneal Wound Healing using Nanofiber-Hydrogel Scaffolds

NASA Astrophysics Data System (ADS)

Fu, Amy

Due to the universal lack of donor tissue, there has been emerging interest in engineering materials to stimulate living cells to restore the features and functions of injured organs. We are particularly interested in developing materials for corneal use, where the necessity to maintain the tissue's transparency presents an additional challenge. Every year, there are 1.5 -- 2 million new cases of monocular blindness due to irregular healing of corneal injuries, dwarfing the approximately 150,000 corneal transplants performed. The large gap between the need and availability of cornea transplantation motivates us to develop a wound-healing scaffold that can prevent corneal blindness. To develop such a scaffold, it is necessary to regulate the cells responsible for repairing the damaged cornea, namely myofibroblasts, which are responsible for the disordered and non-refractive index matched scar that leads to corneal blindness. Using in vitro assays, we identified that protein nanofibers of certain orientation can promote cell migration and modulate the myofibroblast phenotype. The nanofibers are also transparent, easy to handle and non-cytotoxic. To adhere the nanofibers to a wound bed, we examined the use of two different in situ forming hydrogels: an artificial extracellular matrix protein (aECM)-based gel and a photo-crosslinkable heparin-based gel. Both hydrogels can be formed within minutes, are transparent upon gelation and are easily tunable. Using an in vivo mouse model for epithelial defects, we show that our corneal scaffolds (nanofibers together with hydrogel) are well-tolerated (no inflammatory response or turbidity) and support epithelium regrowth. We developed an ex vivo corneal tissue culture model where corneas that are wounded and treated with our scaffold can be cultured while retaining their ability to repair wounds for up to 21 days. Using this technique, we found that the aECM-based treatment induced a more favorable wound response than the heparin-based treatment, prompting us to further examine the efficacy of the aECM-based treatment in vivo using a rabbit model for stromal wounds. Results show that treated corneas have fewer myofibroblasts and immune cells than untreated ones, indicating that our corneal scaffold shows promise in promoting a calmer wound response and preventing corneal haze formation.

Mechanical characterization and modeling of sponge-reinforced hydrogel composites under compression.

PubMed

Wu, Lei; Mao, Guoyong; Nian, Guodong; Xiang, Yuhai; Qian, Jin; Qu, Shaoxing

2018-05-30

Load-bearing applications of hydrogels call for materials with excellent mechanical properties. Despite the considerable progress in developing tough hydrogels, there is still a requirement to prepare high-performance hydrogels using simple strategies. In this paper, a sponge-reinforced hydrogel composite is synthesized by combining poly(acrylamide) (PAAm) hydrogel and polyurethane (PU) sponge. Uniaxial compressive testing of the hydrogel composites reveals that both the compressive modulus and the strength of the hydrogel composites are much higher than those of the PAAm hydrogel or sponge. In order to predict the compressive modulus of the hydrogel composite, we develop a theoretical model that is validated by experiments and numerical simulations. The present work may guide the design and manufacture of hydrogel-based composite materials, especially for biomaterial scaffolds and soft transducers.