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Sample records for functionalized agarose hydrogels

  1. Augmenting Protein Release from Layer- by-Layer Functionalized Agarose Hydrogels

    PubMed Central

    Lynam, Daniel; Peterson, Chelsea; Maloney, Ryan; Shahriari, Dena; Garrison, Alexa; Saleh, Sara; Mehrotra, Sumit; Chan, Christina; Sakamoto, Jeff

    2014-01-01

    Recent work demonstrated the efficacy of combining layer-by-layer assembly with hydrogels to provide the controlled delivery of proteins for use in nerve repair scaffolds. In this work, we augmented the protein dose response by controlling and increasing the hydrogel internal surface area. Sucrose was added to agarose during gelation to homogenize the nanopore morphology, resulting in increased surface area per unit volume of hydrogel. The surface area of a range of compositions (1.5 to 5.0 wt% agarose and 0, 50 and 65 wt% sucrose) was measured. Gels were supercritically dried to preserve porosity enabling detailed pore morphology measurements using nitrogen adsorption and high resolution scanning electron microscopy. The resulting surface area, normalized by superficial gel volume, ranged between 6 and 56m2/ccgel. Using the layer-by-layer process to load lysozyme, a neurotrophic factor analog, a relationship was observed between surface area and cumulative dose response ranging from 176 to 2556 μg/mL, which is in the range of clinical relevance for the delivery of growth factors. In this work, we demonstrated that the ability to control porosity is key in tuning drug delivery dose response from layer-by-layer modified hydrogels. PMID:24528743

  2. Optical investigation of diffusion of levofloxacin mesylate in agarose hydrogel

    NASA Astrophysics Data System (ADS)

    Tan, Shuaixia; Dai, Hongjun; Wu, Juejie; Zhao, Ning; Zhang, Xiaoli; Xu, Jian

    2009-09-01

    Real-time electronic speckle pattern interferometry method has been applied to study the diffusion behavior of levofloxacin mesylate (MSALVFX) in agarose hydrogel. The results show that the diffusivity of solute decreases with the increase of concentration of agarose and adapts to Kohlrausch's law. Furthermore, Amsden's model, based on the retardance effect associated with polymer chain flexibility, was employed to simulate the diffusion behavior. The consistent results suggest that the retardance effect dominates the diffusion process of MSALFVX in hydrogel; moreover, polymer chain flexibility greatly affects drug transport within the polymer matrix.

  3. Agarose and methylcellulose hydrogel blends for nerve regeneration applications

    NASA Astrophysics Data System (ADS)

    Martin, Benton C.; Minner, Eric J.; Wiseman, Sherri L.; Klank, Rebecca L.; Gilbert, Ryan J.

    2008-06-01

    Trauma sustained to the central nervous system is a debilitating problem for thousands of people worldwide. Neuronal regeneration within the central nervous system is hindered by several factors, making a multi-faceted approach necessary. Two factors contributing to injury are the irregular geometry of injured sites and the absence of tissue to hold potential nerve guides and drug therapies. Biocompatible hydrogels, injectable at room temperature, that rapidly solidify at physiological temperatures (37 °C) are beneficial materials that could hold nerve guidance channels in place and be loaded with therapeutic agents to aid wound healing. Our studies have shown that thermoreversible methylcellulose can be combined with agarose to create hydrogel blends that accommodate these properties. Three separate novel hydrogel blends were created by mixing methylcellulose with one of the three different agaroses. Gelation time tests show that the blends solidify at a faster rate than base methylcellulose at 37 °C. Rheological data showed that the elastic modulus of the hydrogel blends rapidly increases at 37 °C. Culturing experiments reveal that the morphology of dissociated dorsal root ganglion neurons was not altered when the hydrogels were placed onto the cells. The different blends were further assessed using dissolution tests, pore size evaluations using scanning electron microscopy and measuring the force required for injection. This research demonstrates that blends of agarose and methylcellulose solidify much more quickly than plain methylcellulose, while solidifying at physiological temperatures where agarose cannot. These hydrogel blends, which solidify at physiological temperatures naturally, do not require ultraviolet light or synthetic chemical cross linkers to facilitate solidification. Thus, these hydrogel blends have potential use in delivering therapeutics and holding scaffolding in place within the nervous system.

  4. Injectable Amorphous Chitin-Agarose Composite Hydrogels for Biomedical Applications

    PubMed Central

    Priya, Murali Vishnu; Kumar, Rajendran Arun; Sivashanmugam, Amirthalingam; Nair, Shantikumar Vasudevan; Jayakumar, Rangasamy

    2015-01-01

    Injectable hydrogels are gaining popularity as tissue engineering constructs because of their ease of handling and minimal invasive delivery. Making hydrogels from natural polymers helps to overcome biocompatibility issues. Here, we have developed an Amorphous Chitin (ACh)-Agarose (Agr) composite hydrogel using a simpletechnique. Rheological studies, such as viscoelastic behavior (elastic modulus, viscous modulus, yield stress, and consistency), inversion test, and injectability test, were carried out for different ACh-Agr concentrations. The composite gel, having a concentration of 1.5% ACh and 0.25% Agr, showed good elastic modulus (17.3 kPa), yield stress (3.8 kPa), no flow under gravity, injectability, and temperature stability within the physiological range. Based on these studies, the optimum concentration for injectability was found to be 1.5% ACh and 0.25% Agr. This optimized concentration was used for further studies and characterized using FT-IR and SEM. FT-IR studies confirmed the presence of ACh and Agr in the composite gel. SEM results showed that the lyophilized composite gel had good porosity and mesh like networks. The cytocompatibility of the composite gel was studied using human mesenchymal stem cells (hMSCs). The composite gels showed good cell viability.These results indicated that this injectable composite gel can be used for biomedical applications. PMID:26308065

  5. Combination of fibrin-agarose hydrogels and adipose-derived mesenchymal stem cells for peripheral nerve regeneration

    NASA Astrophysics Data System (ADS)

    Carriel, Víctor; Garrido-Gómez, Juan; Hernández-Cortés, Pedro; Garzón, Ingrid; García-García, Salomé; Sáez-Moreno, José Antonio; Sánchez-Quevedo, María del Carmen; Campos, Antonio; Alaminos, Miguel

    2013-04-01

    Objective. The objective was to study the effectiveness of a commercially available collagen conduit filled with fibrin-agarose hydrogels alone or with fibrin-agarose hydrogels containing autologous adipose-derived mesenchymal stem cells (ADMSCs) in a rat sciatic nerve injury model. Approach. A 10 mm gap was created in the sciatic nerve of 48 rats and repaired using saline-filled collagen conduits or collagen conduits filled with fibrin-agarose hydrogels alone (acellular conduits) or with hydrogels containing ADMSCs (ADMSC conduits). Nerve regeneration was assessed in clinical, electrophysiological and histological studies. Main results. Clinical and electrophysiological outcomes were more favorable with ADMSC conduits than with the acellular or saline conduits, evidencing a significant recovery of sensory and motor functions. Histological analysis showed that ADMSC conduits produce more effective nerve regeneration by Schwann cells, with higher remyelination and properly oriented axonal growth that reached the distal areas of the grafted conduits, and with intensely positive expressions of S100, neurofilament and laminin. Extracellular matrix was also more abundant and better organized around regenerated nerve tissues with ADMSC conduits than those with acellular or saline conduits. Significance. Clinical, electrophysiological and histological improvements obtained with tissue-engineered ADMSC conduits may contribute to enhancing axonal regeneration by Schwann cells.

  6. IPN hydrogel nanocomposites based on agarose and ZnO with antifouling and bactericidal properties.

    PubMed

    Wang, Jingjing; Hu, Hongkai; Yang, Zhonglin; Wei, Jun; Li, Juan

    2016-04-01

    Nanocomposite hydrogels with interpenetrating polymer network (IPN) structure based on poly(ethylene glycol) methyl ether methacrylate modified ZnO (ZnO-PEGMA) and 4-azidobenzoic agarose (AG-N3) were prepared by a one-pot strategy under UV irradiation. The hydrogels exhibited a highly macroporous spongelike structure, and the pore size decreased with the increase of the ZnO-PEGMA content. Due to the entanglement and favorable interactions between the two crosslinked networks, the IPN hydrogels exhibited excellent mechanical strength and light transmittance. The maximum compressive and tensile strengths of the IPN hydrogels reached 24.8 and 1.98 MPa respectively. The transparent IPN hydrogels transmitted more than 85% of visible light at all wavelengths (400-800 nm). The IPN hydrogels exhibited anti-adhesive property towards Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus), and the bactericidal activity increased with the ZnO-PEGMA content. The incorporation of ZnO-PEGMA did not reduce the biocompatibility of the IPN hydrogels and all the IPN nanocomposites showed negligible cytotoxicity. The present study not only provided a facile method for preparing hydrogel nanocomposites with IPN structure but also developed a new hydrogel material which might be an excellent candidate for wound dressings. PMID:26838864

  7. Oxidized dextrins as alternative crosslinking agents for polysaccharides: application to hydrogels of agarose-chitosan.

    PubMed

    Gómez-Mascaraque, Laura G; Méndez, José Alberto; Fernández-Gutiérrez, Mar; Vázquez, Blanca; San Román, Julio

    2014-02-01

    Hydrogel networks that combine suitable physical and biomechanical characteristics for tissue engineering scaffolds are in demand. The aim of this work was the development of hydrogel networks based on agarose and chitosan using oxidized dextrins as low cytotoxicity crosslinking agents, paying special attention to the study of the influence of the polysaccharide composition and oxidation degree of the dextrins in the final characteristics of the network. The results show that the formation of an interpenetrating or a semi-interpenetrating polymer network was mainly dependent on a minimum agarose content and degree of oxidation of dextrin. Spectroscopic, thermal and swelling analysis revealed good compatibility with an absence of phase separation of polysaccharides at agarose:chitosan proportions of 50:50 and 25:75. The analysis of atomic force microscopy images showed the formation of a fibrillar microstructure whose distribution within the crosslinked chitosan depended mainly on the crosslinker. All materials exhibited the viscoelastic behaviour typical of gels, with a constant storage modulus independent of frequency for all compositions. The stiffness was strongly influenced by the degree of oxidation of the crosslinker. Cellular response to the hydrogels was studied with cells of different strains, and cell adhesion and proliferation was correlated with the homogeneity of the samples and their elastic properties. Some hydrogel formulations seemed to be candidates for tissue engineering applications such as wound healing or soft tissue regeneration. PMID:24121253

  8. Rheological and mechanical behavior of polyacrylamide hydrogels chemically crosslinked with allyl agarose for two-dimensional gel electrophoresis.

    PubMed

    Suriano, R; Griffini, G; Chiari, M; Levi, M; Turri, S

    2014-02-01

    Two-dimensional (2-D) gel electrophoresis currently represents one of the most standard techniques for protein separation. In addition to the most commonly employed polyacrylamide crosslinked hydrogels, acrylamide-agarose copolymers have been proposed as promising systems for separation matrices in 2-D electrophoresis, because of the good resolution of both high and low molecular mass proteins made possible by careful control and optimization of the hydrogel pore structure. As a matter of fact, a thorough understanding of the nature of the hydrogel pore structure as well as of the parameters by which it is influenced is crucial for the design of hydrogel systems with optimal sieving properties. In this work, a series of acrylamide-based hydrogels covalently crosslinked with different concentrations of allyl agarose (0.2-1%) is prepared and characterized by creep-recovery measurements, dynamic rheology and tensile tests, in the attempt to gain a clearer understanding of structure-property relationships in crosslinked polyacrylamide-based hydrogels. The rheological and mechanical properties of crosslinked acrylamide-agarose hydrogels are found to be greatly affected by crosslinker concentration. Dynamic rheological tests show that hydrogels with a percentage of allyl agarose between 0.2% and 0.6% have a low density of elastically effective crosslinks, explaining the good separation of high molecular mass proteins in 2-D gel electrophoresis. Over the same range of crosslinker concentration, creep-recovery measurements reveal the presence of non-permanent crosslinks in the hydrogel network that justifies the good resolution of low molecular mass proteins as well. In tensile tests, the hydrogel crosslinked with 0.4% of allyl agarose exhibits the best results in terms of mechanical strength and toughness. Our results show how the control of the viscoelastic and the mechanical properties of these materials allow the design of mechanically stable hydrogels with improved

  9. Direct electrochemistry of cytochrome c entrapped in agarose hydrogel in room temperature ionic liquids.

    PubMed

    Wang, Sui; Guo, Zhiyong; Zhang, Huina

    2011-08-01

    Direct electrochemistry of cytochrome c (cyt-c) entrapped in agarose hydrogel on gold electrode (Au), edge plane pyrolytic graphite electrode (EPPGE) and glassy carbon electrode (GC) in two room temperature ionic liquids was investigated. The effects of the addition of N,N-dimethylformamide (DMF) in the agarose-cyt-c film, water concentration in ionic liquids and exterior metal ions on the electrochemical behavior of cyt-c were monitored, and electrocatalytic properties of cyt-c were also done. Results showed that a good quasi-reversible redox behavior of cyt-c could be found after adding DMF in agarose-cyt-c film, and peak shape would not change after continuously scanning for 50 cycles. In addition, a certain amount of water in hydrophilic ionic liquids is necessary to maintain electrochemical activities of cyt-c, electrochemical performance of cyt-c is the best when the water content is 5.2% and 5.8% for 1-butyl-3-methylimidazolium bromide ([Bmim][Br]) and 1-butyl-3-methylimidazolium tetrafluoroborate([Bmim][BF(4)]) respectively. However, electrochemical activities of cyt-c are inhibited by exterior metal ions. Interestingly, cyt-c entrapped in agarose hydrogel on EPPGE and GC could catalyze the electroreduction of trichloroacetic acid (TCA) and tert-butyl hydroperoxide (t-BuOOH) in [Bmim][BF(4)], but could not in [Bmim][Br]. Reasons for above-mentioned differences of electrochemical properties of cyt-c in different ionic liquids were preliminarily discussed. PMID:21659008

  10. Delivery of DNA vaccines by agarose hydrogel implants facilitates genetic immunization in cattle.

    PubMed

    Toussaint, J F; Dubois, A; Dispas, M; Paquet, D; Letellier, C; Kerkhofs, P

    2007-01-26

    The present study demonstrates the interest of two slow-release systems as vaccination tools in cattle. Two experiments show that a first intradermal administration of one DNA vaccine dose combined with the slow-release of a second dose conduct to a priming of the bovine herpesvirus 1-specific immune response similar to the one generated by two discrete administrations 4 weeks apart. The first experiment demonstrates the efficacy of the slow-release system with well-characterized Alzet osmotic pumps, whereas the second experiment extends the same concept with innovative agarose hydrogel implants. These latter implants are cheaper and more convenient than the osmotic pumps or repeated intradermal administrations since they contribute to an efficient priming of the immune response in a single manipulation of the animals. PMID:17084488

  11. Functionalized Agarose Self-Healing Ionogels Suitable for Supercapacitors.

    PubMed

    Trivedi, Tushar J; Bhattacharjya, Dhrubajyoti; Yu, Jong-Sung; Kumar, Arvind

    2015-10-12

    Agarose has been functionalized (acetylated/carbanilated) in an ionic liquid (IL) medium of 1-butyl-3-methylimidazolium acetate at ambient conditions. The acetylated agarose showed a highly hydrophobic nature, whereas the carbanilated agarose could be dissolved in water as well as in the IL medium. Thermoreversible ionogels were obtained by cooling the IL sols of carbanilated agarose at room temperature. The ionogel prepared from a protic-aprotic mixed-IL system (1-butyl-3-methylimidazolium chloride and N-(2-hydroxyethyl)ammonium formate) demonstrated a superior self-healing property, as confirmed from rheological measurements. The superior self-healing property of such an ionogel has been attributed to the unique inter-intra hydrogen-bonding network of functional groups inserted in the agarose. The ionogel was tested as a flexible solid electrolyte for an activated-carbon-based supercapacitor cell. The measured specific capacitance was found to be comparable with that of a liquid electrolyte system at room temperature and was maintained for up to 1000 charge-discharge cycles. Such novel functionalized-biopolymer self-healing ionogels with flexibility and good conductivity are desirable for energy-storage devices and electronic skins with superior lifespans and robustness. PMID:26280813

  12. Tuning mechanical performance of poly(ethylene glycol) and agarose interpenetrating network hydrogels for cartilage tissue engineering

    PubMed Central

    Rennerfeldt, DA; Renth, AN; Talata, Z; Gehrke, SH; Detamore, MS

    2013-01-01

    Hydrogels are attractive for tissue engineering applications due to their incredible versatility, but they can be limited in cartilage tissue engineering applications due to inadequate mechanical performance. In an effort to address this limitation, our team previously reported the drastic improvement in the mechanical performance of interpenetrating networks (IPNs) of poly(ethylene glycol) diacrylate (PEG-DA) and agarose relative to pure PEG-DA and agarose networks. The goal of the current study was specifically to determine the relative importance of PEG-DA concentration, agarose concentration, and PEG-DA molecular weight in controlling mechanical performance, swelling characteristics, and network parameters. IPNs consistently had compressive and shear moduli greater than the additive sum of either single network when compared to pure PEG-DA gels with a similar PEG-DA content. IPNs withstood a maximum stress of up to 4.0 MPa in unconfined compression, with increased PEG-DA molecular weight being the greatest contributing factor to improved failure properties. However, aside from failure properties, PEG-DA concentration was the most influential factor for the large majority of properties. Increasing the agarose and PEG-DA concentrations as well as the PEG-DA molecular weight of agarose/PEG-DA IPNs and pure PEG-DA gels improved moduli and maximum stresses by as much as an order of magnitude or greater compared to pure PEG-DA gels in our previous studies. Although the viability of encapsulated chondrocytes was not significantly affected by IPN formulation, glycosaminoglycan (GAG) content was significantly influenced, with a 12-fold increase over a three-week period in gels with a lower PEG-DA concentration. These results suggest that mechanical performance of IPNs may be tuned with partial but not complete independence from biological performance of encapsulated cells. PMID:23932504

  13. Silk microfiber-reinforced silk hydrogel composites for functional cartilage tissue repair

    PubMed Central

    Yodmuang, Supansa; McNamara, Stephanie L.; Nover, Adam B.; Mandal, Biman B.; Agarwal, Monica; Kelly, Terri-Ann N.; Chao, Pen-hsiu Grace; Hung, Clark; Kaplan, David L.; Vunjak-Novakovic, Gordana

    2014-01-01

    Cartilage tissue lacks an intrinsic capacity for self-regeneration due to slow matrix turnover, a limited supply of mature chondrocytes and insufficient vasculature. Although cartilage tissue engineering has achieved some success using agarose as a scaffolding material, major challenges of agarose-based cartilage repair, including non-degradability, poor tissue–scaffold integration and limited processing capability, have prompted the search for an alternative biomaterial. In this study, silk fiber–hydrogel composites (SF–silk hydrogels) made from silk microfibers and silk hydrogels were investigated for their potential use as a support material for engineered cartilage. We demonstrated the use of 100% silk-based fiber–hydrogel composite scaffolds for the development of cartilage constructs with properties comparable to those made with agarose. Cartilage constructs with an equilibrium modulus in the native tissue range were fabricated by mimicking the collagen fiber and proteoglycan composite architecture of native cartilage using biocompatible, biodegradable silk fibroin from Bombyx mori. Excellent chondrocyte response was observed on SF–silk hydrogels, and fiber reinforcement resulted in the development of more mechanically robust constructs after 42 days in culture compared to silk hydrogels alone. Thus, we demonstrate the versatility of silk fibroin as a composite scaffolding material for use in cartilage tissue repair to create functional cartilage constructs that overcome the limitations of agarose biomaterials, and provide a much-needed alternative to the agarose standard. PMID:25281788

  14. Using chondroitin sulfate to improve the viability and biosynthesis of chondrocytes encapsulated in interpenetrating network (IPN) hydrogels of agarose and poly(ethylene glycol) diacrylate.

    PubMed

    Ingavle, Ganesh C; Dormer, Nathan H; Gehrke, Stevin H; Detamore, Michael S

    2012-01-01

    We recently introduced agarose-poly(ethylene glycol) diacrylate (PEGDA) interpenetrating network (IPN) hydrogels to cartilage tissue engineering that were able to encapsulate viable cells and provide a significant improvement in mechanical performance relative to its two constituent hydrogels. The goal of the current study was to develop a novel synthesis protocol to incorporate methacrylated chondroitin sulfate (MCS) into the IPN design hypothesized to improve cell viability and biosynthesis. The IPN was formed by encapsulating porcine chondrocytes in agarose, soaking the construct in a solution of 1:10 MCS:PEGDA, which was then photopolymerized to form a copolymer network as the second network. The IPN with incorporated CS (CS-IPN) (~0.5 wt%) resulted in a 4- to 5-fold increase in the compressive elastic modulus relative to either the PEGDA or agarose gels. After 6 weeks of in vitro culture, more than 50% of the encapsulated chondrocytes remained viable within the CS-modified IPN, in contrast to 35% viability observed in the unmodified. At week 6, the CS-IPN had significantly higher normalized GAG contents (347 ± 34 μg/μg) than unmodified IPNs (158 ± 27 μg/μg, P < 0.05). Overall, the approach of incorporating biopolymers such as CS from native tissue may provide favorable micro-environment and beneficial signals to cells to enhance their overall performance in IPNs. PMID:22116661

  15. Homogeneous tosylation of agarose as an approach toward novel functional polysaccharide materials.

    PubMed

    Gericke, Martin; Heinze, Thomas

    2015-01-01

    The homogeneous tosylation of agarose was studied with respect to the effects of reaction parameters, such as reaction medium, time, and molar ratio, on the reaction course, the degree of substitution (DS) with tosyl/chloro deoxy groups, and the molecular structure. Tosyl agaroses (TOSA) with DS tosyl ≤ 1 .81 could be obtained in completely homogeneous reactions by using N,N-dimethylacetamide (DMA)/LiCl or 1,3-dimethyl-2-imidazolidinone (DMI) as solvents. The products were characterized by FT-IR and NMR spectroscopy and it was demonstrated that two types of substitution pattern can be achieved: (i) non-preferential substitution at position 6 of the 1 → 3-linked β-d-galactose unit (G-6) and position 2 of the 1 → 4-linked 3,6-anyhdro-α-L-galactose unit (LA-2) and (ii) regioselective tosylation at G-6, depending on whether the reaction is performed with or without LiCl. Finally, the nucleophilic displacement reaction of TOSA was studied using azide and ethylenediamine as representative nucleophiles. Novel deoxy-agarose derivatives were obtained that showed an interesting solubility behavior and will be used for creating functional polysaccharide materials. PMID:25965480

  16. 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. PMID:27077566

  17. Functionalized injectable hydrogels for controlled insulin delivery.

    PubMed

    Huynh, Dai P; Nguyen, Minh K; Pi, Bong S; Kim, Min S; Chae, Su Y; Lee, Kang C; Kim, Bong S; Kim, Sung W; Lee, Doo S

    2008-06-01

    The concept of this research is using poly(beta-amino ester) (PAE) as a duo-functional group for synthesis of the novel sensitive injectable hydrogel for controlled drug/protein delivery. Firstly, PAE made of 1,4-butanediol diacrylate and 4,4'-trimethylene dipiperidine is used as a pH-sensitive moiety to conjugate to the temperature-sensitive biodegradable triblock copolymer of poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) to manufacture pH/temperature-sensitive injectable hydrogel of pentablock copolymer PAE-PCL-PEG-PCL-PAE. Furthermore, the cationic nature of PAE is used as the second function to make the ionic complexes with anionic biomolecule loaded into the hydrogel such as insulin. As a result, the release of drug/protein from this hydrogel device can be controlled by the degradation of copolymer. Sol-gel phase transition behavior of PAE-PCL-PEG-PCL-PAE block copolymer was investigated; the results showed that the aqueous media of the pentablock copolymer changed from a sol to a gel phase with increasing temperature and pH. The effect of anionic biomolecule such as insulin on sol-gel phase transition, degradation of the complex gel of the material with insulin was studied in vitro. Then the schematic of the ionic complexes between positive charges in PAE and the negatively charges in protein was simulated. In addition, the mechanism of controlled release behavior of insulin from the complex gel was supposed, which includes the chemically-controlled and diffusion-controlled stages. To prove the simulations, the cumulative release of the protein from the complex gel was investigated in vitro with different methods. Furthermore, the pharmacokinetic release of insulin from the complex gel in vivo on male Sprague-Dawley (SD) rats was compared with that from triblock copolymer hydrogel of PCL-PEG-PCL. PMID:18329707

  18. Functional Hydrogel Materials Inspired by Amyloid

    NASA Astrophysics Data System (ADS)

    Schneider, Joel

    2012-02-01

    Protein assembly resulting in the formation of amyloid fibrils, assemblies rich in cross beta-sheet structure, is normally thought of as a deleterious event associated with disease. However, amyloid formation is also involved in a diverse array of normal biological functions such as cell adhesion, melanin synthesis, insect defense mechanism and modulation of water surface tension by fungi and bacteria. These findings indicate that Nature has evolved to take advantage of large, proteinaceous fibrillar assemblies to elicit function. We are designing functional materials, namely hydrogels, from peptides that self-assembled into fibrillar networks, rich in cross beta-sheet structure. These gels can be used for the direct encapsulation and delivery of small molecule-, protein- and cell-based therapeutics. Loaded gels exhibit shear-thinning/self-healing mechanical properties enabling their delivery via syringe. In addition to their use for delivery, we have found that some of these gels display antibacterial activity. Although cytocompatible towards mammalian cells, the hydrogels can kill a broad spectrum of bacteria on contact.

  19. Enzymatic regulation of functional vascular networks using gelatin hydrogels

    PubMed Central

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

    2015-01-01

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

  20. Flexible hydrogel-based functional composite materials

    SciTech Connect

    Song, Jie; Saiz, Eduardo; Bertozzi, Carolyn R; Tomasia, Antoni P

    2013-10-08

    A composite having a flexible hydrogel polymer formed by mixing an organic phase with an inorganic composition, the organic phase selected from the group consisting of a hydrogel monomer, a crosslinker, a radical initiator, and/or a solvent. A polymerization mixture is formed and polymerized into a desired shape and size.

  1. Agarose functionalization: Synthesis of PEG-agarose amino acid nano-conjugate - its structural ramifications and interactions with BSA in a varying pH regime.

    PubMed

    Chudasama, Nishith A; Prasad, Kamalesh; Siddhanta, Arup Kumar

    2016-10-20

    In a rapid one-step method protein-mimicking large agarose amino acid framework (AAE; GPC 156.7kDa) was conjugated with polyethylene glycol (PEG 9kDa) affording nano-sized PEGylated amphoteric agarose (PEG-AAE; <10nm; DLS) containing amino, carboxyl and ester groups [overall degree of substitution (DS) 0.91]. The PEG groups were at the residual free carboxylic acid groups of succinate half-ester moiety at C-6 positions of the 1, 3 β-d-galactopyranose moieties of AAE. This new nano-sized PEG-AAE performed like a giant protein conjugate (GPC 331.2kDa) and exhibited pH-responsive interconversion between the triple helix and single-stranded random structures (optical rotatory dispersion) presenting a mixed solubility pattern like random coil (soluble), helical (soluble) and aggregate (precipitation) formations. Circular dichroism studies showed its pH-dependent complexation and decomplexation with bovine serum albumin (BSA). Such pH-responsive PEG-conjugate may be of pronounced therapeutic potential in the area of pharmacology as well as in sensing applications. PMID:27474620

  2. Functional hyaluronic acid hydrogels prepared by a novel method.

    PubMed

    Cui, Ning; Qian, Junmin; Zhao, Na; Wang, Hongjie

    2014-12-01

    In this study, a novel simple method was developed to prepare functional hyaluronic acid (HA) hydrogels simultaneously containing hydrazone and disulfide bonds in their crossbridges. The HA hydrogels were formed by directly reacting 2,5-hexanedione and 3,3'-dithiodipropionate hydrazide-modified HA, and were characterized by FT-IR, SEM, TGA and mechanical tests. The results showed that the formation of HA hydrogels was a result of the reaction between ketone and hydrazide groups. The resultant HA hydrogels exhibited a porous morphology with a pore size range of 50 μm to 400 μm, and their compressive modulus and G″/G' ratio were 18.8±0.6 kPa and 0.002, respectively. Both swelling and degradation ratios gradually decreased with the increasing degree of crosslinking. However, the degree of crosslinking had a slight effect on the decomposition temperature of the HA hydrogels. It can be concluded that the simple method presented in this study is feasible to prepare HA hydrogels through hydrazone bond crosslinking by reacting diketone molecules and hydrazide-modified HA, and the HA hydrogels have potential in biomedical applications. PMID:25491866

  3. Glycomimetic functionalized collagen hydrogels for peripheral nerve repair

    NASA Astrophysics Data System (ADS)

    Masand, Shirley Narain

    Despite the innate regenerative potential of the peripheral nervous system, functional recovery is often limited. The goal of this dissertation was to develop a clinically relevant biomaterial strategy to (1) encourage the regrowth of axons and (2) direct them down their appropriate motor tracts. To this end, we use peptide mimics of two glycans, polysialic acid (PSA) and an epitope first discovered on human natural killer cells (HNK-1), to functionalize type I collagen hydrogels. Previous studies have shown that these molecules, in their glycan and glycomimetic form, are associated with acceleration of neurite outgrowth, glial cell proliferation, and motoneuron targeting. In vitro, we demonstrated the retained functionality of the peptide glycomimetics after conjugation to a type I collagen backbone. While HNK-functionalized collagen increased motor neurite outgrowth, PSA-functionalized collagen encouraged motor and sensory neurite outgrowth and Schwann cell extension and proliferation. When we introduce these glycomimetic-functionalized collagen hydrogels into a critical gap femoral nerve model, we show that both PSA and HNK-functionalized hydrogels yielded a significant increase in functional recovery when compared to saline, native and scramble-coupled hydrogels. However, there was an interesting divergence in the morphological results: PSA-functionalized hydrogels increased axon count and HNK-functionalized hydrogels increased motoneuron targeting and myelination. We believed that these differences may be attributed to distinct mechanisms by which the glycomimetics impart their benefit. Interestingly, however, we found no synergistic gain in recovery with the use of our composite hydrogels which we speculated may be due to an inadequate dose of the individual glycomimetic. To address this possibility, we show that increasing the amount of functionalized peptide functionalized in our composite hydrogels led to increases in axon count and area of regeneration

  4. Tunable drug delivery using chemoselective functionalization of hydrogels.

    PubMed

    Mauri, Emanuele; Rossi, Filippo; Sacchetti, Alessandro

    2016-04-01

    In the last decades interests on cleavable linkers are growing due to the need to develop controlled drug delivery systems in biochemical and therapeutic applications. The synthesis of hydrogels as devices capable to maintain the drug level within a desired range for a long and sustained period of time is a leading strategy for this aim. However with respect to the good results obtained with antibodies and peptides there are a lot of problems related to the quick and uncontrolled diffusion of small molecules through hydrogel pores. In this work, we propose the functionalization of polyethylene glycol (PEG) chains with two different pH-sensitive linkers, ester and hydrazone, and their application as building blocks of microwave-assisted hydrogels for controlled delivery of small hydrophilic drugs. As drug mimetic we used Rhodamine B, a harmless fluorophore with steric hindrance and reactive groups similar to many small hydrophilic drugs. At physiological and low basic conditions, the cleavability of ester and hydrazone spacer evidenced the possibility to delay the release of drugs from the scaffold compared to hydrogels where drug was entrapped within the network only due to its steric hindrance. The obtained release profiles were compared, underlining the opportunity to tune the release rate using the synthesized hydrogels. PMID:26838916

  5. Hydrogels from biopolymer hybrid for biomedical, food, and functional food applications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hybrid hydrogels from biopolymers have been applied for various indications across a wide range of biomedical, pharmaceutical, and functional food industries. In particular, hybrid hydrogels synthesized from two biopolymers have attracted increasing attention. The inclusion of a second biopolymer st...

  6. Functional Human Vascular Network Generated in Photocrosslinkable Gelatin Methacrylate Hydrogels.

    PubMed

    Chen, Ying-Chieh; Lin, Ruei-Zeng; Qi, Hao; Yang, Yunzhi; Bae, Hojae; Melero-Martin, Juan M; Khademhosseini, Ali

    2012-05-23

    The generation of functional, 3D vascular networks is a fundamental prerequisite for the development of many future tissue engineering-based therapies. Current approaches in vascular network bioengineering are largely carried out using natural hydrogels as embedding scaffolds. However, most natural hydrogels present a poor mechanical stability and a suboptimal durability, which are critical limitations that hamper their widespread applicability. The search for improved hydrogels has become a priority in tissue engineering research. Here, the suitability of a photopolymerizable gelatin methacrylate (GelMA) hydrogel to support human progenitor cell-based formation of vascular networks is demonstrated. Using GelMA as the embedding scaffold, it is shown that 3D constructs containing human blood-derived endothelial colony-forming cells (ECFCs) and bone marrow-derived mesenchymal stem cells (MSCs) generate extensive capillary-like networks in vitro. These vascular structures contain distinct lumens that are formed by the fusion of ECFC intracellular vacuoles in a process of vascular morphogenesis. The process of vascular network formation is dependent on the presence of MSCs, which differentiate into perivascular cells occupying abluminal positions within the network. Importantly, it is shown that implantation of cell-laden GelMA hydrogels into immunodeficient mice results in a rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, it is shown that the degree of methacrylation of the GelMA can be used to modulate the cellular behavior and the extent of vascular network formation both in vitro and in vivo. These data suggest that GelMA hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues. PMID:22907987

  7. Functional Human Vascular Network Generated in Photocrosslinkable Gelatin Methacrylate Hydrogels

    PubMed Central

    Chen, Ying-Chieh; Lin, Ruei-Zeng; Qi, Hao; Yang, Yunzhi; Bae, Hojae

    2012-01-01

    The generation of functional, 3D vascular networks is a fundamental prerequisite for the development of many future tissue engineering-based therapies. Current approaches in vascular network bioengineering are largely carried out using natural hydrogels as embedding scaffolds. However, most natural hydrogels present a poor mechanical stability and a suboptimal durability, which are critical limitations that hamper their widespread applicability. The search for improved hydrogels has become a priority in tissue engineering research. Here, the suitability of a photopolymerizable gelatin methacrylate (GelMA) hydrogel to support human progenitor cell-based formation of vascular networks is demonstrated. Using GelMA as the embedding scaffold, it is shown that 3D constructs containing human blood-derived endothelial colony-forming cells (ECFCs) and bone marrow-derived mesenchymal stem cells (MSCs) generate extensive capillary-like networks in vitro. These vascular structures contain distinct lumens that are formed by the fusion of ECFC intracellular vacuoles in a process of vascular morphogenesis. The process of vascular network formation is dependent on the presence of MSCs, which differentiate into perivascular cells occupying abluminal positions within the network. Importantly, it is shown that implantation of cell-laden GelMA hydrogels into immunodeficient mice results in a rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, it is shown that the degree of methacrylation of the GelMA can be used to modulate the cellular behavior and the extent of vascular network formation both in vitro and in vivo. These data suggest that GelMA hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues. PMID:22907987

  8. Skin-inspired hydrogel-elastomer hybrids with robust interfaces and functional microstructures.

    PubMed

    Yuk, Hyunwoo; Zhang, Teng; Parada, German Alberto; Liu, Xinyue; Zhao, Xuanhe

    2016-01-01

    Inspired by mammalian skins, soft hybrids integrating the merits of elastomers and hydrogels have potential applications in diverse areas including stretchable and bio-integrated electronics, microfluidics, tissue engineering, soft robotics and biomedical devices. However, existing hydrogel-elastomer hybrids have limitations such as weak interfacial bonding, low robustness and difficulties in patterning microstructures. Here, we report a simple yet versatile method to assemble hydrogels and elastomers into hybrids with extremely robust interfaces (interfacial toughness over 1,000 Jm(-2)) and functional microstructures such as microfluidic channels and electrical circuits. The proposed method is generally applicable to various types of tough hydrogels and diverse commonly used elastomers including polydimethylsiloxane Sylgard 184, polyurethane, latex, VHB and Ecoflex. We further demonstrate applications enabled by the robust and microstructured hydrogel-elastomer hybrids including anti-dehydration hydrogel-elastomer hybrids, stretchable and reactive hydrogel-elastomer microfluidics, and stretchable hydrogel circuit boards patterned on elastomer. PMID:27345380

  9. Skin-inspired hydrogel-elastomer hybrids with robust interfaces and functional microstructures

    NASA Astrophysics Data System (ADS)

    Yuk, Hyunwoo; Zhang, Teng; Parada, German Alberto; Liu, Xinyue; Zhao, Xuanhe

    2016-06-01

    Inspired by mammalian skins, soft hybrids integrating the merits of elastomers and hydrogels have potential applications in diverse areas including stretchable and bio-integrated electronics, microfluidics, tissue engineering, soft robotics and biomedical devices. However, existing hydrogel-elastomer hybrids have limitations such as weak interfacial bonding, low robustness and difficulties in patterning microstructures. Here, we report a simple yet versatile method to assemble hydrogels and elastomers into hybrids with extremely robust interfaces (interfacial toughness over 1,000 Jm-2) and functional microstructures such as microfluidic channels and electrical circuits. The proposed method is generally applicable to various types of tough hydrogels and diverse commonly used elastomers including polydimethylsiloxane Sylgard 184, polyurethane, latex, VHB and Ecoflex. We further demonstrate applications enabled by the robust and microstructured hydrogel-elastomer hybrids including anti-dehydration hydrogel-elastomer hybrids, stretchable and reactive hydrogel-elastomer microfluidics, and stretchable hydrogel circuit boards patterned on elastomer.

  10. Functionalized α-Helical Peptide Hydrogels for Neural Tissue Engineering

    PubMed Central

    2015-01-01

    Trauma to the central and peripheral nervous systems often lead to serious morbidity. Current surgical methods for repairing or replacing such damage have limitations. Tissue engineering offers a potential alternative. Here we show that functionalized α-helical-peptide hydrogels can be used to induce attachment, migration, proliferation and differentiation of murine embryonic neural stem cells (NSCs). Specifically, compared with undecorated gels, those functionalized with Arg-Gly-Asp-Ser (RGDS) peptides increase the proliferative activity of NSCs; promote their directional migration; induce differentiation, with increased expression of microtubule-associated protein-2, and a low expression of glial fibrillary acidic protein; and lead to the formation of larger neurospheres. Electrophysiological measurements from NSCs grown in RGDS-decorated gels indicate developmental progress toward mature neuron-like behavior. Our data indicate that these functional peptide hydrogels may go some way toward overcoming the limitations of current approaches to nerve-tissue repair. PMID:26240838

  11. Functional stimuli responsive hydrogel devices by self-folding

    NASA Astrophysics Data System (ADS)

    Yoon, ChangKyu; Xiao, Rui; Park, JaeHyun; Cha, Jaepyeong; Nguyen, Thao D.; Gracias, David H.

    2014-09-01

    We describe a photolithographic approach to create functional stimuli responsive, self-folding, microscale hydrogel devices using thin, gradient cross-linked hinges and thick, fully cross-linked panels. The hydrogels are composed of poly (N-isopropylacrylamide-co-acrylic acid) (pNIPAM-AAc) with reversible stimuli responsive properties just below physiological temperatures. We show that a variety of three-dimensional structures can be formed and reversibly actuated by temperature or pH. We experimentally characterized the swelling and mechanical properties of pNIPAM-AAc and developed a finite element model to rationalize self-folding and its variation with hinge thickness and swelling ratio. Finally, we highlight applications of this approach in the creation of functional devices such as self-folding polymeric micro-capsules, untethered micro-grippers and thermally steered micro-mirror systems.

  12. Highly Elastic Micropatterned Hydrogel for Engineering Functional Cardiac Tissue

    PubMed Central

    Annabi, Nasim; Tsang, Kelly; Mithieux, Suzanne M.; Nikkhah, Mehdi; Ameri, Afshin

    2013-01-01

    Heart failure is a major international health issue. Myocardial mass loss and lack of contractility are precursors to heart failure. Surgical demand for effective myocardial repair is tempered by a paucity of appropriate biological materials. These materials should conveniently replicate natural human tissue components, convey persistent elasticity, promote cell attachment, growth and conformability to direct cell orientation and functional performance. Here, microfabrication techniques are applied to recombinant human tropoelastin, the resilience-imparting protein found in all elastic human tissues, to generate photocrosslinked biological materials containing well-defined micropatterns. These highly elastic substrates are then used to engineer biomimetic cardiac tissue constructs. The micropatterned hydrogels, produced through photocrosslinking of methacrylated tropoelastin (MeTro), promote the attachment, spreading, alignment, function, and intercellular communication of cardiomyocytes by providing an elastic mechanical support that mimics their dynamic mechanical properties in vivo. The fabricated MeTro hydrogels also support the synchronous beating of cardiomyocytes in response to electrical field stimulation. These novel engineered micropatterned elastic gels are designed to be amenable to 3D modular assembly and establish a versatile, adaptable foundation for the modeling and regeneration of functional cardiac tissue with potential for application to other elastic tissues. PMID:24319406

  13. Near-infrared light responsive multi-compartmental hydrogel particles synthesized through droplets assembly induced by superhydrophobic surface.

    PubMed

    Luo, Rongcong; Cao, Ye; Shi, Peng; Chen, Chia-Hung

    2014-12-10

    Light-responsive hydrogel particles with multi-compartmental structure are useful for applications in microreactors, drug delivery and tissue engineering because of their remotely-triggerable releasing ability and combinational functionalities. The current methods of synthesizing multi-compartmental hydrogel particles typically involve multi-step interrupted gelation of polysaccharides or complicated microfluidic procedures with limited throughput. In this study, a two-step sequential gelation process is developed to produce agarose/alginate double network multi-compartmental hydrogel particles using droplets assemblies induced by superhydrophobic surface as templates. The agarose/alginate double network multi-compartmental hydrogel particles can be formed with diverse hierarchical structures showing combinational functionalities. The synthesized hydrogel particles, when loaded with polypyrrole (PPy) nanoparticles that act as photothermal nanotransducers, are demonstrated to function as near-infrared (NIR) light triggerable and deformation-free hydrogel materials. Periodic NIR laser switching is applied to stimulate these hydrogel particles, and pulsatile release profiles are collected. Compared with massive reagents released from single-compartmental hydrogel particles, more regulated release profiles of the multi-compartmental hydrogel particles are observed. PMID:25059988

  14. Colorimetric logic response based on aptamer functionalized colloidal crystal hydrogels

    NASA Astrophysics Data System (ADS)

    Ye, Baofen; Wang, Huan; Ding, Haibo; Zhao, Yuanjin; Pu, Yuepu; Gu, Zhongze

    2015-04-01

    A novel colorimetric logic system based on the aptamer-cross-linked colloidal crystal hydrogel (CCH) was developed. With the input stimuli of Hg2+ and Ag+, the CCH displayed shrinking response and colour change corresponding to the logical ``OR'' and ``AND'' gate. The visualization of the logic output signals is realized.A novel colorimetric logic system based on the aptamer-cross-linked colloidal crystal hydrogel (CCH) was developed. With the input stimuli of Hg2+ and Ag+, the CCH displayed shrinking response and colour change corresponding to the logical ``OR'' and ``AND'' gate. The visualization of the logic output signals is realized. Electronic supplementary information (ESI) available: I. Experimental section. II. Photograph of the aptamer functionalized CCH in the presence of different targets. III. The specificity of the aptamer functionalized CCH. IV. Relationship between the input ion concentration and the reflection wavelength blue shift. V. The logic swelling kinetics of CCH. See DOI: 10.1039/c5nr00586h

  15. Molecularly imprinted hydrogels as functional active packaging materials.

    PubMed

    Benito-Peña, Elena; González-Vallejo, Victoria; Rico-Yuste, Alberto; Barbosa-Pereira, Letricia; Cruz, José Manuel; Bilbao, Ainhoa; Alvarez-Lorenzo, Carmen; Moreno-Bondi, María Cruz

    2016-01-01

    This paper describes the synthesis of novel molecularly imprinted hydrogels (MIHs) for the natural antioxidant ferulic acid (FA), and their application as packaging materials to prevent lipid oxidation of butter. A library of MIHs was synthesized using a synthetic surrogate of FA, 3-(4-hydroxy-3-methoxyphenyl)propionic acid (HFA), as template molecule, ethyleneglycol dimethacrylate (EDMA) as cross-linker, and 1-allylpiperazine (1-ALPP) or 2-(dimethylamino)ethyl methacrylate (DMAEMA), in combination with 2-hydroxyethyl methacrylate (HEMA) as functional monomers, at different molar concentrations. The DMAEMA/HEMA-based MIHs showed the greatest FA loading capacity, while the 1-ALLP/HEMA-based polymers exhibited the highest imprinting effect. During cold storage, FA-loaded MIHs protected butter from oxidation and led to TBARs values that were approximately half those of butter stored without protection and 25% less than those recorded for butter covered with hydrogels without FA, potentially extending the shelf life of butter. Active packaging is a new field of application for MIHs with great potential in the food industry. PMID:26213001

  16. The modulation of cardiac progenitor cell function by hydrogel-dependent Notch1activation

    PubMed Central

    Boopathy, Archana V.; Che, Pao Lin; Somasuntharam, Inthirai; Fiore, Vincent F.; Cabigas, E. Bernadette; Ban, Kiwon; Brown, Milton E.; Narui, Yoshie; Barker, Thomas H.; Yoon, Young-sup; Salaita, Khalid; García, Andrés J.; Davis, Michael E.

    2014-01-01

    Myocardial infarction is the leading cause of death worldwide and phase I clinical trials utilizing cardiac progenitor cells (CPCs) have shown promising outcomes. Notch1 signaling plays a critical role in cardiac development and in the survival, cardiogenic lineage commitment, and differentiation of cardiac stem/progenitor cells. In this study, we functionalized self-assembling peptide (SAP) hydrogels with a peptide mimic of the Notch1 ligand Jagged1 (RJ) to evaluate the therapeutic benefit of CPC delivery in the hydrogels in a rat model of myocardial infarction. The behavior of CPCs cultured in the 3D hydrogels in vitro including gene expression, proliferation, and growth factor production was evaluated. Interestingly, we observed Notch1 activation to be dependent on hydrogel polymer density/stiffness with synergistic increase in presence of RJ. Our results show that RJ mediated Notch1 activation depending on hydrogel concentration differentially regulated cardiogenic gene expression, proliferation, and growth factor production in CPCs in vitro. In rats subjected to experimental myocardial infarction, improvement in acute retention and cardiac function was observed following cell therapy in RJ hydrogels compared to unmodified or scrambled peptide containing hydrogels. This study demonstrates the potential therapeutic benefit of functionalizing SAP hydrogels with RJ for CPC based cardiac repair. PMID:24974008

  17. Functional nucleic acid-based hydrogels for bioanalytical and biomedical applications.

    PubMed

    Li, Juan; Mo, Liuting; Lu, Chun-Hua; Fu, Ting; Yang, Huang-Hao; Tan, Weihong

    2016-03-01

    Hydrogels are crosslinked hydrophilic polymers that can absorb a large amount of water. By their hydrophilic, biocompatible and highly tunable nature, hydrogels can be tailored for applications in bioanalysis and biomedicine. Of particular interest are DNA-based hydrogels owing to the unique features of nucleic acids. Since the discovery of the DNA double helical structure, interest in DNA has expanded beyond its genetic role to applications in nanotechnology and materials science. In particular, DNA-based hydrogels present such remarkable features as stability, flexibility, precise programmability, stimuli-responsive DNA conformations, facile synthesis and modification. Moreover, functional nucleic acids (FNAs) have allowed the construction of hydrogels based on aptamers, DNAzymes, i-motif nanostructures, siRNAs and CpG oligodeoxynucleotides to provide additional molecular recognition, catalytic activities and therapeutic potential, making them key players in biological analysis and biomedical applications. To date, a variety of applications have been demonstrated with FNA-based hydrogels, including biosensing, environmental analysis, controlled drug release, cell adhesion and targeted cancer therapy. In this review, we focus on advances in the development of FNA-based hydrogels, which have fully incorporated both the unique features of FNAs and DNA-based hydrogels. We first introduce different strategies for constructing DNA-based hydrogels. Subsequently, various types of FNAs and the most recent developments of FNA-based hydrogels for bioanalytical and biomedical applications are described with some selected examples. Finally, the review provides an insight into the remaining challenges and future perspectives of FNA-based hydrogels. PMID:26758955

  18. Microfluidic Fabrication of Hydrogel Microparticles Containing Functionalized Viral Nanotemplates

    PubMed Central

    Lewis, Christina L.; Lin, Yan; Yang, Cuixian; Manocchi, Amy K.; Yuet, Kai P.; Doyle, Patrick S.; Yi, Hyunmin

    2010-01-01

    We demonstrate rapid microfluidic fabrication of hybrid microparticles composed of functionalized viral nanotemplates directly embedded in polymeric hydrogels. Specifically, genetically modified tobacco mosaic virus (TMV) templates were covalently labeled with fluorescent markers or metalized with palladium (Pd) nanoparticles (Pd-TMV), then suspended in a poly(ethylene glycol)-based solution. Upon formation in a flow-focusing device, droplets were photopolymerized with UV light to form microparticles. Fluorescence and confocal microscopy images of microparticles containing fluorescently labeled TMV show uniform distribution of TMV nanotemplates throughout the microparticles. Catalytic activity, via the dichromate reduction reaction, is also demonstrated with microparticles containing Pd-TMV complexes. Additionally, Janus microparticles were fabricated containing viruses embedded in one side and magnetic nanoparticles in the other, that enabled simple separation from bulk solution. These results represent a facile route to directly harness the advantages of viral nanotemplates into a readily usable and stable 3D assembled format. PMID:20695589

  19. Controlling Affinity Binding with Peptide-Functionalized Poly(ethylene glycol) Hydrogels**

    PubMed Central

    Lin, Chien-Chi; Anseth, Kristi S.

    2009-01-01

    Poly(ethylene glycol) (PEG) hydrogels functionalized with peptide moieties have been widely used in regenerative medicine applications. While many studies have suggested the importance of affinity binding within PEG hydrogels, the relationships between the structures of the peptide motifs and their binding to protein therapeutics remain largely unexplored, especially in the recently developed thiol-acrylate photopolymerization systems. Herein, we employ Förster resonance energy transfer (FRET) and thiol-acrylate photopolymerizations to investigate how the architectures of affinity peptides in crosslinked hydrogels affect their binding to diffusible proteins. The binding between diffusible streptavidin and biotinylated peptide immobilized to PEG hydrogel network was used as a model system to reveal the interplay between affinity binding and peptide sequences/architectures. In addition, we design peptides with different structures to enhance affinity binding within PEG hydrogels and to provide tunable affinity-based controlled delivery of basic fibroblast growth factor (bFGF). This study demonstrates the importance of affinity binding in controlling the availability of hydrogel-encapsulated proteins and provides strategies for enhancing affinity binding of protein therapeutics to bound peptide moieties in thiol-acrylate photopolymerized PEG hydrogels. The results presented herein should find useful on the design and fabrication of hydrogels to retain and sustained release of growth factors for promoting tissue regeneration. PMID:20148198

  20. Smart hydrogel-functionalized textile system with moisture management property for skin application

    NASA Astrophysics Data System (ADS)

    Wang, Xiaowen; Hu, Huawen; Yang, Zongyue; He, Liang; Kong, Yeeyee; Fei, Bin; Xin, John H.

    2014-12-01

    In this study, a functional textile-based material for topical skin application was fabricated by coating a thermoresponsive hydrogel onto one side of absorbent nonwoven fabric. The thermoresponsive hydrogel was synthesized easily through coupling of poly (ethylene glycol) (PEG) and poly (ɛ-caprolactone) (PCL) with hexamethylene diisocyanate (HMDI) as a chemical linker. The chemical structure of the as-prepared triblock copolymer hydrogel was unraveled by FTIR and 1H NMR analysis. The hydrogel showed a temperature-triggered sol-gel transition behavior and high potential for use as drug controlled release. When the surrounding temperature was close to the skin temperature of around 34 °C, it became a moisture management system where the liquids including sweat, blood, and other body fluids can be transported unidirectionally from one fabric side with the hydrophobic hydrogel coating to the untreated opposite side. This thereby showed that the thermoresponsive hydrogel-coated textile materials had a function to keep topical skin area clean, breathable, and comfortable, thus suggesting a great potential and significance for long-term skin treatment application. The structure and surface morphology of the thermoresponsive hydrogel, in vitro drug release behavior, and the mechanism of unidirectional water transport were investigated in detail. Our success in preparation of the functional textile composites will pave the way for development of various polymer- or textile-based functional materials that are applicable in the real world.

  1. Controlled degradation of hydrogels using multi-functional cross-linking molecules.

    PubMed

    Lee, Kuen Yong; Bouhadir, Kamal H; Mooney, David J

    2004-06-01

    Hydrogels, chemically cross-linked or physically entangled, have found a number of applications as novel delivery vehicles of drugs and cells. However, the narrow ranges of degradation rates and mechanical strength currently available from many hydrogels limits their applications. We have hypothesized that utilization of multi-functional cross-linking molecules to form hydrogels could provide a wider range and tighter control over the degradation rates and mechanical stiffness of gels than bi-functional cross-linking molecules. To address the possibility, we isolated alpha-L-guluronate residues of sodium alginate, and oxidized them to prepare poly(aldehyde guluronate) (PAG). Hydrogels were formed with either poly(acrylamide-co-hydrazide) (PAH) as a multi-functional cross-linking molecule or adipic acid dihydrazide (AAD) as a bi-functional cross-linking molecule. The initial properties and degradation behavior of both PAG gel types were monitored. PAG/PAH hydrogels showed higher mechanical stiffness before degradation and degraded more slowly than PAG/AAD gels, at the same concentration of cross-linking functional groups. The enhanced mechanical stiffness and prolonged degradation behavior could be attributed to the multiple attachment points of PAH in the gel at the same concentration of functional groups. This approach to regulating gel properties with multifunctional cross-linking molecules could be broadly used in hydrogels. PMID:14751730

  2. Wheat Germ Agglutinin Functionalized Complexation Hydrogels for Oral Insulin Delivery

    PubMed Central

    Wood, Kristy M.; Stone, Gregory M.; Peppas, Nicholas A.

    2011-01-01

    Insulin was loaded into hydrogel microparticles after two hours with loading efficiencies greater than 70% for both poly(methacrylic acid-grafted-ethylene glycol) (P(MAA-g-EG)) and poly(methacrylic acid-grafted-ethylene glycol) functionalized with wheat germ agglutinin (P(MAA-g-EG) WGA). The pH-responsive release results demonstrated that the pH shift from the stomach to the small intestine can be used as a physiologic trigger to release insulin from P(MAA-g-EG) and P(MAA-g-EG) WGA microparticles, thus limiting release of insulin into the acidic environment of the stomach. Microplates were successfully treated with PGM to create a surface that allowed for specific binding between mucins and lectins. The 1% PGM treatment followed by a 2 h BSA blocking step gave the most consistent results when incubated with F-WGA. In addition, the PGM-treated microplates were shown to create specific interactions between F-WGA and the PGM by use of a competitive carbohydrate. The 1% PGM treated microplates were also used to show that adhesion was improved in the P(MAA-g-EG) WGA microparticles over the P(MAA-g-EG) microparticles. The interaction between the PGM-treated microplate and P(MAA-g-EG) WGA was again shown to be specific by adding a competitive carbohydrate, whilethe interaction between P(MAA-g-EG) and the PGM-treated microplate was nonspecific. Cellular monolayers were used as another method for demonstrating that the functionalized microparticles increase adhesion over the nonfunctionalized microparticles. This work has focused on improving the mucoadhesive nature of P(MAA-g-EG) by functionalizing these hydrogel carriers with wheat germ agglutinin (WGA) to create a specific mucosal interaction and then evaluating the potential of these carriers as oral insulin delivery systems by in vitro methods. From these studies, it is concluded that the addition of the WGA on the microparticles produces a specific adhesion to carbohydrate-containing surfaces and that P(MAA-g-EG) WGA

  3. Effect of the hydration on the biomechanical properties in a fibrin-agarose tissue-like model.

    PubMed

    Scionti, Giuseppe; Moral, Monica; Toledano, Manuel; Osorio, Raquel; Durán, Juan D G; Alaminos, Miguel; Campos, Antonio; López-López, Modesto T

    2014-08-01

    The effect of hydration on the biomechanical properties of fibrin and fibrin-agarose (FA) tissue-like hydrogels is reported. Native hydrogels with approximately 99.5% of water content and hydrogels with water content reduced until 90% and 80% by means of plastic compression (nanostructuration) were generated. The biomechanical properties of the hydrogels were investigated by tensile, compressive, and shear tests. Experimental results indicate that nanostructuration enhances the biomechanical properties of the hydrogels. This improvement is due to the partial draining of the water that fills the porous network of fibers that the plastic compression generates, which produces a denser material, as confirmed by scanning electron microscopy. Results also indicate that the characteristic compressive and shear parameters increase with agarose concentration, very likely due to the high water holding capacity of agarose, which reduces the compressibility and gives consistency to the hydrogels. However, results of tensile tests indicate a weakening of the hydrogels as agarose concentration increases, which evidences the anisotropic nature of these biomaterials. Interestingly, we found that by adjusting the water and agarose contents it is possible to tune the biomechanical properties of FA hydrogels for a broad range, within which the properties of many native tissues fall. PMID:23963645

  4. Biomechanical study of the edge outgrowth phenomenon of encapsulated chondrocytic isogenous groups in the surface layer of hydrogel scaffolds for cartilage tissue engineering.

    PubMed

    Ng, Soon Seng; Su, Kai; Li, Chuan; Chan-Park, Mary B; Wang, Dong-An; Chan, Vincent

    2012-01-01

    In cartilage tissue engineering, hydrogel is widely used as the scaffold for hosting and culturing chondrocyte suspension during neo-tissue formation. In order to develop cultured chondrocytes into a functional cartilage equivalent, the hydrogel must provide an ideal microenvironment for the rapidly proliferating chondrocytes. At the same time, the essential functions of chondrocytes, such as the secretion of type II collagen and glycosaminoglycans, must be maintained. In these studies, we quantitatively characterize the mechanobiology underlying a newly discovered "edge flourish" phenomenon of cultured chondrocytes within a three-dimensional agarose hydrogel, which may ultimately nurture scaffold-free cartilaginous tissue regeneration. First, real-time microscopy was used to track the spatiotemporal distributions of chondrocytes at different focal planes. The chondrocytes were observed to exhibit abundant neo-tissue outgrowth and significant cartilaginous phenotype at the edge of the hydrogel compared to those inside the hydrogel bulk. Secondly, the hydrogel surface stresses induced by the encapsulated chondrocytes were characterized quantitatively in real time using the finite-element method. Finally, the real-time three-dimensional matrix deformations of agarose hydrogel under the influence of chondrocytes were measured using a multiple-particle tracking assay. Our results indicate that the mechanism of the "edge flourish" phenomenon is induced by the oriented outgrowth of chondrocytic isogenous groups located at the edge of hydrogel. These isogenous groups exhibit directed outgrowth towards the surface of the hydrogel and eventually generate substantial surface tension on the interface of hydrogel and medium. Ultimately, the encapsulated chondrocytes closest to the hydrogel/medium interface will spontaneously sprout out of the hydrogel and form a layer of rich proliferative and chondrocytic extracellular matrix secreting chondrocytes at the surface of the

  5. Aptamer-functionalized hydrogel as effective anti-cancer drugs delivery agents.

    PubMed

    Wang, Zonghua; Xia, Jianfei; Cai, Feng; Zhang, Feifei; Yang, Min; Bi, Sai; Gui, Rijun; Li, Yanhui; Xia, Yanzhi

    2015-10-01

    An aptamer-functionalized hydrogel has been developed, which can be regulated by the AS1411 aptamer with the sol-gel conversion. Also the hydrogel can be further utilized for the controlled encapsulation and release of the cancer drugs. Specially, the AS1411 initiates the hybridization of acrydite-modified oligonucleotides to form the hydrogels and the presence of the target protein nucleolin leads the gel to dissolve as a result of reducing the cross-linking density by competitive target-aptamer binding. Based on the rheology of hydrogels, it is possible to utilize this material for storing and releasing molecules. In this research, the cancer drug doxorubicin is encapsulated inside the gel during the formation of the hydrogel and then released in the presence of nucleolin. Further experiments are carried out to prove the specific recognition of target matter. In vitro researches confirm that the aptamer-functionalized hydrogels can be used as drug carriers in targeted therapy and other biotechnological applications. PMID:26142627

  6. 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

  7. Chemotaxis: Under Agarose Assay.

    PubMed

    Brazill, Derrick

    2016-01-01

    The unicellular eukaryote Dictyostelium discoideum represents a superb model for examining chemotaxis. Under vegetative conditions, the amoebae are chemotactically responsive to pterins, such as folate. Under starved conditions, they lose their sensitivity to pterins, and become chemotactically responsive to cAMP. As an NIH model system, Dictyostelium offers a variety of advantages in studying chemotaxis, including its conservation of mammalian signaling pathways, its ease of growth, and its genetic tractability. In this chapter, we describe the use of the under agarose chemotaxis assay to identify proteins involved in controlling motility and directional sensing in Dictyostelium discoideum. Given the similarities between Dictyostelium and mammalian cells, this allows us to dissect the conserved pathways involved in eukaryotic chemotaxis. PMID:26498795

  8. E-beam crosslinked, biocompatible functional hydrogels incorporating polyaniline nanoparticles

    NASA Astrophysics Data System (ADS)

    Dispenza, C.; Sabatino, M.-A.; Niconov, A.; Chmielewska, D.; Spadaro, G.

    2012-09-01

    PANI aqueous nanocolloids in their acid-doped, inherently conductive form were synthesised by means of suitable water soluble polymers used as stabilisers. In particular, poly(vinyl alcohol) (PVA) or chitosan (CT) was used to stabilise PANI nanoparticles, thus preventing PANI precipitation during synthesis and upon storage. Subsequently, e-beam irradiation of the PANI dispersions has been performed with a 12 MeV Linac accelerator. PVA-PANI nanocolloid has been transformed into a PVA-PANI hydrogel nanocomposite by radiation induced crosslinking of PVA. CT-PANI nanoparticles dispersion, in turn, was added to PVA to obtain wall-to-wall gels, as chitosan mainly undergoes chain scission under the chosen irradiation conditions. While the obtainment of uniform PANI particle size distribution was preliminarily ascertained with laser light scattering and TEM microscopy, the typical porous structure of PVA-based freeze dried hydrogels was observed with SEM microscopy for the hydrogel nanocomposites. UV-visible absorption spectroscopy demonstrates that the characteristic, pH-dependent and reversible optical absorption properties of PANI are conferred to the otherwise optically transparent PVA hydrogels. Selected formulations have been also subjected to MTT assays to prove the absence of cytotoxicity.

  9. Resilin-Like Polypeptide Hydrogels Engineered for Versatile Biological Functions.

    PubMed

    Li, Linqing; Tong, Zhixiang; Jia, Xinqiao; Kiick, Kristi L

    2013-01-01

    Natural resilin, the rubber-like protein that exists in specialized compartments of most arthropods, possesses excellent mechanical properties such as low stiffness, high resilience and effective energy storage. Recombinantly-engineered resilin-like polypeptides (RLPs) that possess the favorable attributes of native resilin would be attractive candidates for the modular design of biomaterials for engineering mechanically active tissues. Based on our previous success in creating a novel RLP-based hydrogel and demonstrating useful mechanical and cell-adhesive properties, we have produced a suite of new RLP-based constructs, each equipped with 12 repeats of the putative resilin consensus sequence and a single, distinct biologically active domain. This approach allows independent control over the concentrations of cell-binding, MMP-sensitive, and polysaccharide-sequestration domains in hydrogels comprising mixtures of the various RLPs. The high purity, molecular weight and correct compositions of each new polypeptide have been confirmed via high performance liquid chromatography (HPLC), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), and amino acid analysis. These RLP-based polypeptides exhibit largely random-coil conformation, both in solution and in the cross-linked hydrogels, as indicated by circular dichroic and infrared spectroscopic analyses. Hydrogels of various compositions, with a range of elastic moduli (1kPa to 25kPa) can be produced from these polypeptides, and the activity of the cell-binding and matrix metalloproteinase (MMP) sensitive domains was confirmed. Tris(hydroxymethyl phosphine) cross-linked RLP hydrogels were able to maintain their mechanical integrity as well as the viability of encapsulated primary human mesenchymal stem cells (MSCs). These results validate the promising properties of these RLP-based elastomeric biomaterials. PMID:23505396

  10. Functional surface engineering of quantum dot hydrogels for selective fluorescence imaging of extracellular lactate release.

    PubMed

    Zhang, Xiaomeng; Ding, Shushu; Cao, Sumei; Zhu, Anwei; Shi, Guoyue

    2016-06-15

    Selective and sensitive detection of extracellular lactate is of fundamental significance for studying the metabolic alterations in tumor progression. Here we report the rational design and synthesis of a quantum-dot-hydrogel-based fluorescent probe for biosensing and bioimaging the extracellular lactate. By surface engineering the destabilized quantum dot sol with Nile Blue, the destabilized Nile-Blue-functionalized quantum dot sol cannot only self-assemble forming quantum dot hydrogel but also monitor lactate in the presence of nicotinamide adenine dinucleotide cofactor and lactate dehydrogenase through fluorescence resonance energy transfer. Notably, the surface engineered quantum dot hydrogel show high selectivity toward lactate over common metal ions, amino acids and other small molecules that widely coexist in biological system. Moreover, the destabilized Nile-Blue-functionalized quantum dots can encapsulate isolated cancer cells when self-assembled into a hydrogel and thus specifically detect and image the extracellular lactate metabolism. By virtue of these properties, the functionalized quantum dot hydrogel was further successfully applied to monitor the effect of metabolic agents. PMID:26852200

  11. Integrin-specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical-size bone defects.

    PubMed

    García, José R; Clark, Amy Y; García, Andrés J

    2016-04-01

    Vascularization of bone defects is considered a crucial component to the successful regeneration of large bone defects. Although vascular endothelial growth factor (VEGF) has been delivered to critical-size bone defect models to augment blood vessel infiltration into the defect area, its potential to increase bone repair remains ambiguous. In this study, we investigated whether integrin-specific biomaterials modulate the effects of VEGF on bone regeneration. We engineered protease-degradable, VEGF-loaded poly(ethylene glycol) (PEG) hydrogels functionalized with either a triple-helical, α2 β1 integrin-specific peptide GGYGGGP(GPP)5 GFOGER(GPP)5 GPC (GFOGER) or an αv β3 integrin-targeting peptide GRGDSPC (RGD). Covalent incorporation of VEGF into the PEG hydrogel allowed for protease degradation-dependent release of the protein while maintaining VEGF bioactivity. When applied to critical-size segmental defects in the murine radius, GFOGER-functionalized VEGF-free hydrogels exhibited significantly increased vascular volume and density and resulted in a larger number of thicker blood vessels compared to RGD-functionalized VEGF-free hydrogels. VEGF-loaded RGD hydrogels increased vascularization compared to VEGF-free RGD hydrogels, but the levels of vascularization for these VEGF-containing RGD hydrogels were similar to those of VEGF-free GFOGER hydrogels. VEGF transiently increased bone regeneration in RGD hydrogels but had no effect at later time points. In GFOGER hydrogels, VEGF did not show an effect on bone regeneration. However, VEGF-free GFOGER hydrogels resulted in increased bone regeneration compared to VEGF-free RGD hydrogels. These findings demonstrate the importance of integrin-specificity in engineering constructs for vascularization and associated bone regeneration. PMID:26662727

  12. Biohybrid Carbon Nanotube/Agarose Fibers for Neural Tissue Engineering

    PubMed Central

    Lewitus, Dan Y.; Landers, John; Branch, Jonathan; Smith, Karen L.; Callegari, Gerardo

    2011-01-01

    We report a novel approach for producing carbon nanotube fibers (CNF) composed with the polysaccharide agarose. Current attempts to make CNF’s require the use of a polymer or precipitating agent in the coagulating bath that may have negative effects in biomedical applications. We show that by taking advantage of the gelation properties of agarose one can substitute the bath with distilled water or ethanol and hence reduce the complexity associated with alternating the bath components or the use of organic solvents. We also demonstrate that these CNF can be chemically functionalized to express biological moieties through available free hydroxyl groups in agarose. We corroborate that agarose CNF are not only conductive and nontoxic, but their functionalization can facilitate cell attachment and response both in vitro and in vivo. Our findings suggest that agarose/CNT hybrid materials are excellent candidates for applications involving neural tissue engineering and biointerfacing with the nervous system. PMID:21887125

  13. Characterization of a Functional Hydrogel Layer on a Silicon-Based Grating Waveguide for a Biochemical Sensor

    PubMed Central

    Hong, Yoo-Seung; Kim, Jongseong; Sung, Hyuk-Kee

    2016-01-01

    We numerically demonstrated the characteristics of a functional hydrogel layer on a silicon-based grating waveguide for a simple, cost-effective refractive index (RI) biochemical sensor. The RI of the functional hydrogel layer changes when a specific biochemical interaction occurs between the hydrogel-linked receptors and injected ligand molecules. The transmission spectral profile of the grating waveguide shifts depends on the amount of RI change caused by the functional layer. Our characterization includes the effective RI change caused by the thickness, functional volume ratio, and functional strength of the hydrogel layer. The results confirm the feasibility of, and set design rules for, hydrogel-assisted silicon-based grating waveguides. PMID:27322286

  14. Characterization of a Functional Hydrogel Layer on a Silicon-Based Grating Waveguide for a Biochemical Sensor.

    PubMed

    Hong, Yoo-Seung; Kim, Jongseong; Sung, Hyuk-Kee

    2016-01-01

    We numerically demonstrated the characteristics of a functional hydrogel layer on a silicon-based grating waveguide for a simple, cost-effective refractive index (RI) biochemical sensor. The RI of the functional hydrogel layer changes when a specific biochemical interaction occurs between the hydrogel-linked receptors and injected ligand molecules. The transmission spectral profile of the grating waveguide shifts depends on the amount of RI change caused by the functional layer. Our characterization includes the effective RI change caused by the thickness, functional volume ratio, and functional strength of the hydrogel layer. The results confirm the feasibility of, and set design rules for, hydrogel-assisted silicon-based grating waveguides. PMID:27322286

  15. Tunable functional hydrogels formed from a versatile water-soluble chitosan.

    PubMed

    Xiao, Congming; You, Rongrui; Fan, Ying; Zhang, Yue

    2016-04-01

    A versatile water-soluble chitosan (WSC) was applied to construct two kinds of controllable functional hydrogels. Magnetic beads were prepared by physical cross-linking WSC with sodium alginate, soaking particles with ferrous chloride and being subjected to self-oxidation. Magnetic character of the beads was tunable by simply changing the initial concentration of ferrous ions. The beads could bind compounds that contained different charges. Their adsorption capacities for coomassie brilliant blue, rhodamine and hemoglobin were 1, 0.5 and 2.3mg/g respectively. Another kind of functional hydrogel was prepared through radical cross-linking reaction between WSC and a macromonomer (PVAM) derived from well-defined polyvinyl alcohol. The dynamic mechanical thermal analysis and thermogravimetric analysis results revealed that the mechanical strength and thermal stability of this hydrogel depended on the structure of PVAM. The capability to bind heavy metal ions of the hydrogel also relied on the structure of PVAM. The adsorption capacities of the hydrogels for Cu(2+) and Pb(2+) could reach 20.3 and 60.1mg/g respectively. PMID:26772916

  16. Bioengineering mini functional thymic units with EAK16-II/EAKIIH6 self-assembling hydrogel.

    PubMed

    Tajima, Asako; Liu, Wen; Pradhan, Isha; Bertera, Suzanne; Bagia, Christina; Trucco, Massimo; Meng, Wilson S; Fan, Yong

    2015-09-01

    Herein, we highlight the technical feasibility of generating a functional mini thymus with a novel hydrogel system, based on a peptide-based self-assembly platform that can induce the formation of 3-D thymic epithelial cell (TEC) clusters. Amphiphilic peptide EAK16-II co-assembled with its histidinylated analogue EAKIIH6 into beta-sheet fibrils. When adaptor complexes (recombinant protein A/G molecules loaded with both anti-His and anti-EpCAM IgGs) were added to the mix, TECs were tethered to the hydrogel and formed 3-D mini clusters. TECs bound to the hydrogel composites retained their molecular properties; and when transplanted into athymic nude mice, they supported the development of functional T-cells. These mini thymic units of TECs can be useful in clinical applications to reconstitute T-cell adaptive immunity. PMID:25805654

  17. Peptide Functionalized Oxime Hydrogels with Tunable Mechanical Properties and Gelation Behavior

    PubMed Central

    Lin, Fei; Yu, Jiayi; Tang, Wen; Zheng, Jukuan; Defante, Adrian; Guo, Kai; Wesdemiotis, Chrys; Becker, Matthew L.

    2013-01-01

    We demonstrate the formation of polyethylene glycol (PEG) based hydrogels via oxime ligation and the photo-initiated thiol-ene 3D patterning of peptides within the hydrogel matrix post-gelation. The gelation process and final mechanical strength of hydrogels can be tuned using pH and the catalyst concentration. The time scale to reach the gel point and complete gelation can be shortened from hours to seconds using both pH and aniline catalyst, which facilitates the tuning of the storage modulus from 0.3 kPa to over 15 kPa. Azide and alkene functionalized hydrogels were also synthesized and we have shown the post gelation “click” type Husigen 1,3 cycloaddition and thiolene-based radical reactions for spatially defined peptide incorporation. These materials are the initial demonstration for translationally relevant hydrogel materials that possess tunable mechanical regimes attractive to soft tissue engineering and possess atom neutral chemistries attractive for post gelation patterning in the presence or absence of cells. PMID:24050500

  18. Controlled release of functional proteins through designer self-assembling peptide nanofiber hydrogel scaffold

    PubMed Central

    Koutsopoulos, Sotirios; Unsworth, Larry D.; Nagai, Yusuke; Zhang, Shuguang

    2009-01-01

    The release kinetics for a variety of proteins of a wide range of molecular mass, hydrodynamic radii, and isoelectric points through a nanofiber hydrogel scaffold consisting of designer self-assembling peptides were studied by using single-molecule fluorescence correlation spectroscopy (FCS). In contrast to classical diffusion experiments, the single-molecule approach allowed for the direct determination of diffusion coefficients for lysozyme, trypsin inhibitor, BSA, and IgG both inside the hydrogel and after being released into the solution. The results of the FCS analyses and the calculated pristine in-gel diffusion coefficients were compared with the values obtained from the Stokes–Einstein equation, Fickian diffusion models, and the literature. The release kinetics suggested that protein diffusion through nanofiber hydrogels depended primarily on the size of the protein. Protein diffusivities decreased, with increasing hydrogel nanofiber density providing a means of controlling the release kinetics. Secondary and tertiary structure analyses and biological assays of the released proteins showed that encapsulation and release did not affect the protein conformation and functionality. Our results show that this biocompatible and injectable designer self-assembling peptide hydrogel system may be useful as a carrier for therapeutic proteins for sustained release applications. PMID:19273853

  19. Scaffold porosity and oxygenation of printed hydrogel constructs affect functionality of embedded osteogenic progenitors.

    PubMed

    Fedorovich, Natalja E; Kuipers, Elske; Gawlitta, Debby; Dhert, Wouter J A; Alblas, Jacqueline

    2011-10-01

    Insufficient supply of oxygen and nutrients throughout the graft is considered one of the principal limitations in development of large, tissue-engineered bone grafts. Organ or tissue printing by means of three-dimensional (3D) fiber deposition is a novel modality in regenerative medicine that combines pore formation and defined cell placement, and is used here for development of cell-laden hydrogel structures with reproducible internal architecture to sustain oxygen supply and to support adequate tissue development. In this study we tested the effect of porosity on multipotent stromal cells (MSCs) embedded in hydrogel constructs printed with a 3D fiber deposition (3DF) machine. For this, porous and solid alginate hydrogel scaffolds, with MSCs homogeneously dispersed throughout the construct, were printed and analyzed in vitro for the presence of hypoxia markers, metabolism, survival, and osteogenic differentiation. We demonstrated that porosity promotes oxygenation of MSCs in printed hydrogel scaffolds and supported the viability and osteogenic differentiation of embedded cells. Porous and solid printed constructs were subsequently implanted subcutaneously in immunodeficient mice to analyze tissue formation in relation to hypoxia responses of embedded cells. Implantation of printed grafts resulted in ingrowth of vascularized tissue and significantly enhanced oxygenation of embedded MSCs. In conclusion, the introduction of pores significantly enhances the conductive properties of printed hydrogel constructs and contributes to the functionality of embedded osteogenic progenitors. PMID:21599540

  20. Tannic acid functionalized graphene hydrogel for entrapping gold nanoparticles with high catalytic performance toward dye reduction.

    PubMed

    Luo, Jing; Zhang, Nan; Lai, Jianping; Liu, Ren; Liu, Xiaoya

    2015-12-30

    In this work, a simple, cost-effective, and environmental-friendly strategy was developed to synthesize gold nanoparticles (Au NPs) decorated graphene hydrogel with the use of tannic acid. This facile route involved the reduction of graphene oxide (GO) in the presence of tannic acid to form tannic acid functionalized graphene hydrogel, followed by loading and in situ reduction of AuCl4(-) ions in the graphene hydrogel network benefiting from the abundant phenol groups of tannic acid. Tannic acid (TA), a typical plant polyphenol widely present in woods, not only reduced GO and induced the self-assembly of reduced graphene oxide into graphene hydrogel, but also served as the reducing agent and stabilizer for the synthesis and immobilization of Au NPs, avoiding extra chemical reagent and any stabilizer. The obtained Au NPs decorated graphene hydrogel (Au@TA-GH) was fully characterized and exhibited much higher catalytic activities than the unsupported and other polymer-supported Au NPs toward the reduction of methylene blue (MB). In addition, the high catalytic activity of Au@TA-GH could withhold in different pH solution conditions. Another distinct advantage of Au@TA-GH as catalysts is that it can be easily recovered and reused for five cycles. PMID:26275351

  1. Injectable biodegradable hydrogels for embryonic stem cell transplantation: improved cardiac remodelling and function of myocardial infarction

    PubMed Central

    Wang, Haibin; Liu, Zhiqiang; Li, Dexue; Guo, Xuan; Kasper, F Kurtis; Duan, Cuimi; Zhou, Jin; Mikos, Antonios G; Wang, Changyong

    2012-01-01

    Abstract In this study, an injectable, biodegradable hydrogel composite of oligo[poly(ethylene glycol) fumarate] (OPF) was investigated as a carrier of mouse embryonic stem cells (mESCs) for the treatment of myocardial infarction (MI). The OPF hydrogels were used to encapsulate mESCs. The cell differentiation in vitro over 14 days was determined via immunohistochemical examination. Then, mESCs encapsulated in OPF hydrogels were injected into the LV wall of a rat MI model. Detailed histological analysis and echocardiography were used to determine the structural and functional consequences after 4 weeks of transplantation. With ascorbic acid induction, mESCs could differentiate into cardiomyocytes and other cell types in all three lineages in the OPF hydrogel. After transplantation, both the 24-hr cell retention and 4-week graft size were significantly greater in the OPF + ESC group than that of the PBS + ESC group (P < 0.01). Four weeks after transplantation, OPF hydrogel alone significantly reduced the infarct size and collagen deposition and improved the cardiac function. The heart function and revascularization improved significantly, while the infarct size and fibrotic area decreased significantly in the OPF + ESC group compared with that of the PBS + ESC, OPF and PBS groups (P < 0.01). All treatments had significantly reduced MMP2 and MMP9 protein levels compared to the PBS control group, and the OPF + ESC group decreased most by Western blotting. Transplanted mESCs expressed cardiovascular markers. This study suggests the potential of a method for heart regeneration involving OPF hydrogels for stem cell encapsulation and transplantation. PMID:21838774

  2. Studying functional properties of hydrogel and silicone-hydrogel contact lenses with PALS, MIR and Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Filipecki, J.; Sitarz, M.; Kocela, A.; Kotynia, K.; Jelen, P.; Filipecka, K.; Gaweda, M.

    2014-10-01

    Determination of free volume holes of the hydrogel and silicone-hydrogel polymer contact lenses were investigated. Two types of polymer contact lenses were used as materials: the first is a hydrogel contact lenses Proclear family (Omafilcon A), while the second is a silicone-hydrogel contact lens of the family Biofinity (Comfilcon A). Positron annihilation lifetime spectroscopy PALS was used to characterize geometrical sizes and fraction of the free volume holes in the investigated samples. There is a clear difference in the free volume sizes and their fractions between silicone-hydrogel and polymer hydrogel contact lenses which in turn are connected with oxygen permeability in these lenses. Apart from that, spectroscopic (middle infrared) MIR and Raman examinations were carried out in order to demonstrate the differences of the water content in the test contact lenses.

  3. Arginine-glycine-aspartic acid functional branched semi-interpenetrating hydrogels.

    PubMed

    Plenderleith, Richard A; Pateman, Christopher J; Rodenburg, Cornelia; Haycock, John W; Claeyssens, Frederik; Sammon, Chris; Rimmer, Stephen

    2015-10-14

    For the first time a series of functional hydrogels based on semi-interpenetrating networks with both branched and crosslinked polymer components have been prepared and we show the successful use of these materials as substrates for cell culture. The materials consist of highly branched poly(N-isopropyl acrylamide)s with peptide functionalised end groups in a continuous phase of crosslinked poly(vinyl pyrrolidone). Functionalisation of the end groups of the branched polymer component with the GRGDS peptide produces a hydrogel that supports cell adhesion and proliferation. The materials provide a new synthetic functional biomaterial that has many of the features of extracellular matrix, and as such can be used to support tissue regeneration and cell culture. This class of high water content hydrogel material has important advantages over other functional hydrogels in its synthesis and does not require post-processing modifications nor are functional-monomers, which change the polymerisation process, required. Thus, the systems are amenable to large scale and bespoke manufacturing using conventional moulding or additive manufacturing techniques. Processing using additive manufacturing is exemplified by producing tubes using microstereolithography. PMID:26280624

  4. Injectable thermosensitive hydrogel composite with surface-functionalized calcium phosphate as raw materials

    PubMed Central

    Fan, RangRang; Deng, XiaoHui; Zhou, LiangXue; Gao, Xiang; Fan, Min; Wang, YueLong; Guo, Gang

    2014-01-01

    In this study, L-lactide was used to modify the tricalcium phosphate (β-TCP) and tetracalcium phosphate (TTCP) surface which can form functionalized poly(l-lactic acid) (PLLA)-grafted β-TCP (g-β-TCP) and PLLA-grafted TTCP (g-TTCP) particles. The g-β-TCP and g-TTCP obtained were incorporated into a PEG-PCL-PEG (PECE) matrix to prepare injectable thermosensitive hydrogel composites. The morphology of the hydrogel composites showed that the g-β-TCP and g-TTCP particles dispersed homogeneously into the polymer matrix, and each hydrogel composite had a three-dimensional network structure. Rheologic analysis showed that the composite had good thermosensitivity. Changes in calcium concentration and pH in simulated body fluid solutions confirmed the feasibility of surface-functionalized calcium phosphate for controlled release of calcium. All the results indicate that g-β-TCP/PECE and g-TTCP/PECE hydrogels might be a promising protocol for tissue engineering. PMID:24489468

  5. Hydrogel Bioprinted Microchannel Networks for Vascularization of Tissue Engineering Constructs

    PubMed Central

    Bertassoni, Luiz E.; Cecconi, Martina; Manoharan, Vijayan; Nikkhah, Mehdi; Hjortnaes, Jesper; Cristino, Ana Luiza; Barabaschi, Giada; Demarchi, Danilo; Dokmeci, Mehmet R.; Yang, Yunzhi; Khademhosseini, Ali

    2014-01-01

    Vascularization remains a critical challenge in tissue engineering. The development of vascular networks within densely populated and metabolically functional tissues facilitate transport of nutrients and removal of waste products, thus preserving cellular viability over a long period of time. Despite tremendous progress in fabricating complex tissue constructs in the past few years, approaches for controlled vascularization within hydrogel based engineered tissue constructs have remained limited. Here, we report a three dimensional (3D) micromolding technique utilizing bioprinted agarose template fibers to fabricate microchannel networks with various architectural features within photo cross linkable hydrogel constructs. Using the proposed approach, we were able to successfully embed functional and perfusable microchannels inside methacrylated gelatin (GelMA), star poly (ethylene glycol-co-lactide) acrylate (SPELA), poly (ethylene glycol) dimethacrylate (PEGDMA) and poly (ethylene glycol) diacrylate (PEGDA) hydrogels at different concentrations. In particular, GelMA hydrogels were used as a model to demonstrate the functionality of the fabricated vascular networks in improving mass transport, cellular viability and differentiation within the cell-laden tissue constructs. In addition, successful formation of endothelial monolayers within the fabricated channels was confirmed. Overall, our proposed strategy represents an effective technique for vascularization of hydrogel constructs with useful applications in tissue engineering and organs on a chip. PMID:24860845

  6. Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs.

    PubMed

    Bertassoni, Luiz E; Cecconi, Martina; Manoharan, Vijayan; Nikkhah, Mehdi; Hjortnaes, Jesper; Cristino, Ana Luiza; Barabaschi, Giada; Demarchi, Danilo; Dokmeci, Mehmet R; Yang, Yunzhi; Khademhosseini, Ali

    2014-07-01

    Vascularization remains a critical challenge in tissue engineering. The development of vascular networks within densely populated and metabolically functional tissues facilitate transport of nutrients and removal of waste products, thus preserving cellular viability over a long period of time. Despite tremendous progress in fabricating complex tissue constructs in the past few years, approaches for controlled vascularization within hydrogel based engineered tissue constructs have remained limited. Here, we report a three dimensional (3D) micromolding technique utilizing bioprinted agarose template fibers to fabricate microchannel networks with various architectural features within photocrosslinkable hydrogel constructs. Using the proposed approach, we were able to successfully embed functional and perfusable microchannels inside methacrylated gelatin (GelMA), star poly(ethylene glycol-co-lactide) acrylate (SPELA), poly(ethylene glycol) dimethacrylate (PEGDMA) and poly(ethylene glycol) diacrylate (PEGDA) hydrogels at different concentrations. In particular, GelMA hydrogels were used as a model to demonstrate the functionality of the fabricated vascular networks in improving mass transport, cellular viability and differentiation within the cell-laden tissue constructs. In addition, successful formation of endothelial monolayers within the fabricated channels was confirmed. Overall, our proposed strategy represents an effective technique for vascularization of hydrogel constructs with useful applications in tissue engineering and organs on a chip. PMID:24860845

  7. Graphene oxide-based hydrogels to make metal nanoparticle-containing reduced graphene oxide-based functional hybrid hydrogels.

    PubMed

    Adhikari, Bimalendu; Biswas, Abhijit; Banerjee, Arindam

    2012-10-24

    In this study, stable supramolecular hydrogels have been obtained from the assembly of graphene oxide (GO) in presence of polyamines including tris(aminoethyl)amine, spermine, and spermidine [biologically active molecule]. One of these hydrogels has been well characterized by various techniques including field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray diffraction (XRD) study, and Raman spectroscopy. TEM and AFM studies of one of these hydrogels have revealed the presence of a network structure of cross-linked nanosheets. This suggests the supramolecular assembly of GO in the presence of polyamines using the acid-base type electrostatic interaction. In presence of a mild reducing agent (vitamin C), one of these GO hydrogels has been transformed into a reduced graphene oxide (RGO)-based hydrogel by a simple in situ reduction of GO sheets within the hydrogel matrix. Moreover, noble metal nanoparticle containing RGO based hybrid hydrogels have been obtained using in situ and simultaneous co-reduction of GO and noble metal precursors within the GO gel matrix. The elegance of this method is in situ, "green chemical" and simultaneous reduction of GO and metal salts within the hydrogel matrix to form RGO-based hybrid gel and concomitant stabilization of metal nanoparticles (MNPs) within the gel system. The nascently formed MNPs are homogeneously and uniformly distributed on the surface of the RGO nanosheets within the hybrid gel. Interestingly, this MNP containing RGO-based hybrid hydrogel matrix acts as a potential catalyst for the reduction of aromatic nitro to amino group. The catalyst (hybrid gel matrix) can be separated easily after the reaction and reused several times. PMID:22970805

  8. Agarose microwell based neuronal micro-circuit arrays on microelectrode arrays for high throughput drug testing.

    PubMed

    Kang, Gyumin; Lee, Ji-Hye; Lee, Chang-Soo; Nam, Yoonkey

    2009-11-21

    For cell-based biosensor applications, dissociated neurons have been cultured on planar microelectrode arrays (MEAs) to measure the network activity with substrate-embedded microelectrodes. There has been a need for a multi-well type platform to reduce the data collection time and increase the statistical power for data analysis. This study presents a novel method to convert a conventional MEA into a multi-well MEA with an array of micrometre-sized neuronal culture ('neuronal micro-circuit array'). An MEA was coated first with cell-adhesive layer (poly-D-lysine) which was subsequently patterned with a cell-repulsive layer (agarose hydrogel) to both pattern the cell adhesive region and isolate neuronal micro-circuits from each other. For a few weeks, primary hippocampal neurons were cultured on the agarose microwell MEA and the development of spontaneous electrical activities were characterized with extracellular action potentials. Using neurotransmission modulators, the simultaneous monitoring of drug responses from neuronal micro-circuit arrays was also demonstrated. The proposed approach will be powerful for neurobiological functional assay studies or neuron-based biosensor fields which require repeated trials to obtain a single data point due to biological variations. PMID:19865730

  9. Multi-Functional Macromers for Hydrogel Design in Biomedical Engineering and Regenerative Medicine

    PubMed Central

    Hacker, Michael C.; Nawaz, Hafiz Awais

    2015-01-01

    Contemporary biomaterials are expected to provide tailored mechanical, biological and structural cues to encapsulated or invading cells in regenerative applications. In addition, the degradative properties of the material also have to be adjustable to the desired application. Oligo- or polymeric building blocks that can be further cross-linked into hydrogel networks, here addressed as macromers, appear as the prime option to assemble gels with the necessary degrees of freedom in the adjustment of the mentioned key parameters. Recent developments in the design of multi-functional macromers with two or more chemically different types of functionalities are summarized and discussed in this review illustrating recent trends in the development of advanced hydrogel building blocks for regenerative applications. PMID:26610468

  10. Mercapto functionalized silica entrapped polyacrylamide hydrogel: Arsenic adsorption behaviour from aqueous solution.

    PubMed

    Kumar, Rajesh; Jain, S K; Verma, S; Malodia, P

    2015-10-15

    In this article, 3-mercaptopropyl functionalized silica entrapped polyacrylamide hydrogel (MPFS-PAA) was prepared and characterized by FT-IR, scanning electron microscopy (SEM) and energy dispersion X-ray spectroscopy (EDS). Synthesized hydrogel was evaluated for removal of arsenic(III) from aqueous solution. Adsorption studies were carried out by batch method as function of contact time, initial concentration of arsenic and pH. As(III) adsorption data fitted well with Langmuir and Freundlich isotherm models. Adsorption capacity of arsenic 92.5 μg/g was obtained at initial concentration of 100 μg/L by Langmuir isotherm. Adsorption kinetics was tested for pseudo-second order reaction at different contact time. The rate constants of pseudo second order reaction were calculated and good correlation coefficient R(2) 99.67 obtained. The results indicates that MPFS-PAA is an effective adsorbent for removal of As(III) from aqueous solution. PMID:26151463

  11. Multi-Functional Macromers for Hydrogel Design in Biomedical Engineering and Regenerative Medicine.

    PubMed

    Hacker, Michael C; Nawaz, Hafiz Awais

    2015-01-01

    Contemporary biomaterials are expected to provide tailored mechanical, biological and structural cues to encapsulated or invading cells in regenerative applications. In addition, the degradative properties of the material also have to be adjustable to the desired application. Oligo- or polymeric building blocks that can be further cross-linked into hydrogel networks, here addressed as macromers, appear as the prime option to assemble gels with the necessary degrees of freedom in the adjustment of the mentioned key parameters. Recent developments in the design of multi-functional macromers with two or more chemically different types of functionalities are summarized and discussed in this review illustrating recent trends in the development of advanced hydrogel building blocks for regenerative applications. PMID:26610468

  12. Heparin-chitosan nanoparticle functionalization of porous poly(ethylene glycol) hydrogels for localized lentivirus delivery of angiogenic factors

    PubMed Central

    Thomas, Aline M.; Gomez, Andrew J.; Palma, Jaime L.; Yap, Woon Teck

    2014-01-01

    Hydrogels have been extensively used for regenerative medicine strategies given their tailorable mechanical and chemical properties. Gene delivery represents a promising strategy by which to enhance the bioactivity of the hydrogels, though the efficiency and localization of gene transfer have been challenging. Here, we functionalized porous poly(ethylene glycol) hydrogels with heparin-chitosan nanoparticles to retain the vectors locally and enhance lentivirus delivery while minimizing changes to hydrogel architecture and mechanical properties. The immobilization of nanoparticles, as compared to homogeneous heparin and/or chitosan, is essential to lentivirus immobilization and retention of activity. Using this gene-delivering platform, we over-expressed the angiogenic factors sonic hedgehog (Shh) and vascular endothelial growth factor (Vegf) to promote blood vessel recruitment to the implant site. Shh enhanced endothelial recruitment and blood vessel formation around the hydrogel compared to both Vegf-delivering and control hydrogels. The nanoparticle-modified porous hydrogels for delivering gene therapy vectors can provide a platform for numerous regenerative medicine applications. PMID:25023395

  13. Administration of cells with thermosensitive hydrogel enhances the functional recovery in ischemic rat heart

    PubMed Central

    Matsushita, Satoshi; Forrester, James S; Li, Chuan; Sato, Mitsuru; Li, Zhengqing; Guo, Xiaolei; Guan, Jianjun; Amano, Atsushi

    2016-01-01

    The lack of cell retention clearly represents a potentially serious limitation for therapeutic efficacy of stem cells. To enhance the efficacy, we developed a novel hydrogel that is thermosensitive and biodegradable and possesses desirable stiffness in a solid form. Immediately after induction of myocardial infarction of male rat, cardiac outgrowth cells embedded in hydrogel (HG) or saline (CO) were injected directly into the peri-infarct area. Left ventricular ejection fraction, cell retention rate, and a spectrum of biochemical markers were measured to evaluate the effect of the treatment. Left ventricular ejection fraction was significantly higher in the cell-injected groups (HG and CO) than in the control group at 1 week after treatment. This functional benefit was continued only in the HG group, accompanied with more retained cells. Furthermore, the expression of insulin-like growth factor-1 was significantly higher in the HG group with less progression of cell apoptosis. PMID:27213036

  14. Stimuli-responsive releasing of gold nanoparticles and liposomes from aptamer-functionalized hydrogels

    NASA Astrophysics Data System (ADS)

    El-Hamed, Firas; Dave, Neeshma; Liu, Juewen

    2011-12-01

    Controlled release of therapeutic agents is important for improving drug efficacy and reducing toxicity. Recently, hydrogels have been used for controlled release applications. While the majority of the previous work focused on releasing the cargo in response to physical stimuli such as temperature, light, electric field, and pH, we aim to trigger cargo release in the presence of small metabolites. In our system a DNA aptamer that can bind to adenosine, AMP, and ATP was used as a linker to attach either DNA-functionalized gold nanoparticles or liposomes to DNA-functionalized hydrogels. In the presence of the metabolite, both the nanoparticle and liposome cargos were released. The effect of salt, temperature, target concentration, and drying has been systematically studied. Interestingly, we found that the gel can be completely dried while retaining the DNA linkages and adenosine induced release was still achieved after rehydration. Our work demonstrates that aptamers can be used to control the release of drugs and other materials attached to hydrogels.

  15. Exploring cell compatibility of a fibronectin-functionalized physically crosslinked poly(vinyl alcohol) hydrogel.

    PubMed

    Millon, Leonardo E; Padavan, Donna T; Hamilton, Amanda M; Boughner, Derek R; Wan, Wankei

    2012-01-01

    Physically crosslinked poly(vinyl alcohol) (PVA) hydrogels prepared using a low-temperature thermally cycled process have tunable mechanical properties that fall within the range of soft tissues, including cardiovascular tissue. An approach to render it hemocompatible is by endothelization, but its hydrophilic nature is not conducive to cell adhesion and spreading. We investigated the functionalization reaction of this class of PVA hydrogel with fibronectin (FN) for adhesion and spreading of primary porcine radial artery cells and vascular endothelial cells. These are cells relevant to small-diameter vascular graft development. FN functionalization was achieved using a multistep reaction, but the activation step involving carbonyl diimidazole normally required for chemically crosslinked PVA was found to be unnecessary. The reaction resulted in an increase in the elastic modulus of the PVA hydrogel but is still well within the range of cardiovascular tissue. Confocal microscopy confirmed the adhesion and spreading of both cell types on the PVA-FN surfaces, whereas cells failed to adhere to the PVA control. This is a first step toward an alternative for the realization of a synthetic replacement small-diameter vascular graft. PMID:21998037

  16. Functional fabrication of recombinant human collagen-phosphorylcholine hydrogels for regenerative medicine applications.

    PubMed

    Mirazul Islam, M; Cėpla, Vytautas; He, Chaoliang; Edin, Joel; Rakickas, Tomas; Kobuch, Karin; Ruželė, Živilė; Jackson, W Bruce; Rafat, Mehrdad; Lohmann, Chris P; Valiokas, Ramūnas; Griffith, May

    2015-01-01

    The implant-host interface is a critical element in guiding tissue or organ regeneration. We previously developed hydrogels comprising interpenetrating networks of recombinant human collagen type III and 2-methacryloyloxyethyl phosphorylcholine (RHCIII-MPC) as substitutes for the corneal extracellular matrix that promote endogenous regeneration of corneal tissue. To render them functional for clinical application, we have now optimized their composition and thereby enhanced their mechanical properties. We have demonstrated that such optimized RHCIII-MPC hydrogels are suitable for precision femtosecond laser cutting to produce complementing implants and host surgical beds for subsequent tissue welding. This avoids the tissue damage and inflammation associated with manual surgical techniques, thereby leading to more efficient healing. Although we previously demonstrated in clinical testing that RHCIII-based implants stimulated cornea regeneration in patients, the rate of epithelial cell coverage of the implants needs improvement, e.g. modification of the implant surface. We now show that our 500μm thick RHCIII-MPC constructs comprising over 85% water are suitable for microcontact printing with fibronectin. The resulting fibronectin micropatterns promote cell adhesion, unlike the bare RHCIII-MPC hydrogel. Interestingly, a pattern of 30μm wide fibronectin stripes enhanced cell attachment and showed the highest mitotic rates, an effect that potentially can be utilized for faster integration of the implant. We have therefore shown that laboratory-produced mimics of naturally occurring collagen and phospholipids can be fabricated into robust hydrogels that can be laser profiled and patterned to enhance their potential function as artificial substitutes of donor human corneas. PMID:25448347

  17. Mullins effect behaviour under compression in micelle-templated silica and micelle-templated silica/agarose systems.

    PubMed

    Puértolas, J A; Vadillo, J L; Sánchez-Salcedo, S; Nieto, A; Gómez-Barrena, E; Vallet-Regí, M

    2012-02-01

    The mechanical properties of bioceramic conformed pieces based on micelle-templated silica (MTS) such as SBA15, MCM41 and MCM48 as well as MTS/agarose systems have been evaluated under static and cyclic compressive tests. The MTS pieces exhibited a brittle behaviour. Agarose, a biocompatible and biodegradable hydrogel, has been used to shape ceramic-agarose pieces following a low temperature shaping method. Agarose conferred toughness, ductility and a rubbery consistency up to a 60% strain in ceramic MTS/agarose systems leading to a maximum strength of 10-50 MPa, without losing their initial cylindrical structure. This combination of ceramic and organic matrix contributes to avoiding the inherent brittleness of the bioceramic and enhances the compression resistance of hydrogel. The presence of mechanical hysteresis, permanent deformation after the first cycle and recovery of the master monotonous curve of MTS/agarose systems indicate a Mullins-like effect similar to that found in carbon-filled rubber systems. We report this type of mechanical behaviour, the Mullins effect, for the first time in MTS bioceramics and MTS bioceramic/agarose systems. PMID:22076528

  18. Enzymatic conjugation of a bioactive peptide into an injectable hyaluronic acid-tyramine hydrogel system to promote the formation of functional vasculature.

    PubMed

    Wang, Li-Shan; Lee, Fan; Lim, Jaehong; Du, Chan; Wan, Andrew C A; Lee, Su Seong; Kurisawa, Motoichi

    2014-06-01

    In this study, one-step enzyme-mediated preparation of a multi-functional injectable hyaluronic-acid-based hydrogel system is reported. Hydrogel was formed through the in situ coupling of phenol moieties by horseradish peroxidase (HRP) and hydrogen peroxide (H2O2), and bioactive peptides were simultaneously conjugated into the hydrogel during the gel formation process. The preparation of this multi-functional hydrogel was made possible by synthesizing peptides containing phenols which could couple with the phenol moieties of hyaluronic-acid-tyramine (HA-Tyr) during the HRP-mediated crosslinking reaction. Preliminary studies demonstrated that two phenol moieties per molecule resulted in a consistently high degree of conjugation into the HA-Tyr hydrogel network, unlike the one modified with one phenol moiety per molecule. Therefore, an Arg-Gly-Asp (RGD) peptide bearing two phenol moieties (phenol2-poly(ethylene glycol)-RGD) was designed for conjugation to endow the HA-Tyr hydrogel with adhesion signals and enhance its bioactivities. Human umbilical vein endothelial cells (HUVECs) cultured on or within the RGD-modified hydrogels showed significantly different adhesion behavior, from non-adherence on the HA-Tyr hydrogel to strong adhesion on hydrogels modified with phenol2-poly(ethylene glycol)-RGD. This altered cell adhesion behavior led to improved cell proliferation, migration and formation of capillary-like network in the hydrogel in vitro. More importantly, when HUVECs and human fibroblasts (HFF1) were encapsulated together in the RGD-modified HA-Tyr hydrogel, functional vasculature was observed inside the cell-laden gel after 2weeks in the subcutaneous tissue. Taken together, the in situ conjugation of phenol2-poly(ethylene glycol)-RGD into HA-Tyr hydrogel system, coupled with the ease of incorporating cells, offers a simple and effective means to introduce biological signals for preparation of multi-functional injectable hydrogels for tissue engineering

  19. Mechanical Characterization of a Bi-functional Tetronic Hydrogel Adhesive for Soft Tissues

    PubMed Central

    Sanders, Lindsey; Stone, Roland; Webb, C. Kenneth; Mefford, O. Thompson; Nagatomi, Jiro

    2014-01-01

    Although a number of tissue adhesives and sealants for surgical use are currently available, attaining a useful balance in high strength, high compliance, and low swelling has proven difficult. Recent studies have demonstrated that a 4-arm poly(propylene oxide)-poly(ethylene oxide) (PPO-PEO) block copolymer, Tetronic, can be chemically modified to form a hydrogel tissue adhesive21–23. Building on the success of these studies, the present study explored bi-functionalization of Tetronic with acrylates for chemical crosslinking of the hydrogel and N-hydroxysuccinimide (NHS) for reaction with tissue amines. The adhesive bond strengths of various uni- and bi-functional Tetronic blends (T1107 ACR: T1107 ACR/NHS) determined by lap shear testing ranged between 8 and 74 kPa, with the 75:25 (T1107 ACR: T1107 ACR/NHS) blend displaying the highest value. These results indicated that addition of NHS led to improvement of tissue bond strength over acrylation alone Furthermore, ex vivo pressure tests using the rat bladder demonstrated that the bi-functional Tetronic adhesive exhibited high compliance and maintained pressures under hundreds of filling and emptying cycles. Together, the results of the present study provided evidence that the bi-functional Tetronic adhesive with a proper blend ratio may be used to achieve an accurate balance in bulk and tissue bond strengths, as well as the compliance and durability for soft tissue such as the bladder. PMID:25111445

  20. ALS/FTD Mutation-Induced Phase Transition of FUS Liquid Droplets and Reversible Hydrogels into Irreversible Hydrogels Impairs RNP Granule Function

    PubMed Central

    Murakami, Tetsuro; Qamar, Seema; Lin, Julie Qiaojin; Schierle, Gabriele S. Kaminski; Rees, Eric; Miyashita, Akinori; Costa, Ana R.; Dodd, Roger B.; Chan, Fiona T.S.; Michel, Claire H.; Kronenberg-Versteeg, Deborah; Li, Yi; Yang, Seung-Pil; Wakutani, Yosuke; Meadows, William; Ferry, Rodylyn Rose; Dong, Liang; Tartaglia, Gian Gaetano; Favrin, Giorgio; Lin, Wen-Lang; Dickson, Dennis W.; Zhen, Mei; Ron, David; Schmitt-Ulms, Gerold; Fraser, Paul E.; Shneider, Neil A.; Holt, Christine; Vendruscolo, Michele; Kaminski, Clemens F.; St George-Hyslop, Peter

    2015-01-01

    Summary The mechanisms by which mutations in FUS and other RNA binding proteins cause ALS and FTD remain controversial. We propose a model in which low-complexity (LC) domains of FUS drive its physiologically reversible assembly into membrane-free, liquid droplet and hydrogel-like structures. ALS/FTD mutations in LC or non-LC domains induce further phase transition into poorly soluble fibrillar hydrogels distinct from conventional amyloids. These assemblies are necessary and sufficient for neurotoxicity in a C. elegans model of FUS-dependent neurodegeneration. They trap other ribonucleoprotein (RNP) granule components and disrupt RNP granule function. One consequence is impairment of new protein synthesis by cytoplasmic RNP granules in axon terminals, where RNP granules regulate local RNA metabolism and translation. Nuclear FUS granules may be similarly affected. Inhibiting formation of these fibrillar hydrogel assemblies mitigates neurotoxicity and suggests a potential therapeutic strategy that may also be applicable to ALS/FTD associated with mutations in other RNA binding proteins. PMID:26526393

  1. ALS/FTD Mutation-Induced Phase Transition of FUS Liquid Droplets and Reversible Hydrogels into Irreversible Hydrogels Impairs RNP Granule Function.

    PubMed

    Murakami, Tetsuro; Qamar, Seema; Lin, Julie Qiaojin; Schierle, Gabriele S Kaminski; Rees, Eric; Miyashita, Akinori; Costa, Ana R; Dodd, Roger B; Chan, Fiona T S; Michel, Claire H; Kronenberg-Versteeg, Deborah; Li, Yi; Yang, Seung-Pil; Wakutani, Yosuke; Meadows, William; Ferry, Rodylyn Rose; Dong, Liang; Tartaglia, Gian Gaetano; Favrin, Giorgio; Lin, Wen-Lang; Dickson, Dennis W; Zhen, Mei; Ron, David; Schmitt-Ulms, Gerold; Fraser, Paul E; Shneider, Neil A; Holt, Christine; Vendruscolo, Michele; Kaminski, Clemens F; St George-Hyslop, Peter

    2015-11-18

    The mechanisms by which mutations in FUS and other RNA binding proteins cause ALS and FTD remain controversial. We propose a model in which low-complexity (LC) domains of FUS drive its physiologically reversible assembly into membrane-free, liquid droplet and hydrogel-like structures. ALS/FTD mutations in LC or non-LC domains induce further phase transition into poorly soluble fibrillar hydrogels distinct from conventional amyloids. These assemblies are necessary and sufficient for neurotoxicity in a C. elegans model of FUS-dependent neurodegeneration. They trap other ribonucleoprotein (RNP) granule components and disrupt RNP granule function. One consequence is impairment of new protein synthesis by cytoplasmic RNP granules in axon terminals, where RNP granules regulate local RNA metabolism and translation. Nuclear FUS granules may be similarly affected. Inhibiting formation of these fibrillar hydrogel assemblies mitigates neurotoxicity and suggests a potential therapeutic strategy that may also be applicable to ALS/FTD associated with mutations in other RNA binding proteins. PMID:26526393

  2. Modulation of Huh7.5 Spheroid Formation and Functionality Using Modified PEG-Based Hydrogels of Different Stiffness

    PubMed Central

    Lee, Bae Hoon; Kim, Myung Hee; Lee, Jae Ho; Seliktar, Dror; Cho, Nam-Joon; Tan, Lay Poh

    2015-01-01

    Physical cues, such as cell microenvironment stiffness, are known to be important factors in modulating cellular behaviors such as differentiation, viability, and proliferation. Apart from being able to trigger these effects, mechanical stiffness tuning is a very convenient approach that could be implemented readily into smart scaffold designs. In this study, fibrinogen-modified poly(ethylene glycol)-diacrylate (PEG-DA) based hydrogels with tunable mechanical properties were synthesized and applied to control the spheroid formation and liver-like function of encapsulated Huh7.5 cells in an engineered, three-dimensional liver tissue model. By controlling hydrogel stiffness (0.1–6 kPa) as a cue for mechanotransduction representing different stiffness of a normal liver and a diseased cirrhotic liver, spheroids ranging from 50 to 200 μm were formed over a three week time-span. Hydrogels with better compliance (i.e. lower stiffness) promoted formation of larger spheroids. The highest rates of cell proliferation, albumin secretion, and CYP450 expression were all observed for spheroids in less stiff hydrogels like a normal liver in a healthy state. We also identified that the hydrogel modification by incorporation of PEGylated-fibrinogen within the hydrogel matrix enhanced cell survival and functionality possibly owing to more binding of autocrine fibronectin. Taken together, our findings establish guidelines to control the formation of Huh7.5 cell spheroids in modified PEGDA based hydrogels. These spheroids may serve as models for applications such as screening of pharmacological drug candidates. PMID:25692976

  3. Triple-helical collagen hydrogels via covalent aromatic functionalization with 1,3-Phenylenediacetic acid

    PubMed Central

    Tronci, Giuseppe; Doyle, Amanda; Russell, Stephen J.; Wood, David J.

    2016-01-01

    Chemical crosslinking of collagen is a general strategy to reproduce macroscale tissue properties in physiological environment. However, simultaneous control of protein conformation, material properties and biofunctionality is highly challenging with current synthetic strategies. Consequently, the potentially-diverse clinical applications of collagen-based biomaterials cannot be fully realised. In order to establish defined biomacromolecular systems for mineralised tissue applications, type I collagen was functionalised with 1,3-Phenylenediacetic acid (Ph) and investigated at the molecular, macroscopic and functional levels. Preserved triple helix conformation was observed in obtained covalent networks via ATR-FTIR (AIII/A1450 ~ 1) and WAXS, while network crosslinking degree (C: 87-99 mol.-%) could be adjusted based on specific reaction conditions. Decreased swelling ratio (SR: 823-1285 wt.-%) and increased thermo-mechanical (Td: 80-88 °C; E: 28-35 kPa; σmax: 6-8 kPa; εb: 53-58 %) properties were observed compared to state-of-the-art carbodiimide (EDC)-crosslinked collagen controls, likely related to the intermolecular covalent incorporation of the aromatic segment. Ph-crosslinked hydrogels displayed nearly intact material integrity and only a slight mass decrease (MR: 5-11 wt. %) following 1-week incubation in either PBS or simulated body fluid (SBF), in contrast to EDC-crosslinked collagen (MR: 33-58 wt. %). Furthermore, FTIR, SEM and EDS revealed deposition of a calcium-phosphate phase on SBF-retrieved samples, whereby an increased calcium phosphate ratio (Ca/P: 0.84-1.41) was observed in hydrogels with higher Ph content. 72-hour material extracts were well tolerated by L929 mouse fibroblasts, whereby cell confluence and metabolic activity (MTS assay) were comparable to those of cells cultured in cell culture medium (positive control). In light of their controlled structure-function properties, these biocompatible collagen hydrogels represent attractive

  4. A functionalized, injectable hydrogel for localized drug delivery with tunable thermosensitivity: synthesis and characterization of physical and toxicological properties.

    PubMed

    Elias, Paul Z; Liu, Gary W; Wei, Hua; Jensen, Michael C; Horner, Philip J; Pun, Suzie H

    2015-06-28

    Thermosensitive injectable hydrogels have been used for the delivery of pharmacological and cellular therapies in a variety of soft tissue applications. A promising class of synthetic, injectable hydrogels based upon oligo(ethylene glycol) methacrylate (OEGMA) monomers has been previously reported, but these polymers lack reactive groups for covalent attachment of therapeutic molecules. In this work, thermosensitive, amine-reactive and amine-functionalized polymers were developed by incorporation of methacrylic acid N-hydroxysuccinimide ester or 2-aminoethyl methacrylate into OEGMA-based polymers. A model therapeutic peptide, bivalirudin, was conjugated to the amine-reactive hydrogel to investigate effects on the polymer thermosensitivity and gelation properties. The ability to tune the thermosensitivity of the polymer in order to compensate for peptide hydrophilicity and maintain gelation capability below physiological temperature was demonstrated. Cell encapsulation studies using an H9 T-cell line (CD4+) were conducted to evaluate feasibility of the hydrogel as a carrier for cellular therapies. Although this class of polymers is generally considered to be non-toxic, it was found that concentrations required for gelation were incompatible with cell survival. Investigation into the cause of cytotoxicity revealed that a hydrolysis byproduct, diethylene glycol monomethyl ether, is likely a contributing factor. While modifications to structure or composition will be required to enable viable cell encapsulation, the functionalized injectable hydrogel has the potential for controlled delivery of a wide range of drugs. PMID:25747144

  5. Multi-responsive Hydrogels Derived from the Self-assembly of Tethered Allyl-functionalized Racemic Oligopeptides

    PubMed Central

    He, Xun; Fan, Jingwei; Zhang, Fuwu; Li, Richen; Pollack, Kevin A.; Raymond, Jeffery E.; Zou, Jiong; Wooley, Karen L.

    2014-01-01

    A multi-responsive triblock hydrogelator oligo(dl-allylglycine)-block-poly(ethylene glycol)-block-oligo(dl-allylglycine) (ODLAG-b-PEG-b-ODLAG) was synthesized facilely by ring-opening polymerization (ROP) of DLAG N-carboxyanhydride (NCA) with a diamino-terminated PEG as the macroinitiator. This system exhibited heat-induced sol-to-gel transitions and either sonication- or enzyme-induced gel-to-sol transitions. The β-sheeting of the oligopeptide segments was confirmed by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and wide-angle X-ray scattering (WAXS). The β-sheets further displayed tertiary ordering into fibrillar structures that, in turn generated a porous and interconnected hydrogel matrix, as observed via transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The reversible macroscopic sol-to-gel transitions triggered by heat and gel-to-sol transitions triggered by sonication were correlated with the transformation of nanostructural morphologies, with fibrillar structures observed in gel and spherical aggregates in sol, respectively. The enzymatic breakdown of the hydrogels was also investigated. This allyl-functionalized hydrogelator can serve as a platform for the design of smart hydrogels, appropriate for expansion into biological systems as bio-functional and bio-responsive materials. PMID:25485113

  6. Directed assembly of cell-laden hydrogels for engineering functional tissues

    PubMed Central

    Kachouie, Nezamoddin N; Du, Yanan; Bae, Hojae; Khabiry, Masoud; Ahari, Amirhossein F; Zamanian, Behnam; Fukuda, Junji

    2010-01-01

    Tissue engineering aims to develop functionalized tissues for organ replacement or restoration. Biodegradable scaffolds have been used in tissue engineering to support cell growth and maintain mechanical and biological properties of tissue constructs. Ideally cells on these scaffolds adhere, proliferate and deposit matrix at a rate that is consistent with scaffold degradation. However, the cellular rearrangement within these scaffolds often does not recapitulate the architecture of the native tissues. Directed assembly of tissue-like structures is an attractive alternative to scaffold-based approach for tissue engineering which potentially can build tissue constructs with biomimetic architecture and function. In directed assembly, shape-controlled microstructures are fabricated in which organized structures of different cell types can be used as tissue building blocks. To fabricate tissue building blocks, hydrogels are commonly used as biomaterials for cell encapsulation to mimic the matrix in vivo. The hydrogel-based tissue building blocks can be arranged in pre-defined architectures by various directed tissue assembly techniques. In this paper, recent advances in directed assembly-based tissue engineering are summarized as an emerging alternative to meet challenges associated with scaffold-based tissue engineering and future directions are addressed. PMID:21220962

  7. Magnetic Hydrogels from Alkyne/Cobalt Carbonyl-Functionalized ABA Triblock Copolymers.

    PubMed

    Jiang, Bingyin; Hom, Wendy L; Chen, Xianyin; Yu, Pengqing; Pavelka, Laura C; Kisslinger, Kim; Parise, John B; Bhatia, Surita R; Grubbs, Robert B

    2016-04-01

    A series of alkyne-functionalized poly(4-(phenylethynyl)styrene)-block-poly(ethylene oxide)-block-poly(4-(phenylethynyl)styrene) (PPES-b-PEO-b-PPES) ABA triblock copolymers was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. PESn[Co2(CO)6]x-EO800-PESn[Co2(CO)6]x ABA triblock copolymer/cobalt adducts (10-67 wt % PEO) were subsequently prepared by reaction of the alkyne-functionalized PPES block with Co2(CO)8 and their phase behavior was studied by TEM. Heating triblock copolymer/cobalt carbonyl adducts at 120 °C led to cross-linking of the PPES/Co domains and the formation of magnetic cobalt nanoparticles within the PPES/Co domains. Magnetic hydrogels could be prepared by swelling the PEO domains of the cross-linked materials with water. Swelling tests, rheological studies and actuation tests demonstrated that the water capacity and modulus of the hydrogels were dependent upon the composition of the block copolymer precursors. PMID:26958699

  8. Functionalized graphene oxide quantum dot-PVA hydrogel: a colorimetric sensor for Fe2+, Co2+ and Cu2+ ions

    NASA Astrophysics Data System (ADS)

    Baruah, Upama; Chowdhury, Devasish

    2016-04-01

    Functionalized graphene oxide quantum dots (GOQDs)-poly(vinyl alcohol) (PVA) hybrid hydrogels were prepared using a simple, facile and cost-effective strategy. GOQDs bearing different surface functional groups were introduced as the cross-linking agent into the PVA matrix thereby resulting in gelation. The four different types of hybrid hydrogels were prepared using graphene oxide, reduced graphene oxide, ester functionalized graphene oxide and amine functionalized GOQDs as cross-linking agents. It was observed that the hybrid hydrogel prepared with amine functionalized GOQDs was the most stable. The potential applicability of using this solid sensing platform has been subsequently explored in an easy, simple, effective and sensitive method for optical detection of M2+ (Fe2+, Co2+ and Cu2+) in aqueous media involving colorimetric detection. Amine functionalized GOQDs-PVA hybrid hydrogel when put into the corresponding solution of Fe2+, Co2+ and Cu2+ renders brown, orange and blue coloration respectively of the solution detecting the presence of Fe2+, Co2+ and Cu2+ ions in the solution. The minimum detection limit observed was 1 × 10-7 M using UV-visible spectroscopy. Further, the applicability of the sensing material was also tested for a mixture of co-existing ions in solution to demonstrate the practical applicability of the system. Insight into the probable mechanistic pathway involved in the detection process is also being discussed.

  9. Agarose-Based Substrate Modification Technique for Chemical and Physical Guiding of Neurons In Vitro.

    PubMed

    Krumpholz, Katharina; Rogal, Julia; El Hasni, Akram; Schnakenberg, Uwe; Bräunig, Peter; Bui-Göbbels, Katrin

    2015-08-26

    A new low cost and highly reproducible technique is presented that provides patterned cell culture substrates. These allow for selective positioning of cells and a chemically and mechanically directed guiding of their extensions. The patterned substrates consist of structured agarose hydrogels molded from reusable silicon micro templates. These templates consist of pins arranged equidistantly in squares, connected by bars, which mold corresponding wells and channels in the nonadhesive agarose hydrogel. Subsequent slice production with a standard vibratome, comprising the described template pattern, completes substrate production. Invertebrate neurons of locusts and pond snails are used for this application as they offer the advantage over vertebrate cells as being very large and suitable for cultivation in low cell density. Their neurons adhere to and grow only on the adhesive areas not covered by the agarose. Agarose slices of 50 μm thickness placed on glass, polystyrene, or MEA surfaces position and immobilize the neurons in the wells, and the channels guide their neurite outgrowth toward neighboring wells. In addition to the application with invertebrate neurons, the technique may also provide the potential for the application of a wide range of cell types. Long-term objective is the achievement of isolated low-density neuronal networks on MEAs or different culture substrates for various network analysis applications. PMID:26237337

  10. Salivary gland acinar cells regenerate functional glandular structures in modified hydrogels

    NASA Astrophysics Data System (ADS)

    Pradhan, Swati

    Xerostomia, a condition resulting from irradiation of the head and neck, affects over 40,000 cancer patients each year in the United States. Direct radiation damage of the acinar cells that secrete fluid and protein results in salivary gland hypofunction. Present medical management for xerostomia for patients treated for upper respiratory cancer is largely ineffective. Patients who have survived their terminal diagnosis are often left with a diminished quality of life and are unable to enjoy the simple pleasures of eating and drinking. This project aims to ultimately reduce human suffering by developing a functional implantable artificial salivary gland. The goal was to create an extracellular matrix (ECM) modified hyaluronic acid (HA) based hydrogel culture system that allows for the growth and differentiation of salivary acinar cells into functional acini-like structures capable of secreting large amounts of protein and fluid unidirectionally and to ultimately engineer a functional artificial salivary gland that can be implanted into an animal model. A tissue collection protocol was established and salivary gland tissue was obtained from patients undergoing head and neck surgery. The tissue specimen was assessed by histology and immunohistochemistry to establish the phenotype of normal salivary gland cells including the native basement membranes. Hematoxylin and eosin staining confirmed normal glandular tissue structures including intercalated ducts, striated ducts and acini. alpha-Amylase and periodic acid schiff stain, used for structures with a high proportion of carbohydrate macromolecules, preferentially stained acinar cells in the tissue. Intercalated and striated duct structures were identified using cytokeratins 19 and 7 staining. Myoepithelial cells positive for cytokeratin 14 were found wrapped around the serous and mucous acini. Tight junction components including ZO-1 and E-cadherin were present between both ductal and acinar cells. Ductal and acinar

  11. RGDS-functionalized polyethylene glycol hydrogel-coated magnetic iron oxide nanoparticles enhance specific intracellular uptake by HeLa cells

    PubMed Central

    Nazli, Caner; Ergenc, Tugba Ipek; Yar, Yasemin; Acar, Havva Yagci; Kizilel, Seda

    2012-01-01

    The objective of this study was to develop thin, biocompatible, and biofunctional hydrogel-coated small-sized nanoparticles that exhibit favorable stability, viability, and specific cellular uptake. This article reports the coating of magnetic iron oxide nanoparticles (MIONPs) with covalently cross-linked biofunctional polyethylene glycol (PEG) hydrogel. Silanized MIONPs were derivatized with eosin Y, and the covalently cross-linked biofunctional PEG hydrogel coating was achieved via surface-initiated photopolymerization of PEG diacrylate in aqueous solution. The thickness of the PEG hydrogel coating, between 23 and 126 nm, was tuned with laser exposure time. PEG hydrogel-coated MIONPs were further functionalized with the fibronectin-derived arginine-glycine-aspartic acid-serine (RGDS) sequence, in order to achieve a biofunctional PEG hydrogel layer around the nanoparticles. RGDS-bound PEG hydrogel-coated MIONPs showed a 17-fold higher uptake by the human cervical cancer HeLa cell line than that of amine-coated MIONPs. This novel method allows for the coating of MIONPs with nano-thin biofunctional hydrogel layers that may prevent undesirable cell and protein adhesion and may allow for cellular uptake in target tissues in a specific manner. These findings indicate that the further biofunctional PEG hydrogel coating of MIONPs is a promising platform for enhanced specific cell targeting in biomedical imaging and cancer therapy. PMID:22619531

  12. Chondrocyte spheroids on microfabricated PEG hydrogel surface and their noninvasive functional monitoring

    NASA Astrophysics Data System (ADS)

    Otsuka, Hidenori; Nagamura, Masako; Kaneko, Akie; Kutsuzawa, Koichi; Sakata, Toshiya; Miyahara, Yuji

    2012-12-01

    A two-dimensional microarray of 10 000 (100 × 100) chondrocyte spheroids was constructed with a 100 μm spacing on a micropatterned gold electrode that was coated with poly(ethylene glycol) (PEG) hydrogels. The PEGylated surface as a cytophobic region was regulated by controlling the gel structure through photolithography. In this way, a PEG hydrogel was modulated enough to inhibit outgrowth of chondrocytes from a cell adhering region in the horizontal direction, which is critical for inducing formation of three-dimensional chondrocyte aggregations (spheroids) within 24 h. We further report noninvasive monitoring of the cellular functional change at the cell membrane using a chondrocyte-based field effect transistor. This measurement is based on detection of extracellular potential change induced as a result of the interaction between extracellular matrix protein secreted from spheroid and substrate at the cell membrane. The interface potential change at the cell membrane/gate interface can be monitored during the differentiation of spheroids without any labeling materials. Our measurements of the time evolution of the interface potential provide important information for understanding the uptake kinetics for cellular differentiation.

  13. Biomimetic hydrogel materials

    DOEpatents

    Bertozzi, Carolyn; Mukkamala, Ravindranath; Chen, Qing; Hu, Hopin; Baude, Dominique

    2000-01-01

    Novel biomimetic hydrogel materials and methods for their preparation. Hydrogels containing acrylamide-functionalized carbohydrate, sulfoxide, sulfide or sulfone copolymerized with a hydrophilic or hydrophobic copolymerizing material selected from the group consisting of an acrylamide, methacrylamide, acrylate, methacrylate, vinyl and a derivative thereof present in concentration from about 1 to about 99 wt %. and methods for their preparation. The method of use of the new hydrogels for fabrication of soft contact lenses and biomedical implants.

  14. Biomimetic Hydrogel Materials

    DOEpatents

    Bertozzi, Carolyn , Mukkamala, Ravindranath , Chen, Oing , Hu, Hopin , Baude, Dominique

    2003-04-22

    Novel biomimetic hydrogel materials and methods for their preparation. Hydrogels containing acrylamide-functionalized carbohydrate, sulfoxide, sulfide or sulfone copolymerized with a hydrophilic or hydrophobic copolymerizing material selected from the group consisting of an acrylamide, methacrylamide, acrylate, methacrylate, vinyl and a derivative thereof present in concentration from about 1 to about 99 wt %. and methods for their preparation. The method of use of the new hydrogels for fabrication of soft contact lenses and biomedical implants.

  15. Dual Delivery of Hepatocyte and Vascular Endothelial Growth Factors via a Protease-Degradable Hydrogel Improves Cardiac Function in Rats

    PubMed Central

    Boopathy, Archana V.; Che, Pao-lin; Brown, Milton; García, Andrés J.; Davis, Michael E.

    2012-01-01

    Acute myocardial infarction (MI) caused by ischemia and reperfusion (IR) is the most common cause of cardiac dysfunction due to local cell death and a temporally regulated inflammatory response. Current therapeutics are limited by delivery vehicles that do not address spatial and temporal aspects of healing. The aim of this study was to engineer biotherapeutic delivery materials to harness endogenous cell repair to enhance myocardial repair and function. We have previously engineered poly(ethylene glycol) (PEG)-based hydrogels to present cell adhesive motifs and deliver VEGF to promote vascularization in vivo. In the current study, bioactive hydrogels with a protease-degradable crosslinker were loaded with hepatocyte and vascular endothelial growth factors (HGF and VEGF, respectively) and delivered to the infarcted myocardium of rats. Release of both growth factors was accelerated in the presence of collagenase due to hydrogel degradation. When delivered to the border zones following ischemia-reperfusion injury, there was no acute effect on cardiac function as measured by echocardiography. Over time there was a significant increase in angiogenesis, stem cell recruitment, and a decrease in fibrosis in the dual growth factor delivery group that was significant compared with single growth factor therapy. This led to an improvement in chronic function as measured by both invasive hemodynamics and echocardiography. These data demonstrate that dual growth factor release of HGF and VEGF from a bioactive hydrogel has the capacity to significantly improve cardiac remodeling and function following IR injury. PMID:23226440

  16. Control of growth factor binding and release in bisphosphonate functionalized hydrogels guides rapid differentiation of precursor cells in vitro.

    PubMed

    Kootala, Sujit; Zhang, Yu; Ghalib, Sara; Tolmachev, Vladimir; Hilborn, Jöns; Ossipov, Dmitri A

    2016-02-01

    An in situ cross-linkable hyaluronan hydrogel functionalized with bisphosphonate (BP) groups allows tunable release of bone morphogenetic protein-2 (BMP-2) determined by the amount of BP groups. The high affinity of matrix-anchored BP groups towards BMP-2 permits guided differentiation of entrapped progenitor cells in 3-D cultures. PMID:26610690

  17. Hydrogel-based encapsulation of biological, functional tissue: fundamentals, technologies and applications

    NASA Astrophysics Data System (ADS)

    Zimmermann, H.; Ehrhart, F.; Zimmermann, D.; Müller, K.; Katsen-Globa, A.; Behringer, M.; Feilen, P. J.; Gessner, P.; Zimmermann, G.; Shirley, S. G.; Weber, M. M.; Metze, J.; Zimmermann, U.

    2007-12-01

    Replacing dysfunctional endocrine cells or tissues (e.g. islets, parathyroid tissue) by functional, foreign material without using immunosuppressives could soon become reality. Immunological reactions are avoided by encapsulating cells/tissues in hydrogel (e.g. alginate) microcapsules, preventing interaction of the enclosed material with the host’s immune system while permitting the unhindered passage of nutrients, oxygen and secreted therapeutic factors. Detailed investigations of the physical, physico-chemical and immunological parameters of alginate-based microcapsules have led recently to the development of a novel class of cell-entrapping microcapsules that meet the demands of biocompatibility, long-term integrity and function. This together with the development of ‘good medical practice’ microfluidic chip technology and of advanced cryopreservation technology for generation and storage of immunoisolated transplants will bring cell-based therapy to clinics and the market.

  18. Salivary gland acinar cells regenerate functional glandular structures in modified hydrogels

    NASA Astrophysics Data System (ADS)

    Pradhan, Swati

    Xerostomia, a condition resulting from irradiation of the head and neck, affects over 40,000 cancer patients each year in the United States. Direct radiation damage of the acinar cells that secrete fluid and protein results in salivary gland hypofunction. Present medical management for xerostomia for patients treated for upper respiratory cancer is largely ineffective. Patients who have survived their terminal diagnosis are often left with a diminished quality of life and are unable to enjoy the simple pleasures of eating and drinking. This project aims to ultimately reduce human suffering by developing a functional implantable artificial salivary gland. The goal was to create an extracellular matrix (ECM) modified hyaluronic acid (HA) based hydrogel culture system that allows for the growth and differentiation of salivary acinar cells into functional acini-like structures capable of secreting large amounts of protein and fluid unidirectionally and to ultimately engineer a functional artificial salivary gland that can be implanted into an animal model. A tissue collection protocol was established and salivary gland tissue was obtained from patients undergoing head and neck surgery. The tissue specimen was assessed by histology and immunohistochemistry to establish the phenotype of normal salivary gland cells including the native basement membranes. Hematoxylin and eosin staining confirmed normal glandular tissue structures including intercalated ducts, striated ducts and acini. alpha-Amylase and periodic acid schiff stain, used for structures with a high proportion of carbohydrate macromolecules, preferentially stained acinar cells in the tissue. Intercalated and striated duct structures were identified using cytokeratins 19 and 7 staining. Myoepithelial cells positive for cytokeratin 14 were found wrapped around the serous and mucous acini. Tight junction components including ZO-1 and E-cadherin were present between both ductal and acinar cells. Ductal and acinar

  19. Nanocomposite hydrogels for biomedical applications

    PubMed Central

    Gaharwar, Akhilesh K.

    2014-01-01

    Hydrogels mimic native tissue microenvironment due to their porous and hydrated molecular structure. An emerging approach to reinforce polymeric hydrogels and to include multiple functionalities focuses on incorporating nanoparticles within the hydrogel network. A wide range of nanoparticles, such as carbon-based, polymeric, ceramic, and metallic nanomaterials can be integrated within the hydrogel networks to obtain nanocomposites with superior properties and tailored functionality. Nanocomposite hydrogels can be engineered to possess superior physical, chemical, electrical, and biological properties. This review focuses on the most recent developments in the field of nanocomposite hydrogels with emphasis on biomedical and pharmaceutical applications. In particular, we discuss synthesis and fabrication of nanocomposite hydrogels, examine their current limitations and conclude with future directions in designing more advanced nanocomposite hydrogels for biomedical and biotechnological applications. PMID:24264728

  20. Thermoresponsive hyperbranched copolymer with multi acrylate functionality for in situ cross-linkable hyaluronic acid composite semi-IPN hydrogel.

    PubMed

    Dong, Yixiao; Hassan, Waqar; Zheng, Yu; Saeed, Aram Omer; Cao, Hongliang; Tai, Hongyun; Pandit, Abhay; Wang, Wenxin

    2012-01-01

    Thermoresponsive polymers have been widely used for in situ formed hydrogels in drug delivery and tissue engineering as they are easy to handle and their shape can easily conform to tissue defects. However, non-covalent bonding and mechanical weakness of these hydrogels limit their applications. In this study, a physically and chemically in situ cross-linkable hydrogel system was developed from a novel thermoresponsive hyperbranched PEG based copolymer with multi acrylate functionality, which was synthesized via an 'one pot and one step' in situ deactivation enhanced atom transfer radical co-polymerization of poly(ethylene glycol) diacrylate (PEGDA, M(n) = 258 g mol(-1)), poly(ethylene glycol) methyl ether methacrylate (PEGMEMA, M(n )= 475 g mol(-1)) and (2-methoxyethoxy) ethyl methacrylate (MEO(2)MA). This hyperbranched copolymer was tailored to have the lower critical solution temperature to form physical gelation around 37°C. Meanwhile, with high level of acrylate functionalities, a chemically cross-linked gel was formed from this copolymer using thiol functional cross-linker of pentaerythritol tetrakis (3-mercaptopropionate) (QT) via thiol-ene Michael addition reaction. Furthermore, a semi-interpenetrated polymer networks (semi-IPN) structure was developed by combining this polymer with hyaluronic acid (HA), leading to an in situ cross-linkable hydrogel with significantly increased porosity, enhanced swelling behavior and improved cell adhesion and viability both in 2D and 3D cell culture models. PMID:22143908

  1. Functional Elastic Hydrogel as Recyclable Membrane for the Adsorption and Degradation of Methylene Blue

    PubMed Central

    Bao, Song; Wu, Dongbei; Wang, Qigang; Su, Teng

    2014-01-01

    Developing the application of high-strength hydrogels has gained much attention in the fields of medical, pharmacy, and pollutant removal due to their versatility and stimulus-responsive properties. In this presentation, a high-strength freestanding elastic hydrogel membrane was constructed by clay nanosheets, N, N-dimethylacrylamide and 2-acrylamide-2-methylpropanesulfonic acid for adsorption of methylene blue and heavy metal ions. The maximum values of elongation and Young’s modulus for 0.5% AMPSNa hydrogel were 1901% and 949.4 kPa, respectively, much higher than those of traditional hydrogels. The adsorptions were confirmed to follow pseudo-second kinetic equation and Langmuir isotherm model fits the data well. The maximum adsorption capacity of hydrogel towards methylene blue was 434.8 mg g−1. The hydrogel also exhibited higher separation selectivity to Pb2+ than Cu2+. The methylene blue adsorbed onto the hydrogel membrane can be photocatalytically degraded by Fenton agent and the hydrogel membrane could be recycled at least five times without obvious loss in mechanical properties. In conclusion, this presentation demonstrates a convenient strategy to prepare tough and elastic clay nanocomposite hydrogel, which can not only be applied as recyclable membrane for the photocatalytic degradation of organic dye, but also for the recovery of valuables. PMID:24586396

  2. Composite three-dimensional woven scaffolds with interpenetrating network hydrogels to create functional synthetic articular cartilage.

    PubMed

    Liao, I-Chien; Moutos, Franklin T; Estes, Bradley T; Zhao, Xuanhe; Guilak, Farshid

    2013-12-17

    The development of synthetic biomaterials that possess mechanical properties that mimic those of native tissues remains an important challenge to the field of materials. In particular, articular cartilage is a complex nonlinear, viscoelastic, and anisotropic material that exhibits a very low coefficient of friction, allowing it to withstand millions of cycles of joint loading over decades of wear. Here we show that a three-dimensionally woven fiber scaffold that is infiltrated with an interpenetrating network hydrogel can provide a functional biomaterial that provides the load-bearing and tribological properties of native cartilage. An interpenetrating dual-network "tough-gel" consisting of alginate and polyacrylamide was infused into a porous three-dimensionally woven poly(ε-caprolactone) fiber scaffold, providing a versatile fiber-reinforced composite structure as a potential acellular or cell-based replacement for cartilage repair. PMID:24578679

  3. Catechol-Functionalized Hyaluronic Acid Hydrogels Enhance Angiogenesis and Osteogenesis of Human Adipose-Derived Stem Cells in Critical Tissue Defects.

    PubMed

    Park, Hyun-Ji; Jin, Yoonhee; Shin, Jisoo; Yang, Kisuk; Lee, Changhyun; Yang, Hee Seok; Cho, Seung-Woo

    2016-06-13

    Over the last few decades, stem cell therapies have been highlighted for their potential to heal damaged tissue and aid in tissue reconstruction. However, materials used to deliver and support implanted cells often display limited efficacy, which has resulted in delaying translation of stem cell therapies into the clinic. In our previous work, we developed a mussel-inspired, catechol-functionalized hyaluronic acid (HA-CA) hydrogel that enabled effective cell transplantation due to its improved biocompatibility and strong tissue adhesiveness. The present study was performed to further expand the utility of HA-CA hydrogels for use in stem cell therapies to treat more clinically relevant tissue defect models. Specifically, we utilized HA-CA hydrogels to potentiate stem cell-mediated angiogenesis and osteogenesis in two tissue defect models: critical limb ischemia and critical-sized calvarial bone defect. HA-CA hydrogels were found to be less cytotoxic to human adipose-derived stem cells (hADSCs) in vitro compared to conventional photopolymerized HA hydrogels. HA-CA hydrogels also retained the angiogenic functionality of hADSCs and supported osteogenic differentiation of hADSCs. Because of their superior tissue adhesiveness, HA-CA hydrogels were able to mediate efficient engraftment of hADSCs into the defect regions. When compared to photopolymerized HA hydrogels, HA-CA hydrogels significantly enhanced hADSC-mediated therapeutic angiogenesis (promoted capillary/arteriole formation, improved vascular perfusion, attenuated ischemic muscle degeneration/fibrosis, and reduced limb amputation) and bone reconstruction (mineralized bone formation, enhanced osteogenic marker expression, and collagen deposition). This study proves the feasibility of using bioinspired HA-CA hydrogels as functional biomaterials for improved tissue regeneration in critical tissue defects. PMID:27112904

  4. Biomimetically-mineralized composite coatings on titanium functionalized with gelatin methacrylate hydrogels

    NASA Astrophysics Data System (ADS)

    Tan, Guoxin; Zhou, Lei; Ning, Chengyun; Tan, Ying; Ni, Guoxin; Liao, Jingwen; Yu, Peng; Chen, Xiaofeng

    2013-08-01

    Immobilizing organic-inorganic hybrid composites onto the implant surface is a promising strategy to improve host acceptance of the implant. The objective of this present study was to obtain a unique macroporous titanium-surface with the organic-mineral composite coatings consisting of gelatin methacrylate hydrogel (GelMA) and hydroxyapatite (HA). A 3-(trimethoxysilyl) propyl methacrylate (TMSPMA) layer was first coated onto the titanium surface, and surface was then covalently functionalized with GelMA using a photochemical method. Mineralization of the GelMA coating on the titanium surface was subsequently carried out by a biomimetic method. After 3-day mineralization, a large number of mineral phases comprising spherical amorphous nanoparticles were found randomly deposited inside GelMA matrix. The resulting mineralized hydrogel composites exhibited a unique rough surface of macroporous structure. The structure of the prepared GelMA/HA composite coating was studied by field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectra (EDS), attenuated total refraction Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). Water contact angle measurement revealed the hydrophilicity properties of composite coatings. GelMA/HA on titanium after the TMSPMA treatment is very stable when tested in vitro with a PBS solution at 37 °C, due to the role of TMSPMA as a molecular bridge. It was expected that the macroporous GelMA/HA composite coatings might potentially promote and accelerate titanium (Ti)-based implants osseointegration for bone repair and regeneration.

  5. 3D Cell Entrapment as a Function of the Weight Percent of Peptide-Amphiphile Hydrogels

    PubMed Central

    Scott, Carolyn M.; Forster, Colleen L.; Kokkoli, Efrosini

    2015-01-01

    The design of scaffolds which mimic the stiffness, nanofiber structure, and biochemistry of the native extra-cellular matrix (ECM) has been a major objective for the tissue engineering field. Furthermore, mimicking the innate three dimensional (3D) environment of the ECM has been shown to significantly alter cellular response compared to traditional two dimensional (2D) culture. We report the development of a self-assembling, fibronectin-mimetic, peptide-amphiphile nanofiber scaffold for 3D cell culture. To form such a scaffold, 5 mol% of a bioactive PR_g fibronectin-mimetic peptide-amphiphile was mixed with 95 mol% of a diluent peptide-amphiphile (E2) whose purpose was to neutralize electrostatic interactions, increase the gelation kinetics and promote cell survival. Atomic force microscopy verified the fibrilar structure of the gels and the mechanical properties were characterized for various weight percent (wt%) formulations of the 5 mol% PR_g - 95 mol% E2 peptide-amphiphile mixture. The 0.5 wt% formulations had an elastic modulus of 429.0 ± 21.3 Pa while the 1.0 wt% peptide-amphiphile hydrogels had an elastic modulus of 808.6 ± 38.1 Pa. The presence of entrapped cells in the gels decreased the elastic modulus and the decrease was a function of the cell loading. While both formulations supported cell proliferation, the 0.5 wt% gels supported significantly greater NIH3T3/GFP fibroblast cell proliferation throughout the gels than the 1.0 wt% gels. However, compared to the 0.5 wt% formulations, the 1.0 wt% hydrogels promoted greater increase in mRNA expression and production of fibronectin and type IV collagen ECM proteins. This study suggests that this fibronectin-mimetic scaffold holds great promise in the advance of 3D culture applications and cell therapies. PMID:25970351

  6. Dual-functional transdermal drug delivery system with controllable drug loading based on thermosensitive poloxamer hydrogel for atopic dermatitis treatment.

    PubMed

    Wang, Wenyi; Wat, Elaine; Hui, Patrick C L; Chan, Ben; Ng, Frency S F; Kan, Chi-Wai; Wang, Xiaowen; Hu, Huawen; Wong, Eric C W; Lau, Clara B S; Leung, Ping-Chung

    2016-01-01

    The treatment of atopic dermatitis (AD) has long been viewed as a problematic issue by the medical profession. Although a wide variety of complementary therapies have been introduced, they fail to combine the skin moisturizing and drug supply for AD patients. This study reports the development of a thermo-sensitive Poloxamer 407/Carboxymethyl cellulose sodium (P407/CMCs) composite hydrogel formulation with twin functions of moisture and drug supply for AD treatment. It was found that the presence of CMCs can appreciably improve the physical properties of P407 hydrogel, which makes it more suitable for tailored drug loading. The fabricated P407/CMCs composite hydrogel was also characterized in terms of surface morphology by field emission scanning electron microscopy (FE-SEM), rheological properties by a rheometer, release profile in vitro by dialysis method and cytotoxicity test. More importantly, the findings from transdermal drug delivery behavior revealed that P407/CMCs showed desirable percutaneous performance. Additionally, analysis of cytotoxicity test suggested that P407/CMCs composite hydrogel is a high-security therapy for clinical trials and thus exhibits a promising way to treat AD with skin moisturizing and medication. PMID:27090158

  7. Dual-functional transdermal drug delivery system with controllable drug loading based on thermosensitive poloxamer hydrogel for atopic dermatitis treatment

    PubMed Central

    Wang, Wenyi; Wat, Elaine; Hui, Patrick C. L.; Chan, Ben; Ng, Frency S. F.; Kan, Chi-Wai; Wang, Xiaowen; Hu, Huawen; Wong, Eric C. W.; Lau, Clara B. S.; Leung, Ping-Chung

    2016-01-01

    The treatment of atopic dermatitis (AD) has long been viewed as a problematic issue by the medical profession. Although a wide variety of complementary therapies have been introduced, they fail to combine the skin moisturizing and drug supply for AD patients. This study reports the development of a thermo-sensitive Poloxamer 407/Carboxymethyl cellulose sodium (P407/CMCs) composite hydrogel formulation with twin functions of moisture and drug supply for AD treatment. It was found that the presence of CMCs can appreciably improve the physical properties of P407 hydrogel, which makes it more suitable for tailored drug loading. The fabricated P407/CMCs composite hydrogel was also characterized in terms of surface morphology by field emission scanning electron microscopy (FE-SEM), rheological properties by a rheometer, release profile in vitro by dialysis method and cytotoxicity test. More importantly, the findings from transdermal drug delivery behavior revealed that P407/CMCs showed desirable percutaneous performance. Additionally, analysis of cytotoxicity test suggested that P407/CMCs composite hydrogel is a high-security therapy for clinical trials and thus exhibits a promising way to treat AD with skin moisturizing and medication. PMID:27090158

  8. Dual-functional transdermal drug delivery system with controllable drug loading based on thermosensitive poloxamer hydrogel for atopic dermatitis treatment

    NASA Astrophysics Data System (ADS)

    Wang, Wenyi; Wat, Elaine; Hui, Patrick C. L.; Chan, Ben; Ng, Frency S. F.; Kan, Chi-Wai; Wang, Xiaowen; Hu, Huawen; Wong, Eric C. W.; Lau, Clara B. S.; Leung, Ping-Chung

    2016-04-01

    The treatment of atopic dermatitis (AD) has long been viewed as a problematic issue by the medical profession. Although a wide variety of complementary therapies have been introduced, they fail to combine the skin moisturizing and drug supply for AD patients. This study reports the development of a thermo-sensitive Poloxamer 407/Carboxymethyl cellulose sodium (P407/CMCs) composite hydrogel formulation with twin functions of moisture and drug supply for AD treatment. It was found that the presence of CMCs can appreciably improve the physical properties of P407 hydrogel, which makes it more suitable for tailored drug loading. The fabricated P407/CMCs composite hydrogel was also characterized in terms of surface morphology by field emission scanning electron microscopy (FE-SEM), rheological properties by a rheometer, release profile in vitro by dialysis method and cytotoxicity test. More importantly, the findings from transdermal drug delivery behavior revealed that P407/CMCs showed desirable percutaneous performance. Additionally, analysis of cytotoxicity test suggested that P407/CMCs composite hydrogel is a high-security therapy for clinical trials and thus exhibits a promising way to treat AD with skin moisturizing and medication.

  9. Fibronectin- and Collagen-Mimetic Ligands Regulate BMSC Chondrogenesis in 3D Hydrogels

    PubMed Central

    Connelly, J.T.; Petrie, T.A.; García, A.J.; Levenston, M.E.

    2016-01-01

    Modification of tissue engineering scaffolds with bioactive molecules is a potential strategy for modulating cell behavior and guiding tissue regeneration. While adhesion to RGD peptides has been shown to inhibit in vitro chondrogenesis, the effects of extracellular matrix (ECM)-mimetic ligands with complex secondary and tertiary structures are unknown. This study aimed to determine whether collagen- and fibronectin-mimetic ligands would retain biologic functionality in three-dimensional (3D) hydrogels, whether different ECM-mimetic ligands differentially influence in vitro chondrogenesis, and if effects of ligands on differentiation depend on soluble biochemical stimuli. A linear RGD peptide, a recombinant fibronectin fragment containing the seven to 10 Type III repeats (FnIII7-10) and a triple helical, collagen mimetic peptide with the GFOGER motif were covalently coupled to agarose gels using the sulfo-SANPAH crosslinker, and bone marrow stromal cells (BMSCs) were cultured within the 3D hydrogels.. The ligands retained biologic functionality within the agarose gels and promoted density-dependent BMSC spreading. Interactions with all adhesive ligands inhibited stimulation by chondrogenic factors of collagen Type II and aggrecanmRNA levels and deposition of sulfated glycosaminoglycans. In medium containing fetal bovine serum, interactions with the GFOGER peptide enhanced mRNA expression of the osteogenic gene osteocalcin whereas FnIII7-10 inhibited osteocalcin expression. In conclusion, modification of agarose hydrogels with ECM-mimetic ligands can influence the differentiation of BMSCs in a manner that depends strongly on the presence and nature of soluble biochemical stimuli. PMID:21932193

  10. Experimental and numerical tribological studies of a boundary lubricant functionalized poro-viscoelastic PVA hydrogel in normal contact and sliding.

    PubMed

    Blum, Michelle M; Ovaert, Timothy C

    2012-10-01

    Hydrogels are a cross-linked network of polymers swollen with liquid and have the potential to be used as a synthetic replacement for local defects in load bearing tissues such as articular cartilage. Hydrogels display viscoelastic time dependent behavior, therefore experimental analysis of stresses at the surface and within the gel is difficult to perform. A three-dimensional model of a hydrogel was developed in the commercial finite element software ABAQUS™, implementing a poro-viscoelastic constitutive model along with a contact-dependent flow state and friction conditions. Water content measurements, sliding, and indentation experiments were performed on neat polyvinyl alcohol (PVA), and on low friction boundary lubricant functionalized (BLF-PVA) hydrogels, both manufactured by freeze-thaw processes. Modulus results from the indentation experiments and coefficient of friction values from the sliding experiments were used as material property inputs to the model, while water content was used to calculate initial flow conditions. Tangential force and normal displacement data from a three-dimensional simulation of sliding were compared with the experiments. The tangential force patterns indicated important similarities with the fabricated hydrogels that included an initially high force value due to time dependent deformation followed by a decrease in a stabile value. A similar trend was observed with the normal displacement. These comparisons rendered the model suitable as a representation and were used to analyze the development and propagation of stresses in the immediate surface region. The results showed that in a three-dimensional stress field during sliding, the maximum stress shifted to the surface and rotated closer to the leading edge of contact. This occurred because the stress field becomes dominated by an amplified compressive stress at the leading edge due to the biphasic viscoelastic response of the material during sliding. Also, the complex multi

  11. A photolabile hydrogel for guided three-dimensional cell growth and migration

    NASA Astrophysics Data System (ADS)

    Luo, Ying; Shoichet, Molly S.

    2004-04-01

    Tissue engineering aims to replace, repair or regenerate tissue/organ function, by delivering signalling molecules and cells on a three-dimensional (3D) biomaterials scaffold that supports cell infiltration and tissue organization. To control cell behaviour and ultimately induce structural and functional tissue formation on surfaces, planar substrates have been patterned with adhesion signals that mimic the spatial cues to guide cell attachment and function. The objective of this study is to create biochemical channels in 3D hydrogel matrices for guided axonal growth. An agarose hydrogel modified with a cysteine compound containing a sulphydryl protecting group provides a photolabile substrate that can be patterned with biochemical cues. In this transparent hydrogel we immobilized the adhesive fibronectin peptide fragment, glycine-arginine-glycine-aspartic acid-serine (GRGDS), in selected volumes of the matrix using a focused laser. We verified in vitro the guidance effects of GRGDS oligopeptide-modified channels on the 3D cell migration and neurite outgrowth. This method for immobilizing biomolecules in 3D matrices can generally be applied to any optically clear hydrogel, offering a solution to construct scaffolds with programmed spatial features for tissue engineering applications.

  12. N-terminal specific conjugation of extracellular matrix proteins to 2-pyridinecarboxaldehyde functionalized polyacrylamide hydrogels.

    PubMed

    Lee, Jessica P; Kassianidou, Elena; MacDonald, James I; Francis, Matthew B; Kumar, Sanjay

    2016-09-01

    Polyacrylamide hydrogels have been used extensively to study cell responses to the mechanical and biochemical properties of extracellular matrix substrates. A key step in fabricating these substrates is the conjugation of cell adhesion proteins to the polyacrylamide surfaces, which typically involves nonspecifically anchoring these proteins via side-chain functional groups. This can result in a loss of presentation control and altered bioactivity. Here, we describe a new functionalization strategy in which we anchor full-length extracellular matrix proteins to polyacrylamide substrates using 2-pyridinecarboxaldehyde, which can be co-polymerized into polyacrylamide gels and used to immobilize proteins by their N-termini. This one-step reaction proceeds under mild aqueous conditions and does not require additional reagents. We demonstrate that these substrates can readily conjugate to various extracellular matrix proteins, as well as promote cell adhesion and spreading. Notably, this chemistry supports the assembly and cellular remodeling of large collagen fibers, which is not observed using conventional side-chain amine-conjugation chemistry. PMID:27348850

  13. Poly(vinyl alcohol)-Poly(ethylene glycol) Double-Network Hydrogel: A General Approach to Shape Memory and Self-Healing Functionalities.

    PubMed

    Li, Guo; Zhang, Hongji; Fortin, Daniel; Xia, Hesheng; Zhao, Yue

    2015-10-27

    A double-network polymer hydrogel composed of chemically cross-linked poly(ethylene glycol) (PEG) and physically cross-linked poly(vinyl alcohol) (PVA) was prepared. When the hydrogel (70 wt % of water) is subjected to freezing/thawing treatment under strain, the enhanced physical network as a result of crystallization of PVA chains can stabilize the hydrogel deformation after removal of the external force at room temperature. Subsequent disruption of the physical network of PVA by heating allows for the recovery of the initial shape of the hydrogel. Moreover, the double-network hydrogel exhibits self-healing capability stemming from the physical network of PVA by virtue of the extensive interchain hydrogen bonding between the hydroxyl side groups. This study thus demonstrates a general approach to imparting both the shape memory and self-healing properties to chemically cross-linked hydrogels that otherwise do not have such functionalities. Moreover, by making use of the fixed hydrogel elongation, the effect of anisotropy arising from chain orientation on the self-healing was also observed. PMID:26442631

  14. Hydrogel-assisted functional reconstitution of human P-glycoprotein (ABCB1) in giant liposomes

    PubMed Central

    Horger, Kim S.; Liu, Haiyan; Rao, Divya K.; Shukla, Suneet; Sept, David; Ambudkar, Suresh V.; Mayer, Michael

    2015-01-01

    This paper describes the formation of giant proteoliposomes containing P-glycoprotein (P-gp) from a solution of small proteoliposomes that had been deposited and partially dried on a film of agarose. This preparation method generated a significant fraction of giant proteoliposomes that were free of internalized vesicles, making it possible to determine the accessible liposome volume. Measuring the intensity of the fluorescent substrate rhodamine 123 (Rho123) inside and outside these giant proteoliposomes determined the concentration of transported substrates of P-gp. Fitting a kinetic model to the fluorescence data revealed the rate of passive diffusion as well as active transport by reconstituted P-gp in the membrane. This approach determined estimates for the membrane permeability coefficient (Ps) of passive diffusion and rate constants of active transport (kT) by P-gp as a result of different experimental conditions. The Ps value for Rho123 was larger in membranes containing P-gp under all assay conditions than in membranes without P-gp indicating increased leakiness in the presence of reconstituted transmembrane proteins. For P-gp liposomes, the kT value was significantly higher in the presence of ATP than in its absence or in the presence of ATP and the competitive inhibitor verapamil. This difference in kT values verified that P-gp was functionally active after reconstitution and quantified the rate of active transport. Lastly, patch clamp experiments on giant proteoliposomes showed ion channel activity consistent with a chloride ion channel protein that co-purified with P-gp. Together, these results demonstrate several advantages of using giant rather than small proteoliposomes to characterize transport properties of transport proteins and ion channels. PMID:25450342

  15. Hydrogel-assisted functional reconstitution of human P-glycoprotein (ABCB1) in giant liposomes.

    PubMed

    Horger, Kim S; Liu, Haiyan; Rao, Divya K; Shukla, Suneet; Sept, David; Ambudkar, Suresh V; Mayer, Michael

    2015-02-01

    This paper describes the formation of giant proteoliposomes containing P-glycoprotein (P-gp) from a solution of small proteoliposomes that had been deposited and partially dried on a film of agarose. This preparation method generated a significant fraction of giant proteoliposomes that were free of internalized vesicles, making it possible to determine the accessible liposome volume. Measuring the intensity of the fluorescent substrate rhodamine 123 (Rho123) inside and outside these giant proteoliposomes determined the concentration of transported substrates of P-gp. Fitting a kinetic model to the fluorescence data revealed the rate of passive diffusion as well as active transport by reconstituted P-gp in the membrane. This approach determined estimates for the membrane permeability coefficient (Ps) of passive diffusion and rate constants of active transport (kT) by P-gp as a result of different experimental conditions. The Ps value for Rho123 was larger in membranes containing P-gp under all assay conditions than in membranes without P-gp indicating increased leakiness in the presence of reconstituted transmembrane proteins. For P-gp liposomes, the kT value was significantly higher in the presence of ATP than in its absence or in the presence of ATP and the competitive inhibitor verapamil. This difference in kT values verified that P-gp was functionally active after reconstitution and quantified the rate of active transport. Lastly, patch clamp experiments on giant proteoliposomes showed ion channel activity consistent with a chloride ion channel protein that co-purified with P-gp. Together, these results demonstrate several advantages of using giant rather than small proteoliposomes to characterize transport properties of transport proteins and ion channels. PMID:25450342

  16. Porous Polyelectrolyte Hydrogels With Enhanced Swelling Properties Prepared Via Thermal Reverse Casting Technique

    NASA Astrophysics Data System (ADS)

    Salerno, Aurelio; Netti, Paolo A.

    2010-06-01

    In this work we investigated the preparation and characterization of porous polyelectrolyte hydrogels via thermal reverse casting technique. Polyacrylamide hydrogels were synthesized by free-radical crosslinking polymerization into the space of an agarose gel which, after the setting of the chemical gel, was removed to allow the formation of an interconnected porosity pathway. Two different monomer/agarose solution ratios were selected for the reverse casting process and, the resulting hydrogels characterized in terms of morphological, micro-structural and thermal properties, as well as swelling capability in solutions at different ionic strength. The results of this study demonstrated that proposed technique allowed the design of porous polyacrylamide hydrogels with well controlled pore structures. Furthermore, if compared to non porous polyacrylamide hydrogel, the as obtained hydrogels were characterized by enhanced swelling properties and that, these properties were fine tuned by the appropriate selection of the templating agent concentration.

  17. Amphiphilic agarose-based adsorbents for chromatography. Comparative study of adsorption capacities and desorption efficiencies.

    PubMed

    Oscarsson, S; Angulo-Tatis, D; Chaga, G; Porath, J

    1995-01-01

    A number of hydrophobic derivatives attached to cross-linked agarose were studied as protein adsorbents. Differences in the adsorption and desorption behaviour were determined as functions of type and concentration of selected salts. Whereas octyl- and phenyl-Sepharose adsorb serum albumin preferentially, pyridyl-S-agarose shows a much stronger preferential affinity for IgG in the presence of high concentrations of lyotropic salts, such as sulphates. In contrast to pyridyl-S-agarose, a large portion of proteins remained fixed to octyl- and phenyl-Sepharose after extensive washing with 1 M NaOH. PMID:7881534

  18. Supplementation of Exogenous Adenosine 5′-Triphosphate Enhances Mechanical Properties of 3D Cell–Agarose Constructs for Cartilage Tissue Engineering

    PubMed Central

    Gadjanski, Ivana; Yodmuang, Supansa; Spiller, Kara; Bhumiratana, Sarindr

    2013-01-01

    Formation of tissue-engineered cartilage is greatly enhanced by mechanical stimulation. However, direct mechanical stimulation is not always a suitable method, and the utilization of mechanisms underlying mechanotransduction might allow for a highly effective and less aggressive alternate means of stimulation. In particular, the purinergic, adenosine 5′-triphosphate (ATP)-mediated signaling pathway is strongly implicated in mechanotransduction within the articular cartilage. We investigated the effects of transient and continuous exogenous ATP supplementation on mechanical properties of cartilaginous constructs engineered using bovine chondrocytes and human mesenchymal stem cells (hMSCs) encapsulated in an agarose hydrogel. For both cell types, we have observed significant increases in equilibrium and dynamic compressive moduli after transient ATP treatment applied in the fourth week of cultivation. Continuous ATP treatment over 4 weeks of culture only slightly improved the mechanical properties of the constructs, without major changes in the total glycosaminoglycan (GAG) and collagen content. Structure–function analyses showed that transiently ATP-treated constructs, and in particular those based on hMSCs, had the highest level of correlation between compositional and mechanical properties. Transiently treated groups showed intense staining of the territorial matrix for GAGs and collagen type II. These results indicate that transient ATP treatment can improve functional mechanical properties of cartilaginous constructs based on chondrogenic cells and agarose hydrogels, possibly by improving the structural organization of the bulk phase and territorial extracellular matrix (ECM), that is, by increasing correlation slopes between the content of the ECM components (GAG, collagen) and mechanical properties of the construct. PMID:23651296

  19. Functional Performance of Human Cardiosphere-derived Cells Delivered in an In Situ Polymerizable Hyaluronan-Gelatin Hydrogel

    PubMed Central

    Cheng, Ke; Blusztajn, Agnieszka; Shen, Deliang; Li, Tao-Sheng; Sun, Baiming; Galang, Giselle; Zarembinski, Thomas I.; Prestwich, Glenn D.; Marbán, Eduardo; Smith, Rachel R.; Marbán, Linda

    2015-01-01

    The vast majority of cells delivered into the heart by conventional means are lost within the first 24 hours. Methods are needed to enhance cell retention, so as to minimize loss of precious material and maximize effectiveness of the therapy. We tested a cell-hydrogel delivery strategy. Cardiosphere-derived cells (CDCs) were grown from adult human cardiac biopsy specimens. In situ polymerizable hydrogels made of hyaluronan and porcine gelatin (Hystem®-C™) were formulated as a liquid at room temperature so as to gel within 20 minutes at 37°C. CDC viability and migration were not compromised in Hystem-C™. Myocardial infarction was created in SCID mice and CDCs were injected intramyocardially in the infarct border zone. Real time PCR revealed engraftment of CDCs delivered in Hystem-C™ was increased by nearly an order of magnitude. LVEF (left ventricular ejection fraction) deteriorated in the control (PBS only) group over the 3-week time course. Hystem-C™ alone or CDCs alone preserved LVEF relative to baseline, while CDCs delivered in Hystem-C™ resulted in a sizable boost in LVEF. Heart morphometry revealed the greatest attenuation of LV remodeling in the CDC + Hystem-C™ group. Histological analysis suggested cardiovascular differentiation of the CDCs in Hystem-C™. However, the majority of functional benefit is likely from paracrine mechanisms such as tissue preservation and neovascularization. A CDC/hydrogel formulation suitable for catheter-based intramyocardial injection exhibits superior engraftment and functional benefits relative to naked CDCs. PMID:22560668

  20. Phenotypic Stability, Matrix Elaboration, and Functional Maturation of Nucleus Pulposus Cells Encapsulated in Photocrosslinkable Hyaluronic Acid Hydrogels

    PubMed Central

    Kim, Dong Hwa; Martin, John T.; Elliott, Dawn M.; Smith, Lachlan J.; Mauck, Robert L.

    2014-01-01

    Degradation of the nucleus pulposus (NP) is an early hallmark of intervertebral disc degeneration. The capacity for endogenous regeneration in the NP is limited due to the low cellularity and poor nutrient supply of this avascular tissue. Towards restoring the NP, a number of biomaterials have been explored for cell delivery. These materials must support the NP cell phenotype while promoting the elaboration of an NP-like extracellular matrix in the shortest possible time. Our previous work with chondrocytes and mesenchymal stem cells demonstrated that hydrogels based on hyaluronic acid (HA) are effective at promoting matrix production and the development of functional material properties. However, this material has not been evaluated in the context of NP cells. Therefore, to test this material for NP regeneration, bovine NP cells were encapsulated in 1% w/vol HA hydrogels at either a low seeding density (20 × 106 cells/ml) or a high seeding density (60 × 106 cells/ml), and constructs were cultured over an 8 week period. These engineered NP cell-laden HA hydrogels showed functional matrix accumulation, with increasing matrix content and mechanical properties with time in culture at both seeding densities. Furthermore, encapsulated cells showed NP-specific gene expression profiles that were significantly higher than expanded NP cells prior to encapsulation, suggesting a restoration of phenotype. Interestingly, these levels were higher at the lower seeding density compared to the higher seeding density. These findings support the use of HA-based hydrogels for NP tissue engineering and cellular therapies directed at restoration or replacement of the endogenous NP. PMID:25448344

  1. Development of functionalized multi-walled carbon-nanotube-based alginate hydrogels for enabling biomimetic technologies

    PubMed Central

    Joddar, Binata; Garcia, Eduardo; Casas, Atzimba; Stewart, Calvin M.

    2016-01-01

    Alginate is a hydrogel commonly used for cell culture by ionically crosslinking in the presence of divalent Ca2+ ions. However these alginate gels are mechanically unstable, not permitting their use as scaffolds to engineer robust biological bone, breast, cardiac or tumor tissues. This issue can be addressed via encapsulation of multi-walled carbon nanotubes (MWCNT) serving as a reinforcing phase while being dispersed in a continuous phase of alginate. We hypothesized that adding functionalized MWCNT to alginate, would yield composite gels with distinctively different mechanical, physical and biological characteristics in comparison to alginate alone. Resultant MWCNT-alginate gels were porous, and showed significantly less degradation after 14 days compared to alginate alone. In vitro cell-studies showed enhanced HeLa cell adhesion and proliferation on the MWCNT-alginate compared to alginate. The extent of cell proliferation was greater when cultured atop 1 and 3 mg/ml MWCNT-alginate; although all MWCNT-alginates lead to enhanced cell cluster formation compared to alginate alone. Among all the MWCNT-alginates, the 1 mg/ml gels showed significantly greater stiffness compared to all other cases. These results provide an important basis for the development of the MWCNT-alginates as novel substrates for cell culture applications, cell therapy and tissue engineering. PMID:27578567

  2. Development of functionalized multi-walled carbon-nanotube-based alginate hydrogels for enabling biomimetic technologies.

    PubMed

    Joddar, Binata; Garcia, Eduardo; Casas, Atzimba; Stewart, Calvin M

    2016-01-01

    Alginate is a hydrogel commonly used for cell culture by ionically crosslinking in the presence of divalent Ca(2+) ions. However these alginate gels are mechanically unstable, not permitting their use as scaffolds to engineer robust biological bone, breast, cardiac or tumor tissues. This issue can be addressed via encapsulation of multi-walled carbon nanotubes (MWCNT) serving as a reinforcing phase while being dispersed in a continuous phase of alginate. We hypothesized that adding functionalized MWCNT to alginate, would yield composite gels with distinctively different mechanical, physical and biological characteristics in comparison to alginate alone. Resultant MWCNT-alginate gels were porous, and showed significantly less degradation after 14 days compared to alginate alone. In vitro cell-studies showed enhanced HeLa cell adhesion and proliferation on the MWCNT-alginate compared to alginate. The extent of cell proliferation was greater when cultured atop 1 and 3 mg/ml MWCNT-alginate; although all MWCNT-alginates lead to enhanced cell cluster formation compared to alginate alone. Among all the MWCNT-alginates, the 1 mg/ml gels showed significantly greater stiffness compared to all other cases. These results provide an important basis for the development of the MWCNT-alginates as novel substrates for cell culture applications, cell therapy and tissue engineering. PMID:27578567

  3. Gelatin methacrylate as a promising hydrogel for 3D microscale organization and proliferation of dielectrophoretically patterned cells.

    PubMed

    Ramón-Azcón, Javier; Ahadian, Samad; Obregón, Raquel; Camci-Unal, Gulden; Ostrovidov, Serge; Hosseini, Vahid; Kaji, Hirokazu; Ino, Kosuke; Shiku, Hitoshi; Khademhosseini, Ali; Matsue, Tomokazu

    2012-08-21

    Establishing the 3D microscale organization of cells has numerous practical applications, such as in determining cell fate (e.g., proliferation, migration, differentiation, and apoptosis) and in making functional tissue constructs. One approach to spatially pattern cells is by dielectrophoresis (DEP). DEP has characteristics that are important for cell manipulation, such as high accuracy, speed, scalability, and the ability to handle both adherent and non-adherent cells. However, widespread application of this method is largely restricted because there is a limited number of suitable hydrogels for cell encapsulation. To date, polyethylene glycol-diacrylate (PEG-DA) and agarose have been used extensively for dielectric patterning of cells. In this study, we propose gelatin methacrylate (GelMA) as a promising hydrogel for use in cell dielectropatterning because of its biocompatibility and low viscosity. Compared to PEG hydrogels, GelMA hydrogels showed superior performance when making cell patterns for myoblast (C2C12) and endothelial (HUVEC) cells as well as in maintaining cell viability and growth. We also developed a simple and robust protocol for co-culture of these cells. Combined application of the GelMA hydrogels and the DEP technique is suitable for creating highly complex microscale tissues with important applications in fundamental cell biology and regenerative medicine in a rapid, accurate, and scalable manner. PMID:22773042

  4. Development of a strategy to functionalize a dextrin-based hydrogel for animal cell cultures using a starch-binding module fused to RGD sequence

    PubMed Central

    Moreira, Susana M; Andrade, Fábia K; Domingues, Lucíla; Gama, Miguel

    2008-01-01

    Background Several approaches can be used to functionalize biomaterials, such as hydrogels, for biomedical applications. One of the molecules often used to improve cells adhesion is the peptide Arg-Gly-Asp (RGD). The RGD sequence, present in several proteins from the extra-cellular matrix (ECM), is a ligand for integrin-mediated cell adhesion; this sequence was recognized as a major functional group responsible for cellular adhesion. In this work a bi-functional recombinant protein, containing a starch binding module (SBM) and RGD sequence was used to functionalize a dextrin-based hydrogel. The SBM, which belongs to an α-amylase from Bacillus sp. TS-23, has starch (and dextrin, depolymerized starch) affinity, acting as a binding molecule to adsorb the RGD sequence to the hydrogel surface. Results The recombinant proteins SBM and RGD-SBM were cloned, expressed, purified and tested in in vitro assays. The evaluation of cell attachment, spreading and proliferation on the dextrin-based hydrogel surface activated with recombinant proteins were performed using mouse embryo fibroblasts 3T3. A polystyrene cell culture plate was used as control. The results showed that the RGD-SBM recombinant protein improved, by more than 30%, the adhesion of fibroblasts to dextrin-based hydrogel. In fact, cell spreading on the hydrogel surface was observed only in the presence of the RGD-SBM. Conclusion The fusion protein RGD-SBM provides an efficient way to functionalize the dextrin-based hydrogel. Many proteins in nature that hold a RGD sequence are not cell adhesive, probably due to the conformation/accessibility of the peptide. We therefore emphasise the successful expression of a bi-functional protein with potential for different applications. PMID:18854017

  5. Micropatterned cell-cell interactions enable functional encapsulation of primary hepatocytes in hydrogel microtissues.

    PubMed

    Li, Cheri Y; Stevens, Kelly R; Schwartz, Robert E; Alejandro, Brian S; Huang, Joanne H; Bhatia, Sangeeta N

    2014-08-01

    Drug-induced liver injury is a major cause of drug development failures and postmarket withdrawals. In vitro models that incorporate primary hepatocytes have been shown to be more predictive than model systems which rely on liver microsomes or hepatocellular carcinoma cell lines. Methods to phenotypically stabilize primary hepatocytes ex vivo often rely on mimicry of hepatic microenvironmental cues such as cell-cell interactions and cell-matrix interactions. In this work, we sought to incorporate phenotypically stable hepatocytes into three-dimensional (3D) microtissues, which, in turn, could be deployed in drug-screening platforms such as multiwell plates and diverse organ-on-a-chip devices. We first utilize micropatterning on collagen I to specify cell-cell interactions in two-dimensions, followed by collagenase digestion to produce well-controlled aggregates for 3D encapsulation in polyethylene glycol (PEG) diacrylate. Using this approach, we examined the influence of homotypic hepatocyte interactions and composition of the encapsulating hydrogel, and achieved the maintenance of liver-specific function for over 50 days. Optimally preaggregated structures were subsequently encapsulated using a microfluidic droplet-generator to produce 3D microtissues. Interactions of engineered hepatic microtissues with drugs was characterized by flow cytometry, and yielded both induction of P450 enzymes in response to prototypic small molecules and drug-drug interactions that give rise to hepatotoxicity. Collectively, this study establishes a pipeline for the manufacturing of 3D hepatic microtissues that exhibit stabilized liver-specific functions and can be incorporated into a wide array of emerging drug development platforms. PMID:24498910

  6. Micropatterned Cell–Cell Interactions Enable Functional Encapsulation of Primary Hepatocytes in Hydrogel Microtissues

    PubMed Central

    Li, Cheri Y.; Stevens, Kelly R.; Schwartz, Robert E.; Alejandro, Brian S.; Huang, Joanne H.

    2014-01-01

    Drug-induced liver injury is a major cause of drug development failures and postmarket withdrawals. In vitro models that incorporate primary hepatocytes have been shown to be more predictive than model systems which rely on liver microsomes or hepatocellular carcinoma cell lines. Methods to phenotypically stabilize primary hepatocytes ex vivo often rely on mimicry of hepatic microenvironmental cues such as cell–cell interactions and cell–matrix interactions. In this work, we sought to incorporate phenotypically stable hepatocytes into three-dimensional (3D) microtissues, which, in turn, could be deployed in drug-screening platforms such as multiwell plates and diverse organ-on-a-chip devices. We first utilize micropatterning on collagen I to specify cell–cell interactions in two-dimensions, followed by collagenase digestion to produce well-controlled aggregates for 3D encapsulation in polyethylene glycol (PEG) diacrylate. Using this approach, we examined the influence of homotypic hepatocyte interactions and composition of the encapsulating hydrogel, and achieved the maintenance of liver-specific function for over 50 days. Optimally preaggregated structures were subsequently encapsulated using a microfluidic droplet-generator to produce 3D microtissues. Interactions of engineered hepatic microtissues with drugs was characterized by flow cytometry, and yielded both induction of P450 enzymes in response to prototypic small molecules and drug–drug interactions that give rise to hepatotoxicity. Collectively, this study establishes a pipeline for the manufacturing of 3D hepatic microtissues that exhibit stabilized liver-specific functions and can be incorporated into a wide array of emerging drug development platforms. PMID:24498910

  7. Separations of Short DNA in Agarose Gels: What Model Applies?

    NASA Astrophysics Data System (ADS)

    Beheshti, Afshin

    2000-03-01

    Gel Electrophoresis is used ubiquitously for separating proteins and DNA fragments from mixtures into individual components. Molecules separate because their mobilities, μ = v / E, depend on their effective charge and effective friction imposed by the gel. Models describing the dependence of μ on molecular parameters are inadequate. For example, the reptation theory as applied in other studies suggests μ proportional to (1/L). We asked whether the relationship (1/μ) proportional to AL + B, where A and B are independent parameters, would better describe electrophoretic separations of DNA fragments over a wide range of fragment lengths. A series of DNA ladders were electrophoresed in Seakem and in Metaphor agarose and mobilities studied as a function of their DNA length. In the Metaphor agarose a range of 10 bp to 1500 bp DNA fragments were observed. While in the Seakem agarose the study was done with DNA fragments ranging from 100 bp to 10 kbp. Results of the fits for μ vs. L indicate the dependence is more complex than these simple models suggest. Supported by NSF BES 9521381 and NSF Research Training Grant Fellowship 130362022.

  8. Effect of an Adipose-Derived Stem Cell and Nerve Growth Factor-Incorporated Hydrogel on Recovery of Erectile Function in a Rat Model of Cavernous Nerve Injury

    PubMed Central

    Kim, In Gul; Piao, Shuyu; Lee, Ji Young; Hong, Sung Hoo; Hwang, Tae-Kon; Kim, Sae Woong; Kim, Choung Soo; Ra, Jeong Chan; Noh, Insup

    2013-01-01

    Postprostatectomy erectile dysfunction (ED) is the major problem for patients with clinically localized prostate cancer. Recently, gene and stem cell-based therapy of the corpus cavernosum has been attempted for postprostatectomy ED, but those therapies are limited by rapid blood flow and disruption of the normal architecture of the corpus cavernosum. In this study, we attempted to regenerate the damaged cavernous nerve (CN), which is the main cause of ED. We investigated the effectiveness of human adipose-derived stem cell (hADSC) and nerve growth factor-incorporated hyaluronic acid-based hydrogel (NGF-hydrogel) application on the CN in a rat model of bilateral cavernous nerve crush injury. Four weeks after the operation, erectile function was assessed by detecting the intracavernous pressure (ICP)/arterial pressure level by CN electrostimulation. The ICP was significantly increased by application of hADSC with NGF-hydrogel compared to the other experimental groups. CN and penile tissue were collected for histological examination. PKH-26 labeled hADSC colocalized with beta III tubulin were shown in CN tissue sections. hADSC/NGF-hydrogel treatment prevented smooth muscle atrophy in the corpus cavernosum. In addition, the hADSC/NGF-hydrogel group showed increased endothelial nitric oxide synthase protein expression. This study suggests that application of hADSCs with NGF-hydrogel on the CN might be a promising treatment for postprostatectomy ED. PMID:22834730

  9. Impact of hydrogel nanoparticle size and functionalization on in vivo behavior for lung imaging and therapeutics.

    PubMed

    Liu, Yongjian; Ibricevic, Aida; Cohen, Joel A; Cohen, Jessica L; Gunsten, Sean P; Fréchet, Jean M J; Walter, Michael J; Welch, Michael J; Brody, Steven L

    2009-01-01

    Polymer chemistry offers the possibility of synthesizing multifunctional nanoparticles which incorporate moieties that enhance diagnostic and therapeutic targeting of cargo delivery to the lung. However, since rules for predicting particle behavior following modification are not well-defined, it is essential that probes for tracking fate in vivo are also included. Accordingly, we designed polyacrylamide-based hydrogel particles of differing sizes, functionalized with a nona-arginine cell-penetrating peptide (Arg(9)), and labeled with imaging components to assess lung retention and cellular uptake after intratracheal administration. Radiolabeled microparticles (1-5 microm diameter) and nanoparticles (20-40 nm diameter) without and with Arg(9) showed diffuse airspace distribution by positron emission tomography imaging. Biodistribution studies revealed that particle clearance and extrapulmonary distribution was, in part, size dependent. Microparticles were rapidly cleared by mucociliary routes but, unexpectedly, also through the circulation. In contrast, nanoparticles had prolonged lung retention enhanced by Arg(9) and were significantly restricted to the lung. For all particle types, uptake was predominant in alveolar macrophages and, to a lesser extent, lung epithelial cells. In general, particles did not induce local inflammatory responses, with the exception of microparticles bearing Arg(9). Whereas microparticles may be advantageous for short-term applications, nanosized particles constitute an efficient high-retention and non-inflammatory vehicle for the delivery of diagnostic imaging agents and therapeutics to lung airspaces and alveolar macrophages that can be enhanced by Arg(9). Importantly, our results show that minor particle modifications may significantly impact in vivo behavior within the complex environments of the lung, underscoring the need for animal modeling. PMID:19852512

  10. Nitrocinnamate-functionalized gelatin: synthesis and "smart"hydrogel formation via photo-cross-linking.

    PubMed

    Gattás-Asfura, Kerim M; Weisman, Eric; Andreopoulos, Fotios M; Micic, Miodrag; Muller, Bill; Sirpal, Sanjeev; Pham, Si M; Leblanc, Roger M

    2005-01-01

    Gelatin having p-nitrocinnamate pendant groups (Gel-NC) was prepared via an efficient one-pot synthesis, yield >87%. (1)H NMR data indicated that 1 mol of gelatin was modified with 18 +/- 6 mol of the photosensitive group. Upon exposure to low-intensity 365 nm UV light and in the absence of photoinitiators or catalysts, Gel-NC cross-linked within minutes into a gelatin-based hydrogel as monitored by UV-vis spectroscopy. The degree of swelling of this biodegradable hydrogel in aqueous solutions responded to changes in Gel-NC concentration levels, the ionic strength of the aqueous solutions, and photo-cross-linking time. Topography changes associated with phase transition resulting from "photocleavage" of the hydrogel network with 254 nm UV light were studied with AFM. Both Gel-NC and its hydrogel expressed low toxicity to human neonatal fibroblast cells. In addition, gelatin-based microgels were prepared via the photo-cross-linking of Gel-NC within inverse micelles. PMID:15877371

  11. Recycling of superfine resolution agarose gel.

    PubMed

    Seng, T-Y; Singh, R; Faridah, Q Z; Tan, S-G; Alwee, S S R S

    2013-01-01

    Genetic markers are now routinely used in a wide range of applications, from forensic DNA analysis to marker-assisted plant and animal breeding. The usual practice in such work is to extract the DNA, prime the markers of interest, and sift them out by electrically driving them through an appropriate matrix, usually a gel. The gels, made from polyacrylamide or agarose, are of high cost, limiting their greater applications in molecular marker work, especially in developing countries where such technology has great potential. Trials using superfine resolution (SFR) agarose for SSR marker screening showed that it is capable of resolving SSR loci and can be reused up to 14 times, thus greatly reducing the cost of each gel run. Furthermore, for certain applications, low concentrations of agarose sufficed and switching to lithium borate buffer, instead of the conventional Tris-borate-ethylenediaminetetraacetic acid buffer, will further save time and cost. The 2.5% gel was prepared following the Agarose SFR(TM) manual by adding 2.5 g agarose powder into 100 mL 1X lithium borate buffer in a 250-mL flask with rapid stirring. Two midigels (105 x 83 mm, 17 wells) or 4 minigels (50 x 83 mm, 8 wells), 4 mm thickness can be prepared from 100 mL gel solution. A total of 1680 PCR products amplified using 140 SSR markers from oil palm DNA samples were tested in this study using SFR recycled gel. As average, the gel can be recycled 8 times with good resolution, but can be recycled up to 14 times before the resolutions get blurred. PMID:23546970

  12. Microwave-assisted Functionalization of Poly(ethylene glycol) and On-resin Peptides for Use in Chain Polymerizations and Hydrogel Formation

    PubMed Central

    Van Hove, Amy H.; Wilson, Brandon D.; Benoit, Danielle S. W.

    2013-01-01

    One of the main benefits to using poly(ethylene glycol) (PEG) macromers in hydrogel formation is synthetic versatility. The ability to draw from a large variety of PEG molecular weights and configurations (arm number, arm length, and branching pattern) affords researchers tight control over resulting hydrogel structures and properties, including Young’s modulus and mesh size. This video will illustrate a rapid, efficient, solvent-free, microwave-assisted method to methacrylate PEG precursors into poly(ethylene glycol) dimethacrylate (PEGDM). This synthetic method provides much-needed starting materials for applications in drug delivery and regenerative medicine. The demonstrated method is superior to traditional methacrylation methods as it is significantly faster and simpler, as well as more economical and environmentally friendly, using smaller amounts of reagents and solvents. We will also demonstrate an adaptation of this technique for on-resin methacrylamide functionalization of peptides. This on-resin method allows the N-terminus of peptides to be functionalized with methacrylamide groups prior to deprotection and cleavage from resin. This allows for selective addition of methacrylamide groups to the N-termini of the peptides while amino acids with reactive side groups (e.g. primary amine of lysine, primary alcohol of serine, secondary alcohols of threonine, and phenol of tyrosine) remain protected, preventing functionalization at multiple sites. This article will detail common analytical methods (proton Nuclear Magnetic Resonance spectroscopy (;H-NMR) and Matrix Assisted Laser Desorption Ionization Time of Flight mass spectrometry (MALDI-ToF)) to assess the efficiency of the functionalizations. Common pitfalls and suggested troubleshooting methods will be addressed, as will modifications of the technique which can be used to further tune macromer functionality and resulting hydrogel physical and chemical properties. Use of synthesized products for the

  13. Agarose particle-templated porous bacterial cellulose and its application in cartilage growth in vitro.

    PubMed

    Yin, Na; Stilwell, Matthew D; Santos, Thiago M A; Wang, Huaping; Weibel, Douglas B

    2015-01-01

    Bacterial cellulose (BC) is a biocompatible hydrogel with a three-dimensional (3-D) structure formed by a dense network of cellulose nanofibers. A limitation of using BC for applications in tissue engineering is that the pore size of the material (∼0.02-10μm) is smaller than the dimensions of mammalian cells and prevents cells from penetrating into the material and growing into 3-D structures that mimic tissues. This paper describes a new route to porous bacterial cellulose (pBC) scaffolds by cultivating Acetobacter xylinum in the presence of agarose microparticles deposited on the surface of a growing BC pellicle. Monodisperse agarose microparticles with a diameter of 300-500μm were created using a microfluidic technique, layered on growing BC pellicles and incorporated into the polymer as A. xylinum cells moved upward through the growing pellicle. Removing the agarose microparticles by autoclaving produced BC gels containing a continuous, interconnected network of pores with diameters ranging from 300 to 500μm. Human P1 chondrocytes seeded on the scaffolds, replicated, invaded the 3-D porous network and distributed evenly throughout the substrate. Chondrocytes grown on pBC substrates displayed a higher viability compared to growth on the surface of unmodified BC substrates. The approach described in this paper introduces a new method for creating pBC substrates with user-defined control over the physical dimensions of the pore network, and demonstrates the application of these materials for tissue engineering. PMID:25449918

  14. Functionalized graphene oxide-based thermosensitive hydrogel for magnetic hyperthermia therapy on tumors.

    PubMed

    Zhu, Xiali; Zhang, Huijuan; Huang, Heqing; Zhang, Yingjie; Hou, Lin; Zhang, Zhenzhong

    2015-09-11

    A novel locally injectable, biodegradable, and thermo-sensitive hydrogel made from chitosan and β-glycerophosphate salt was prepared. It incorporated polyethylenimine (PEI)-modified super-paramagnetic graphene oxide (GO/IONP/PEI) as a form of minimally invasive treatment of cancer lesions by magnetically induced local hyperthermia. Doxorubicin (DOX) was mixed into the hydrogel which was pre-loaded on GO/IONP/PEI to create a drug delivery system DOX-GO/IONP/PEI-gel. In addition to the evaluation of in vitro and in vivo antitumor activities, the physicochemical properties, magnetic properties and DOX release profile of the DOX-GO/IONP/PEI-gel were determined. The aqueous solution of the hydrogel showed a sol-gel transition behavior depending on temperature changes. Magnetization loops indicated the super-paramagnetic properties of GO/IONP/PEI. Compared with free DOX, DOX-GO/IONP/PEI could efficiently pass through cell membranes, leading to more apoptosis and demonstrating higher antitumor efficacy on MCF-7 cells in vitro. Furthermore, DOX-GO/IONP/PEI-gel intratumorally injected (i.t.) showed high antitumor efficacy on tumor-bearing mice in vivo, with no obvious toxicity. The antitumor efficacy was higher when combined with an alternating magnetic field (AMF), showing that DOX-GO/IONP/PEI-gel under AMF has great potential for cancer magnetic hyperthermia therapy. PMID:26291977

  15. Functionalized graphene oxide-based thermosensitive hydrogel for magnetic hyperthermia therapy on tumors

    NASA Astrophysics Data System (ADS)

    Zhu, Xiali; Zhang, Huijuan; Huang, Heqing; Zhang, Yingjie; Hou, Lin; Zhang, Zhenzhong

    2015-09-01

    A novel locally injectable, biodegradable, and thermo-sensitive hydrogel made from chitosan and β-glycerophosphate salt was prepared. It incorporated polyethylenimine (PEI)-modified super-paramagnetic graphene oxide (GO/IONP/PEI) as a form of minimally invasive treatment of cancer lesions by magnetically induced local hyperthermia. Doxorubicin (DOX) was mixed into the hydrogel which was pre-loaded on GO/IONP/PEI to create a drug delivery system DOX-GO/IONP/PEI-gel. In addition to the evaluation of in vitro and in vivo antitumor activities, the physicochemical properties, magnetic properties and DOX release profile of the DOX-GO/IONP/PEI-gel were determined. The aqueous solution of the hydrogel showed a sol-gel transition behavior depending on temperature changes. Magnetization loops indicated the super-paramagnetic properties of GO/IONP/PEI. Compared with free DOX, DOX-GO/IONP/PEI could efficiently pass through cell membranes, leading to more apoptosis and demonstrating higher antitumor efficacy on MCF-7 cells in vitro. Furthermore, DOX-GO/IONP/PEI-gel intratumorally injected (i.t.) showed high antitumor efficacy on tumor-bearing mice in vivo, with no obvious toxicity. The antitumor efficacy was higher when combined with an alternating magnetic field (AMF), showing that DOX-GO/IONP/PEI-gel under AMF has great potential for cancer magnetic hyperthermia therapy.

  16. Crosslinking of agarose bioplastic using citric acid.

    PubMed

    Awadhiya, Ankur; Kumar, David; Verma, Vivek

    2016-10-20

    We report chemical crosslinking of agarose bioplastic using citric acid. Crosslinking was confirmed using Fourier transform infrared (FTIR) spectroscopy. The effects of crosslinking on the tensile strength, swelling, thermal stability, and degradability of the bioplastic were studied in detail. The tensile strength of the bioplastic films increased from 25.1MPa for control films up to a maximum of 52.7MPa for citric acid crosslinked films. At 37°C, the amount of water absorbed by crosslinked agarose bioplastic was only 11.5% of the amount absorbed by non-crosslinked controls. Thermogravimetric results showed that the crosslinked samples retain greater mass at high temperature (>450°C) than control samples. Moreover, while the crosslinked films were completely degradable, the rate of degradation was lower compared to non-crosslinked controls. PMID:27474543

  17. Stretchable Hydrogel Electronics and Devices.

    PubMed

    Lin, Shaoting; Yuk, Hyunwoo; Zhang, Teng; Parada, German Alberto; Koo, Hyunwoo; Yu, Cunjiang; Zhao, Xuanhe

    2016-06-01

    Stretchable hydrogel electronics and devices are designed by integrating stretchable conductors, functional chips, drug-delivery channels, and reservoirs into stretchable, robust, and biocompatible hydrogel matrices. Novel applications include a smart wound dressing capable of sensing the temperatures of various locations on the skin, delivering different drugs to these locations, and subsequently maintaining sustained release of drugs. PMID:26639322

  18. Enhanced selective removal of Cu(II) from aqueous solution by novel polyethylenimine-functionalized ion imprinted hydrogel: Behaviors and mechanisms.

    PubMed

    Wang, Jingjing; Li, Zhengkui

    2015-12-30

    A novel polyethylenimine-functionalized ion-imprinted hydrogel (Cu(II)-p(PEI/HEA)) was newly synthesized by (60)Co-γ-induced polymerization for the selective removal of Cu(II) from aqueous solution. The adsorption performances including the adsorption capacity and selectivity of the novel hydrogel were much better than those of similar adsorbents reported. The hydrogel was characterized via scanning electron microscope, transmission electron microscopy, Fourier transform infrared spectra, thermal gravimetric analysis and X-ray photoelectron spectroscopy to determine the structure and mechanisms. The adsorption process was pH and temperature sensitive, better fitted to pseudo-second-order equation, and was Langmuir monolayer adsorption. The maximum adsorption capacity for Cu(II) was 40.00 mg/g. The selectivity coefficients of ion-imprinted hydrogel for Cu(II)/Pb(II), Cu(II)/Cd(II) and Cu(II)/Ni(II) were 55.09, 107.47 and 63.12, respectively, which were 3.93, 4.25 and 3.53 times greater than those of non-imprinted hydrogel, respectively. Moreover, the adsorption capacity of Cu(II)-p(PEI/HEA) could still keep more than 85% after four adsorption-desorption cycles. Because of such enhanced selective removal performance and excellent regeneration property, Cu(II)-p(PEI/HEA) is a promising adsorbent for the selective removal of copper ions from wastewater. PMID:26151381

  19. Controlled formation of heterotypic hepatic micro-organoids in anisotropic hydrogel microfibers for long-term preservation of liver-specific functions.

    PubMed

    Yamada, Masumi; Utoh, Rie; Ohashi, Kazuo; Tatsumi, Kohei; Yamato, Masayuki; Okano, Teruo; Seki, Minoru

    2012-11-01

    We have developed a hydrogel-based cell cultivation platform for forming 3D restiform hepatic micro-organoids consisting of primary rat hepatocytes and feeder cells (Swiss 3T3 cells). Sodium alginate solutions containing hepatocytes/3T3 cells were continuously introduced into a microfluidic channel to produce cell-incorporating anisotropic Ba-alginate hydrogel microfibers, where hepatocytes at the center were closely sandwiched by 3T3 cells. Hydrogel fiber-based cultivation under high oxygen tension enabled the formation of heterotypic micro-organoids with a length of up to 1 mm and a diameter of ∼50 μm, mimicking the hepatic cord structures found in the liver, while maintaining a high hepatocyte viability (∼80%) over 30 days. Long-term observation of up to 90 days revealed a significant enhancement of hepatic functions because of heterotypic and homotypic cell-cell interactions, including albumin secretion and urea synthesis as well as expression of hepatocyte-specific genes, compared with conventional monolayer culture and single cultivation in the hydrogel fibers. The encapsulated hepatic constructs were recovered as scaffold-free micro-organoids by enzymatically digesting the hydrogel matrices using alginate lyase. This technique for creating heterotypic micro-organoids with precisely ordered multiple cell types will be useful for the development of a new liver tissue engineering approach and may be applicable to the fabrication of extracorporeal bioartificial liver (BAL) devices and assessment tools for drug development and testing. PMID:22906609

  20. Patterned and functionalized nanofiber scaffolds in three-dimensional hydrogel constructs enhance neurite outgrowth and directional control

    NASA Astrophysics Data System (ADS)

    McMurtrey, Richard J.

    2014-12-01

    Objective. Neural tissue engineering holds incredible potential to restore functional capabilities to damaged neural tissue. It was hypothesized that patterned and functionalized nanofiber scaffolds could control neurite direction and enhance neurite outgrowth. Approach. A method of creating aligned electrospun nanofibers was implemented and fiber characteristics were analyzed using environmental scanning electron microscopy. Nanofibers were composed of polycaprolactone (PCL) polymer, PCL mixed with gelatin, or PCL with a laminin coating. Three-dimensional hydrogels were then integrated with embedded aligned nanofibers to support neuronal cell cultures. Microscopic images were captured at high-resolution in single and multi-focal planes with eGFP-expressing neuronal SH-SY5Y cells in a fluorescent channel and nanofiber scaffolding in another channel. Neuronal morphology and neurite tracking of nanofibers were then analyzed in detail. Main results. Aligned nanofibers were shown to enable significant control over the direction of neurite outgrowth in both two-dimensional (2D) and three-dimensional (3D) neuronal cultures. Laminin-functionalized nanofibers in 3D hyaluronic acid (HA) hydrogels enabled significant alignment of neurites with nanofibers, enabled significant neurite tracking of nanofibers, and significantly increased the distance over which neurites could extend. Specifically, the average length of neurites per cell in 3D HA constructs with laminin-functionalized nanofibers increased by 66% compared to the same laminin fibers on 2D laminin surfaces, increased by 59% compared to 2D laminin-coated surface without fibers, and increased by 1052% compared to HA constructs without fibers. Laminin functionalization of fibers also doubled average neurite length over plain PCL fibers in the same 3D HA constructs. In addition, neurites also demonstrated tracking directly along the fibers, with 66% of neurite lengths directly tracking laminin-coated fibers in 3D HA

  1. Sustained Release of Engineered Stromal Cell–Derived Factor 1-α From Injectable Hydrogels Effectively Recruits Endothelial Progenitor Cells and Preserves Ventricular Function After Myocardial Infarction

    PubMed Central

    MacArthur, John W.; Purcell, Brendan P.; Shudo, Yasuhiro; Cohen, Jeffrey E.; Fairman, Alex; Trubelja, Alen; Patel, Jay; Hsiao, Philip; Yang, Elaine; Lloyd, Kelsey; Hiesinger, William; Atluri, Pavan; Burdick, Jason A.; Woo, Y. Joseph

    2014-01-01

    Background Exogenously delivered chemokines have enabled neovasculogenic myocardial repair in models of ischemic cardiomyopathy; however, these molecules have short half-lives in vivo. In this study, we hypothesized that the sustained delivery of a synthetic analog of stromal cell–derived factor 1-α (engineered stromal cell–derived factor analog [ESA]) induces continuous homing of endothelial progenitor cells and improves left ventricular function in a rat model of myocardial infarction. Methods and Results Our previously designed ESA peptide was synthesized by the addition of a fluorophore tag for tracking. Hyaluronic acid was chemically modified with hydroxyethyl methacrylate to form hydrolytically degradable hydrogels through free-radical–initiated crosslinking. ESA was encapsulated in hyaluronic acid hydrogels during gel formation, and then ESA release, along with gel degradation, was monitored for more than 4 weeks in vitro. Chemotactic properties of the eluted ESA were assessed at multiple time points using rat endothelial progenitor cells in a transwell migration assay. Finally, adult male Wistar rats (n=33) underwent permanent ligation of the left anterior descending (LAD) coronary artery, and 100 μL of saline, hydrogel alone, or hydrogel+25 μg ESA was injected into the borderzone. ESA fluorescence was monitored in animals for more than 4 weeks, after which vasculogenic, geometric, and functional parameters were assessed to determine the therapeutic benefit of each treatment group. ESA release was sustained for 4 weeks in vitro, remained active, and enhanced endothelial progenitor cell chemotaxis. In addition, ESA was detected in the rat heart >3 weeks when delivered within the hydrogels and significantly improved vascularity, ventricular geometry, ejection fraction, cardiac output, and contractility compared with controls. Conclusions We have developed a hydrogel delivery system that sustains the release of a bioactive endothelial progenitor cell

  2. Topical Anti-Nuclear Factor-Kappa B Small Interfering RNA with Functional Peptides Containing Sericin-Based Hydrogel for Atopic Dermatitis

    PubMed Central

    Kanazawa, Takanori; Shizawa, Yuki; Takeuchi, Mayu; Tamano, Kuniko; Ibaraki, Hisako; Seta, Yasuo; Takashima, Yuuki; Okada, Hiroaki

    2015-01-01

    The small interfering RNA (siRNA) is suggested to offer a novel means of treating atopic dermatitis (AD) because it allows the specific silencing of genes related to AD pathogenesis. In our previous study, we found that siRNA targeted against RelA, an important nuclear factor-kappa B (NF-κB) subdomain, with functional peptides, showed therapeutic effects in a mouse model of AD. In the present study, to develop a topical skin application against AD, we prepared a hydrogel containing anti-RelA siRNA and functional peptides and determined the intradermal permeation and the anti-AD effects in an AD mouse model. We selected the silk protein, sericin (SC), which is a versatile biocompatible biomaterial to prepare hydrogel as an aqueous gel base. We found that the siRNA was more widely delivered to the site of application in AD-induced ear skin of mice after topical application via the hydrogel containing functional peptides than via the preparation without functional peptides. In addition, the ear thickness and clinical skin severity of the AD-induced mice treated with hydrogel containing anti-RelA siRNA with functional peptides improved more than that of mice treated with the preparation formulated with negative siRNA. PMID:26371030

  3. Topical Anti-Nuclear Factor-Kappa B Small Interfering RNA with Functional Peptides Containing Sericin-Based Hydrogel for Atopic Dermatitis.

    PubMed

    Kanazawa, Takanori; Shizawa, Yuki; Takeuchi, Mayu; Tamano, Kuniko; Ibaraki, Hisako; Seta, Yasuo; Takashima, Yuki; Okada, Hiroaki

    2015-01-01

    The small interfering RNA (siRNA) is suggested to offer a novel means of treating atopic dermatitis (AD) because it allows the specific silencing of genes related to AD pathogenesis. In our previous study, we found that siRNA targeted against RelA, an important nuclear factor-kappa B (NF-κB) subdomain, with functional peptides, showed therapeutic effects in a mouse model of AD. In the present study, to develop a topical skin application against AD, we prepared a hydrogel containing anti-RelA siRNA and functional peptides and determined the intradermal permeation and the anti-AD effects in an AD mouse model. We selected the silk protein, sericin (SC), which is a versatile biocompatible biomaterial to prepare hydrogel as an aqueous gel base. We found that the siRNA was more widely delivered to the site of application in AD-induced ear skin of mice after topical application via the hydrogel containing functional peptides than via the preparation without functional peptides. In addition, the ear thickness and clinical skin severity of the AD-induced mice treated with hydrogel containing anti-RelA siRNA with functional peptides improved more than that of mice treated with the preparation formulated with negative siRNA. PMID:26371030

  4. Hydrogel-Assisted Transfer of Graphene Oxides into Nonpolar Organic Media for Oil Decontamination.

    PubMed

    Cheng, Chongling; Wang, Dayang

    2016-06-01

    In this work, graphene oxide (GO)-loaded agarose hydrogel was transferred into oil such as hexadecane via stepwise solvent exchange with no chemical modification of the GO hydrophilic surface and the agarose network. After transfer, the GOs, loaded in the agarose network, could effectively and efficiently adsorb lipophilic dyes in oil via hydrogen bonding between the polar groups of the GOs and the dyes. The maximum adsorption capacity was 355.9 mg g(-1) for Nile red for instance, which is substantially larger than that of pristine agarose hydrogel and hydrophilic GO powder. The dye concentration for effective adsorption can be as low as 0.5 ppm. Thus, the present work demonstrates the promising potential of using hydrophilic adsorbents for efficient removal of polar impurities from oil. PMID:27112433

  5. Functionalization, preparation and use of cell-laden gelatin methacryloyl-based hydrogels as modular tissue culture platforms.

    PubMed

    Loessner, Daniela; Meinert, Christoph; Kaemmerer, Elke; Martine, Laure C; Yue, Kan; Levett, Peter A; Klein, Travis J; Melchels, Ferry P W; Khademhosseini, Ali; Hutmacher, Dietmar W

    2016-04-01

    Progress in advancing a system-level understanding of the complexity of human tissue development and regeneration is hampered by a lack of biological model systems that recapitulate key aspects of these processes in a physiological context. Hence, growing demand by cell biologists for organ-specific extracellular mimics has led to the development of a plethora of 3D cell culture assays based on natural and synthetic matrices. We developed a physiological microenvironment of semisynthetic origin, called gelatin methacryloyl (GelMA)-based hydrogels, which combine the biocompatibility of natural matrices with the reproducibility, stability and modularity of synthetic biomaterials. We describe here a step-by-step protocol for the preparation of the GelMA polymer, which takes 1-2 weeks to complete, and which can be used to prepare hydrogel-based 3D cell culture models for cancer and stem cell research, as well as for tissue engineering applications. We also describe quality control and validation procedures, including how to assess the degree of GelMA functionalization and mechanical properties, to ensure reproducibility in experimental and animal studies. PMID:26985572

  6. Photoclick Hydrogels Prepared from Functionalized Cyclodextrin and Poly(ethylene glycol) for Drug Delivery and in Situ Cell Encapsulation.

    PubMed

    Shih, Han; Lin, Chien-Chi

    2015-07-13

    Polymers or hydrogels containing modified cyclodextrin (CD) are highly useful in drug delivery applications, as CD is a cytocompatible amphiphilic molecule that can complex with a variety of hydrophobic drugs. Here, we designed modular photoclick thiol-ene hydrogels from derivatives of βCD and poly(ethylene glycol) (PEG), including βCD-allylether (βCD-AE), βCD-thiol (βCD-SH), PEG-thiol (PEGSH), and PEG-norbornene (PEGNB). Two types of CD-PEG hybrid hydrogels were prepared using radical-mediated thiol-ene photoclick reactions. Specifically, thiol-allylether hydrogels were formed by reacting multiarm PEGSH and βCD-AE, and thiol-norbornene hydrogels were formed by cross-linking βCD-SH and multiarm PEGNB. We characterized the properties of these two types of thiol-ene hydrogels, including gelation kinetics, gel fractions, hydrolytic stability, and cytocompatibility. Compared with thiol-allylether hydrogels, thiol-norbornene photoclick reaction formed hydrogels with faster gelation kinetics at equivalent macromer contents. Using curcumin, an anti-inflammatory and anticancer hydrophobic molecule, we demonstrated that CD-cross-linked PEG-based hydrogels, when compared with pure PEG-based hydrogels, afforded higher drug loading efficiency and prolonged delivery in vitro. Cytocompatibility of these CD-cross-linked hydrogels were evaluated by in situ encapsulation of radical sensitive pancreatic MIN6 β-cells. All formulations and cross-linking conditions tested were cytocompatible for cell encapsulation. Furthermore, hydrogels cross-linked by βCD-SH showed enhanced cell proliferation and insulin secretion as compared to gels cross-linked by either dithiothreitol (DTT) or βCD-AE, suggesting the profound impact of both macromer compositions and gelation chemistry on cell fate in chemically cross-linked hydrogels. PMID:25996903

  7. A tailored three-dimensionally printable agarose-collagen blend allows encapsulation, spreading, and attachment of human umbilical artery smooth muscle cells.

    PubMed

    Köpf, Marius; Campos, Daniela F Duarte; Blaeser, Andreas; Sen, Kshama S; Fischer, Horst

    2016-01-01

    In recent years, novel biofabrication technologies have enabled the rapid manufacture of hydrogel-cell suspensions into tissue-imitating constructs. The development of novel materials for biofabrication still remains a challenge due to a gap between contradicting requirements such as three-dimensional printability and optimal cytocompatibility. We hypothesise that blending of different hydrogels could lead to a novel material with favourable biological and printing properties. In our work, we combined agarose and type I collagen in order to develop a hydrogel blend capable of long-term cell encapsulation of human umbilical artery smooth muscle cells (HUASMCs) and 3D drop-on-demand printing. Different blends were prepared with 0.25%, 0.5%, 0.75%, and 1.5% agarose and 0.2% type I collagen. The cell morphology of HUASMCs and the printing accuracy were assessed for each agarose-collagen combination, keeping the content of collagen constant. The hydrogel blend which displayed sufficient cell spreading and printing accuracy (0.5% agarose, 0.2% type I collagen, AGR0.5COLL0.2) was then characterised based on swelling and degradation over 21 days and mechanical stiffness. The cellular response regarding cell attachment of HUASMCs embedded in the hydrogel blend was further studied using SEM, TEM, and TPLSM. Printing trials were fabricated in a drop-on-demand printing process. The swelling and degradation evaluation showed an average of 20% mass loss and less than 10% swelling. AGR0.5COLL0.2 exhibited significant increase in stiffness compared to pure agarose and type I collagen. In addition, columns of AGR0.5COLL0.2 three centimeters in height were successfully printed submerged in cooled perfluorocarbon, proving the intrinsic printability of the hydrogel blend. Ultimately, a promising novel hydrogel blend showing cell spreading and attachment as well as suitability for bioprinting was identified and could, for example, serve in the manufacture of in vitro 3D models to

  8. New strategy for chemical modification of hyaluronic acid: preparation of functionalized derivatives and their use in the formation of novel biocompatible hydrogels.

    PubMed

    Bulpitt, P; Aeschlimann, D

    1999-11-01

    Biodegradable materials for spatially and temporally controlled delivery of bioactive agents such as drugs, growth factors, or cytokines are key to facilitating tissue repair. We have developed a versatile method for chemical crosslinking high-molecular-weight hyaluronic acid under physiological conditions yielding biocompatible and biodegradable hydrogels. The method is based on the introduction of functional groups onto hyaluronic acid by formation of an active ester at the carboxylate of the glucuronic acid moiety and subsequent substitution with a side chain containing a nucleophilic group on one end and a (protected) functional group on the other. We have formed hyaluronic acid with amino or aldehyde functionality, and subsequently hydrogels with these hyaluronic acid derivatives and bifunctional crosslinkers or mixtures of the hyaluronic acid derivatives carrying different functionalities using active ester- or aldehyde-mediated reactions. Size analysis of the hyaluronic acid derivatives showed that the chemical modification did not lead to fragmentation of the polysaccharide. Hydrogels formed with hyaluronic acid derivatized to a varying degree and crosslinked with low- or high-molecular-weight crosslinkers were evaluated for biodegradability by digestion with hyaluronidase and for biocompatibility and ectopic bone formation by subcutaneous implantation in rats. Several hydrogel formulations showed excellent cell infiltration and chondro-osseous differentiation when loaded with bone morphogenetic protein-2 (BMP-2). Synergistic action of insulin-like growth factor-1 with BMP-2 promoted cartilage formation in this model, while addition of transforming growth factor-beta and BMP-2 led to rapid replacement of the matrix by bone. PMID:10449626

  9. Simultaneous Exfoliation and Functionalization of MoSe2 Nanosheets to Prepare "Smart" Nanocomposite Hydrogels with Tunable Dual Stimuli-Responsive Behavior.

    PubMed

    Lei, Zhouyue; Zhou, Yuanyuan; Wu, Peiyi

    2016-06-01

    A facile polymer-assisted method achieves simultaneous exfoliation and noncovalent functionalization of MoSe2 nanosheets. The nanosheet dispersion can further assemble into a novel "smart" nanocomposite hydrogel, whose dual-responsive (photo- and thermoresponsive) behavior is reversible and can be controllably tailored by varying the distribution of hydrophilic and hydrophobic groups in the polymer. PMID:27135442

  10. In vivo bioluminescent tracking of mesenchymal stem cells within large hydrogel constructs.

    PubMed

    Allen, Ashley B; Gazit, Zulma; Su, Susan; Stevens, Hazel Y; Guldberg, Robert E

    2014-10-01

    The use of multicomponent scaffolds for cell implantation has necessitated sophisticated techniques for tracking of cell survival in vivo. Bioluminescent imaging (BLI) has emerged as a noninvasive tool for evaluating the therapeutic potential of cell-based tissue engineering strategies. However, the ability to use BLI measurements to longitudinally assess large 3D cellular constructs in vivo and the effects of potential confounding factors are poorly understood. In this study, luciferase-expressing human mesenchymal stem cells (hMSCs) were delivered subcutaneously within agarose and RGD-functionalized alginate hydrogel vehicles to investigate the impact of construct composition and tissue formation on BLI signal. Results showed that alginate constructs exhibited twofold greater BLI counts than agarose constructs at comparable hMSC doses. However, each hydrogel type produced a linear correlation between BLI counts and live cell number, indicating that within a given material, relative differences in cell number could be accurately assessed at early time points. The survival efficiency of delivered hMSCs was highest for the lower cell doses embedded within alginate matrix. BLI signal remained predictive of live cell number through 1 week in vivo, although the strength of correlation decreased over time. Irrespective of hydrogel type or initial hMSC seeding dose, all constructs demonstrated a degree of vascularization and development of a fibrotic capsule after 1 week. Formation of tissue within and adjacent to the constructs was accompanied by an attenuation of BLI signal during the initial period of the image acquisition time-frame. In alginate constructs only, greater vessel volume led to a delayed rise in BLI signal following luciferin delivery. This study identified vascular and fibrotic tissue ingrowth as potential confounding variables for longitudinal BLI studies. Further investigation into the complexities of noninvasive BLI data acquisition from

  11. Injectable composites via functionalization of 1D nanoclays and biodegradable coupling with a polysaccharide hydrogel.

    PubMed

    Del Buffa, Stefano; Rinaldi, Elia; Carretti, Emiliano; Ridi, Francesca; Bonini, Massimo; Baglioni, Piero

    2016-09-01

    The use of injectable materials in minimally invasive surgical procedures could help in facing the bone diseases connected to the ageing of world population. To this aim, materials integrating the rheological properties of biocompatible polymers with the mechanical properties of 1D inorganic nanostructures represent promising scaffolds. Here we describe the preparation of hydrogel composites made of carboxymethyl cellulose (CMC) and halloysite nanotubes (HNT) as injectable materials for the local treatment of bone defects. The rheology and injectability of the materials reflects their structural properties, showing the possibility of successfully injecting the prepared composites over a large range of operative conditions. PMID:27281242

  12. Pulsatile dynamic stiffness of cartilage-like materials and use of agarose gels to validate mechanical methods and models.

    PubMed

    Scandiucci de Freitas, P; Wirz, D; Stolz, M; Göpfert, B; Friederich, N-F; Daniels, A U

    2006-08-01

    Stiffness is a fundamental indicator of the functional state of articular cartilage. Reported test modes include compressive incremental strain to determine the equilibrium modulus, and sinusoidal strain to determine the dynamic modulus and stress/strain loss angle. Here, initial development is described for a method recognizing that gait is pulsatile. Agarose gels have been used by others for validation or comparison of mechanical test methods and models for cartilage and proteoglycan aggregate. Accordingly, gels ranging from 0.5 to 20% agarose were prepared. Pulsatile stiffness in both indentation and unconfined compression were closely reproducible. Stiffness as a function of agarose concentration rose exponentially, as found using other methods. Indentation stiffness was higher than for unconfined compression and ranged from approximately 2.0 kPa for 0.5% gel to approximately 3,800 kPa for 20% gel. Pulsatile dynamic stiffness appears to be a useful method, although further development is needed. Agarose gel stiffness values obtained by other methods were reviewed for comparison. Unfortunately, reported values for a given agarose concentration ranged widely (e.g. fourfold) even when test methods were similar. Causes appear to include differences in molecular weight and gel preparation time-temperature regimens. Also, agarose is hygroscopic, leading to unintended variations in gel composition. Agarose gels are problematic materials for validation or comparison of cartilage mechanical test methods and models. PMID:16470817

  13. Aptamer-functionalized superporous hydrogels for sequestration and release of growth factors regulated via molecular recognition.

    PubMed

    Battig, Mark R; Huang, Yike; Chen, Niancao; Wang, Yong

    2014-09-01

    While the discovery of highly potent biologics has led to the development of promising therapies for various human diseases, biologics can cause severe toxicity if delivered inappropriately. Thus, great efforts have been made to synthesize polymeric systems for safe and efficient delivery of biologics. However, the application of polymeric delivery systems is often limited by problems such as harsh reaction conditions, low drug sequestration efficiency, and difficult drug release regulation. This study was aimed at developing a superporous material system with a hydrogel and an aptamer to overcome these challenges. The results have shown that the superporous hydrogel is capable of instantaneously and fully sequestering a large amount of growth factors, owing to the presence of superporous architectures and aptamers. Moreover, the sequestering and loading procedure does not involve any harsh conditions. The release kinetics of growth factors can be molecularly modulated by either changing the binding affinity of the aptamer or by using a triggering effector. Therefore, this study presents a promising superporous material for the delivery of highly potent biologics such as growth factors for clinical applications. PMID:24954732

  14. Plasma functionalization of poly(vinyl alcohol) hydrogel for cell adhesion enhancement

    PubMed Central

    Ino, Julia M.; Chevallier, Pascale; Letourneur, Didier; Mantovani, Diego; Le Visage, Catherine

    2013-01-01

    Tailoring the interface interactions between a biomaterial and the surrounding tissue is a capital aspect to consider for the design of medical devices. Poly(vinyl alcohol) (PVA) hydrogels present suitable mechanical properties for various biological substitutes, however the lack of cell adhesion on their surface is often a problem. The common approach is to incorporate biomolecules, either by blending or coupling. But these modifications disrupt PVA intra- and intermolecular interactions leading therefore to a loss of its original mechanical properties. In this work, surface modification by glow discharge plasma, technique known to modify only the surface without altering the bulk properties, has been investigated to promote cell attachment on PVA substrates. N2/H2 microwave plasma treatment has been performed, and the chemical composition of PVA surface has been investigated. X-ray photoelectron and Fourier transform infrared analyses on the plasma-treated films revealed the presence of carbonyl and nitrogen species, including amine and amide groups, while the main structure of PVA was unchanged. Plasma modification induced an increase in the PVA surface wettability with no significant change in surface roughness. In contrast to untreated PVA, plasma-modified films allowed successful culture of mouse fibroblasts and human endothelial cells. These results evidenced that the grafting was stable after rehydration and that it displayed cell adhesive properties. Thus plasma amination of PVA is a promising approach to improve cell behavior on contact with synthetic hydrogels for tissue engineering. PMID:23989063

  15. Rapid self-healing hydrogels

    PubMed Central

    Phadke, Ameya; Zhang, Chao; Arman, Bedri; Hsu, Cheng-Chih; Mashelkar, Raghunath A.; Lele, Ashish K.; Tauber, Michael J.; Arya, Gaurav; Varghese, Shyni

    2012-01-01

    Synthetic materials that are capable of autonomous healing upon damage are being developed at a rapid pace because of their many potential applications. Despite these advancements, achieving self-healing in permanently cross-linked hydrogels has remained elusive because of the presence of water and irreversible cross-links. Here, we demonstrate that permanently cross-linked hydrogels can be engineered to exhibit self-healing in an aqueous environment. We achieve this feature by arming the hydrogel network with flexible-pendant side chains carrying an optimal balance of hydrophilic and hydrophobic moieties that allows the side chains to mediate hydrogen bonds across the hydrogel interfaces with minimal steric hindrance and hydrophobic collapse. The self-healing reported here is rapid, occurring within seconds of the insertion of a crack into the hydrogel or juxtaposition of two separate hydrogel pieces. The healing is reversible and can be switched on and off via changes in pH, allowing external control over the healing process. Moreover, the hydrogels can sustain multiple cycles of healing and separation without compromising their mechanical properties and healing kinetics. Beyond revealing how secondary interactions could be harnessed to introduce new functions to chemically cross-linked polymeric systems, we also demonstrate various potential applications of such easy-to-synthesize, smart, self-healing hydrogels. PMID:22392977

  16. Mussel-inspired synthesis of polydopamine-functionalized graphene oxide hydrogel as broad-spectrum antimicrobial material

    NASA Astrophysics Data System (ADS)

    Wang, Xinpeng; Liu, Zhiming; Zhong, Huiqing; Guo, Zhouyi; Yuan, Xiaochan

    2014-09-01

    Recently, three-dimensional GO-based hydrogels have attracted great attention due to the unique advantages. It is generally know that bacteria are everywhere and many of them could cause the diseases and threaten human health. However, developing new antibacterial materials with high-efficiency, low cost, broad-spectrum, and easy recycling is still a great challenge. Herein, inspired by mussel, we synthesized benzalkonium bromide/polydopamine/reduced graphene oxide hydrogel (BKB/PDA/rGOG). The as-prepared three-dimensional hydrogels were characterized by scanning eletron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopy. The resultant hydrogels exhibited strong antibacterial effects to both Gram-negative and Gram-positive bacteria due to the synergistic effect of graphene oxide and benzalkonium bromide. In addition, the resultant hydrogels could be removed easily from the resolution, which was undoubtedly good news for industry application.

  17. Orientation of DNA in agarose gels.

    PubMed Central

    Borejdo, J

    1989-01-01

    An orientation of the lambda DNA during the electrophoresis in agarose gels was measured by a microscopic linear dichroism technique. The method involved staining the DNA with the dye ethidium bromide and measuring under the microscope the polarization properties of the fluorescence field around the electrophoretic band containing the nucleic acid. It was first established that the fluorescence properties of the ethidium bromide-DNA complex were the same in agarose gel and in a solution. Then the linear dichroism method was used to measure the dichroism of the absorption dipole of EB dye bound to lambda DNA. In a typical experiment the orientation of two-tenth of a picogram (2 x 10(-13)g) of DNA was measured. When the electric field was turned on, the dichroism developed rapidly and assumed a steady state value which increased with the strength of the field and with the size of DNA. A linear dichroism equation related the measured dichroism of fluorescence to the mean orientation of the absorption dipole of ethidium bromide and to an extent to which the orientation of this dipole deviated from the mean. The observed development of dichroism in the presence of an electric field was interpreted as an alignment of DNA along the direction of the field. The increase in the steady state value of dichroism with the rise in the strength of the field and with the increase of the size of DNA was interpreted as a better alignment of DNA along the direction of the field and as a smaller deviation from its mean orientation. Images FIGURE 8 PMID:2527571

  18. Smart reticulated hydrogel of functionally decorated gellan copolymer for prolonged delivery of salbutamol sulphate to the gastro-luminal milieu.

    PubMed

    Maiti, Sabyasachi; Ghosh, Sudipa; Mondol, Ranjit; Ray, Somasree; Sa, Biswanath

    2012-01-01

    A partially hydrolysed poly(acrylamide)-grafted-gellan (HPAmGG) copolymer was synthesised and characterised. Temperature- and concentration-dependent rheology and gel-like property of Gelrite gellan (GG) disappeared in HPAmGG copolymer. Smart HPAmGG hydrogel was fabricated with variation in aluminium chloride (AlCl(3)) strength and initial drug loading. The hydrogel reticulates seemed spherical and showed a maximum of ∼65% drug retention, but the assay was ∼22% lower for GG hydrogel. The drug release rate was inversely proportional to AlCl(3) strength in simulated intestinal milieu (pH 7.4), but approximated a proportional relationship with drug load. HPAmGG hydrogel liberated only 10-17% content in simulated gastric milieu (pH 1.2) in 2 h. The release data correlated well with the pH-dependent swelling of hydrogel and indicated the anomalous drug diffusion mechanism. Differential scanning calorimetry, X-ray diffraction, and high-performance liquid chromatography analyses confirmed the amorphous nature of the drug and its stability in fresh and aged hydrogel. Hence, smart HPAmGG hydrogel had the potential to prolong drug release mimicking the variable pH of the gastrointestinal tract. PMID:22594768

  19. Self-assembly with orthogonal-imposed stimuli to impart structure and confer magnetic function to electrodeposited hydrogels.

    PubMed

    Li, Ying; Liu, Yi; Gao, Tieren; Zhang, Boce; Song, Yingying; Terrell, Jessica L; Barber, Nathan; Bentley, William E; Takeuchi, Ichiro; Payne, Gregory F; Wang, Qin

    2015-05-20

    A magnetic nanocomposite film with the capability of reversibly collecting functionalized magnetic particles was fabricated by simultaneously imposing two orthogonal stimuli (electrical and magnetic). We demonstrate that cathodic codeposition of chitosan and Fe3O4 nanoparticles while simultaneously applying a magnetic field during codeposition can (i) organize structure, (ii) confer magnetic properties, and (iii) yield magnetic films that can perform reversible collection/assembly functions. The magnetic field triggered the self-assembly of Fe3O4 nanoparticles into hierarchical "chains" and "fibers" in the chitosan film. For controlled magnetic properties, the Fe3O4-chitosan film was electrodeposited in the presence of various strength magnetic fields and different deposition times. The magnetic properties of the resulting films should enable broad applications in complex devices. As a proof of concept, we demonstrate the reversible capture and release of green fluorescent protein (EGFP)-conjugated magnetic microparticles by the magnetic chitosan film. Moreover, antibody-functionalized magnetic microparticles were applied to capture cells from a sample, and these cells were collected, analyzed, and released by the magnetic chitosan film, paving the way for applications such as reusable biosensor interfaces (e.g., for pathogen detection). To our knowledge, this is the first report to apply a magnetic field during the electrodeposition of a hydrogel to generate magnetic soft matter. Importantly, the simple, rapid, and reagentless fabrication methodologies demonstrated here are valuable features for creating a magnetic device interface. PMID:25923335

  20. Tissue Engineering Special Feature: A macroporous hydrogel for the coculture of neural progenitor and endothelial cells to form functional vascular networks in vivo

    NASA Astrophysics Data System (ADS)

    Ford, Millicent C.; Bertram, James P.; Royce Hynes, Sara; Michaud, Michael; Li, Qi; Young, Michael; Segal, Steven S.; Madri, Joseph A.; Lavik, Erin B.

    2006-02-01

    A microvascular network is critical for the survival and function of most tissues. We have investigated the potential of neural progenitor cells to augment the formation and stabilization of microvascular networks in a previously uncharacterized three-dimensional macroporous hydrogel and the ability of this engineered system to develop a functional microcirculation in vivo. The hydrogel is synthesized by cross-linking polyethylene glycol with polylysine around a salt-leached polylactic-co-glycolic acid scaffold that is degraded in a sodium hydroxide solution. An open macroporous network is formed that supports the efficient formation of tubular structures by brain endothelial cells. After subcutaneous implantation of hydrogel cocultures in mice, blood flow in new microvessels was apparent at 2 weeks with perfused networks established on the surface of implants at 6 weeks. Compared to endothelial cells cultured alone, cocultures of endothelial cells and neural progenitor cells had a significantly greater density of tubular structures positive for platelet endothelial cell adhesion molecule-1 at the 6-week time point. In implant cross sections, the presence of red blood cells in vessel lumens confirmed a functional microcirculation. These findings indicate that neural progenitor cells promote the formation of endothelial cell tubes in coculture and the development of a functional microcirculation in vivo. We demonstrate a previously undescribed strategy for creating stable microvascular networks to support engineered tissues of desired parenchymal cell origin. microvasculature | neural stem cells | polymer | scaffold

  1. Functionalized d-form self-assembling peptide hydrogels for bone regeneration

    PubMed Central

    He, Bin; Ou, Yunsheng; Zhou, Ao; Chen, Shuo; Zhao, Weikang; Zhao, Jinqiu; Li, Hong; Zhu, Yong; Zhao, Zenghui; Jiang, Dianming

    2016-01-01

    Bone defects are very common in orthopedics, and there is great need to develop suitable bone grafts for transplantation in vivo. However, current bone grafts still encounter some limitations, including limited availability, immune rejection, poor osteoinduction and osteoconduction, poor biocompatibility and degradation properties, etc. Self-assembling peptide nanofiber scaffolds have emerged as an important substrate for cell culture and bone regeneration. We report on the structural features (eg, Congo red staining, circular dichroism spectroscopy, transmission electron microscopy, and rheometry assays) and osteogenic ability of d-RADA16-RGD peptide hydrogels (with or without basic fibroblast growth factor) due to the better stability of peptide bonds formed by these peptides compared with those formed by l-form peptides, and use them to fill the femoral condyle defect of Sprague Dawley rat model. The bone morphology change, two-dimensional reconstructions using microcomputed tomography, quantification of the microcomputed tomography analyses as well as histological analyses have demonstrated that RGD-modified d-form peptide scaffolds are able to enhance extensive bone regeneration. PMID:27114701

  2. Finite difference time domain model of ultrasound propagation in agarose scaffold containing collagen or chondrocytes.

    PubMed

    Inkinen, Satu I; Liukkonen, Jukka; Malo, Markus K H; Virén, Tuomas; Jurvelin, Jukka S; Töyräs, Juha

    2016-07-01

    Measurement of ultrasound backscattering is a promising diagnostic technique for arthroscopic evaluation of articular cartilage. However, contribution of collagen and chondrocytes on ultrasound backscattering and speed of sound in cartilage is not fully understood and is experimentally difficult to study. Agarose hydrogels have been used in tissue engineering applications of cartilage. Therefore, the aim of this study was to simulate the propagation of high frequency ultrasound (40 MHz) in agarose scaffolds with varying concentrations of chondrocytes (1 to 32 × 10(6) cells/ml) and collagen (1.56-200 mg/ml) using transversely isotropic two-dimensional finite difference time domain method (FDTD). Backscatter and speed of sound were evaluated from the simulated pulse-echo and through transmission measurements, respectively. Ultrasound backscatter increased with increasing collagen and chondrocyte concentrations. Furthermore, speed of sound increased with increasing collagen concentration. However, this was not observed with increasing chondrocyte concentrations. The present study suggests that the FDTD method may have some applicability in simulations of ultrasound scattering and propagation in constructs containing collagen and chondrocytes. Findings of this study indicate the significant role of collagen and chondrocytes as ultrasound scatterers and can aid in development of modeling approaches for understanding how cartilage architecture affects to the propagation of high frequency ultrasound. PMID:27475127

  3. Characterization of Thiol-Ene Crosslinked PEG Hydrogels

    PubMed Central

    Toepke, Michael W.; Impellitteri, Nicholas A.; Theisen, Jeffrey M.

    2014-01-01

    The properties of synthetic hydrogels can be tuned to address the needs of many tissue-culture applications. This work characterizes the swelling and mechanical properties of thiol-ene crosslinked PEG hydrogels made with varying prepolymer formulations, demonstrating that hydrogels with a compressive modulus exceeding 600 kPa can be formed. The amount of peptide incorporated into the hydrogel is shown to be proportional to the amount of peptide in the prepolymer solution. Cell attachment and spreading on the surface of the peptide-functionalized hydrogels is demonstrated. Additionally, a method for bonding distinct layers of cured hydrogels is used to create a microfluidic channel. PMID:24883041

  4. Interactive forces between sodium dodecyl sulfate-suspended single-walled carbon nanotubes and agarose gels.

    PubMed

    Clar, Justin G; Silvera Batista, Carlos A; Youn, Sejin; Bonzongo, Jean-Claude J; Ziegler, Kirk J

    2013-11-27

    Selective adsorption onto agarose gels has become a powerful method to separate single-walled carbon nanotubes (SWCNTs). A better understanding of the nature of the interactive forces and specific sites responsible for adsorption should lead to significant improvements in the selectivity and yield of these separations. A combination of nonequilibrium and equilibrium studies are conducted to explore the potential role that van der Waals, ionic, hydrophobic, π-π, and ion-dipole interactions have on the selective adsorption between agarose and SWCNTs suspended with sodium dodecyl sulfate (SDS). The results demonstrate that any modification to the agarose gel surface and, consequently, the permanent dipole moments of agarose drastically reduces the retention of SWCNTs. Because these permanent dipoles are critical to retention and the fact that SDS-SWCNTs function as macro-ions, it is proposed that ion-dipole forces are the primary interaction responsible for adsorption. The selectivity of adsorption may be attributed to variations in polarizability between nanotube types, which create differences in both the structure and mobility of surfactant. These differences affect the enthalpy and entropy of adsorption, and both play an integral part in the selectivity of adsorption. The overall adsorption process shows a complex behavior that is not well represented by the Langmuir model; therefore, calorimetric data should be used to extract thermodynamic information. PMID:24164680

  5. Hydrogels functionalized with N-cadherin mimetic peptide enhance osteogenesis of hMSCs by emulating the osteogenic niche.

    PubMed

    Zhu, Meiling; Lin, Sien; Sun, Yuxin; Feng, Qian; Li, Gang; Bian, Liming

    2016-01-01

    N-cadherin is considered to be the key factor in directing cell-cell interactions during mesenchymal condensation, which is essential to osteogenesis. In this study, hyaluronic acid (HA) hydrogels are biofunctionalized with an N-cadherin mimetic peptide to mimic the pro-osteogenic niche in the endosteal space to promote the osteogenesis of human mesenchymal stem cells (hMSCs). Results show that the conjugation of the N-cadherin peptide in the HA hydrogels enhances the expression of the osteogenic marker genes in the seeded hMSCs. Furthermore, the biofunctionalized HA hydrogels promote the alkaline phosphatase activity, type I collagen deposition, and matrix mineralization by the seeded hMSCs under both in vitro and in vivo condition. We postulate that the biofunctionalized hydrogels emulates the N-cadherin-mediated homotypic cell-cell adhesion among MSCs and the "orthotypic" interaction between the osteoblasts and MSCs. These findings demonstrate that the biofunctionalized HA hydrogels provide a supportive niche microenvironment for the osteogenesis of hMSCs. PMID:26580785

  6. Effect of strain on viscoelastic behavior of fresh, swelled and mineralized PVP-CMC hydrogel

    NASA Astrophysics Data System (ADS)

    Saha, Nabanita; Vyroubal, Radek; Shah, Rushita; Kitano, Takeshi; Saha, Petr

    2013-04-01

    Mineralization of calcium carbonate (CaCO3) in hydrogel matrix is one of the most interesting topics of research by material scientists for the development of bio-inspired polymeric biomaterial for biomedical applications especially for bone tissue regeneration. As per our knowledge there was no work reported about rheological properties of CaCO3 mineralized hydrogel though some works have done on mineralization of CaCO3 in various gel membranes, and also it was reported about the viscoelastic properties of Agarose, Cellulose, PVA and PVPCMC hydrogels. This paper mainly focuses about the effect of strain on viscoelastic properties of fresh, swelled and mineralized (CaCO3) PVP-CMC hydrogel. All these three types of hydrogel sustain (or keep) strictly the elastic properties when low strain (1%) is applied, but at higher strain (10%) the viscoelastic moduli (G' and G") show significant change, and the nature of these materials turned from elastic to viscous.

  7. Photocrosslinkable Gelatin Hydrogel for Epidermal Tissue Engineering.

    PubMed

    Zhao, Xin; Lang, Qi; Yildirimer, Lara; Lin, Zhi Yuan; Cui, Wenguo; Annabi, Nasim; Ng, Kee Woei; Dokmeci, Mehmet R; Ghaemmaghami, Amir M; Khademhosseini, Ali

    2016-01-01

    Natural hydrogels are promising scaffolds to engineer epidermis. Currently, natural hydrogels used to support epidermal regeneration are mainly collagen- or gelatin-based, which mimic the natural dermal extracellular matrix but often suffer from insufficient and uncontrollable mechanical and degradation properties. In this study, a photocrosslinkable gelatin (i.e., gelatin methacrylamide (GelMA)) with tunable mechanical, degradation, and biological properties is used to engineer the epidermis for skin tissue engineering applications. The results reveal that the mechanical and degradation properties of the developed hydrogels can be readily modified by varying the hydrogel concentration, with elastic and compressive moduli tuned from a few kPa to a few hundred kPa, and the degradation times varied from a few days to several months. Additionally, hydrogels of all concentrations displayed excellent cell viability (>90%) with increasing cell adhesion and proliferation corresponding to increases in hydrogel concentrations. Furthermore, the hydrogels are found to support keratinocyte growth, differentiation, and stratification into a reconstructed multilayered epidermis with adequate barrier functions. The robust and tunable properties of GelMA hydrogels suggest that the keratinocyte laden hydrogels can be used as epidermal substitutes, wound dressings, or substrates to construct various in vitro skin models. PMID:25880725

  8. Templating hydrogels.

    PubMed

    Texter, John

    2009-03-01

    Templating processes for creating polymerized hydrogels are reviewed. The use of contact photonic crystals and of non-contact colloidal crystalline arrays as templates are described and applications to chemical sensing and device fabrication are illustrated. Emulsion templating is illustrated in the formation of microporous membranes, and templating on reverse emulsions and double emulsions is described. Templating in solutions of macromolecules and micelles is discussed and then various applications of hydrogel templating on surfactant liquid crystalline mesophases are illustrated, including a nanoscale analogue of colloidal crystalline array templating, except that the bead array in this case is a cubic array of nonionic micelles. The use of particles as templates in making core-shell and hollow microgel beads is described, as is the use of membrane pores as another illustration of confinement templating. PMID:19816529

  9. The use of a dual PEDOT and RGD-functionalized alginate hydrogel coating to provide sustained drug delivery and improved cochlear implant function

    PubMed Central

    Chikar, JA; Hendricks, JL; Richardson-Burns, SM; Raphael, Y; Pfingst, BE; Martin, DC

    2011-01-01

    Cochlear implants provide hearing by electrically stimulating the auditory nerve. Implant function can be hindered by device design variables, including electrode size and electrode-to-nerve distance, and cochlear environment variables, including the degeneration of the auditory nerve following hair cell loss. We have developed a dual component cochlear implant coating to improve both the electrical function of the implant and the biological stability of the inner ear, thereby facilitating the long-term perception of sound through a cochlear implant. This coating is a combination of an arginine-glycine-aspartic acid (RGD)-functionalized alginate hydrogel and the conducting polymer poly(3, 4-ethylenedioxythiophene) (PEDOT). Both in vitro and in vivo assays on the effects of these electrode coatings demonstrated improvements in device performance. We found that the coating reduced electrode impedance, improved charge delivery, and locally released significant levels of a trophic factor into cochlear fluids. This coating is non-cytotoxic, clinically relevant, and has the potential to significantly improve the cochlear implant user’s experience. PMID:22182748

  10. Fewer Bacteria Adhere to Softer Hydrogels

    PubMed Central

    Kolewe, Kristopher W.; Peyton, Shelly R.; Schiffman, Jessica D.

    2015-01-01

    Clinically, biofilm-associated infections commonly form on intravascular catheters and other hydrogel surfaces. The overuse of antibiotics to treat these infections has led to the spread of antibiotic resistance and underscores the importance of developing alternative strategies that delay the onset of biofilm formation. Previously, it has been reported that during surface contact, bacteria can detect surfaces through subtle changes in the function of their motors. However, how the stiffness of a polymer hydrogel influences the initial attachment of bacteria is unknown. Systematically, we investigated poly(ethylene glycol) dimethacrylate (PEGDMA) and agar hydrogels that were twenty times thicker than the cumulative size of bacterial cell appendages, as a function of Young’s moduli. Soft (44.05 – 308.5 kPa), intermediate (1495 – 2877 kPa), and stiff (5152 – 6489 kPa) hydrogels were synthesized. Escherichia coli and Staphylococcus aureus attachment onto the hydrogels was analyzed using confocal microscopy after 2 and 24 hr incubation periods. Independent of hydrogel chemistry and incubation time, E. coli and S. aureus attachment correlated positively to increasing hydrogel stiffness. For example, after a 24 hr incubation period, there were 52% and 82% less E. coli adhered to soft PEGDMA hydrogels, than to the intermediate and stiff PEGDMA hydrogels, respectively. A 62% and 79% reduction in the area coverage by the Gram-positive microbe S. aureus occurred after 24 hr incubation on the soft versus intermediate and stiff PEGDMA hydrogels. We suggest that hydrogel stiffness is an easily tunable variable that, potentially, could be used synergistically with traditional antimicrobial strategies to reduce early bacterial adhesion, and therefore the occurrence of biofilm-associated infections. PMID:26291308

  11. A prospective comparison of alginate-hydrogel with standard medical therapy to determine impact on functional capacity and clinical outcomes in patients with advanced heart failure (AUGMENT-HF trial)

    PubMed Central

    Anker, Stefan D.; Coats, Andrew J.S.; Cristian, Gabriel; Dragomir, Dinu; Pusineri, Enrico; Piredda, Massimo; Bettari, Luca; Dowling, Robert; Volterrani, Maurizio; Kirwan, Bridget-Anne; Filippatos, Gerasimos; Mas, Jean-Louis; Danchin, Nicolas; Solomon, Scott D.; Lee, Randall J.; Ahmann, Frank; Hinson, Andy; Sabbah, Hani N.; Mann, Douglas L.

    2015-01-01

    Aims AUGMENT-HF was an international, multi-centre, prospective, randomized, controlled trial to evaluate the benefits and safety of a novel method of left ventricular (LV) modification with alginate-hydrogel. Methods Alginate-hydrogel is an inert permanent implant that is directly injected into LV heart muscle and serves as a prosthetic scaffold to modify the shape and size of the dilated LV. Patients with advanced chronic heart failure (HF) were randomized (1 : 1) to alginate-hydrogel (n = 40) in combination with standard medical therapy or standard medical therapy alone (Control, n = 38). The primary endpoint of AUGMENT-HF was the change in peak VO2 from baseline to 6 months. Secondary endpoints included changes in 6-min walk test (6MWT) distance and New York Heart Association (NYHA) functional class, as well as assessments of procedural safety. Results Enrolled patients were 63 ± 10 years old, 74% in NYHA functional class III, had a LV ejection fraction of 26 ± 5% and a mean peak VO2 of 12.2 ± 1.8 mL/kg/min. Thirty-five patients were successfully treated with alginate-hydrogel injections through a limited left thoracotomy approach without device-related complications; the 30-day surgical mortality was 8.6% (3 deaths). Alginate-hydrogel treatment was associated with improved peak VO2 at 6 months—treatment effect vs. Control: +1.24 mL/kg/min (95% confidence interval 0.26–2.23, P = 0.014). Also 6MWT distance and NYHA functional class improved in alginate-hydrogel-treated patients vs. Control (both P < 0.001). Conclusion Alginate-hydrogel in addition to standard medical therapy for patients with advanced chronic HF was more effective than standard medical therapy alone for improving exercise capacity and symptoms. The results of AUGMENT-HF provide proof of concept for a pivotal trial. Trial Registration Number NCT01311791. PMID:26082085

  12. Synthesis and degradation test of hyaluronic acid hydrogels.

    PubMed

    Hahn, Sei Kwang; Park, Jung Kyu; Tomimatsu, Takashi; Shimoboji, Tsuyoshi

    2007-03-10

    Hyaluronic acid (HA) hydrogels prepared with three different crosslinking reagents were assessed by in vitro and in vivo degradation tests for various tissue engineering applications. Adipic acid dihydrazide grafted HA (HA-ADH) was synthesized and used for the preparation of methacrylated HA (HA-MA) with methacrylic anhydride and thiolated HA (HA-SH) with Traut's reagent (imminothiolane). (1)H NMR analysis showed that the degrees of HA-ADH, HA-MA, and HA-SH modification were 69, 29, and 56 mol%, respectively. HA-ADH hydrogel was prepared by the crosslinking with bis(sulfosuccinimidyl) suberate (BS(3)), HA-MA hydrogel with dithiothreitol (DTT) by Michael addition, and HA-SH hydrogel with sodium tetrathionate by disulfide bond formation. According to in vitro degradation tests, HA-SH hydrogel was degraded very fast, compared to HA-ADH and HA-MA hydrogels. HA-ADH hydrogel was degraded slightly faster than HA-MA hydrogel. Based on these results, HA-MA hydrogels and HA-SH hydrogels were implanted in the back of SD rats and their degradation was assessed according to the pre-determined time schedule. As expected from the in vitro degradation test results, HA-SH hydrogel was in vivo degraded completely only in 2 weeks, whereas HA-MA hydrogels were degraded only partially even in 29 days. The degradation rate of HA hydrogels were thought to be controlled by changing the crosslinking reagents and the functional group of HA derivatives. In addition, the state of HA hydrogel was another factor in controlling the degradation rate. Dried HA hydrogel at 37 degrees C for a day resulted in relatively slow degradation compared to the bulk HA hydrogel. There was no adverse effect during the in vivo tests. PMID:17101173

  13. The trajectories of spheres during agarose gel electrophoresis.

    PubMed

    Griess, G A; Harris, R A; Serwer, P

    1993-01-01

    To develop a physical description of the gel-induced retardation of spheres during gel electrophoresis, the microscopic motion of single electrically charged latex spheres is statistically quantified here, by digital image analysis. To obtain adequate resolution in space, comparatively large spheres, 240 nm in radius, are used. The following observations are made during electrophoresis in a 0.2% agarose gel at 22 degrees C: (a) When a comparatively high field (3.0 V cm-1) is used, inelastic collisions result in field-induced trapping of spheres; no elastic collisions are observed. (b) Reduction of the field from 3.0 to 0.0 V cm-1 results in reverse migration of previously trapped spheres. (c) In the absence of trapping, the electrical field does not cause an alteration in the tortuosity of motion (i.e. motion in a field-perpendicular direction). (d) When results are obtained for a constant time between images (0.2 s), gel-dependent deviations from a true random walk are not observed in the absence of trapping. (e) When results are obtained as a function of time between images, significant gel-dependent deviation from a random walk is observed. In the absence of trapping, the data presented here indicate that retardation is derived primarily from dissipative processes that are concentrated near gel fibers. However, steric effects have not yet been distinguished from hydrodynamic effects. PMID:8199223

  14. Hybrid Multicomponent Hydrogels for Tissue Engineering

    PubMed Central

    Jia, Xinqiao; Kiick, Kristi L.

    2009-01-01

    Artificial ECMs that not only closely mimic the hybrid nature of the natural ECM but also provide tunable material properties and enhanced biological functions are attractive candidates for tissue engineering applications. This review summarizes recent advances in developing multicomponent hybrid hydrogels by integrating modular and heterogeneous building blocks into well-defined, multifunctional hydrogel composites. The individual building blocks can be chemically, morphologically, and functionally diverse, and the hybridization can occur at molecular level or microscopic scale. The modular nature of the designs, combined with the potential synergistic effects of the hybrid systems, has resulted in novel hydrogel matrices with robust structure and defined functions. PMID:19107720

  15. 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. PMID:27072652

  16. Elastic, Conductive, Polymeric Hydrogels and Sponges

    PubMed Central

    Lu, Yun; He, Weina; Cao, Tai; Guo, Haitao; Zhang, Yongyi; Li, Qingwen; Shao, Ziqiang; Cui, Yulin; Zhang, Xuetong

    2014-01-01

    As a result of inherent rigidity of the conjugated macromolecular chains resulted from the delocalized π-electron system along the polymer backbone, it has been a huge challenge to make conducting polymer hydrogels elastic by far. Herein elastic and conductive polypyrrole hydrogels with only conducting polymer as the continuous phase have been simply synthesized in the indispensable conditions of 1) mixed solvent, 2) deficient oxidant, and 3) monthly secondary growth. The elastic mechanism and oxidative polymerization mechanism on the resulting PPy hydrogels have been discussed. The resulting hydrogels show some novel properties, e.g., shape memory elasticity, fast functionalization with various guest objects, and fast removal of organic infectants from aqueous solutions, all of which cannot be observed from traditional non-elastic conducting polymer counterparts. What's more, light-weight, elastic, and conductive organic sponges with excellent stress-sensing behavior have been successfully achieved via using the resulting polypyrrole hydrogels as precursors. PMID:25052015

  17. Polymer-induced compression of biological hydrogels

    NASA Astrophysics Data System (ADS)

    Datta, Sujit; Preska Steinberg, Asher; Ismagilov, Rustem

    Hydrogels - such as mucus, blood clots, and the extracellular matrix - provide critical functions in biological systems. However, little is known about how their structure is influenced by many of the polymeric materials they come into contact with regularly. Here, we focus on one critically important biological hydrogel: colonic mucus. While several biological processes are thought to potentially regulate the mucus hydrogel structure, the polymeric composition of the gut environment has been ignored. We use Flory-Huggins solution theory to characterize polymer-mucus interactions. We find that gut polymers, including those small enough to penetrate the mucus hydrogel, can in fact alter mucus structure, changing its equilibrium degree of swelling and forcing it to compress. The extent of compression increases with increasing polymer concentration and size. We use experiments on mice to verify these predictions with common dietary and therapeutic gut polymers. Our results provide a foundation for investigating similar, previously overlooked, polymer-induced effects in other biological hydrogels.

  18. Elastic, Conductive, Polymeric Hydrogels and Sponges

    NASA Astrophysics Data System (ADS)

    Lu, Yun; He, Weina; Cao, Tai; Guo, Haitao; Zhang, Yongyi; Li, Qingwen; Shao, Ziqiang; Cui, Yulin; Zhang, Xuetong

    2014-07-01

    As a result of inherent rigidity of the conjugated macromolecular chains resulted from the delocalized π-electron system along the polymer backbone, it has been a huge challenge to make conducting polymer hydrogels elastic by far. Herein elastic and conductive polypyrrole hydrogels with only conducting polymer as the continuous phase have been simply synthesized in the indispensable conditions of 1) mixed solvent, 2) deficient oxidant, and 3) monthly secondary growth. The elastic mechanism and oxidative polymerization mechanism on the resulting PPy hydrogels have been discussed. The resulting hydrogels show some novel properties, e.g., shape memory elasticity, fast functionalization with various guest objects, and fast removal of organic infectants from aqueous solutions, all of which cannot be observed from traditional non-elastic conducting polymer counterparts. What's more, light-weight, elastic, and conductive organic sponges with excellent stress-sensing behavior have been successfully achieved via using the resulting polypyrrole hydrogels as precursors.

  19. 3D printing enables separation of orthogonal functions within a hydrogel particle.

    PubMed

    Raman, Ritu; Clay, Nicholas E; Sen, Sanjeet; Melhem, Molly; Qin, Ellen; Kong, Hyunjoon; Bashir, Rashid

    2016-06-01

    Multifunctional particles with distinct physiochemical phases are required by a variety of applications in biomedical engineering, such as diagnostic imaging and targeted drug delivery. This motivates the development of a repeatable, efficient, and customizable approach to manufacturing particles with spatially segregated bioactive moieties. This study demonstrates a stereolithographic 3D printing approach for designing and fabricating large arrays of biphasic poly (ethylene glycol) diacrylate (PEGDA) gel particles. The fabrication parameters governing the physical and biochemical properties of multi-layered particles are thoroughly investigated, yielding a readily tunable approach to manufacturing customizable arrays of multifunctional particles. The advantage in spatially organizing functional epitopes is examined by loading superparamagnetic iron oxide nanoparticles (SPIONs) and bovine serum albumin (BSA) in separate layers of biphasic PEGDA gel particles and examining SPION-induced magnetic resonance (MR) contrast and BSA-release kinetics. Particles with spatial segregation of functional moieties have demonstrably higher MR contrast and BSA release. Overall, this study will contribute significant knowledge to the preparation of multifunctional particles for use as biomedical tools. PMID:27215416

  20. Equilibrium partitioning of Ficoll in composite hydrogels.

    PubMed

    Kosto, Kimberly B; Panuganti, Swapna; Deen, William M

    2004-09-15

    Equilibrium partition coefficients (phi, the concentration in the gel divided by that in free solution) of fluorescein-labeled Ficolls in pure agarose and agarose-dextran composite gels were measured as a function of gel composition and Ficoll size. The four narrow fractions of Ficoll, a spherical polysaccharide, had Stokes-Einstein radii ranging from 2.7 to 5.9 nm. Gels with agarose volume fractions of 0.040 and 0.080 were studied, with dextran volume fractions (calculated as if the chain were a long fiber) up to 0.011. As expected, phi generally decreased as the Ficoll size increased (for a given gel composition) or as the amount of dextran incorporated into the gel increased (for a given agarose concentration and Ficoll size). The decrease in phi that accompanied dextran addition was predicted well by an excluded volume theory in which agarose and dextran were both treated as rigid, straight, randomly positioned and oriented fibers. Modeling dextran as a spherical coil within a fibrous agarose gel produced much less accurate predictions. The diffusional permeabilities of these gels were assessed by combining the current partitioning data with relative diffusivities (Kd, the diffusivity in the gel divided by that in free solution) reported previously. The values of phi Kd for a synthetic gel with 8.0% agarose and 1.1% dextran (by volume) were found to be very similar to those for the glomerular basement membrane, a physiologically important material which also has a total solids content of approximately 10%. PMID:15341852

  1. Transverse agarose pore gradient gel electrophoresis of DNA.

    PubMed

    Fawcett, J S; Wheeler, D; Chrambach, A

    1992-06-01

    Transverse agarose pore gradient gels were prepared on GelBond in the concentration range of nominally 0.2-1.5% SeaKem GTG agarose, using density stabilization by glycerol and incorporation of a dye to define the gel concentration at each point on the pore gradient gel. The distribution of the dye was evaluated by photography, video-acquisition and digitization of the gradient mixture and by densitometry of the gel. The gel was applied to the electrophoresis of a 1-kb standard ladder of DNA fragments, using standard submarine apparatus. The method extends to agarose gel electrophoresis the benefits of semi-automated analysis of 'Ferguson curves' described in application to polyacrylamide gel by Wheeler et al. (J. Biochem. Biophys. Methods 24, 171-180). PMID:1640052

  2. Effect of sugars and polyols on water in agarose gels.

    PubMed

    Nishinari, K; Watase, M; Williams, P A; Phillips, G O

    1991-01-01

    Effects of ribose, glucose, sucrose, ethylene glycol, glycerin, propylene glycol, and sorbitol on water in concentrated agarose gels were studied by differential scanning calorimetry at low temperatures. Changes in the phase transition temperatures of 40% agarose gels, induced by the addition of these chemical reagents, are discussed, together with rheological and thermal data for the same systems at ambient and higher temperatures. Both sugars and polyols are believed to reduce the amount of freezable water and to promote plasticization and molecular mobility of agarose chains in gels, thus shifting the glass transition temperatures to lower temperatures. However, the effects of decreasing freezable water, and the direct effect on the junction zones, produced by sugars seem to be different from the effects produced by polyols. PMID:1746332

  3. Imine Hydrogels with Tunable Degradability

    PubMed Central

    Boehnke, Natalie; Cam, Cynthia; Bat, Erhan; Segura, Tatiana; Maynard, Heather D.

    2015-01-01

    A shortage of available organ donors has created a need for engineered tissues. In this context, polymer-based hydrogels that break down inside the body are often used as constructs for growth factors and cells. Herein, we report imine cross-linked gels where degradation is controllable by the introduction of mixed imine cross-links. Specifically, hydrazide-functionalized poly(ethylene glycol) (PEG) reacts with aldehyde-functionalized PEG (PEG-CHO) to form hydrazone linked hydrogels that degrade quickly in media. The time to degradation can be controlled by changing the structure of the hydrazide group or by introducing hydroxylamines to form non-reversible oxime linkages. Hydrogels containing adipohydrazide-functionalized PEG (PEG-ADH) and PEG-CHO were found to degrade more rapidly than gels formed from carbodihydrazide-functionalized PEG (PEG-CDH). Incorporating oxime linkages via aminooxy-functionalized PEG (PEG-AO) into the hydrazone cross-linked gels further stabilized the hydrogels. This imine crosslinking approach should be useful for modulating the degradation characteristics of 3D cell culture supports for controlled cell release. PMID:26061010

  4. Blinking suppression of single quantum dots in agarose gel

    SciTech Connect

    Ko, H. C.; Yuan, C. T.; Tang, Jau; Lin, S. H.

    2010-01-04

    Fluorescence blinking is commonly observed in single molecule/particle spectroscopy, but it is an undesirable feature in many applications. We demonstrated that single CdSe/ZnS quantum dots in agarose gel exhibited suppressed blinking behavior. In addition, the long-time exponential bending tail of the power-law blinking statistics was found to be influenced by agarose gel concentration. We suggest that electron transfer from the light state to the dark state might be blocked due to electrostatic surrounding of gel with inherent negatively charged fibers.

  5. Reduction of postsurgical adhesion formation with hydrogels synthesized by radiation

    NASA Astrophysics Data System (ADS)

    Nho, Young-Chang; Lee, Joon-Ho

    2005-07-01

    Biocompatible and biodegradable hydrogels based on carboxymethyl cellulose (CMC) and polyethyleneglycol (PEG) were prepared as physical barriers for preventing surgical adhesions. These interpolymeric hydrogels were synthesized by gamma irradiation crosslinking technique. A 1.5 cm × 1.5 cm of cecal serosa and an adjacent abdominal wall were abraded with bone burr until the serosal surface was disrupted and hemorrhagic but not perforated. The denuded cecum was covered with either CMC/PEG hydrogels or a solution from a CMC/PEG hydrogel. Control rat serosa was not covered. Two weeks later, the rats were sacrificed and the adhesion was scored on a 0-5 scale. Control rat showed a significantly higher incidence of adhesions than either the CMC/PEG hydrogels or a solution from the CMC/PEG hydrogel. In conclusion, these studies demonstrate that CMC/PEG hydrogels have a function of the prevention for an intra abdominal adhesion in a rat model.

  6. Functionalized graphene oxide quantum dot-PVA hydrogel: a colorimetric sensor for Fe²⁺, Co²⁺ and Cu²⁺ ions.

    PubMed

    Baruah, Upama; Chowdhury, Devasish

    2016-04-01

    Functionalized graphene oxide quantum dots (GOQDs)-poly(vinyl alcohol) (PVA) hybrid hydrogels were prepared using a simple, facile and cost-effective strategy. GOQDs bearing different surface functional groups were introduced as the cross-linking agent into the PVA matrix thereby resulting in gelation. The four different types of hybrid hydrogels were prepared using graphene oxide, reduced graphene oxide, ester functionalized graphene oxide and amine functionalized GOQDs as cross-linking agents. It was observed that the hybrid hydrogel prepared with amine functionalized GOQDs was the most stable. The potential applicability of using this solid sensing platform has been subsequently explored in an easy, simple, effective and sensitive method for optical detection of M(2+) (Fe(2+), Co(2+) and Cu(2+)) in aqueous media involving colorimetric detection. Amine functionalized GOQDs-PVA hybrid hydrogel when put into the corresponding solution of Fe(2+), Co(2+) and Cu(2+) renders brown, orange and blue coloration respectively of the solution detecting the presence of Fe(2+), Co(2+) and Cu(2+) ions in the solution. The minimum detection limit observed was 1 × 10(-7) M using UV-visible spectroscopy. Further, the applicability of the sensing material was also tested for a mixture of co-existing ions in solution to demonstrate the practical applicability of the system. Insight into the probable mechanistic pathway involved in the detection process is also being discussed. PMID:26902906

  7. Retention of gene expression in porcine islets after agarose encapsulation and long-term culture.

    PubMed

    Dumpala, Pradeep R; Holdcraft, Robert W; Martis, Prithy C; Laramore, Melissa A; Parker, Thomas S; Levine, Daniel M; Smith, Barry H; Gazda, Lawrence S

    2016-08-01

    Agarose encapsulation of porcine islets allows extended in vitro culture, providing ample time to determine the functional capacity of the islets and conduct comprehensive microbiological safety testing prior to implantation as a treatment for type 1 diabetes mellitus. However, the effect that agarose encapsulation and long-term culture may have on porcine islet gene expression is unknown. The aim of the present study was to compare the transcriptome of encapsulated porcine islets following long-term in vitro culture against free islets cultured overnight. Global gene expression analysis revealed no significant change in the expression of 98.47% of genes. This indicates that the gene expression profile of free islets is highly conserved following encapsulation and long-term culture. Importantly, the expression levels of genes that code for critical hormones secreted by islets (insulin, glucagon, and somatostatin) as well as transcripts encoding proteins involved in their packaging and secretion are unchanged. While a small number of genes known to play roles in the insulin secretion and insulin signaling pathways are differentially expressed, our results show that overall gene expression is retained following islet isolation, agarose encapsulation, and long-term culture. PMID:27261433

  8. Antifungal hydrogels

    PubMed Central

    Zumbuehl, Andreas; Ferreira, Lino; Kuhn, Duncan; Astashkina, Anna; Long, Lisa; Yeo, Yoon; Iaconis, Tiffany; Ghannoum, Mahmoud; Fink, Gerald R.; Langer, Robert; Kohane, Daniel S.

    2007-01-01

    Fungi are increasingly identified as major pathogens in bloodstream infections, often involving indwelling devices. Materials with antifungal properties may provide an important deterrent to these infections. Here we describe amphogel, a dextran-based hydrogel into which amphotericin B is adsorbed. Amphogel kills fungi within 2 h of contact and can be reused for at least 53 days without losing its effectiveness against Candida albicans. The antifungal material is biocompatible in vivo and does not cause hemolysis in human blood. Amphogel inoculated with C. albicans and implanted in mice prevents fungal infection. Amphogel also mitigates fungal biofilm formation. An antifungal matrix with these properties could be used to coat a variety of medical devices such as catheters as well as industrial surfaces. PMID:17664427

  9. Evaluation of the friction coefficient, the radial stress, and the damage work during needle insertions into agarose gels.

    PubMed

    Urrea, Fabián A; Casanova, Fernando; Orozco, Gustavo A; García, José J

    2016-03-01

    Agarose hydrogels have been extensively used as a phantom material to mimic the mechanical behavior of soft biological tissues, e.g. in studies aimed to analyze needle insertions into the organs producing tissue damage. To better predict the radial stress and damage during needle insertions, this study was aimed to determine the friction coefficient between the material of commercial catheters and hydrogels. The friction coefficient, the tissue damage and the radial stress were evaluated at 0.2, 1.8, and 10mm/s velocities for 28, 30, and 32 gauge needles of outer diameters equal to 0.36, 0.31, and 0.23mm, respectively. Force measurements during needle insertions and retractions on agarose gel samples were used to analyze damage and radial stress. The static friction coefficient (0.295±0.056) was significantly higher than the dynamic (0.255±0.086). The static and dynamic friction coefficients were significantly smaller for the 0.2mm/s velocity compared to those for the other two velocities, and there was no significant difference between the friction coefficients for 1.8 and 10mm/s. Radial stress averages were 131.2±54.1, 248.3±64.2, and 804.9±164.3Pa for the insertion velocity of 0.2, 1.8, and 10mm/s, respectively. The radial stress presented a tendency to increase at higher insertion velocities and needle size, which is consistent with other studies. However, the damage work did not show to be a good predictor of tissue damage, which appears to be due to simplifications in the analytical model. Differently to other approaches, the method proposed here based on radial stress may be extended in future studies to quantity tissue damage in vivo along the entire needle track. PMID:26700572

  10. A serum amyloid P-binding hydrogel speeds healing of partial thickness wounds in pigs

    PubMed Central

    Gomer, Richard H.; Pilling, Darrell; Kauvar, Lawrence M.; Ellsworth, Stote; Ronkainen, Sanna D.; Roife, David; Davis, Stephen C.

    2010-01-01

    During wound healing, some circulating monocytes enter the wound, differentiate into fibroblast-like cells called fibrocytes, and appear to then further differentiate into myofibroblasts, cells that play a key role in collagen deposition, cytokine release, and wound contraction. The differentiation of monocytes into fibrocytes is inhibited by the serum protein serum amyloid P (SAP). Depleting SAP at a wound site thus might speed wound healing. SAP binds to some types of agarose in the presence of Ca2+. We found that human SAP binds to an agarose with a KD of 7×10−8M and a Bmax of 2.1 μg SAP/mg wet weight agarose. Mixing this agarose 1: 5 w/v with 30 μg/mL human SAP (the average SAP concentration in normal serum) in a buffer containing 2mM Ca2+ reduced the free SAP concentration to ~0.02 μg/mL, well below the concentration that inhibits fibrocyte differentiation. Compared with a hydrogel dressing and a foam dressing, dressings containing this agarose and Ca2+ significantly increased the speed of wound healing in partial thickness wounds in pigs. This suggests that agarose/Ca2+ dressings may be beneficial for wound healing in humans. PMID:19660048

  11. Hydrogels and their medical applications

    NASA Astrophysics Data System (ADS)

    Rosiak, Janusz M.; Yoshii, Fumio

    1999-05-01

    Biomaterials play a key role in most approaches for engineering tissues as substitutes for functional replacement, for components of devices related to therapy and diagnosis, for drug delivery systems and supportive scaffolds for guided tissue growth. Modern biomaterials could be composed of various components, e.g. metals, ceramics, natural tissues, polymers. In this last group, the hydrogels, hydrophilic polymeric gels with requested biocompatibility and designed interaction with living surrounding seem to be one of the most promising group of biomaterials. Especially, if they are formed by means of ionizing radiation. In early 1950s, the pioneers of the radiation chemistry of polymers began some experiments with radiation crosslinking of hydrophilic polymers. However, hydrogels were analyzed mainly from the point of view of the phenomenon associated with radiation synthesis, with topology of network and relation between radiation parameters of the processes. Fundamental monographs on radiation polymer physics and chemistry written by A. Charlesby (Atomic Radition and polymers, Pergamon Press, Oxford, 1960) and A. Chapiro (Radiation Chemistry of Polymeric Systems, Interscience, New York, 1962) proceed from this time. The noticeable interest in the application of radiation techniques to obtain hydrogels for biomedical purposes began in the late sixties as a result of the papers and patents invented by Japanese and American scientists, headed by Kaetsu in Japan and Hoffman in USA. Immobilization of biologically active species in hydrogel matrices, their use as drug delivery systems and enzyme traps as well as the modification of material surfaces to improve biocompatibility and their ability to bond antigens and antibodies had been the main subjects of these investigations. In this article a brief summary of investigations on mechanism and kinetics of radiation formation of hydrogels as well as some examples of commercialized hydrogel biomaterials have been

  12. 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. PMID:26448049

  13. Serum-free, chemically defined medium with TGF-beta(3) enhances functional properties of nucleus pulposus cell-laden carboxymethylcellulose hydrogel constructs.

    PubMed

    Reza, Anna T; Nicoll, Steven B

    2010-02-01

    Degeneration of the nucleus pulposus (NP) has been implicated as a major cause of low back pain. Tissue engineering strategies may provide a viable NP replacement therapy; however, culture conditions must be optimized to promote functional tissue development. In this study, a standard serum-containing medium formulation was compared to a chemically defined, serum-free medium to determine the effect on matrix elaboration and functional properties of NP cell-laden carboxymethylcellulose (CMC) hydrogels. Additionally, both media were further supplemented with transforming growth factor-beta 3 (TGF-beta(3)). Glycosaminoglycan (GAG) content increased in both TGF-beta(3)-treated groups and was highest for treated, serum-free constructs (9.46 +/- 1.51 microg GAG/mg wet weight), while there were no quantifiable GAGs in untreated serum-containing samples. Histology revealed uniform, interterritorial staining for chondroitin sulfate proteoglycan throughout the treated, serum-free constructs. Type II collagen content was greater in both serum-free groups and highest in treated, serum-free constructs. The equilibrium Young's modulus was highest in serum-free samples supplemented with TGF-beta(3) (18.54 +/- 1.92 kPa), and the equilibrium weight swelling ratio of these constructs approached that of the native NP tissue (22.19 +/- 0.46 vs. 19.94 +/- 3.09, respectively). Taken together, these results demonstrate enhanced functional matrix development by NP cells when cultured in CMC hydrogels maintained in serum-free, TGF-beta(3) supplemented medium, indicating the importance of medium formulation in NP construct development. PMID:19777586

  14. Adaptable Hydrogel Networks with Reversible Linkages for Tissue Engineering

    PubMed Central

    Wang, Huiyuan

    2015-01-01

    Adaptable hydrogels have recently emerged as a promising platform for three-dimensional (3D) cell encapsulation and culture. In conventional, covalently crosslinked hydrogels, degradation is typically required to allow complex cellular functions to occur, leading to bulk material degradation. In contrast, adaptable hydrogels are formed by reversible crosslinks. Through breaking and re-forming of the reversible linkages, adaptable hydrogels can be locally modified to permit complex cellular functions while maintaining their long-term integrity. In addition, these adaptable materials can have biomimetic viscoelastic properties that make them well suited for several biotechnology and medical applications. In this review, adaptable hydrogel design considerations and linkage selections are overviewed, with a focus on various cell compatible crosslinking mechanisms that can be exploited to form adaptable hydrogels for tissue engineering. PMID:25989348

  15. Thermoresponsive Agarose Based Microparticles for Antibody Separation.

    PubMed

    Ooi, Huey Wen; Ketterer, Benedikt; Trouillet, Vanessa; Franzreb, Matthias; Barner-Kowollik, Christopher

    2016-01-11

    We report the development of thermoresponsive 4-mercaptoethylpyridine (MEP)-based chromatographic microsphere based resins for antibody separation that show switchable release abilities by adsorbing immunoglobulins at 40 °C and releasing the proteins at 5 °C. The thermoswitchable release properties were introduced to the porous resins by the grafting of linear poly(N-isopropylacrylamide) (PNIPAM) chains synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, which were modified to possess MEP end functionalities. Adsorption of γ-globulins as a model antibody on the shortest PNIPAM-MEP (3 kDa) grafted microparticles display binding capacities of up to 20 g L(-1) at 40 °C and a significant decrease in binding capacity to less than 2.5 g L(-1) at 5 °C. By switching the temperature to 5 °C, the release of bound γ-globulins is shown to be as high as 90%. The effects of polymer chain length on the binding capacity are studied in detail and found to be critical as they influence the density of MEP functionalities on the particle surfaces. PMID:26626821

  16. Hybrid polymeric hydrogels for ocular drug delivery: nanoparticulate systems from copolymers of acrylic acid-functionalized chitosan and N-isopropylacrylamide or 2-hydroxyethyl methacrylate

    NASA Astrophysics Data System (ADS)

    Barbu, Eugen; Verestiuc, Liliana; Iancu, Mihaela; Jatariu, Anca; Lungu, Adriana; Tsibouklis, John

    2009-06-01

    Nanoparticulate hybrid polymeric hydrogels (10-70 nm) have been obtained via the radical-induced co-polymerization of acrylic acid-functionalized chitosan with either N-isopropylacrylamide or 2-hydroxyethyl methacrylate, and the materials have been investigated for their ability to act as controlled release vehicles in ophthalmic drug delivery. Studies on the effects of network structure upon swelling properties, adhesiveness to substrates that mimic mucosal surfaces and biodegradability, coupled with in vitro drug release investigations employing ophthalmic drugs with differing aqueous solubilities, have identified nanoparticle compositions for each of the candidate drug molecules. The hybrid nanoparticles combine the temperature sensitivity of N-isopropylacrylamide or the good swelling characteristics of 2-hydroxyethyl methacrylate with the susceptibility of chitosan to lysozyme-induced biodegradation.

  17. Laccase-assisted formation of bioactive chitosan/gelatin hydrogel stabilized with plant polyphenols.

    PubMed

    Rocasalbas, Guillem; Francesko, Antonio; Touriño, Sonia; Fernández-Francos, Xavier; Guebitz, Georg M; Tzanov, Tzanko

    2013-02-15

    Laccase-assisted simultaneous cross-linking and functionalization of chitosan/gelatin blends with phenolic compounds from Hamamelis virginiana was investigated for the development of bioactive hydrogel dressings. The potential of these hydrogels for chronic wound treatment was evaluated in vitro, assessing their antibacterial and inhibitory effect on myeloperoxidase and collagenase. Rheological studies revealed that the mechanical properties of the hydrogels were a function of the enzymatic reaction time. Stable hydrogels and resistant to lysozyme degradation were achieved after 2 h laccase reaction. The inhibitory capacity of the hydrogel for myeloperoxidase and collagenase was 32% and 79% respectively after 24 h incubation. Collagenase activity was additionally suppressed by adsorption (20%) of the enzyme onto the hydrogel. Therefore, the bioactive properties of the hydrogels were due to the effect of both released phenolic compounds and the permanently functionalized platform itself. The hydrogels showed antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus. PMID:23399119

  18. Augmentation of Left Ventricular Wall Thickness With Alginate Hydrogel Implants Improves Left Ventricular Function and Prevents Progressive Remodeling in Dogs With Chronic Heart Failure

    PubMed Central

    Sabbah, Hani N.; Wang, Mengjun; Gupta, Ramesh C.; Rastogi, Sharad; Ilsar, Itamar; Sabbah, Michael S.; Kohli, Smita; Helgerson, Sam; Lee, Randall J.

    2013-01-01

    Objectives The study tested the hypothesis that augmentation of the left ventricular (LV) wall thickness with direct intramyocardial injections of alginate hydrogel implants (AHI) reduces LV cavity size, restores LV shape, and improves LV function in dogs with heart failure (HF). Background Progressive LV dysfunction, enlargement, and chamber sphericity are features of HF associated with increased mortality and morbidity. Methods Studies were performed in 14 dogs with HF produced by intracoronary microembolizations (LV ejection fraction [EF] <30%). Dogs were randomized to AHI treatment (n = 8) or to sham-operated control (n = 6). During an open-chest procedure, dogs received either intramyocardial injections of 0.25 to 0.35 ml of alginate hydrogel (Algisyl-LVR, LoneStar Heart, Inc., Laguna Hills, California) or saline. Seven injections were made ∼1.0 to 1.5 cm apart (total volume 1.8 to 2.1 ml) along the circumference of the LV free wall halfway between the apex and base starting from the anteroseptal groove and ending at the posteroseptal groove. Hemodynamic and ventriculographic measurements were made before treatment (PRE) and repeated post-surgery for up to 17 weeks (POST). Results Compared to control, AHI significantly reduced LV end-diastolic and end-systolic volumes and improved LV sphericity. AHI treatment significantly increased EF (26 ± 0.4% at PRE to 31 ± 0.4% at POST; p < 0.05) compared to the decreased EF seen in control dogs (27 ± 0.3% at PRE to 24 ± 1.3% at POST; p < 0.05). AHI treatment was well tolerated and was not associated with increased LV diastolic stiffness. Conclusions In HF dogs, circumferential augmentation of LV wall thickness with AHI improves LV structure and function. The results support continued development of AHI for the treatment of patients with advanced HF. PMID:23998003

  19. Electrophoresis and orientation of F-actin in agarose gels.

    PubMed Central

    Borejdo, J; Ortega, H

    1989-01-01

    F-Actin was electrophoresed on agarose gels. In the presence of 2 mM MgCl2 and above pH 8.5 F-actin entered 1% agarose; when the electric field was 2.1 V/cm and the pH was 8.8, F-actin migrated through a gel as a single band at a rate of 2.5 mm/h. Labeling of actin with fluorophores did not affect its rate of migration, but an increase in ionic strength slowed it down. After the electrophoresis actin was able to bind phalloidin and heavy meromyosin (HMM) and it activated Mg2+-dependent ATPase activity of HMM. The mobility of F-actin increased with the rise in pH. Acto-S-1 complex was also able to migrate in agarose at basic pH, but at a lower rate than F-actin alone. The orientation of fluorescein labeled F-actin and of fluorescein labeled S-1 which formed rigor bonds with F-actin was measured during the electrophoresis by the fluorescence detected linear dichroism method. The former showed little orientation, probably because the dye was mobile on the surface of actin, but we were able to measure the orientation of the absorption dipole of the dye bound to S-1 which was attached to F-actin, and found that it assumed an orientation largely parallel to the direction of the electric field. These results show that actin can migrate in agarose gels in the F form and that it is oriented during the electrophoresis. Images FIGURE 1 FIGURE 3 FIGURE 4 PMID:2528384

  20. Posing for a picture: vesicle immobilization in agarose gel.

    PubMed

    Lira, Rafael B; Steinkühler, Jan; Knorr, Roland L; Dimova, Rumiana; Riske, Karin A

    2016-01-01

    Taking a photo typically requires the object of interest to stand still. In science, imaging is potentiated by optical and electron microscopy. However, living and soft matter are not still. Thus, biological preparations for microscopy usually include a fixation step. Similarly, immobilization strategies are required for or substantially facilitate imaging of cells or lipid vesicles, and even more so for acquiring high-quality data via fluorescence-based techniques. Here, we describe a simple yet efficient method to immobilize objects such as lipid vesicles with sizes between 0.1 and 100 μm using agarose gel. We show that while large and giant unilamellar vesicles (LUVs and GUVs) can be caged in the pockets of the gel meshwork, small molecules, proteins and micelles remain free to diffuse through the gel and interact with membranes as in agarose-free solutions, and complex biochemical reactions involving several proteins can proceed in the gel. At the same time, immobilization in agarose has no adverse effect on the GUV size and stability. By applying techniques such as FRAP and FCS, we show that the lateral diffusion of lipids is not affected by the gel. Finally, our immobilization strategy allows capturing high-resolution 3D images of GUVs. PMID:27140695

  1. Posing for a picture: vesicle immobilization in agarose gel

    PubMed Central

    Lira, Rafael B.; Steinkühler, Jan; Knorr, Roland L.; Dimova, Rumiana; Riske, Karin A.

    2016-01-01

    Taking a photo typically requires the object of interest to stand still. In science, imaging is potentiated by optical and electron microscopy. However, living and soft matter are not still. Thus, biological preparations for microscopy usually include a fixation step. Similarly, immobilization strategies are required for or substantially facilitate imaging of cells or lipid vesicles, and even more so for acquiring high-quality data via fluorescence-based techniques. Here, we describe a simple yet efficient method to immobilize objects such as lipid vesicles with sizes between 0.1 and 100 μm using agarose gel. We show that while large and giant unilamellar vesicles (LUVs and GUVs) can be caged in the pockets of the gel meshwork, small molecules, proteins and micelles remain free to diffuse through the gel and interact with membranes as in agarose-free solutions, and complex biochemical reactions involving several proteins can proceed in the gel. At the same time, immobilization in agarose has no adverse effect on the GUV size and stability. By applying techniques such as FRAP and FCS, we show that the lateral diffusion of lipids is not affected by the gel. Finally, our immobilization strategy allows capturing high-resolution 3D images of GUVs. PMID:27140695

  2. Posing for a picture: vesicle immobilization in agarose gel

    NASA Astrophysics Data System (ADS)

    Lira, Rafael B.; Steinkühler, Jan; Knorr, Roland L.; Dimova, Rumiana; Riske, Karin A.

    2016-05-01

    Taking a photo typically requires the object of interest to stand still. In science, imaging is potentiated by optical and electron microscopy. However, living and soft matter are not still. Thus, biological preparations for microscopy usually include a fixation step. Similarly, immobilization strategies are required for or substantially facilitate imaging of cells or lipid vesicles, and even more so for acquiring high-quality data via fluorescence-based techniques. Here, we describe a simple yet efficient method to immobilize objects such as lipid vesicles with sizes between 0.1 and 100 μm using agarose gel. We show that while large and giant unilamellar vesicles (LUVs and GUVs) can be caged in the pockets of the gel meshwork, small molecules, proteins and micelles remain free to diffuse through the gel and interact with membranes as in agarose-free solutions, and complex biochemical reactions involving several proteins can proceed in the gel. At the same time, immobilization in agarose has no adverse effect on the GUV size and stability. By applying techniques such as FRAP and FCS, we show that the lateral diffusion of lipids is not affected by the gel. Finally, our immobilization strategy allows capturing high-resolution 3D images of GUVs.

  3. Dynamic behaviors of astrocytes in chemically modified fibrin and collagen hydrogels.

    PubMed

    Seyedhassantehrani, Negar; Li, Yongchao; Yao, Li

    2016-05-16

    Astrocytes play a critical role in supporting the normal physiological function of neurons in the central nervous system (CNS). Astrocyte transplantation can potentially promote axonal regeneration and functional recovery after spinal cord injury (SCI). Fibrin and collagen hydrogels provide growth-permissive substrates and serve as carriers for therapeutic cell transplantation into an injured spinal cord. However, the application of fibrin and collagen hydrogels may be limited due to their relatively rapid degradation rate in vivo. In this study, immature astrocytes isolated from neonatal rats were grown in fibrin hydrogels containing aprotinin and collagen hydrogels crosslinked with poly(ethylene glycol) ether tetrasuccinimidyl glutarate (4S-StarPEG), and the cell behavior in these hydrogels was studied. The cell viability of astrocytes in the hydrogels was tested using the LIVE/DEAD® assay and the AlamarBlue® assay, and this study showed that astrocytes maintained good viability in these hydrogels. The cell migration study showed that astrocytes migrated in the fibrin and collagen hydrogels, and the migration speed is similar in these hydrogels. The crosslinking of collagen hydrogels with 4S-StarPEG did not change the astrocyte migration speed. However, the addition of aprotinin in the fibrin hydrogel inhibited astrocyte migration. The expression of chondroitin sulfate proteoglycan (CSPG), including NG2, neurocan, and versican, by astrocytes grown in the hydrogels was analyzed by quantitative RT-PCR. The expression of NG2, neurocan, and versican by the cells in these hydrogels was not significantly different. PMID:27079938

  4. Exceptionally tough and notch-insensitive magnetic hydrogels.

    PubMed

    Haider, Hussain; Yang, Can Hui; Zheng, Wen Jiang; Yang, Jian Hai; Wang, Mei Xiang; Yang, Sen; Zrínyi, Miklós; Osada, Yoshihito; Suo, Zhigang; Zhang, Qiqing; Zhou, Jinxiong; Chen, Yong Mei

    2015-11-14

    Most existing magnetic hydrogels are weak and brittle. The development of strong and tough magnetic hydrogels would extend their applications into uncultivated areas, such as in actuators for soft machines and guided catheters for magnetic navigation systems, which is still a big challenge. Here a facile and versatile approach to fabricating highly stretchable, exceptionally tough and notch-insensitive magnetic hydrogels, Fe(3)O(4)@Fe-alginate/polyacrylamide (PAAm), is developed, by dispersing alginate-coated Fe(3)O(4) nanoparticles into the interpenetrating polymer networks of alginate and PAAm, with hybrid physical and chemical crosslinks. A cantilever bending beam actuator as well as a proof-of-concept magnetically guided hydrogel catheter is demonstrated. The method proposed in this work can be integrated into other strong and tough magnetic hydrogels for the development of novel hydrogel nanocomposites with both desirable functionality and superior mechanical properties. PMID:26350404

  5. Three-dimensional hMSC Motility within Peptide-Functionalized PEG-Based Hydrogel of Varying Adhesivity and Crosslinking Density

    PubMed Central

    Kyburz, Kyle A; Anseth, Kristi S

    2013-01-01

    Human mesenchymal stem cell (hMSC) migration and recruitment play a critical role during bone fracture healing. Within the complex 3D in vivo microenvironment, hMSC migration is regulated through a myriad of extracellular cues. Here, we use a thiol-ene photopolymerized hydrogel to recapitulate structural and bioactive inputs in a tunable manner to understand their role in regulating 3D hMSC migration. Specifically, peptide-functionalized poly(ethylene glycol) hydrogels were used to encapsulate hMSC while varying the crosslinking density, 0.18 ± 0.02 - 1.60 ± 0.04 mM, and the adhesive ligand density, 0.001 to 1.0 mM. Using live cell videomicroscopy migratory cell paths were tracked and fit to a persistent random walk model. It was shown that hMSC migrating through the lowest crosslinking density and highest adhesivity had more sustained polarization, higher migrating speeds (17.6 ± 0.9 μm/hr), and higher cell spreading (Elliptical Form Factor = 3.9 ± 0.2). However, manipulation of these material properties did not significantly affect migration persistence. Further, there was a monotonic increase in cell speed and spreading with increasing adhesivity showing a lack of the biphasic trend seen in two dimensional cell migration. Immunohistochemistry showed well-formed actin fibers and β1 integrin staining at the ends of stress fibers. This thiol-ene platform provides a highly tunable substrate to characterize 3D hMSC migration with application as an implantable cell carrier platform or for the recruitment of endogenous hMSC in vivo. PMID:23376239

  6. Antifouling properties of hydrogels

    NASA Astrophysics Data System (ADS)

    Murosaki, Takayuki; Ahmed, Nafees; Gong, Jian Ping

    2011-12-01

    Marine sessile organisms easily adhere to submerged solids such as rocks, metals and plastics, but not to seaweeds and fishes, which are covered with soft and wet 'hydrogel'. Inspired by this fact, we have studied long-term antifouling properties of hydrogels against marine sessile organisms. Hydrogels, especially those containing hydroxy group and sulfonic group, show excellent antifouling activity against barnacles both in laboratory assays and in the marine environment. The extreme low settlement on hydrogels in vitro and in vivo is mainly caused by antifouling properties against the barnacle cypris.

  7. 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. PMID:26485407

  8. Cell-laden microengineered gelatin methacrylate hydrogels.

    PubMed

    Nichol, Jason W; Koshy, Sandeep T; Bae, Hojae; Hwang, Chang M; Yamanlar, Seda; Khademhosseini, Ali

    2010-07-01

    The cellular microenvironment plays an integral role in improving the function of microengineered tissues. Control of the microarchitecture in engineered tissues can be achieved through photopatterning of cell-laden hydrogels. However, despite high pattern fidelity of photopolymerizable hydrogels, many such materials are not cell-responsive and have limited biodegradability. Here, we demonstrate gelatin methacrylate (GelMA) as an inexpensive, cell-responsive hydrogel platform for creating cell-laden microtissues and microfluidic devices. Cells readily bound to, proliferated, elongated, and migrated both when seeded on micropatterned GelMA substrates as well as when encapsulated in microfabricated GelMA hydrogels. The hydration and mechanical properties of GelMA were demonstrated to be tunable for various applications through modification of the methacrylation degree and gel concentration. The pattern fidelity and resolution of GelMA were high and it could be patterned to create perfusable microfluidic channels. Furthermore, GelMA micropatterns could be used to create cellular micropatterns for in vitro cell studies or 3D microtissue fabrication. These data suggest that GelMA hydrogels could be useful for creating complex, cell-responsive microtissues, such as endothelialized microvasculature, or for other applications that require cell-responsive microengineered hydrogels. PMID:20417964

  9. BIOMIMETIC GRADIENT HYDROGELS FOR TISSUE ENGINEERING

    PubMed Central

    Sant, Shilpa; Hancock, Matthew J.; Donnelly, Joseph P.; Iyer, Dharini; Khademhosseini, Ali

    2011-01-01

    During tissue morphogenesis and homeostasis, cells experience various signals in their environments, including gradients of physical and chemical cues. Spatial and temporal gradients regulate various cell behaviours such as proliferation, migration, and differentiation during development, inflammation, wound healing, and cancer. One of the goals of functional tissue engineering is to create microenvironments that mimic the cellular and tissue complexity found in vivo by incorporating physical, chemical, temporal, and spatial gradients within engineered three-dimensional (3D) scaffolds. Hydrogels are ideal materials for 3D tissue scaffolds that mimic the extracellular matrix (ECM). Various techniques from material science, microscale engineering, and microfluidics are used to synthesise biomimetic hydrogels with encapsulated cells and tailored microenvironments. In particular, a host of methods exist to incorporate micrometer to centimetre scale chemical and physical gradients within hydrogels to mimic the cellular cues found in vivo. In this review, we draw on specific biological examples to motivate hydrogel gradients as tools for studying cell–material interactions. We provide a brief overview of techniques to generate gradient hydrogels and showcase their use to study particular cell behaviours in two-dimensional (2D) and 3D environments. We conclude by summarizing the current and future trends in gradient hydrogels and cell–material interactions in context with the long-term goals of tissue engineering. PMID:21874065

  10. BIOMIMETIC GRADIENT HYDROGELS FOR TISSUE ENGINEERING.

    PubMed

    Sant, Shilpa; Hancock, Matthew J; Donnelly, Joseph P; Iyer, Dharini; Khademhosseini, Ali

    2010-12-01

    During tissue morphogenesis and homeostasis, cells experience various signals in their environments, including gradients of physical and chemical cues. Spatial and temporal gradients regulate various cell behaviours such as proliferation, migration, and differentiation during development, inflammation, wound healing, and cancer. One of the goals of functional tissue engineering is to create microenvironments that mimic the cellular and tissue complexity found in vivo by incorporating physical, chemical, temporal, and spatial gradients within engineered three-dimensional (3D) scaffolds. Hydrogels are ideal materials for 3D tissue scaffolds that mimic the extracellular matrix (ECM). Various techniques from material science, microscale engineering, and microfluidics are used to synthesise biomimetic hydrogels with encapsulated cells and tailored microenvironments. In particular, a host of methods exist to incorporate micrometer to centimetre scale chemical and physical gradients within hydrogels to mimic the cellular cues found in vivo. In this review, we draw on specific biological examples to motivate hydrogel gradients as tools for studying cell-material interactions. We provide a brief overview of techniques to generate gradient hydrogels and showcase their use to study particular cell behaviours in two-dimensional (2D) and 3D environments. We conclude by summarizing the current and future trends in gradient hydrogels and cell-material interactions in context with the long-term goals of tissue engineering. PMID:21874065

  11. Tissue responses against tissue-engineered cartilage consisting of chondrocytes encapsulated within non-absorbable hydrogel.

    PubMed

    Kanazawa, Sanshiro; Fujihara, Yuko; Sakamoto, Tomoaki; Asawa, Yukiyo; Komura, Makoto; Nagata, Satoru; Takato, Tsuyoshi; Hoshi, Kazuto

    2013-01-01

    To disclose the influence of foreign body responses raised against a non-absorbable hydrogel consisting of tissue-engineered cartilage, we embedded human/canine chondrocytes within agarose and transplanted them into subcutaneous pockets in nude mice and donor beagles. One month after transplantation, cartilage formation was observed in the experiments using human chondrocytes in nude mice. No significant invasion of blood cells was noted in the areas where the cartilage was newly formed. Around the tissue-engineered cartilage, agarose fragments, a dense fibrous connective tissue and many macrophages were observed. On the other hand, no cartilage tissue was detected in the autologous transplantation of canine chondrocytes. Few surviving chondrocytes were observed in the agarose and no accumulation of blood cells was observed in the inner parts of the transplants. Localizations of IgG and complements were noted in areas of agarose, and also in the devitalized cells embedded within the agarose. Even if we had inhibited the proximity of the blood cells to the transplanted cells, the survival of the cells could not be secured. We suggest that these cytotoxic mechanisms seem to be associated not only with macrophages but also with soluble factors, including antibodies and complements. PMID:21916014

  12. Cyclodextrin-grafted chitosan hydrogels for controlled drug delivery.

    PubMed

    Kono, Hiroyuki; Teshirogi, Taku

    2015-01-01

    A series of β-cyclodextrin-grafted carboxymethyl chitosan hydrogels (CD-g-CMCs) were prepared from carboxymethyl chitosan (CMC) and carboxymethyl β-chitosan (CMCD) using a water-soluble carbodiimide as a crosslinker in the presence of N-hydroxysuccinimide. Details of the hydrogel structures were determined via FTIR and solid-state NMR spectroscopic analyses. Increasing the feed ratio of CMCD to CMC in the reaction mixture led to an increase in CD grafting within the gel networks comprising CMC; this was confirmed by SEM observations and rheological analysis of the swollen hydrogels. The prepared CD-g-CMC hydrogels exhibited absorption properties toward acetylsalicylic acid (ASA, or Aspirin) due to the presence of CD in the structure; the amount of ASA absorbed into the hydrogels was enhanced with an increase in the amount of CD incorporated within the hydrogels. In addition, CD-g-CMC hydrogels provided a slower release of the entrapped ASA in comparison to the ASA release profile of a solely CMC-containing hydrogel. From these results, CD-g-CMC hydrogels have the potential to function as a biodegradable active material with controlled drug release ability. PMID:25192852

  13. Responsive DNA-based hydrogels and their applications

    PubMed Central

    Xiong, Xiangling; Zhou, Cuisong; Wu, Cuichen; Zhu, Guizhi; Chen, Zhuo; Tan, Weihong

    2015-01-01

    The term hydrogel describes a type of soft and wet material formed by crosslinked hydrophilic polymers. The distinct feature of hydrogels is their ability to absorb a large amount of water and swell. The properties of a hydrogel are usually determined by the type of polymer and crosslinker, the degree of crosslinking, and the water content. However, a group of hydrogels, called “smart hydrogels”, changes properties in response to environmental changes or external stimuli. Recently, DNA or DNA-inspired responsive hydrogels have attracted considerable attention in construction of smart hydrogels because of the intrinsic advantages of DNA. As a biological polymer, DNA is hydrophilic, biocompatible, and highly programmable by Watson-Crick base pairing. DNA can form a hydrogel by itself under certain conditions, and it can also be incorporated into synthetic polymers to form DNA-hybrid hydrogels. Functional DNAs, such as aptamers and DNAzymes, provide additional molecular recognition capabilities and versatility. In this review, we discuss DNA-based hydrogels in terms of their stimulus response, as well as their applications. PMID:23857726

  14. Biodegradable HEMA-based hydrogels with enhanced mechanical properties.

    PubMed

    Moghadam, Mohamadreza Nassajian; Pioletti, Dominique P

    2016-08-01

    Hydrogels are widely used in the biomedical field. Their main purposes are either to deliver biological active agents or to temporarily fill a defect until they degrade and are followed by new host tissue formation. However, for this latter application, biodegradable hydrogels are usually not capable to sustain any significant load. The development of biodegradable hydrogels presenting load-bearing capabilities would open new possibilities to utilize this class of material in the biomedical field. In this work, an original formulation of biodegradable photo-crosslinked hydrogels based on hydroxyethyl methacrylate (HEMA) is presented. The hydrogels consist of short-length poly(2-hydroxyethyl methacrylate) (PHEMA) chains in a star shape structure, obtained by introducing a tetra-functional chain transfer agent in the backbone of the hydrogels. They are cross-linked with a biodegradable N,O-dimethacryloyl hydroxylamine (DMHA) molecule sensitive to hydrolytic cleavage. We characterized the degradation properties of these hydrogels submitted to mechanical loadings. We showed that the developed hydrogels undergo long-term degradation and specially meet the two essential requirements of a biodegradable hydrogel suitable for load bearing applications: enhanced mechanical properties and low molecular weight degradation products. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1161-1169, 2016. PMID:26061346

  15. Force-compensated hydrogel-based pH sensor

    NASA Astrophysics Data System (ADS)

    Deng, Kangfa; Gerlach, Gerald; Guenther, Margarita

    2015-04-01

    This paper presents the design, simulation, assembly and testing of a force-compensated hydrogel-based pH sensor. In the conventional deflection method, a piezoresistive pressure sensor is used as a chemical-mechanical-electronic transducer to measure the volume change of a pH-sensitive hydrogel. In this compensation method, the pH-sensitive hydrogel keeps its volume constant during the whole measuring process, independent of applied pH value. In order to maintain a balanced state, an additional thermal actuator is integrated into the close-loop sensor system with higher precision and faster dynamic response. Poly (N-isopropylacrylamide) (PNIPAAm) with 5 mol% monomer 3-acrylamido propionic acid (AAmPA) is used as the temperature-sensitive hydrogel, while poly (vinyl alcohol) with poly (acrylic acid) (PAA) serves as the pH-sensitive hydrogel. A thermal simulation is introduced to assess the temperature distribution of the whole microsystem, especially the temperature influence on both hydrogels. Following tests are detailed to verify the working functions of a sensor based on pH-sensitive hydrogel and an actuator based on temperature-sensitive hydrogel. A miniaturized prototype is assembled and investigated in deionized water: the response time amounts to about 25 min, just half of that one of a sensor based on the conventional deflection method. The results confirm the applicability of t he compensation method to the hydrogel-based sensors.

  16. Mechanical Behavior of Tough Hydrogels for Structural Applications

    NASA Astrophysics Data System (ADS)

    Illeperuma, Widusha Ruwangi Kaushalya

    novel applications. This thesis aims to investigate the broader applications, well beyond those investigated so far. We show fiber reinforced tough hydrogels can dissipate a significant amount of energy at a tunable level of stress, making them suitable for energy absorbing applications such as inner layer of helmets. We develop inexpensive fire-retarding materials using tough hydrogels that provide superior protection from burn injuries. We also study hydrogels as actuators that can be used in soft robotics. Hydrogels contain mostly water and they freeze when the temperature drops below 00C and lose its functions. We demonstrate a new class of hydrogels that do not freeze and hydrogels that partially freeze below water freezing temperature. Partially freezing hydrogels are ideal for cooling applications such as gel packs and non-freezing hydrogels are useful in all the structural applications at low temperatures. This thesis will enable the use of inexpensive hydrogels in a new class of non-traditional structural applications where the mechanical behavior of the hydrogel is of prime importance.

  17. Structural and molecular micropatterning of dual hydrogel constructs for neural growth models using photochemical strategies

    PubMed Central

    Horn-Ranney, Elaine L.; Curley, J. Lowry; Catig, Gary C.; Huval, Renee M.; Moore, Michael J.

    2013-01-01

    Chemotactic and haptotactic cues guide neurite growth toward appropriate targets by eliciting attractive or repulsive responses from the neurite growth cones. Here we present an integrated system allowing both structural and molecular micropatterning in dual hydrogel 3D tissue culture constructs for directing in vitro neuronal growth via structural, immobilized, and soluble guidance cues. These tissue culture constructs were fabricated into specifiable geometries using UV light reflected from a digital micromirror device acting as a dynamic photomask, resulting in dual hydrogel constructs consisting of a cell growth-restrictive polyethylene glycol (PEG) boundary with a cell growth-permissive interior of photolabile α-carboxy-2-nitrobenzyl cysteine agarose (CNBC-A). This CNBC-A was irradiated in discrete areas and subsequently tagged with maleimide-conjugated biomolecules. Fluorescent microscopy showed biomolecule binding only at the sites of irradiation in CNBC-A, and confocal microscopy confirmed 3D binding through the depth of the construct. Neurite outgrowth studies showed contained growth throughout CNBC-A. The diffusion rate of soluble fluorescein-bovine serum albumin through the dual hydrogel construct was controlled by PEG concentration and the distance between the protein source and the agarose interior; the timescale for a transient protein gradient changed with these parameters. These findings suggest the dual hydrogel system is a usefulplatform for manipulating a 3D in vitro microenvironment with patterned structural and molecular guidance cues for modeling neural growth and guidance. PMID:22903647

  18. Encapsulation of adult human mesenchymal stem cells within collagen-agarose microenvironments.

    PubMed

    Batorsky, Anna; Liao, Jiehong; Lund, Amanda W; Plopper, George E; Stegemann, Jan P

    2005-11-20

    Reliable control over the process of cell differentiation is a major challenge in moving stem cell-based therapies forward. The composition of the extracellular matrix (ECM) is known to play an important role in modulating differentiation. We have developed a system to encapsulate adult human mesenchymal stem cells (hMSC) within spherical three-dimensional (3D) microenvironments consisting of a defined mixture of collagen Type I and agarose polymers. These protein-based beads were produced by emulsification of liquid hMSC-matrix suspensions in a silicone fluid phase and subsequent gelation to form hydrogel beads, which were collected by centrifugation and placed in culture. Bead size and size distribution could be varied by changing the encapsulation parameters (impeller speed and blade separation), and beads in the range of 30-150 microns in diameter were reliably produced. Collagen concentrations up to 40% (wt/wt) could be incorporated into the bead matrix. Visible light and fluorescence microscopy confirmed that the collagen matrix was uniformly distributed throughout the beads. Cell viability post-encapsulation was in the range of 75-90% for all bead formulations (similar to control slab gels) and remained at this level for 8 days in culture. Fluorescent staining of the actin cytoskeleton revealed that hMSC spreading increased with increasing collagen concentration. This system of producing 3D microenvironments of defined matrix composition therefore offers a way to control cell-matrix interactions and thereby guide hMSC differentiation. The bead format allows the use of small amounts of matrix proteins, and such beads can potentially be used as a cell delivery vehicle in tissue repair applications. PMID:16080186

  19. Refractive-index-matched hydrogel materials for measuring flow-structure interactions

    NASA Astrophysics Data System (ADS)

    Byron, Margaret L.; Variano, Evan A.

    2013-02-01

    In imaging-based studies of flow around solid objects, it is useful to have materials that are refractive-index-matched to the surrounding fluid. However, materials currently in use are usually rigid and matched to liquids that are either expensive or highly viscous. This does not allow for measurements at high Reynolds number, nor accurate modeling of flexible structures. This work explores the use of two hydrogels (agarose and polyacrylamide) as refractive-index-matched models in water. These hydrogels are inexpensive, can be cast into desired shapes, and have flexibility that can be tuned to match biological materials. The use of water as the fluid phase allows this method to be implemented immediately in many experimental facilities and permits investigation of high-Reynolds-number phenomena. We explain fabrication methods and present a summary of the physical and optical properties of both gels, and then show measurements demonstrating the use of hydrogel models in quantitative imaging.

  20. New in situ crosslinking chemistries for hydrogelation

    NASA Astrophysics Data System (ADS)

    Roberts, Meredith Colleen

    Over the last half century, hydrogels have found immense value as biomaterials in a vast number of biomedical and pharmaceutical applications. One subset of hydrogels receiving increased attention is in situ forming gels. Gelling by either bioresponsive self-assembly or mixing of binary crosslinking systems, these technologies are useful in minimally invasive applications as well as drug delivery systems in which the sol-to-gel transition aids the formulation's performance. Thus far, the field of in situ crosslinking hydrogels has received limited attention in the development of new crosslinking chemistries. Moreover, not only does the chemical nature of the crosslinking moieties allow these systems to perform in situ, but they contribute dramatically to the mechanical properties of the hydrogel networks. For example, reversible crosslinks with finite lifetimes generate dynamic viscoelastic gels with time-dependent properties, whereas irreversible crosslinks form highly elastic networks. The aim of this dissertation is to explore two new covalent chemistries for their ability to crosslink hydrogels in situ under physiological conditions. First, reversible phenylboronate-salicylhydroxamate crosslinking was implemented in a binary, multivalent polymeric system. These gels formed rapidly and generated hydrogel networks with frequency-dependent dynamic rheological properties. Analysis of the composition-structure-property relationships of these hydrogels---specifically considering the effects of pH, degree of polymer functionality, charge of the polymer backbone and polymer concentration on dynamic theological properties---was performed. These gels demonstrate diverse mechanical properties, due to adjustments in the binding equilibrium of the pH-sensitive crosslinks, and thus have the potential to perform in a range of dynamic or bioresponsive applications. Second, irreversible catalyst-free "click" chemistry was employed in the hydrogelation of multivalent azide-functionalized

  1. Hydrogels Constructed from Engineered Proteins.

    PubMed

    Li, Hongbin; Kong, Na; Laver, Bryce; Liu, Junqiu

    2016-02-24

    Due to their various potential biomedical applications, hydrogels based on engineered proteins have attracted considerable interest. Benefitting from significant progress in recombinant DNA technology and protein engineering/design techniques, the field of protein hydrogels has made amazing progress. The latest progress of hydrogels constructed from engineered recombinant proteins are presented, mainly focused on biorecognition-driven physical hydrogels as well as chemically crosslinked hydrogels. The various bio-recognition based physical crosslinking strategies are discussed, as well as chemical crosslinking chemistries used to engineer protein hydrogels, and protein hydrogels' various biomedical applications. The future perspectives of this fast evolving field of biomaterials are also discussed. PMID:26707834

  2. Porous ceramic/agarose composite adsorbents for fast protein liquid chromatography.

    PubMed

    Xia, Haifeng; Jin, Xionghua; Wu, Puqiang; Zheng, Zhiyong

    2012-02-01

    Porous ceramic/agarose composite adsorbents were designed and prepared with silica ceramic beads and 4% agarose gel, and then functionalized with a special ligand carboxymethyl. A novel method was introduced to fabricating of the porous silica ceramic beads. The morphology of SEM shows a spherical shape and a porous structure of the ceramic beads. Nitrogen adsorption-desorption analysis gives an average pore size of 287.5 Å, a BET surface area of 29.33 m²/g and a porosity of 41.8%, respectively. Additionally, X-ray diffraction pattern indicates that the amorphous silica has been transformed into two crystal phases of quartz and cristobalite, leading to a porous and rigid skeleton and ensuring the application of the composite beads at high flow velocities. Lysozyme of hen egg-white with the activity of 12,700 U/mg was purified by the composite ion-exchanger in one step and the recovery and purification factor reaches 95.2% and 7.9, respectively. PMID:22226554

  3. Fabrication of poly(ethylene glycol) hydrogel micropatterns with osteoinductive growth factors and evaluation of the effects on osteoblast activity and function

    NASA Astrophysics Data System (ADS)

    Subramani, K.; Birch, M. A.

    2006-09-01

    The aims of this study were to fabricate poly(ethylene glycol) (PEG) hydrogel micropatterns on a biomaterial surface to guide osteoblast behaviour and to study how incorporating vascular endothelial growth factor (VEGF) within the adhered hydrogel influenced cell morphology. Standard photolithographic procedures or photopolymerization through a poly(dimethyl siloxane) (PDMS) mould were used to fabricate patterned PEG hydrogels on the surface of silanized silicon wafers. Hydrogel patterns were evaluated by light microscopy and surface profilometry. Rat osteoblasts were cultured on these surfaces and cell morphology investigated by fluorescence microscopy, scanning electron microscopy (SEM) and atomic force microscopy (AFM). Release of protein trapped in the polymerized PEG was evaluated and VEGF-PEG surfaces were characterized for their ability to support cell growth. These studies show that photopolymerized PEG can be used to create anti-adhesive structures on the surface of silicon that completely control where cell interaction with the substrate takes place. Using conventional lithography, structures down to 50 µm were routinely fabricated with the boundaries exhibiting sloping sides. Using the PDMS mould approach, structures were fabricated as small as 10 µm and boundaries were very sharp and vertical. Osteoblasts exhibiting typical morphology only grew on the silicon wafer surface that was not coated with PEG. Adding BSA to the monomer solution showed that protein could be released from the hydrogel for up to 7 days in vitro. Incorporating VEGF in the hydrogel produced micropatterns that dramatically altered osteoblast behaviour. At boundaries with the VEGF-PEG hydrogel, there was striking formation of cellular processes and membrane ruffling indicative of a change in cell morphology. This study has explored the morphogenetic properties of VEGF and the applications of nano/microfabrication techniques for guided tissue (bone) regeneration in dental and

  4. A mathematical model for electrical impedance spectroscopy of zwitterionic hydrogels.

    PubMed

    Feicht, Sarah E; Khair, Aditya S

    2016-08-17

    We report a mathematical model for ion transport and electrical impedance in zwitterionic hydrogels, which possess acidic and basic functional groups that carry a net charge at a pH not equal to the isoelectric point. Such hydrogels can act as an electro-mechanical interface between a relatively hard biosensor and soft tissue in the body. For this application, the electrical impedance of the hydrogel must be characterized to ensure that ion transport to the biosensor is not significantly hindered. The electrical impedance is the ratio of the applied voltage to the measured current. We consider a simple model system, wherein an oscillating voltage is applied across a hydrogel immersed in electrolyte and sandwiched between parallel, blocking electrodes. We employ the Poisson-Nernst-Planck (PNP) equations coupled with acid-base dissociation reactions for the charge on the hydrogel backbone to model the ionic transport across the hydrogel. The electrical impedance is calculated from the numerical solution to the PNP equations and subsequently analyzed via an equivalent circuit model to extract the hydrogel capacitance, resistance, and the capacitance of electrical double layers at the electrode-hydrogel interface. For example, we predict that an increase in pH from the isoelectric point, pH = 6.4 for a model PCBMA hydrogel, to pH = 8 reduces the resistance of the hydrogel by ∼40% and increases the double layer capacitance by ∼250% at an electrolyte concentration of 0.1 mM. The significant impact of charged hydrogel functional groups to the impedance is damped at higher electrolyte concentration. PMID:27464763

  5. Hypoxia-Inducible Hydrogels

    PubMed Central

    Park, Kyung Min; Gerecht, Sharon

    2014-01-01

    Oxygen is vital for the existence of all multicellular organisms, acting as a signaling molecule regulating cellular activities. Specifically, hypoxia, which occurs when the partial pressure of oxygen falls below 5%, plays a pivotal role during development, regeneration, and cancer. Here we report a novel hypoxia-inducible (HI) hydrogel composed of gelatin and ferulic acid that can form hydrogel networks via oxygen consumption in a laccase-mediated reaction. Oxygen levels and gradients within the hydrogels can be accurately controlled and precisely predicted. We demonstrate that HI hydrogels guide vascular morphogenesis in vitro via hypoxia-inducible factors activation of matrix metalloproteinases and promote rapid neovascularization from the host tissue during subcutaneous wound healing. The HI hydrogel is a new class of biomaterials that may prove useful in many applications, ranging from fundamental studies of developmental, regenerative and disease processes through the engineering of healthy and diseased tissue models towards the treatment of hypoxia-regulated disorders. PMID:24909742

  6. Aromatic–Aromatic Interactions Enhance Interfiber Contacts for Enzymatic Formation of a Spontaneously Aligned Supramolecular Hydrogel

    PubMed Central

    2015-01-01

    Anisotropy or alignment is a critical feature of functional soft materials in living organisms, but it remains a challenge for spontaneously generating anisotropic gel materials. Here we report a molecular design that increases intermolecular aromatic–aromatic interactions of hydrogelators during enzymatic hydrogelation for spontaneously forming an anisotropic hydrogel. This process, relying on both aromatic–aromatic interactions and enzyme catalysis, results in spontaneously aligned supramolecular nanofibers as the matrices of a monodomain hydrogel that exhibits significant birefringence. This work, as the first example of monodomain hydrogels formed via an enzymatic reaction, illustrates a new biomimetic approach for generating aligned anisotropic soft materials. PMID:24512553

  7. On the development of multifunctional luminescent supramolecular hydrogel of gold and egg white.

    PubMed

    Patra, Sudeshna; Ravulapalli, Sathyavathi; Hahm, Myung Gwan; Tadi, Kiran Kumar; Narayanan, Tharangattu N

    2016-10-14

    Highly stable, luminescent, and printable/paintable supramolecular egg white hydrogel-based surface enhanced Raman scattering (SERS) matrix is created by an in situ synthesis of gold clusters inside a luminescent egg white hydrogel (Au-Gel). The synthesis of stable luminescent egg-white-based hydrogel, where the hydrogel can act as a three dimensional (3D) matrix, using a simple cross-linking chemistry, has promising application in the biomedical field including in 3D cell culturing. Furthermore, this functional hydrogel is demonstrated for micromolar-level detection of Rhodamine 6G using the SERS technique, where Au-Gel is painted over a flexible cellulose pad. PMID:27608886

  8. Hybrid Supramolecular and Colloidal Hydrogels that Bridge Multiple Length Scales†

    PubMed Central

    Janeček, Emma‐Rose; McKee, Jason R.; Tan, Cindy S. Y.; Nykänen, Antti; Kettunen, Marjo; Laine, Janne

    2015-01-01

    Abstract Hybrid nanocomposites were constructed based on colloidal nanofibrillar hydrogels with interpenetrating supramolecular hydrogels, displaying enhanced rheological yield strain and a synergistic improvement in storage modulus. The supramolecular hydrogel consists of naphthyl‐functionalized hydroxyethyl cellulose and a cationic polystyrene derivative decorated with methylviologen moieties, physically cross‐linked with cucurbit[8]uril macrocyclic hosts. Fast exchange kinetics within the supramolecular system are enabled by reversible cross‐linking through the binding of the naphthyl and viologen guests. The colloidal hydrogel consists of nanofibrillated cellulose that combines a mechanically strong nanofiber skeleton with a lateral fibrillar diameter of a few nanometers. The two networks interact through hydroxyethyl cellulose adsorption to the nanofibrillated cellulose surfaces. This work shows methods to bridge the length scales of molecular and colloidal hybrid hydrogels, resulting in synergy between reinforcement and dynamics. PMID:27478263

  9. Hybrid Supramolecular and Colloidal Hydrogels that Bridge Multiple Length Scales**

    PubMed Central

    Janeček, Emma-Rose; McKee, Jason R; Tan, Cindy S Y; Nykänen, Antti; Kettunen, Marjo; Laine, Janne; Ikkala, Olli; Scherman, Oren A

    2015-01-01

    Hybrid nanocomposites were constructed based on colloidal nanofibrillar hydrogels with interpenetrating supramolecular hydrogels, displaying enhanced rheological yield strain and a synergistic improvement in storage modulus. The supramolecular hydrogel consists of naphthyl-functionalized hydroxyethyl cellulose and a cationic polystyrene derivative decorated with methylviologen moieties, physically cross-linked with cucurbit[8]uril macrocyclic hosts. Fast exchange kinetics within the supramolecular system are enabled by reversible cross-linking through the binding of the naphthyl and viologen guests. The colloidal hydrogel consists of nanofibrillated cellulose that combines a mechanically strong nanofiber skeleton with a lateral fibrillar diameter of a few nanometers. The two networks interact through hydroxyethyl cellulose adsorption to the nanofibrillated cellulose surfaces. This work shows methods to bridge the length scales of molecular and colloidal hybrid hydrogels, resulting in synergy between reinforcement and dynamics. PMID:25772264

  10. In vitro study of using calcium phosphate cement as immunoisolative device to enclose insulinoma/agarose microspheres as bioartificial pancreas.

    PubMed

    Kai-Chiang, Yang; Ching-Yao, Yang; Chang-Chin, Wu; Tzong-Fu, Kuo; Feng-Huei, Lin

    2007-12-15

    In this study, the feasibility of using calcium phosphate cement (CPC) as immunoisolative device to enclose insulinoma/agarose microspheres as bioartificial pancreas was evaluated. We fabricated a chamber by CPC and utilized X-ray diffraction, Scanning electron microscope and Mercury intrusion porosimetry to identify the characters of the CPC chamber. The nominal molecular weight cut-off and cytotoxicity of CPC chamber were also evaluated. An insulinoma cell line (RIN-m5F) was chosen as insulin source and encapsulated in agarose microspheres and then enclosed in preformed CPC chamber. Insulin secretion was analyzed by Enzyme-linked immunosorbant assay to evaluate the function of insulinoma enclosed in CPC chamber. Results showed that the CPC chamber was non-cytotoxicity to insulinoma and can block the penetration of molecules which molecular weight larger than 12.4 kDa. Insulinoma inside the CPC chamber can secrete insulin in stable level for 30 days. This study indicated that we may use CPC as immunoisolative material to enclose insulinoma/agarose microspheres as bioartificial pancreas. PMID:17514757

  11. Hydrogels derived from demineralized and decellularized bone extracellular matrix

    PubMed Central

    Sawkins, M.J.; Bowen, W.; Dhadda, P.; Markides, H.; Sidney, L.E.; Taylor, A.J.; Rose, F.R.A.J.; Badylak, S.F.; Shakesheff, K.M.; White, L.J.

    2013-01-01

    The extracellular matrix (ECM) of mammalian tissues has been isolated, decellularized and utilized as a scaffold to facilitate the repair and reconstruction of numerous tissues. Recent studies have suggested that superior function and complex tissue formation occurred when ECM scaffolds were derived from site-specific homologous tissues compared with heterologous tissues. The objectives of the present study were to apply a stringent decellularization process to demineralized bone matrix (DBM), prepared from bovine bone, and to characterize the structure and composition of the resulting ECM materials and DBM itself. Additionally, we sought to produce a soluble form of DBM and ECM which could be induced to form a hydrogel. Current clinical delivery of DBM particles for treatment of bone defects requires incorporation of the particles within a carrier liquid. Differences in osteogenic activity, inflammation and nephrotoxicity have been reported with various carrier liquids. The use of hydrogel forms of DBM or ECM may reduce the need for carrier liquids. DBM and ECM hydrogels exhibited sigmoidal gelation kinetics consistent with a nucleation and growth mechanism, with ECM hydrogels characterized by lower storage moduli than the DBM hydrogels. Enhanced proliferation of mouse primary calvarial cells was achieved on ECM hydrogels, compared with collagen type I and DBM hydrogels. These results show that DBM and ECM hydrogels have distinct structural, mechanical and biological properties and have the potential for clinical delivery without the need for carrier liquids. PMID:23624219

  12. Application of Hydrogels in Heart Valve Tissue Engineering

    PubMed Central

    Zhang, Xing; Xu, Bin; Puperi, Daniel S.; Wu, Yan; West, Jennifer L.; Grande-Allen, K. Jane

    2015-01-01

    With an increasing number of patients requiring valve replacement, there is heightened interest in advancing heart valve tissue engineering (HVTE) to provide solutions to the many limitations of current surgical treatments. A variety of materials have been developed as scaffolds for HVTE including natural polymers, synthetic polymers, and decellularized valvular matrices. Among them, biocompatible hydrogels are generating growing interest. Natural hydrogels, such as collagen and fibrin, generally show good bioactivity, but poor mechanical durability. Synthetic hydrogels, on the other hand, have tunable mechanical properties; however, appropriate cell-matrix interactions are difficult to obtain. Moreover, hydrogels can be used as cell carriers when the cellular component is seeded into the polymer meshes or decellularized valve scaffolds. In this review, we discuss current research strategies for HVTE with an emphasis on hydrogel applications. The physicochemical properties and fabrication methods of these hydrogels, as well as their mechanical properties and bioactivities are described. Performance of some hydrogels including in vitro evaluation using bioreactors and in vivo tests in different animal models are also discussed. For future HVTE, it will be compelling to examine how hydrogels can be constructed from composite materials to replicate mechanical properties and mimic biological functions of the native heart valve. PMID:25955010

  13. Cloning of DNA fragments: ligation reactions in agarose gel.

    PubMed

    Furtado, Agnelo

    2014-01-01

    Ligation reactions to ligate a desired DNA fragment into a vector can be challenging to beginners and especially if the amount of the insert is limiting. Although additives known as crowding agents, such as PEG 8000, added to the ligation mixes can increase the success one has with ligation reactions, in practice the amount of insert used in the ligation can determine the success or the failure of the ligation reaction. The method described here, which uses insert DNA in gel slice added directly into the ligation reaction, has two benefits: (a) using agarose as the crowding agent and (b) reducing steps of insert purification. The use of rapid ligation buffer and incubation of the ligation reaction at room temperature greatly increase the efficiency of the ligation reaction even for blunt-ended ligation. PMID:24243199

  14. Robust fluidic connections to freestanding microfluidic hydrogels

    PubMed Central

    Baer, Bradly B.; Larsen, Taylor S. H.

    2015-01-01

    Biomimetic scaffolds approaching physiological scale, whose size and large cellular load far exceed the limits of diffusion, require incorporation of a fluidic means to achieve adequate nutrient/metabolite exchange. This need has driven the extension of microfluidic technologies into the area of biomaterials. While construction of perfusable scaffolds is essentially a problem of microfluidic device fabrication, functional implementation of free-standing, thick-tissue constructs depends upon successful integration of external pumping mechanisms through optimized connective assemblies. However, a critical analysis to identify optimal materials/assembly components for hydrogel substrates has received little focus to date. This investigation addresses this issue directly by evaluating the efficacy of a range of adhesive and mechanical fluidic connection methods to gelatin hydrogel constructs based upon both mechanical property analysis and cell compatibility. Results identify a novel bioadhesive, comprised of two enzymatically modified gelatin compounds, for connecting tubing to hydrogel constructs that is both structurally robust and non-cytotoxic. Furthermore, outcomes from this study provide clear evidence that fluidic interconnect success varies with substrate composition (specifically hydrogel versus polydimethylsiloxane), highlighting not only the importance of selecting the appropriately tailored components for fluidic hydrogel systems but also that of encouraging ongoing, targeted exploration of this issue. The optimization of such interconnect systems will ultimately promote exciting scientific and therapeutic developments provided by microfluidic, cell-laden scaffolds. PMID:26045731

  15. Hydrophilic Organic Electrodes on Flexible Hydrogels.

    PubMed

    Moser, Thierry; Celma, Coralie; Lebert, Audrey; Charrault, Eric; Brooke, Robert; Murphy, Peter J; Browne, Gareth; Young, Richard; Higgs, Timothy; Evans, Drew

    2016-01-13

    Prompted by the rapidly developing field of wearable electronics, research into biocompatible substrates and coatings is intensifying. Acrylate-based hydrogel polymers have gained widespread use as biocompatible articles in applications such as contact and intraocular lenses. Surface treatments and/or coatings present one strategy to further enhance the performance of these hydrogels or even realize novel functionality. In this study, the conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) is deposited from the vapor phase onto hydrated hydrogel substrates and blended with biocompatibilizing coconstituents incorporating polyethylene glycol (PEG) and polydimethyl siloxane (PDMS) moieties. Plasma pretreatment of the dehydrated hydrogel substrate modifies its surface topography and chemical composition to facilitate the attachment of conductive PEDOT-based surface layers. Manipulating the vapor phase polymerization process and constituent composition, the PEDOT-based coating is engineered to be both hydrophilic (i.e. to promote biocompatibility) and highly conductive. The fabrication of this conductively coated hydrogel has implications for the future of wearable electronic devices. PMID:26698297

  16. Micro-environmentally restricted hybridoma cell growth within polysaccharide hydrogel microbeads.

    PubMed

    Pajic-Lijakovic, Ivana

    2013-01-01

    The mechanism of micro-environmentally restricted hybridoma cell growth caused by action of local mechanical compression stress generated within various polysaccharide hydrogel matrixes is estimated by comparing the growth of hybridoma cells within (1) 1.5% Ca-alginate microbeads from Bugarski et al. [in: Fundamentals of Animal Cells Immobilization and Microencapsulation, M.F.A. Goosen, ed., CRC Press, Boca Raton, FL, 1993, p. 267] and (2) 1.3% alginate-agarose microbeads from Shen et al. [Animal Cell Technology: Basic & Applied Aspects, H. Murakami ed., Kluwer Academic Publishers, The Netherlands, 1992, p. 173].Consideration of restricted cell growth dynamics based on developed kinetic model and kinetic 3D Monte Carlo simulation include: (1) changes the fraction of active proliferating cells in the exponential phase and (2) changes of non-proliferating cell concentration in the plateau phase.Higher value of the specific decrease of active fraction of proliferating cells κ is obtained for 1.3% alginate-agarose compared to 1.5% alginate microbeads. It corresponds to higher compression stress generated within hydrogel matrix during cell growth obtained for 1.3% alginate-agarose microbeads. PMID:23988708

  17. Anion-Responsive Metallopolymer Hydrogels for Healthcare Applications

    PubMed Central

    Zhang, Jiuyang; Yan, Jing; Pageni, Parasmani; Yan, Yi; Wirth, Adam; Chen, Yun-Ping; Qiao, Yali; Wang, Qian; Decho, Alan W.; Tang, Chuanbing

    2015-01-01

    Metallopolymers combine a processable, versatile organic polymeric skeleton with functional metals, providing multiple functions and methodologies in materials science. Taking advantage of cationic cobaltocenium as the key building block, organogels could be simply switched to hydrogels via a highly efficient ion exchange. With the unique ionic complexion ability, cobaltocenium moieties provide a robust soft substrate for recycling antibiotics from water. The essential polyelectrolyte nature offers the metallopolymer hydrogels to kill multidrug resistant bacteria. The multifunctional characteristics of these hydrogels highlight the potential for metallopolymers in the field of healthcare and environmental treatment. PMID:26202475

  18. Binding of regulatory subunits of cyclic AMP-dependent protein kinase to cyclic CMP agarose.

    PubMed

    Hammerschmidt, Andreas; Chatterji, Bijon; Zeiser, Johannes; Schröder, Anke; Genieser, Hans-Gottfried; Pich, Andreas; Kaever, Volkhard; Schwede, Frank; Wolter, Sabine; Seifert, Roland

    2012-01-01

    The bacterial adenylyl cyclase toxins CyaA from Bordetella pertussis and edema factor from Bacillus anthracis as well as soluble guanylyl cyclase α(1)β(1) synthesize the cyclic pyrimidine nucleotide cCMP. These data raise the question to which effector proteins cCMP binds. Recently, we reported that cCMP activates the regulatory subunits RIα and RIIα of cAMP-dependent protein kinase. In this study, we used two cCMP agarose matrices as novel tools in combination with immunoblotting and mass spectrometry to identify cCMP-binding proteins. In agreement with our functional data, RIα and RIIα were identified as cCMP-binding proteins. These data corroborate the notion that cAMP-dependent protein kinase may serve as a cCMP target. PMID:22808067

  19. Fractionation of SWNT/nucleic acid complexes by agarose gel electrophoresis

    NASA Astrophysics Data System (ADS)

    Vetcher, Alexandre A.; Srinivasan, Srimeenakshi; Vetcher, Ivan A.; Abramov, Semen M.; Kozlov, Mikhail; Baughman, Ray H.; Levene, Stephen D.

    2006-08-01

    We show that aqueous dispersions of single-walled carbon nanotubes (SWNTs), prepared with the aid of nucleic acids (NAs) such as RNA or DNA, can be separated into fractions using agarose gel electrophoresis. In a DC electric field, SWNT/NA complexes migrate in the gel in the direction of positive potential to form well-defined bands. Raman spectroscopy as a function of band position shows that nanotubes having different spectroscopic properties possess different electrophoretic mobilities. The migration patterns for SWNT/RNA and SWNT/DNA complexes differ. Parallel elution of the SWNT/NA complexes from the gel during electrophoresis and subsequent characterization by AFM reveals differences in nanotube diameter, length and curvature. The results suggest that fractionation of nanotubes can be achieved by this procedure. We discuss factors affecting the mobility of the nanotube complexes and propose analytical applications of this technique.

  20. Stem Cells in Aggregate Form to Enhance Chondrogenesis in Hydrogels

    PubMed Central

    Sridharan, BanuPriya; Lin, Staphany M.; Hwu, Alexander T.; Laflin, Amy D.; Detamore, Michael S.

    2015-01-01

    There are a variety of exciting hydrogel technologies being explored for cartilage regenerative medicine. Our overall goal is to explore whether using stem cells in an aggregate form may be advantageous in these applications. 3D stem cell aggregates hold great promise as they may recapitulate the in vivo skeletal tissue condensation, a property that is not typically observed in 2D culture. We considered two different stem cell sources, human umbilical cord Wharton’s jelly cells (hWJCs, currently being used in clinical trials) and rat bone marrow-derived mesenchymal stem cells (rBMSCs). The objective of the current study was to compare the influence of cell phenotype, aggregate size, and aggregate number on chondrogenic differentiation in a generic hydrogel (agarose) platform. Despite being differing cell sources, both rBMSC and hWJC aggregates were consistent in outperforming cell suspension control groups in biosynthesis and chondrogenesis. Higher cell density impacted biosynthesis favorably, and the number of aggregates positively influenced chondrogenesis. Therefore, we recommend that investigators employing hydrogels consider using cells in an aggregate form for enhanced chondrogenic performance. PMID:26719986

  1. Injectable and pH-Responsive Silk Nanofiber Hydrogels for Sustained Anticancer Drug Delivery.

    PubMed

    Wu, Hongchun; Liu, Shanshan; Xiao, Liying; Dong, Xiaodan; Lu, Qiang; Kaplan, David L

    2016-07-13

    Silk is useful as a drug carrier due to its biocompatibility, tunable degradation, and outstanding capacity in maintaining the function of drugs. Injectable silk hydrogels could deliver doxorubicin (DOX) for localized chemotherapy for breast cancer. To improve hydrogel properties, thixotropic silk nanofiber hydrogels in an all-aqueous solution were prepared and used to locally deliver DOX. The silk hydrogels displayed thixotropic capacity, allowing for easy injectability followed by solidification in situ. The hydrogels were loaded with DOX and released the drug over eight weeks with pH- and concentration-dependent release kinetics. In vitro and in vivo studies demonstrated that DOX-loaded silk hydrogels had good antitumor response, outperforming the equivalent dose of free DOX administered intravenously. Thixotropic silk hydrogels provide improved injectability to support sustained release, suggesting promising applications for localized chemotherapy. PMID:27315327

  2. Nanocellulose-alginate hydrogel for cell encapsulation.

    PubMed

    Park, Minsung; Lee, Dajung; Hyun, Jinho

    2015-02-13

    TEMPO-oxidized bacterial cellulose (TOBC)-sodium alginate (SA) composites were prepared to improve the properties of hydrogel for cell encapsulation. TOBC fibers were obtained using a TEMPO/NaBr/NaClO system at pH 10 and room temperature. The fibrillated TOBCs mixed with SA were cross-linked in the presence of Ca(2+) solution to form hydrogel composites. The compression strength and chemical stability of the TOBC/SA composites were increased compared with the SA hydrogel, which indicated that TOBC performed an important function in enhancing the structural, mechanical and chemical stability of the composites. Cells were successfully encapsulated in the TOBC/SA composites, and the viability of cells was investigated. TOBC/SA composites can be a potential candidate for cell encapsulation engineering. PMID:25458293

  3. Purification of CD47-streptavidin fusion protein from bacterial lysate using biotin-agarose affinity chromatography.

    PubMed

    Salehi, Nasrin; Peng, Ching-An

    2016-07-01

    CD47 is a widely expressed transmembrane glycoprotein that modulates the activity of a plethora of immune cells via its extracellular domain. Therefore, CD47 plays important roles in the regulation of immune responses and may serve as targets for the development of immunotherapeutic agents. To make sure CD47 functionality is intact under the process of protein conjugation, CD47-streptavidin fusion protein was expressed and purified because it can easily bind to biotin-tagged materials via the unique biotin-streptavidin affinity. In this study, gene sequences of CD47 extracellular domain (CD47ECD) and core streptavidin (coreSA) with a total 834 bp were inserted into pET20b plasmid to construct recombinant plasmid encoding CD47-SA fusion gene. After bacteria transformation, the CD47-SA fusion protein was expressed by isopropyl-β-d-thiogalactopyranoside (IPTG) induction. The collected bacteria lysate was loaded on biotinylated agarose to proceed the purification of CD47-SA fusion protein. Due to the unexpected high affinity between biotin and coreSA, standard washing and elution approaches (e.g., varying pH, using biotin, and applying guanidine hydrochloride) reported for biotin-streptavidin affinity chromatography were not able to separate the target fusion protein. Instead, using low concentration of the non-ionic detergent Triton X-100 followed with alkaline buffer could efficiently weaken the binding between biotin and coreSA, thereby eluting out CD47-SA fusion protein from the biotin agarose column. The purified CD47-SA fusion protein was further characterized by molecular biology methods and its antiphagocytic functionality was confirmed by the phagocytosis assay. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:949-958, 2016. PMID:27110670

  4. New antifouling silica hydrogel.

    PubMed

    Beltrán-Osuna, Ángela A; Cao, Bin; Cheng, Gang; Jana, Sadhan C; Espe, Matthew P; Lama, Bimala

    2012-06-26

    In this work, a new antifouling silica hydrogel was developed for potential biomedical applications. A zwitterionic polymer, poly(carboxybetaine methacrylate) (pCBMA), was produced via atom-transfer radical polymerization and was appended to the hydrogel network in a two-step acid-base-catalyzed sol-gel process. The pCBMA silica aerogels were obtained by drying the hydrogels under supercritical conditions using CO(2). To understand the effect of pCBMA on the gel structure, pCBMA silica aerogels with different pCBMA contents were characterized using scanning electron microscopy (SEM), nuclear magnetic resonance (NMR) spectroscopy, and the surface area from Brauner-Emmet-Teller (BET) measurements. The antifouling property of pCBMA silica hydrogel to resist protein (fibrinogen) adsorption was measured using enzyme-linked immunosorbent assay (ELISA). SEM images revealed that the particle size and porosity of the silica network decreased at low pCBMA content and increased at above 33 wt % of the polymer. The presence of pCBMA increased the surface area of the material by 91% at a polymer content of 25 wt %. NMR results confirmed that pCBMA was incorporated completely into the silica structure at a polymer content below 20 wt %. A protein adsorption test revealed a reduction in fibrinogen adsorption by 83% at 25 wt % pCBMA content in the hydrogel compared to the fibrinogen adsorption in the unmodified silica hydrogel. PMID:22607091

  5. 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

  6. Characterization of agarose as an encapsulation medium for particulate specimens for transmission electron microscopy.

    PubMed

    Wood, J I; Klomparens, K L

    1993-07-01

    Agarose, agar, and gelatin were initially compared as encapsulation media for 3 structurally diverse particulate specimens: bacteria, yeast, and mitochondria. Agarose proved superior to both gelatin and agar for ease of handling and overall image quality (minimum background). All sample types exhibited high quality fixation and structural detail with no heat damage from the agarose medium. Based on this finding, we further characterized agarose encapsulation as affected by post-fixation, en bloc staining and resin type. Osmium tetroxide post-fixation, followed by en bloc uranyl acetate staining, could be performed without an increase in the electron density of the encapsulation medium. Agarose proved successful as an encapsulation medium regardless of the resin type or preparation protocol, thus providing flexibility in experimental design and excellent results over a range of variables. PMID:8358076

  7. Structural analysis of dextran-based hydrogels obtained chemoenzymatically.

    PubMed

    Ferreira, L; Figueiredo, M M; Gil, M H; Ramos, M A

    2006-04-01

    This work reports the results of structural analysis in novel dextran-acrylate (dexT70-VA) hydrogels generated chemoenzymatically. Porous structure as well as hydrogel surface and interior morphologies were evaluated by mercury intrusion porosimetry (MIP), nitrogen adsorption (NA), and scanning electron microscopy (SEM) analyses, as a function of the degree of substitution (DS), and initial water content used in the preparation of the hydrogel. MIP analysis showed that the overall networks were clearly macroporous with pore sizes ranging from 0.065 to 10 microm. As expected, the average pore size decreased as DS increased and as initial water content decreased. Moreover, the porosity values ranged from 75 up 90%, which shows that these hydrogels present an interconnected pore structure. Nitrogen adsorption analyses showed that the specific surface area of dexT70-VA hydrogels increased either by increasing the DS or by decreasing the initial water content of the hydrogel. SEM results revealed that the surface of hydrogels with lower DS presented either a porous structure or a polymeric "skin" covering the pores, whereas hydrogels with higher DS were totally porous. Furthermore, the interior morphology varied according to the DS and the initial water content of the hydrogels. Finally, the average pore size was also determined from the swelling of hydrogel using a theoretical model developed by Flory-Rehner. The comparison of the SEM and MIP results with the ones obtained by the equilibrium swelling theory of Flory-Rehner shows that this approach highly underestimates the average pore size. PMID:16211568

  8. A Bioengineered Hydrogel System Enables Targeted and Sustained Intramyocardial Delivery of Neuregulin, Activating the Cardiomyocyte Cell Cycle and Enhancing Ventricular Function in a Murine Model of Ischemic Cardiomyopathy

    PubMed Central

    Cohen, Jeffrey E.; Purcell, Brendan P.; MacArthur, John W.; Mu, Anbin; Shudo, Yasuhiro; Patel, Jay B.; Brusalis, Christopher M.; Trubelja, Alen; Fairman, Alexander S.; Edwards, Bryan B.; Davis, Mollie S.; Hung, George; Hiesinger, William; Atluri, Pavan; Margulies, Kenneth B.; Burdick, Jason A.; Woo, Y. Joseph

    2014-01-01

    Background Neuregulin (NRG) is a member of the epidermal growth factor family possessing a critical role in cardiomyocyte development and proliferation. Systemic administration of NRG demonstrated efficacy in cardiomyopathy animal models, leading to clinical trials employing daily NRG infusions. This approach is hindered by requiring daily infusions and off-target exposure. Therefore, this study aimed to encapsulate NRG in a hydrogel (HG) to be directly delivered to the myocardium, accomplishing sustained localized NRG delivery. Methods and Results NRG was encapsulated in HG and release over 14 days confirmed by ELISA in vitro. Sprague-Dawly rats were utilized for cardiomyocyte isolation. Cells were stimulated by PBS, NRG, HG, or NRG-HG and evaluated for proliferation. Cardiomyocytes demonstrated EdU and phosphorylated histone-H3 (PH3) positivity in the NRG-HG group only. For in vivo studies, 2 month old mice (n=60) underwent LAD ligation and were randomized to the 4 treatment groups mentioned. Only NRG-HG treated mice demonstrated PH3 and Ki67 positivity along with decreased caspase-3 activity compared to all controls. NRG was detected in myocardium 6 days following injection without evidence of off-target exposure in NRG-HG animals. At 2 weeks, the NRG-HG group exhibited enhanced LVEF, decreased LV area, and augmented borderzone thickness. Conclusions Targeted and sustained delivery of NRG directly to the myocardial borderzone augments cardiomyocyte mitotic activity, decreases apoptosis, and greatly enhances LV function in a model of ICM. This novel approach to NRG administration avoids off-target exposure and represents a clinically translatable strategy in myocardial regenerative therapeutics. PMID:24902740

  9. Microscale characterization of the viscoelastic properties of hydrogel biomaterials using dual-mode ultrasound elastography.

    PubMed

    Hong, Xiaowei; Stegemann, Jan P; Deng, Cheri X

    2016-05-01

    Characterization of the microscale mechanical properties of biomaterials is a key challenge in the field of mechanobiology. Dual-mode ultrasound elastography (DUE) uses high frequency focused ultrasound to induce compression in a sample, combined with interleaved ultrasound imaging to measure the resulting deformation. This technique can be used to non-invasively perform creep testing on hydrogel biomaterials to characterize their viscoelastic properties. DUE was applied to a range of hydrogel constructs consisting of either hydroxyapatite (HA)-doped agarose, HA-collagen, HA-fibrin, or preosteoblast-seeded collagen constructs. DUE provided spatial and temporal mapping of local and bulk displacements and strains at high resolution. Hydrogel materials exhibited characteristic creep behavior, and the maximum strain and residual strain were both material- and concentration-dependent. Burger's viscoelastic model was used to extract characteristic parameters describing material behavior. Increased protein concentration resulted in greater stiffness and viscosity, but did not affect the viscoelastic time constant of acellular constructs. Collagen constructs exhibited significantly higher modulus and viscosity than fibrin constructs. Cell-seeded collagen constructs became stiffer with altered mechanical behavior as they developed over time. Importantly, DUE also provides insight into the spatial variation of viscoelastic properties at sub-millimeter resolution, allowing interrogation of the interior of constructs. DUE presents a novel technique for non-invasively characterizing hydrogel materials at the microscale, and therefore may have unique utility in the study of mechanobiology and the characterization of hydrogel biomaterials. PMID:26928595

  10. The design of conductimetric biosensors based on environmentally responsive hydrogels

    NASA Astrophysics Data System (ADS)

    Lesho, Matthew Jerome

    Responsive hydrogels are hydrophilic, crosslinked polymers that undergo large changes in hydration in response to environmental stimuli such as changing temperature, pH, electric field, and ionic strength. Accompanying this change in hydration are changes in material properties of the hydrogel, which has led to their application in controlled drug delivery, separations, and as superabsorbants. The present study investigated the hydration-dependent electrical conductivity of a pH-responsive hydrogel and its application as a transduction layer for microfabricated, conductimetric pH and glucose sensors. The investigation was divided into four parts. First, the material properties of a copolymer of 2-hydroxyethyl methacrylate (HEMA) and N,N-dimethylaminoethyl methacrylate (DMA), crosslinked with tetraethylene glycol diacrylate (TEGDA), were examined with respect to its ability to detect changes in pH. It was determined that the electrical conductivity of the hydrogel was a sensitive measure of hydration and was a function of pH, hydrogel composition, buffer concentration, buffer identity, and ionic strength. Second, a method was developed for reproducibly depositing thin (1-25 mum), adherent hydrogel layers by photolithographic patterning techniques. Third, sensors were developed that utilized planar interdigitated electrode arrays to probe the change in electrical conductivity of hydrogel membranes. The sensitivity, response time, operating range and lifetime of pH sensors were functions of pH, hydrogel composition, buffer concentration, buffer identity, and ionic strength. Glucose sensors were developed by incorporating glucose oxidase into the pH-responsive hydrogel and measuring the decrease in pH that accompanies the enzymatic generation of protons. Finally, a model was formulated to relate the measured sensor responses to the measured material properties. Information from model simulations was incorporated into the design of next-generation sensors.