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Sample records for functionalized agarose hydrogels

  1. Fabrication of Self-Healable and Patternable Polypyrrole/Agarose Hybrid Hydrogels for Smart Bioelectrodes.

    PubMed

    Park, Nokyoung; Chae, Seung Chul; Kim, Il Tae; Hur, Jaehyun

    2016-02-01

    We present a new class of electrically conductive, mechanically moldable, and thermally self-healable hybrid hydrogels. The hybrid gels consist of polypyrrole and agarose as the conductive component and self-healable matrix, respectively. By using the appropriate oxidizing agent under conditions of mild temperature, the polymerization of pyrrole occurred along the three-dimensional network of the agarose hydrogel matrix. In contrast to most commercially available hydrogels, the physical crosslinking of agarose gel allows for reversible gelation in the case of our hybrid gel, which could be manipulated by temperature variation, which controls the electrical on/off behavior of the hybrid gel electrode. Exploiting this property, we fabricated a hybrid conductive hydrogel electrode which also self-heals thermally. The novel composite material we report here will be useful for many technological and biological applications, especially in reactive biomimetic functions and devices, artificial muscles, smart membranes, smart full organic batteries, and artificial chemical synapses. PMID:27433594

  2. Thermoresponsive chitosan-agarose hydrogel for skin regeneration.

    PubMed

    Miguel, Sónia P; Ribeiro, Maximiano P; Brancal, Hugo; Coutinho, Paula; Correia, Ilídio J

    2014-10-13

    Healing enhancement and pain control are critical issues on wound management. So far, different wound dressings have been developed. Among them, hydrogels are the most applied. Herein, a thermoresponsive hydrogel was produced using chitosan (deacetylation degree 95%) and agarose. Hydrogel bactericidal activity, biocompatibility, morphology, porosity and wettability were characterized by confocal microscopy, MTS assay and SEM. The performance of the hydrogel in the wound healing process was evaluated through in vivo assays, during 21 days. The attained results revealed that hydrogel has a pore size (90-400 μm) compatible with cellular internalization and proliferation. A bactericidal activity was observed for hydrogels containing more than 188 μg/mL of chitosan. The improved healing and the lack of a reactive or a granulomatous inflammatory reaction in skin lesions treated with hydrogel demonstrate its suitability to be used in a near future as a wound dressing. PMID:25037363

  3. 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.

  4. Rheological study of reinforcement of agarose hydrogels by cellulose nanowhiskers.

    PubMed

    Le Goff, Kevin J; Gaillard, Cedric; Helbert, William; Garnier, Catherine; Aubry, Thierry

    2015-02-13

    The influence of the addition of tunicate cellulose nanowhiskers on the structural and rheological properties of an agarose hydrogel matrix has been studied, with the objective to design innovative green material, with good mechanical properties. The cellulose nanowhiskers were characterized using transmission electron microscopy, and their charge surface density was determined by a titration method. Oscillatory shear and stress relaxation tests were performed in order to characterize the rheological properties of the agarose matrix, and of the agarose hydrogels filled by nanowhiskers at volume fractions below 0.2%. The results show a significant reinforcement effect due to the addition of nanowhiskers, and suggest changes in the matrix network structure induced by the cellulose nanoparticles. PMID:25458280

  5. Hierarchically Designed Agarose and Poly(Ethylene Glycol) Interpenetrating Network Hydrogels for Cartilage Tissue Engineering

    PubMed Central

    DeKosky, Brandon J.; Dormer, Nathan H.; Ingavle, Ganesh C.; Roatch, Christopher H.; Lomakin, Joseph; Detamore, Michael S.

    2010-01-01

    A new method for encapsulating cells in interpenetrating network (IPN) hydrogels of superior mechanical integrity was developed. In this study, two biocompatible materials—agarose and poly(ethylene glycol) (PEG) diacrylate—were combined to create a new IPN hydrogel with greatly enhanced mechanical performance. Unconfined compression of hydrogel samples revealed that the IPN displayed a fourfold increase in shear modulus relative to a pure PEG-diacrylate network (39.9 vs. 9.9 kPa) and a 4.9-fold increase relative to a pure agarose network (8.2 kPa). PEG and IPN compressive failure strains were found to be 71% ± 17% and 74% ± 17%, respectively, while pure agarose gels failed around 15% strain. Similar mechanical property improvements were seen when IPNs-encapsulated chondrocytes, and LIVE/DEAD cell viability assays demonstrated that cells survived the IPN encapsulation process. The majority of IPN-encapsulated chondrocytes remained viable 1 week postencapsulation, and chondrocytes exhibited glycosaminoglycan synthesis comparable to that of agarose-encapsulated chondrocytes at 3 weeks postencapsulation. The introduction of a new method for encapsulating cells in a hydrogel with enhanced mechanical performance is a promising step toward cartilage defect repair. This method can be applied to fabricate a broad variety of cell-based IPNs by varying monomers and polymers in type and concentration and by adding functional groups such as degradable sequences or cell adhesion groups. Further, this technology may be applicable in other cell-based applications where mechanical integrity of cell-containing hydrogels is of great importance. PMID:20626274

  6. Function, structure, and stability of enzymes confined in agarose gels.

    PubMed

    Kunkel, Jeffrey; Asuri, Prashanth

    2014-01-01

    Research over the past few decades has attempted to answer how proteins behave in molecularly confined or crowded environments when compared to dilute buffer solutions. This information is vital to understanding in vivo protein behavior, as the average spacing between macromolecules in the cell cytosol is much smaller than the size of the macromolecules themselves. In our study, we attempt to address this question using three structurally and functionally different model enzymes encapsulated in agarose gels of different porosities. Our studies reveal that under standard buffer conditions, the initial reaction rates of the agarose-encapsulated enzymes are lower than that of the solution phase enzymes. However, the encapsulated enzymes retain a higher percentage of their activity in the presence of denaturants. Moreover, the concentration of agarose used for encapsulation had a significant effect on the enzyme functional stability; enzymes encapsulated in higher percentages of agarose were more stable than the enzymes encapsulated in lower percentages of agarose. Similar results were observed through structural measurements of enzyme denaturation using an 8-anilinonaphthalene-1-sulfonic acid fluorescence assay. Our work demonstrates the utility of hydrogels to study protein behavior in highly confined environments similar to those present in vivo; furthermore, the enhanced stability of gel-encapsulated enzymes may find use in the delivery of therapeutic proteins, as well as the design of novel strategies for biohybrid medical devices.

  7. Porous Agarose-Based Semi-IPN Hydrogels: Characterization and Cell Affinity Studies.

    PubMed

    Vardar, E; Vert, Michel; Coudane, Jean; Hasirci, V; Hasirci, N

    2012-01-01

    Hydrogels are frequently considered for medical applications due to the ease of preparation in different forms and high water content that makes them comparable to natural tissues. However, these general properties are not sufficient to make any hydrogel suitable for cell attachment and growth which are necessary for their use in tissue regeneration. Besides, the high water content makes the hydrogels mechanically weak. The formation of semi-interpenetrating networks (semi-IPNs) can be used in attempts to enhance physical, mechanical and thermal properties. In this study, semi-IPNs of agarose were prepared with chitosan and alginate, two polyelectrolytes that are positively and negatively charged under physiological conditions, respectively. Zeta potential was used to confirm the formation of charged hydrogels. All hydrogels had ultimate compression strengths in the range of 91-210 Pa where the value for pure agarose was about 103 Pa. Chitosan increased the compressive strength about two folds whereas the alginate had opposite effects. The amount of strongly bound water present in the hydrogels were estimated from TGA and DSC analysis and the highest value was found for alginate-agarose hydrogels as about 15%. The attachment and the migration of L929 fibroblasts were monitored in vitro using the MTS assay and confocal microscopy. The highest cell proliferation and penetration were observed for positively charged chitosan-agarose semi-IPN hydrogels.

  8. 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.

  9. Fenugreek hydrogel-agarose composite entrapped gold nanoparticles for acetylcholinesterase based biosensor for carbamates detection.

    PubMed

    Kestwal, Rakesh Mohan; Bagal-Kestwal, Dipali; Chiang, Been-Huang

    2015-07-30

    A biosensor was fabricated to detect pesticides in food samples. Acetylcholinesterase was immobilized in a novel fenugreek hydrogel-agarose matrix with gold nanoparticles. Transparent thin films with superior mechanical strength and stability were obtained with 2% fenugreek hydrogel and 2% agarose. Immobilization of acetylcholinesterase on the membrane resulted in high enzyme retention efficiency (92%) and a significantly prolonged shelf life of the enzyme (half-life, 55 days). Transmission electron microscopy revealed that, gold nanoparticles (10-20 nm in diameter) were uniformly dispersed in the fenugreek hydrogel-agarose-acetylcholinesterase membrane. This immobilized enzyme-gold nanoparticle dip-strip system detected various carbamates, including carbofuran, oxamyl, methomyl, and carbaryl, with limits of detection of 2, 21, 113, and 236 nM (S/N = 3), respectively. Furthermore, the fabricated biosensor exhibited good testing capabilities when used to detect carbamates added to various fruit and vegetable samples. PMID:26320646

  10. Fenugreek hydrogel-agarose composite entrapped gold nanoparticles for acetylcholinesterase based biosensor for carbamates detection.

    PubMed

    Kestwal, Rakesh Mohan; Bagal-Kestwal, Dipali; Chiang, Been-Huang

    2015-07-30

    A biosensor was fabricated to detect pesticides in food samples. Acetylcholinesterase was immobilized in a novel fenugreek hydrogel-agarose matrix with gold nanoparticles. Transparent thin films with superior mechanical strength and stability were obtained with 2% fenugreek hydrogel and 2% agarose. Immobilization of acetylcholinesterase on the membrane resulted in high enzyme retention efficiency (92%) and a significantly prolonged shelf life of the enzyme (half-life, 55 days). Transmission electron microscopy revealed that, gold nanoparticles (10-20 nm in diameter) were uniformly dispersed in the fenugreek hydrogel-agarose-acetylcholinesterase membrane. This immobilized enzyme-gold nanoparticle dip-strip system detected various carbamates, including carbofuran, oxamyl, methomyl, and carbaryl, with limits of detection of 2, 21, 113, and 236 nM (S/N = 3), respectively. Furthermore, the fabricated biosensor exhibited good testing capabilities when used to detect carbamates added to various fruit and vegetable samples.

  11. Potential of Agarose/Silk Fibroin Blended Hydrogel for in Vitro Cartilage Tissue Engineering.

    PubMed

    Singh, Yogendra Pratap; Bhardwaj, Nandana; Mandal, Biman B

    2016-08-24

    An osteoarthritis pandemic has accelerated exploration of various biomaterials for cartilage reconstruction with a special emphasis on silk fibroin from mulberry (Bombyx mori) and non-mulberry (Antheraea assamensis) silk worms. Retention of positive attributes of the agarose standard and nullification of its negatives are central to the current agarose/silk fibroin hydrogel design. In this study, hydrogels of mulberry and non-mulberry silk fibroin blended with agarose were fabricated and evaluated in vitro for two weeks for cartilaginous tissue formation. The fabricated hydrogels were physicochemically characterized and analyzed for cell viability, proliferation, and extra cellular matrix deposition. The amalgamation of silk fibroin with agarose impacted the pore size, as illustrated by field emission scanning electron microscopy studies, swelling behavior, and in vitro degradation of the hydrogels. Fourier transform infrared spectroscopy results indicated the blend formation and confirmed the presence of both components in the fabricated hydrogels. Rheological studies demonstrated enhanced elasticity of blended hydrogels with G' > G″. Biochemical analysis revealed significantly higher levels of sulfated glycosaminoglycans (sGAGs) and collagen (p ≤ 0.01) in blended hydrogels. More specifically, the non-mulberry silk fibroin blend showed sGAG and collagen content (∼1.5-fold) higher than that of the mulberry blend (p ≤ 0.05). Histological and immunohistochemical analyses further validated the enhanced deposition of sGAG and collagen, indicating maintenance of chondrogenic phenotype within constructs after two weeks of culture. Real-time PCR analysis further confirmed up-regulation of cartilage-specific aggrecan, sox-9 (∼1.5-fold) and collagen type II (∼2-fold) marker genes (p ≤ 0.01) in blended hydrogels. The hydrogels demonstrated immunocompatibility, which was evidenced by minimal in vitro secretion of tumor necrosis factor-α (TNF-α) by murine

  12. 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.

  13. 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

  14. 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

  15. In vivo bioengineered ovarian tumors based on collagen, matrigel, alginate and agarose hydrogels: a comparative study.

    PubMed

    Zheng, Li; Hu, Xuefeng; Huang, Yuanjie; Xu, Guojie; Yang, Jinsong; Li, Li

    2015-01-29

    Scaffold-based tumor engineering is rapidly evolving the study of cancer progression. However, the effects of scaffolds and environment on tumor formation have seldom been investigated. In this study, four types of injectable hydrogels, namely, collagen type I, Matrigel, alginate and agarose gels, were loaded with human ovarian cancer SKOV3 cells and then injected into nude mice subcutaneously. The growth of the tumors in vitro was also investigated. After four weeks, the specimens were harvested and analyzed. We found that tumor formation by SKOV3 cells was best supported by collagen, followed by Matrigel, alginate, control (without scaffold) and agarose in vivo. The collagen I group exhibited a larger tumor volume with increased neovascularization and increased necrosis compared with the other materials. Further, increased MMP activity, upregulated expression of laminin and fibronectin and higher levels of HIF-1α and VEGF-A in the collagen group revealed that the engineered tumor is closer to human ovarian carcinoma. In order, collagen, Matrigel, alginate, control (without scaffold) and agarose exhibited decreases in tumor formation. All evidence indicated that the in vivo engineered tumor is scaffold-dependent. Bioactive hydrogels are superior to inert hydrogels at promoting tumor regeneration. In particular, biomimetic hydrogels are advantageous because they provide a microenvironment that mimics the ECM of natural tumors. On the other hand, typical features of cancer cells and the expression of genes related to cancer malignancy were far less similar to the natural tumor in vitro, which indicated the importance of culture environment in vivo. Superior to the in vitro culture, nude mice can be considered satisfactory in vivo 'bioreactors' for the screening of favorable cell vehicles for tumor engineering in vitro.

  16. Carbon dots rooted agarose hydrogel hybrid platform for optical detection and separation of heavy metal ions.

    PubMed

    Gogoi, Neelam; Barooah, Mayuri; Majumdar, Gitanjali; Chowdhury, Devasish

    2015-02-11

    A robust solid sensing platform for an on-site operational and accurate detection of heavy metal is still a challenge. We introduce chitosan based carbon dots rooted agarose hydrogel film as a hybrid solid sensing platform for detection of heavy metal ions. The fabrication of the solid sensing platform is centered on simple electrostatic interaction between the NH3+ group present in the carbon dots and the OH- groups present in agarose. Simply on dipping the hydrogel film strip into the heavy metal ion solution, in particular Cr6+, Cu2+, Fe3+, Pb2+, Mn2+, the strip displays a color change, viz., Cr6+→yellow, Cu2+→blue, Fe3+→brown, Pb2+→white, Mn2+→tan brown. The optical detection limit of the respective metal ion is found to be 1 pM for Cr6+, 0.5 μM for Cu2+, and 0.5 nM for Fe3+, Pb2+, and Mn2+ by studying the changes in UV-visible reflectance spectrum of the hydrogel film. Moreover, the hydrogel film finds applicability as an efficient filtration membrane for separation of these quintet heavy metal ions. The strategic fundamental feature of this sensing platform is the successful capability of chitosan to form colored chelates with transition metals. This proficient hybrid hydrogel solid sensing platform is thus the most suitable to employ as an on-site operational, portable, cheap colorimetric-optical detector of heavy metal ion with potential skill in their separation. Details of the possible mechanistic insight into the colorimetric detection and ion separation are also discussed.

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

    PubMed

    Rennerfeldt, Deena A; Renth, Amanda N; Talata, Zsolt; Gehrke, Stevin H; Detamore, Michael S

    2013-11-01

    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.

  18. 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

  19. Culture phases, cytotoxicity and protein expressions of agarose hydrogel induced Sp2/0, A549, MCF-7 cell line 3D cultures.

    PubMed

    Ravi, Maddaly; Kaviya, S R; Paramesh, V

    2016-05-01

    Advancements in cell cultures are occurring at a rapid pace, an important direction is culturing cells in 3D conditions. We demonstrate the usefulness of agarose hydrogels in obtaining 3 dimensional aggregates of three cell lines, A549, MCF-7 and Sp2/0. The differences in culture phases, susceptibility to cisplatin-induced cytotoxicity are studied. Also, the 3D aggregates of the three cell lines were reverted into 2D cultures and the protein profile differences among the 2D, 3D and revert cultures were studied. The analysis of protein profile differences using UniProt data base further augment the usefulness of agarose hydrogels for obtaining 3D cell cultures.

  20. 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

  1. 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 Central

    Ingavle, Ganesh C.; Dormer, Nathan H.; Gehrke, Stevin H.

    2013-01-01

    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

  2. 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.

  3. 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

  4. Polymer hydrogel functionalized with biodegradable nanoparticles as composite system for controlled drug delivery

    NASA Astrophysics Data System (ADS)

    Rossi, Filippo; Ferrari, Raffaele; Castiglione, Franca; Mele, Andrea; Perale, Giuseppe; Moscatelli, Davide

    2015-01-01

    The possibility to direct pharmacological treatments targeting specific cell lines using polymer nanoparticles is one of the main novelties and perspectives in nanomedicine. However, sometimes, the ability to maintain NPs localized at the site of the injection that work as a drug reservoir can represent a good and complementary option. In this direction we built a composite material made of polymeric hydrogel functionalized with polymer NPs. ɛ-caprolactone and polyethylene glycol have been copolymerized in a two-step synthesis of PEGylated NPs, while hydrogel was synthesized through polycondensation between NPs, agarose and branched polyacrylic acid. NP functionalization was verified with Fourier transform infrared spectroscopy (FTIR), high resolution magic angle spinning-nuclear magnetic resonance (HRMAS-NMR) spectroscopy and release kinetics from a hydrogel matrix and compared with NPs only physically entrapped into a hydrogel matrix. The characteristics of the resulting composite hydrogel-NPs system were studied both in terms of rheological properties and in its ability to sustain the release of To-Pro3, used as a drug mimetic compound to represent a promising drug delivery device.

  5. Using cells encapsulated in agarose microbeads to analyse nuclear structure and functions.

    PubMed

    Jackson, Dean

    2009-01-01

    It is now generally agreed that the nuclei of higher eukaryotes, and particularly of mammalian cells, are highly structured and that different aspects of this structure contribute to the regulation of function (1, 2). Despite the general consensus, the key mechanisms that link nuclear structure and function have proved elusive. A major reason for this is a lack of techniques that allow nuclei to be manipulated in a way that preserves the complex architectural features that are present in vivo. Historically, significant progress in understanding the makeup of nuclei from mammalian cells has been made using cells that are permeabilised in a physiological buffer after being encapsulated in agarose microbeads. By using such beads, cells are protected from shear forces that otherwise can degrade crucial elements of the architecture that it is essential to preserve.

  6. Hydrolysis of chickpea proteins with Flavourzyme immobilized on glyoxyl-agarose gels improves functional properties.

    PubMed

    del Mar Yust, María; del Carmen Millán-Linares, María; Alcaide-Hidalgo, Juan María; Millán, Francisco; Pedroche, Justo

    2013-06-01

    Chickpea protein isolate was hydrolyzed using Flavourzyme immobilized on glyoxyl-agarose beads by multipoint covalent attachment. This Flavourzyme-glyoxyl derivative, produced after 1 h of immobilization at 4 °C followed by 5.5 h at room temperature, presented approximately 51% of the endoprotease activity of Flavourzyme but was around 700 times more stable than soluble enzyme. Chickpea protein hydrolysates ranging from 1% to 10% degree of hydrolysis were produced and their chemical composition was very close to that of protein isolate used as starting material. Solubility, oil absorption, emulsifying activity and stability, and foaming capacity and stability were determined. All protein hydrolysates showed higher solubility than intact proteins, especially at pHs near isoelectric point of native chickpea proteins. Moreover, all hydrolysates had better functional properties, except emulsifying activity, than the original protein isolate.

  7. The bioactivity of agarose-PEGDA interpenetrating network hydrogels with covalently immobilized RGD peptides and physically entrapped aggrecan

    PubMed Central

    Ingavle, Ganesh C.; Gehrke, Stevin H.; Detamore, Michael S.

    2014-01-01

    Our previous reports of interpenetrating networks (IPNs) have demonstrated drastic improvements in mechanical performance relative to individual constituent networks while maintaining viability of encapsulated cells. The current study investigated whether covalent linkage of RGD to the poly(ethylene glycol) diacrylate (PEGDA) network could improve upon cell viability and performance of agarose-PEGDA IPNs compared to unmodified IPNs (control) and to IPNs with different concentrations of physically entrapped aggrecan, providing a point of comparison to previous work. The inclusion of RGD or aggrecan generally did not adversely affect mechanical performance, and significantly improved chondrocyte viability and performance. Although both 4 and 100 μ g/mL of aggrecan improved cell viability, only 100 μ g/mL aggrecan was clearly beneficial to improving biosynthesis, whereas 100 μg/mL of RGD was beneficial to both chondrocyte viability and biosynthesis. Interestingly, clustering of cells within the IPNs with RGD and the higher aggrecan concentration were observed, likely indicating cell migration and/or preferred regional proliferation. This clustering resulted in a clearly visible enhancement of matrix production compared to the other IPNs. With this cell migration, we also observed significant cell proliferation and matrix synthesis beyond the periphery of the IPN, which could have important implications in facilitating integration with surrounding cartilage in vivo. With RGD and aggrecan (at its higher concentration) providing substantial and comparable improvements in cell performance, RGD would be the recommended bioactive signal for this particular IPN formulation and cell source given the significant cost savings and potentially more straightforward regulatory pathway in commercialization. PMID:24462353

  8. Differential maturation and structure-function relationships in mesenchymal stem cell- and chondrocyte-seeded hydrogels.

    PubMed

    Erickson, Isaac E; Huang, Alice H; Chung, Cindy; Li, Ryan T; Burdick, Jason A; Mauck, Robert L

    2009-05-01

    Degenerative disease and damage to articular cartilage represents a growing concern in the aging population. New strategies for engineering cartilage have employed mesenchymal stem cells (MSCs) as a cell source. However, recent work has suggested that chondrocytes (CHs) produce extracellular matrix (ECM) with superior mechanical properties than MSCs do. Because MSC-biomaterial interactions are important for both initial cell viability and subsequent chondrogenesis, we compared the growth of MSC- and CH-based constructs in three distinct hydrogels-agarose (AG), photocrosslinkable hyaluronic acid (HA), and self-assembling peptide (Puramatrix, Pu). Bovine CHs and MSCs were isolated from the same group of donors and seeded in AG, Pu, and HA at 20 million cells/mL. Constructs were cultured for 8 weeks with biweekly analysis of construct physical properties, viability, ECM content, and mechanical properties. Correlation analysis was performed to determine quantitative relationships between formed matrix and mechanical properties for each cell type in each hydrogel. Results demonstrate that functional chondrogenesis, as evidenced by increasing mechanical properties, occurred in each MSC-seeded hydrogel. Interestingly, while CH-seeded constructs were strongly dependent on the 3D environment in which they were encapsulated, similar growth profiles were observed in each MSC-laden hydrogel. In every case, MSC-laden constructs possessed mechanical properties significantly lower than those of CH-seeded AG constructs. This finding suggests that methods for inducing MSC chondrogenesis have yet to be optimized to produce cells whose functional matrix-forming potential matches that of native CHs.

  9. Soft nanotube hydrogels functioning as artificial chaperones.

    PubMed

    Kameta, Naohiro; Masuda, Mitsutoshi; Shimizu, Toshimi

    2012-06-26

    Self-assembly of rationally designed asymmetric amphiphilic monomers in water produced nanotube hydrogels in the presence of chemically denatured proteins (green fluorescent protein, carbonic anhydrase, and citrate synthase) at room temperature, which were able to encapsulate the proteins in the one-dimensional channel of the nanotube consisting of a monolayer membrane. Decreasing the concentrations of the denaturants induced refolding of part of the encapsulated proteins in the nanotube channel. Changing the pH dramatically reduced electrostatic attraction between the inner surface mainly covered with amino groups of the nanotube channel and the encapsulated proteins. As a result, the refolded proteins were smoothly released into the bulk solution without specific additive agents. This recovery procedure also transformed the encapsulated proteins from an intermediately refolding state to a completely refolded state. Thus, the nanotube hydrogels assisted the refolding of the denatured proteins and acted as artificial chaperones. Introduction of hydrophobic sites such as a benzyloxycarbony group and a tert-butoxycarbonyl group onto the inner surface of the nanotube channels remarkably enhanced the encapsulation and refolding efficiencies based on the hydrophobic interactions between the groups and the surface-exposed hydrophobic amino acid residues of the intermediates in the refolding process. Refolding was strongly dependent on the inner diameters of the nanotube channels. Supramolecular nanotechnology allowed us to not only precisely control the diameters of the nanotube channels but also functionalize their surfaces, enabling us to fine-tune the biocompatibility. Hence, these nanotube hydrogel systems should be widely applicable to various target proteins of different molecular weights, charges, and conformations.

  10. Protein functionalized micro hydrogel features for cell-surface interaction.

    PubMed

    Bhatnagar, Parijat; Nixon, Alan J; Kim, Il; Kameoka, Jun

    2008-08-01

    Cross-linked hydrogel features have been patterned using subtractive lift-off of polymerized hydrogel film. Projection lithography and oxygen plasma etch was used to pattern parylene C polymer film. Molecular self-assembly of polymerizable monolayer was obtained in solution-phase and acrylamide based hydrogel was polymerized using free-radical polymerization on this substrate. Parylene C film was mechanically lifted-off to remove the blanket hydrogel film and micro hydrogel features (muhf) were obtained attached to the predefined patterns in the range from 1 to 60 mum. The muhf were functionalized with aldehyde functional groups, and proteins were coupled to them using Schiff base chemistry followed by reductive amination. Interaction of mesenchymal stem cells with transforming growth factor-beta 1 (TGF-beta1) functionalized muhf was studied, and TGF-beta1 was found to retain its tumor suppression activity. PMID:18259869

  11. Enzymatic regulation of functional vascular networks using gelatin hydrogels.

    PubMed

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

    2015-06-01

    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.

  12. 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

  13. Degradation potential of protocatechuate 3,4-dioxygenase from crude extract of Stenotrophomonas maltophilia strain KB2 immobilized in calcium alginate hydrogels and on glyoxyl agarose.

    PubMed

    Guzik, Urszula; Hupert-Kocurek, Katarzyna; Krysiak, Marta; Wojcieszyńska, Danuta

    2014-01-01

    Microbial intradiol dioxygenases have been shown to have a great potential for bioremediation; however, their structure is sensitive to various environmental and chemical agents. Immobilization techniques allow for the improvement of enzyme properties. This is the first report on use of glyoxyl agarose and calcium alginate as matrixes for the immobilization of protocatechuate 3,4-dioxygenase. Multipoint attachment of the enzyme to the carrier caused maintenance of its initial activity during the 21 days. Immobilization of dioxygenase in calcium alginate or on glyoxyl agarose resulted in decrease in the optimum temperature by 5 °C and 10 °C, respectively. Entrapment of the enzyme in alginate gel shifted its optimum pH towards high-alkaline pH while immobilization of the enzyme on glyoxyl agarose did not influence pH profile of the enzyme. Protocatechuate 3,4-dioygenase immobilized in calcium alginate showed increased activity towards 2,5-dihydroxybenzoate, caffeic acid, 2,3-dihydroxybenzoate, and 3,5-dihydroxybenzoate. Slightly lower activity of the enzyme was observed after its immobilization on glyoxyl agarose. Entrapment of the enzyme in alginate gel protected it against chelators and aliphatic alcohols while its immobilization on glyoxyl agarose enhanced enzyme resistance to inactivation by metal ions. PMID:24693536

  14. Degradation potential of protocatechuate 3,4-dioxygenase from crude extract of Stenotrophomonas maltophilia strain KB2 immobilized in calcium alginate hydrogels and on glyoxyl agarose.

    PubMed

    Guzik, Urszula; Hupert-Kocurek, Katarzyna; Krysiak, Marta; Wojcieszyńska, Danuta

    2014-01-01

    Microbial intradiol dioxygenases have been shown to have a great potential for bioremediation; however, their structure is sensitive to various environmental and chemical agents. Immobilization techniques allow for the improvement of enzyme properties. This is the first report on use of glyoxyl agarose and calcium alginate as matrixes for the immobilization of protocatechuate 3,4-dioxygenase. Multipoint attachment of the enzyme to the carrier caused maintenance of its initial activity during the 21 days. Immobilization of dioxygenase in calcium alginate or on glyoxyl agarose resulted in decrease in the optimum temperature by 5 °C and 10 °C, respectively. Entrapment of the enzyme in alginate gel shifted its optimum pH towards high-alkaline pH while immobilization of the enzyme on glyoxyl agarose did not influence pH profile of the enzyme. Protocatechuate 3,4-dioygenase immobilized in calcium alginate showed increased activity towards 2,5-dihydroxybenzoate, caffeic acid, 2,3-dihydroxybenzoate, and 3,5-dihydroxybenzoate. Slightly lower activity of the enzyme was observed after its immobilization on glyoxyl agarose. Entrapment of the enzyme in alginate gel protected it against chelators and aliphatic alcohols while its immobilization on glyoxyl agarose enhanced enzyme resistance to inactivation by metal ions.

  15. 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

  16. 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.

  17. Flexible hydrogel-based functional composite materials

    DOEpatents

    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.

  18. Surface functionalization of hyaluronic acid hydrogels by polyelectrolyte multilayer films.

    PubMed

    Yamanlar, Seda; Sant, Shilpa; Boudou, Thomas; Picart, Catherine; Khademhosseini, Ali

    2011-08-01

    Hyaluronic acid (HA), an anionic polysaccharide, is one of the major components of the natural extracellular matrix (ECM). Although HA has been widely used for tissue engineering applications, it does not support cell attachment and spreading and needs chemical modification to support cellular adhesion. Here, we present a simple approach to functionalize photocrosslinked HA hydrogels by deposition of poly(l-lysine) (PLL) and HA multilayer films made by the layer-by-layer (LbL) technique. PLL/HA multilayer film formation was assessed by using fluorescence microscopy, contact angle measurements, cationic dye loading and confocal microscopy. The effect of polyelectrolyte multilayer film (PEM) formation on the physicochemical and mechanical properties of hydrogels revealed polyelectrolyte diffusion inside the hydrogel pores, increased hydrophobicity of the surface, reduced equilibrium swelling, and reduced compressive moduli of the modified hydrogels. Furthermore, NIH-3T3 fibroblasts seeded on the surface showed improved cell attachment and spreading on the multilayer functionalized hydrogels. Thus, modification of HA hydrogel surfaces with multilayer films affected their physicochemical properties and improved cell adhesion and spreading on these surfaces. This new hydrogel/PEM composite system may offer possibilities for various biomedical and tissue engineering applications, including growth factor delivery and co-culture systems.

  19. Surface Functionalization of Hyaluronic Acid Hydrogels by Polyelectrolyte Multilayer Films

    PubMed Central

    Yamanlar, Seda; Sant, Shilpa; Boudou, Thomas; Picart, Catherine; Khademhosseini, Ali

    2011-01-01

    Hyaluronic acid (HA), an anionic polysaccharide, is one of the major components of the natural extracellular matrix (ECM). Although HA has been widely used for tissue engineering applications, it does not support cell attachment and spreading and needs chemical modification to support cellular adhesion. Here, we present a simple approach to functionalize photocrosslinked HA hydrogels by deposition of poly(L-lysine) (PLL) and HA multilayer films made by the layer-by-layer (LbL) technique. PLL/HA multilayer film formation was assessed by using fluorescence microscopy, contact angle measurements, cationic dye loading and confocal microscopy. The effect of polyelectrolyte multilayer film formation on the physicochemical and mechanical properties of hydrogels revealed polyelectrolyte diffusion inside the hydrogel pores, increased hydrophobicity of the surface, reduced equilibrium swelling, and reduced compressive moduli of the modified hydrogels. Furthermore, NIH-3T3 fibroblasts seeded on the surface showed improved cell attachment and spreading on the multilayer functionalized hydrogels. Thus, modification of HA hydrogel surfaces with multilayer films affected their physicochemical properties and improved cell adhesion and spreading on these surfaces. This new hydrogel/PEM composite system may offer possibilities for various biomedical and tissue engineering applications, including growth factor delivery and co-culture systems. PMID:21571364

  20. Nucleus pulposus cells synthesize a functional extracellular matrix and respond to inflammatory cytokine challenge following long term agarose culture

    PubMed Central

    Smith, Lachlan J.; Chiaro, Joseph A.; Nerurkar, Nandan L.; Cortes, Daniel H.; Horava, Sarena D.; Hebela, Nader M.; Mauck, Robert L.; Dodge, George R.; Elliott, Dawn M.

    2012-01-01

    Intervertebral disc degeneration is characterized by a cascade of cellular, biochemical and structural changes that may lead to functional impairment and low back pain. Interleukin-1 beta (IL-1β) is strongly implicated in the etiology of disc degeneration, however there is currently no direct evidence linking IL-1β upregulation to downstream biomechanical changes. The objective of this study was to evaluate long-term agarose culture of nucleus pulposus (NP) cells as a potential in-vitro model system to investigate this. Bovine NP cells were cultured in agarose for 49 days in a defined medium containing transforming growth factor-beta 3, after which both mechanical properties and composition were evaluated and compared to native NP. The mRNA levels of NP cell markers were compared to those of freshly isolated NP cells. Glycosaminoglycan (GAG) content, aggregate modulus and hydraulic permeability of mature constructs were similar to native NP, and aggrecan and SOX9 mRNA levels were not significantly different from freshly isolated cells. To investigate direct links between IL-1β and biomechanical changes, mature agarose constructs were treated with IL-1β, and effects on biomechanical properties, extracellular matrix composition and mRNA levels were quantified. IL-1β treatment resulted in upregulation of ADAMTS4, MMP13 and INOS, decreased GAG and modulus, and increased permeability. To evaluate the model as a test platform for therapeutic intervention, co-treatment with IL-1β and IL-1 receptor antagonist (IL-1ra) was evaluated. IL-1ra significantly attenuated degradative changes induced by IL-1β. These results suggest that this in vitro model represents a reliable and cost-effective platform for evaluating new therapies for disc degeneration. PMID:22102324

  1. 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

  2. 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...

  3. Microporous Cell-laden Hydrogels for Engineered Tissue Constructs

    PubMed Central

    Park, Jae Hong; Chung, Bong Geun; Lee, Won Gu; Kim, Jinseok; Brigham, Mark D.; Shim, Jaesool; Lee, Seunghwan; Hwang, Changmo; Durmus, Naside Gozde; Demirci, Utkan; Khademhosseini, Ali

    2010-01-01

    In this paper, we describe an approach to generate microporous cell-laden hydrogels for fabricating biomimetic tissue engineered constructs. Micropores at different length scales were fabricated in cell-laden hydrogels by micromolding fluidic channels and leaching sucrose crystals. Microengineered channels were created within cell-laden hydrogel precursors that contained agarose solution mixed with sucrose crystals. The rapid cooling of the agarose solution was used to gel the solution and form micropores in place of the sucrose crystals. The sucrose leaching process generated micropores that were homogeneously distributed within the gels, while enabling the direct immobilization of cells within the gels. We also characterized the physical, mechanical, and biological properties (i.e. microporosity, diffusivity, and cell viability) of cell-laden agarose gels as a function of engineered porosity. The microporosity was controlled from 0% to 40% and the diffusivity of molecules in the porous agarose gels increased as compared to controls. Furthermore, the viability of human hepatocyte cells that were cultured in microporous agarose gels corresponded to the diffusion profile generated away from the microchannels. Based on their enhanced diffusive properties, microporous cell-laden hydrogels containing a microengineered fluidic channel could be a useful tool for generating tissue structures for regenerative medicine and drug discovery applications. PMID:20091766

  4. 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.

  5. Functional hydrogel contact lens for drug delivery in the application of oculopathy therapy.

    PubMed

    Hu, Xiaohong; Tan, Huaping; Hao, Lingyun

    2016-12-01

    Although hydrogel contact lens has attracted increasingly concerns as delivery carriers in the field of oculopathy therapy, traditional hydrogel does not show excellent drug encapsulated and controlled properties due to simple hydrophilic polymer chain lacking extra interaction with drug molecule. Herein, functional hydrogels were synthesized in this research to delivery ophthalmic drug for oculopathy therapy. Functional monomer of mono-GMA-β-CD and functional crosslinker of MA-β-CD were incorporated into hydrogel by copolymerization. For hydrogels, equilibrium swelling ratio and contact angle was influenced by mono-GMA-β-CD ratio and MA-β-CD ratio, respectively. All hydrogels exhibited similar water loss behavior and good transparency. Hydrogels had rheological characteristic of typical elastomer. Viscoelasticity and surface morphology of hydrogel were also affected by mono-GMA-β-CD ratio and MA-β-CD ratio. In the aspect of properties, functional hydrogel containing β-CD domain exhibited better protein resistance capacity and significantly higher equilibrium encapsulated drug amount than traditional hydrogel. Besides the performance, drug release behavior of drug encapsulated hydrogel was adjusted by both mono-GMA-β-CD ratio and MA-β-CD ratio. Preliminary in vivo evaluation revealed that functional hydrogel contact lens had better effect and efficacy on lowering intraocular tension than commercial eye drop. It is inferred from all results that functional contact lens has a bright prospect in the application of oculopathy therapy. PMID:27479893

  6. "Clickable" agarose for affinity chromatography.

    PubMed

    Punna, Sreenivas; Kaltgrad, Eiton; Finn, M G

    2005-01-01

    Successful purification of biological molecules by affinity chromatography requires the attachment of desired ligands to biocompatible chromatographic supports. The Cu(I)-catalyzed cycloaddition of azides and alkynes-the premier example of "click chemistry"-is an efficient way to make covalent connections among diverse molecules and materials. Both azide and alkyne units are highly selective in their reactivity, being inert to most chemical functionalities and stable to wide ranges of solvent, temperature, and pH. We show that agarose beads bearing alkyne and azide groups can be easily made and are practical precursors to functionalized agarose materials for affinity chromatography.

  7. 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.

  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.

    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.

  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. Electroconductive Hydrogel Based on Functional Poly(Ethylenedioxy Thiophene)

    PubMed Central

    2016-01-01

    Poly(ethylene dioxythiophene) with functional pendant groups bearing double bonds is synthesized and employed for the fabrication of electroactive hydrogels with advantageous characteristics: covalently cross-linked porous 3D scaffolds with notable swelling ratio, appropriate mechanical properties, electroactivity in physiological conditions, and suitability for proliferation and differentiation of C2C12 cells. This is a new approach for the fabrication of conductive engineered constructs. PMID:27656042

  13. Electroconductive Hydrogel Based on Functional Poly(Ethylenedioxy Thiophene)

    PubMed Central

    2016-01-01

    Poly(ethylene dioxythiophene) with functional pendant groups bearing double bonds is synthesized and employed for the fabrication of electroactive hydrogels with advantageous characteristics: covalently cross-linked porous 3D scaffolds with notable swelling ratio, appropriate mechanical properties, electroactivity in physiological conditions, and suitability for proliferation and differentiation of C2C12 cells. This is a new approach for the fabrication of conductive engineered constructs.

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

    NASA Astrophysics Data System (ADS)

    Song, Ji Eun; Cho, Eun Chul

    2016-10-01

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

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

    PubMed Central

    Song, Ji Eun; Cho, Eun Chul

    2016-01-01

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

  16. 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.

  17. Enzyme-assisted photolithography for spatial functionalization of hydrogels.

    PubMed

    Gu, Zhen; Tang, Yi

    2010-08-01

    The ability to form functional polymeric patterning structures has important implications for the studies of cell biology, tissue engineering, and medical diagnostics. We have developed a novel enzyme-assisted photolithography (EAPL) method for spatial functionalization of hydrogels via a high throughput fashion. A bisacrylated peptide crosslinker, containing a protease cleavable amino acid sequence and caged by a photolabile moiety, is used during hydrogel polymerization. A facile two-step process is employed, including UV exposure to decage the peptide crosslinker at a desired area and protease development to specifically digest gels at UV treated regions only. Importantly, proteolysis of the peptide bonds generates free nucleophilic amine groups at the patterned area that can be further functionalized. Using this strategy and caspase-3 as the enzyme developer, we demonstrate the simultaneous generation of topographical and functional patterns into poly(ethylene glycol) (PEG) hydrogels. We show that 20 microm-wide line arrays functionalized with arginine-glycine-aspartic acid (RGD)-containing peptides can be used to generate cell patterns with individual cell resolution. We also fabricated arrays 20 mum diameter cavities decorated with B lymphocyte specific anti-CD19, which was used to achieve a 600-fold enrichment of B-cells from a 0.1% starting B-cell mixture. The simple fabrication process, straightforward chemistry and an all-aqueous based biocompatible and environmentally friendly approach render EAPL a versatile platform to construct biologically responsive 2D patterns or 3D scaffolds for lab-on-a-chip systems and tissue engineering.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. Sequential assembly of 3D perfusable microfluidic hydrogels.

    PubMed

    He, Jiankang; Zhu, Lin; Liu, Yaxiong; Li, Dichen; Jin, Zhongmin

    2014-11-01

    Bottom-up tissue engineering provides a promising way to recreate complex structural organizations of native organs in artificial constructs by assembling functional repeating modules. However, it is challenging for current bottom-up strategies to simultaneously produce a controllable and immediately perfusable microfluidic network in modularly assembled 3D constructs. Here we presented a bottom-up strategy to produce perfusable microchannels in 3D hydrogels by sequentially assembling microfluidic modules. The effects of agarose-collagen composition on microchannel replication and 3D assembly of hydrogel modules were investigated. The unique property of predefined microchannels in transporting fluids within 3D assemblies was evaluated. Endothelial cells were incorporated into the microfluidic network of 3D hydrogels for dynamic culture in a house-made bioreactor system. The results indicated that the sequential assembly method could produce interconnected 3D predefined microfluidic networks in optimized agarose-collagen hydrogels, which were fully perfusable and successfully functioned as fluid pathways to facilitate the spreading of endothelial cells. We envision that the presented method could be potentially used to engineer 3D vascularized parenchymal constructs by encapsulating primary cells in bulk hydrogels and incorporating endothelial cells in predefined microchannels. PMID:25027302

  3. 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

  4. Intramyocardial Delivery of Notch Ligand-Containing Hydrogels Improves Cardiac Function and Angiogenesis Following Infarction

    PubMed Central

    Boopathy, Archana V.; Martinez, Mario D.; Smith, Amanda Walker; Brown, Milton E.; García, Andrés J.

    2015-01-01

    Myocardial infarction (MI) is the leading cause of death worldwide. Notch1 signaling plays a critical role in cardiac development, in survival, cardiogenic lineage commitment, differentiation of cardiac stem/progenitor cells, and in regenerative responses following myocardial injury. The objective of this study was the evaluation of the therapeutic effect of delivering the Notch ligand-containing hydrogels in a rat model of MI. Self-assembling peptide (SAP) hydrogels were functionalized with a peptide mimic of the Notch1 ligand Jagged1 (RJ). In rats subjected to experimental MI, delivery of RJ-containing hydrogel to the infarcted heart resulted in improvement in cardiac function back to sham-operated levels. A significant decrease in fibrosis and an increase in the endothelial vessel area and Ki67 expression were also observed in rats treated with the RJ hydrogels compared to untreated rats or rats treated with unmodified or scrambled peptide hydrogels. This study demonstrates the functional benefit of Notch1-activating peptide delivered in SAP hydrogels for cardiac repair. PMID:25982380

  5. 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.

  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. 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

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

    PubMed Central

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

    2012-01-01

    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

  9. 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.

  10. Studying the Effects of Matrix Stiffness on Cellular Function using Acrylamide-based Hydrogels

    PubMed Central

    Cretu, Alexandra; Castagnino, Paola; Assoian, Richard

    2010-01-01

    Tissue stiffness is an important determinant of cellular function, and changes in tissue stiffness are commonly associated with fibrosis, cancer and cardiovascular disease1-11. Traditional cell biological approaches to studying cellular function involve culturing cells on a rigid substratum (plastic dishes or glass coverslips) which cannot account for the effect of an elastic ECM or the variations in ECM stiffness between tissues. To model in vivo tissue compliance conditions in vitro, we and others use ECM-coated hydrogels. In our laboratory, the hydrogels are based on polyacrylamide which can mimic the range of tissue compliances seen biologically12. "Reactive" cover slips are generated by incubation with NaOH followed by addition of 3-APTMS. Glutaraldehyde is used to cross-link the 3-APTMS and the polyacrylamide gel. A solution of acrylamide (AC), bis-acrylamide (Bis-AC) and ammonium persulfate is used for the polymerization of the hydrogel. N-hydroxysuccinimide (NHS) is incorporated into the AC solution to crosslink ECM protein to the hydrogel. Following polymerization of the hydrogel, the gel surface is coated with an ECM protein of choice such as fibronectin, vitronectin, collagen, etc. The stiffness of a hydrogel can be determined by rheology or atomic force microscopy (AFM) and adjusted by varying the percentage of AC and/or bis-AC in the solution12. In this manner, substratum stiffness can be matched to the stiffness of biological tissues which can also be quantified using rheology or AFM. Cells can then be seeded on these hydrogels and cultured based upon the experimental conditions required. Imaging of the cells and their recovery for molecular analysis is straightforward. For this article, we define soft substrata as those having elastic moduli (E) <3000 Pascal and stiff substrata/tissues as those with E >20,000 Pascal. PMID:20736914

  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.

  12. Poly(glycidyl methacrylate)-grafted hydrophobic charge-induction agarose resins with 5-aminobenzimidazole as a functional ligand.

    PubMed

    Liu, Tao; Lin, Dong-Qiang; Wang, Cun-Xiang; Yao, Shan-Jing

    2016-08-01

    Hydrophobic charge-induction chromatography is a new technology for antibody purification. To improve antibody adsorption capacity of hydrophobic charge-induction resins, new poly(glycidyl methacrylate)-grafted hydrophobic charge-induction resins with 5-aminobenzimidazole as a functional ligand were prepared. Adsorption isotherms, kinetics, and dynamic binding behaviors of the poly(glycidyl methacrylate)-grafted resins prepared were investigated using human immunoglobulin G as a model protein, and the effects of ligand density were discussed. At the moderate ligand density of 330 μmol/g, the saturated adsorption capacity and equilibrium constant reached the maximum of 140 mg/g and 25 mL/mg, respectively, which were both much higher than that of non-grafted resin with same ligand. In addition, effective pore diffusivity and dynamic binding capacity of human immunoglobulin G onto the poly(glycidyl methacrylate)-grafted resins also reached the maximum at the moderate ligand density of 330 μmol/g. Dynamic binding capacity at 10% breakthrough was as high as 76.3 mg/g when the linear velocity was 300 cm/h. The results indicated that the suitable polymer grafting combined with the control of ligand density would be a powerful tool to improve protein adsorption of resins, and new poly(glycidyl methacrylate)-grafted hydrophobic charge-induction resins have a promising potential for antibody purification applications. PMID:27465269

  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. 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

  15. Hierarchical hydrogen bonds directed multi-functional carbon nanotube-based supramolecular hydrogels.

    PubMed

    Du, Ran; Wu, Juanxia; Chen, Liang; Huang, Huan; Zhang, Xuetong; Zhang, Jin

    2014-04-01

    Supramolecular hydrogels (SMHs) are three-dimensional networks filled with a large amount of water. The crosslinking force in the 3D network is always constructed by relatively weak and dynamic non-covalent interactions, and thus SMHs usually possess extremely high susceptibility to external environment and can show extraordinary stimuli-responsive, self-healing or other attractive properties. However, the overall crosslinking force in hydrogel networks is difficult to flexibly modulate, and this leads to limited functions of the SMHs. In this regard, hierarchical hydrogen bonds, that is, the mixture of relatively strong and relatively weak hydrogen bonds, are used herein as crosslinking force for the hydrogel preparation. The ratio of strong and weak hydrogen bonds can be finely tuned to tailor the properties of resultant gels. Thus, by delicate manipulation of the overall crosslinking force in the system, a hydrogel with multiple (thermal, pH and NIR light) responsiveness, autonomous self-healing property and interesting temperature dependent, reversible adhesion behavior is obtained. This kind of hierarchical hydrogen bond manipulation is proved to be a general method for multiple-functionality hydrogel preparation, and the resultant material shows potential for a range of applications.

  16. Superporous agarose anion exchangers for plasmid isolation.

    PubMed

    Tiainen, Peter; Gustavsson, Per-Erik; Ljunglöf, Anders; Larsson, Per-Olof

    2007-01-01

    Superporous agarose beads have wide, connecting flow pores allowing large molecules such as plasmids to be transported into the interior of the beads by convective flow. The pore walls provide additional surface for plasmid binding thus increasing the binding capacity of the adsorbent. Novel superporous agarose anion exchangers have been prepared, differing with respect to bead diameter, superpore diameter and type of anion-exchange functional group (poly(ethyleneimine) and quaternary amine). The plasmid binding capacities were obtained from breakthrough curves and compared with the binding capacity of homogeneous agarose beads of the same particle size. Significantly, the smaller diameter superporous agarose beads were found to have four to five times higher plasmid binding capacity than the corresponding homogeneous agarose beads. The experimentally determined plasmid binding capacity was compared with the theoretically calculated surface area for each adsorbent and fair agreement was found. Confocal microscopy studies of beads with adsorbed, fluorescently labelled plasmids aided in the interpretation of the results. Superporous poly(ethyleneimine)-substituted beads with a high ion capacity (230 micromol/ml) showed a plasmid binding of 3-4 mg/ml adsorbent. Superporous quaternary amine-substituted beads had a lower ion capacity (81 micromol/ml) and showed a correspondingly lower plasmid binding capacity (1-2 mg/ml adsorbent). In spite of the lower capacity, the beads with quaternary amine ligand were preferred, due to their much better plasmid recovery (70-100% recovery). Interestingly, both capacity and recovery was improved when the plasmid adsorption step was carried out in the presence of a moderate salt concentration. The most suitable superporous bead type (45-75 microm diameter beads; 4 microm superpores; quaternary amine ligand) was chosen for the capture of plasmid DNA from a clarified alkaline lysate. Two strategies were evaluated, one with and one

  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. Mechanically robust, rapidly actuating, and biologically functionalized macroporous poly(N-isopropylacrylamide)/silk hybrid hydrogels.

    PubMed

    Gil, Eun Seok; Park, Sang-Hyug; Tien, Lee W; Trimmer, Barry; Hudson, Samuel M; Kaplan, David L

    2010-10-01

    A route toward mechanically robust, rapidly actuating, and biologically functionalized polymeric actuators using macroporous soft materials is described. The materials were prepared by combining silk protein and a synthetic polymer (poly(N-isopropylacrylamide) (PNIAPPm)) to form interpenetrating network materials and macroporous structures by freeze-drying, with hundreds of micrometer diameter pores and exploiting the features of both polymers related to dynamic materials and structures. The chemically cross-linked PNIPAAm networks provided stimuli-responsive features, while the silk interpenetrating network formed by inducing protein β-sheet crystallinity in situ for physical cross-links provided material robustness, improved expansion force, and enzymatic degradability. The macroporous hybrid hydrogels showed enhanced thermal-responsive properties in comparison to pure PNIPAAm hydrogels, nonporous silk/PNIPAAm hybrid hydrogels, and previously reported macroporous PNIPAAm hydrogels. These new systems reach near equilibrium sizes in shrunken/swollen states in less than 1 min, with the structural features providing improved actuation rates and stable oscillatory properties due to the macroporous transport and the mechanically robust silk network. Confocal images of the hydrated hydrogels around the lower critical solution temperature (LCST) revealed macropores that could be used to track changes in the real time morphology upon thermal stimulus. The material system transformed from a macroporous to a nonporous structure upon enzymatic degradation. To extend the utility of the system, an affinity platform for a switchable or tunable system was developed by immobilizing biotin and avidin on the macropore surfaces.

  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.

  20. Supplementation of exogenous adenosine 5'-triphosphate enhances mechanical properties of 3D cell-agarose constructs for cartilage tissue engineering.

    PubMed

    Gadjanski, Ivana; Yodmuang, Supansa; Spiller, Kara; Bhumiratana, Sarindr; Vunjak-Novakovic, Gordana

    2013-10-01

    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.

  1. Composition of agarose substrate affects behavioral output of Drosophila larvae

    PubMed Central

    Apostolopoulou, Anthi A.; Hersperger, Fabian; Mazija, Lorena; Widmann, Annekathrin; Wüst, Alexander; Thum, Andreas S.

    2014-01-01

    In the last decade the Drosophila larva has evolved into a simple model organism offering the opportunity to integrate molecular genetics with systems neuroscience. This led to a detailed understanding of the neuronal networks for a number of sensory functions and behaviors including olfaction, vision, gustation and learning and memory. Typically, behavioral assays in use exploit simple Petri dish setups with either agarose or agar as a substrate. However, neither the quality nor the concentration of the substrate is generally standardized across these experiments and there is no data available on how larval behavior is affected by such different substrates. Here, we have investigated the effects of different agarose concentrations on several larval behaviors. We demonstrate that agarose concentration is an important parameter, which affects all behaviors tested: preference, feeding, learning and locomotion. Larvae can discriminate between different agarose concentrations, they feed differently on them, they can learn to associate an agarose concentration with an odor stimulus and change locomotion on a substrate of higher agarose concentration. Additionally, we have investigated the effect of agarose concentration on three quinine based behaviors: preference, feeding and learning. We show that in all cases examined the behavioral output changes in an agarose concentration-dependent manner. Our results suggest that comparisons between experiments performed on substrates differing in agarose concentration should be done with caution. It should be taken into consideration that the agarose concentration can affect the behavioral output and thereby the experimental outcomes per se potentially due to the initiation of an escape response or changes in foraging behavior on more rigid substrates. PMID:24478658

  2. The incorporation of extracellular matrix proteins in protein polymer hydrogels to improve encapsulated beta-cell function.

    PubMed

    Beenken-Rothkopf, Liese N; Karfeld-Sulzer, Lindsay S; Davis, Nicolynn E; Forster, Ryan; Barron, Annelise E; Fontaine, Magali J

    2013-01-01

    Biomaterial encapsulation of islets has been proposed to improve the long-term success of islet transplantation by recreating a suitable microenvironment and enhancing cell-matrix interactions that affect cellular function. Protein polymer hydrogels previously showed promise as a biocompatible scaffold by maintaining high cell viability. Here, enzymatically-crosslinked protein polymers were used to investigate the effects of varying scaffold properties and of introducing ECM proteins on the viability and function of encapsulated MIN6 β-cells. Chemical and mechanical properties of the hydrogel were modified by altering the protein concentrations while collagen IV, fibronectin, and laminin were incorporated to reestablish cell-matrix interactions lost during cell isolation. Rheology indicated all hydrogels formed quickly, resulting in robust, elastic hydrogels with Young's moduli similar to soft tissue. All hydrogels tested supported both high MIN6 β-cell viability and function and have the potential to serve as an encapsulation platform for islet cell delivery in vivo.

  3. Aptamer-functionalized hydrogel diffraction gratings for the human thrombin detection.

    PubMed

    Wang, Xiaoqi; Wang, Xiaogong

    2013-07-01

    The aptamer-functionalized hydrogel diffraction gratings were successfully fabricated by incorporating an aptamer and its complementary sequence as crosslinking junctions in the network structure. The gratings showed a sensitive response to human thrombin as read out from the diffracted light.

  4. Functionalization of multiwalled carbon nanotubes and their pH-responsive hydrogels with amyloid fibrils.

    PubMed

    Li, Chaoxu; Mezzenga, Raffaele

    2012-07-10

    New biocompatible, pH-responsive, and fully fibrous hydrogels have been prepared based on amyloid fibrils hybridized and gelled by functionalized multiwalled carbon nanotubes (MWNTs) far below the gelling concentration of amyloid fibrils. Sulfonic functional groups were introduced on the surfaces of MWNTs either by a covalent diazonium reaction or by physical π-π interactions. The presence of the isoelectric point of amyloid fibrils allows a reversible gelling behavior through ionic interactions with functionalized MWNTs.

  5. Ultrasoft Alginate Hydrogels Support Long-Term Three-Dimensional Functional Neuronal Networks.

    PubMed

    Palazzolo, Gemma; Broguiere, Nicolas; Cenciarelli, Orlando; Dermutz, Harald; Zenobi-Wong, Marcy

    2015-08-01

    Neuron development and function are exquisitely sensitive to the mechanical properties of their surroundings. Three-dimensional (3D) cultures are therefore being explored as they better mimic the features of the native extracellular matrix. Limitations of existing 3D culture models include poorly defined composition, rapid degradation, and suboptimal biocompatibility. Here we show that ionically cross-linked ultrasoft hydrogels made from unmodified alginate can potently promote neuritogenesis. Alginate hydrogels were characterized mechanically and a remarkable range of stiffness (10-4000 Pa) could be produced by varying the macromer content (0.1-0.4% w/v) and CaCl2 concentration. Dissociated rat embryonic cortical neurons encapsulated within the softest of the hydrogels (0.1% w/v, 10 mM CaCl2) showed excellent viability, extensive formation of axons and dendrites, and long-term activity as determined by calcium imaging. In conclusion, alginate is an off-the-shelf, easy to handle, and inexpensive material, which can be used to make ultrasoft hydrogels for the formation of stable and functional 3D neuronal networks. This 3D culture system could have important applications in neuropharmacology, toxicology, and regenerative medicine.

  6. Compression behaviour of biphasic calcium phosphate and biphasic calcium phosphate-agarose scaffolds for bone regeneration.

    PubMed

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

    2011-02-01

    There is an acknowledged need for shaping 3-D scaffolds with adequate porosity and mechanical properties for biomedical applications. The mechanical properties under static and cyclic compressive testing of dense and designed porous architecture bioceramic scaffolds based on the biphasic calcium phosphate (BCP) systems and BCP-agarose systems have been evaluated. The dense and designed porous architecture scaffolds in BCP systems exhibited a brittle behaviour. Agarose, a biocompatible and biodegradable hydrogel, has been used to shape designed architecture ceramic-agarose scaffolds following a low-temperature shaping method. Agarose conferred toughness, ductility and a rubbery consistency for strains of up to 60% of in ceramic BCP-agarose systems. This combination of ceramic and organic matrix helps to avoid 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 indicate a Mullins-like effect such as that observed in carbon-filled rubber systems. We report this type of mechanical behaviour, the Mullins effect, for the first time in bioceramics and bioceramic-agarose systems.

  7. 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

  8. 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.

  9. Hydrogel, aerogel and film of cellulose nanofibrils functionalized with silver nanoparticles.

    PubMed

    Dong, Hong; Snyder, James F; Tran, Dat T; Leadore, Julia L

    2013-06-20

    In this work, we describe hydrogels, aerogels and films of nanofibrillated cellulose (NFC) functionalized with metal nanoparticles using silver as an example. The TEMPO process used to produce NFC generates negatively charged surface carboxylate groups that provide high binding capability to transition metal species such as Ag(+). The gelation of NFC triggered by transition monovalent metal ions was revealed for the first time. The interaction was utilized to bind Ag(+) on the NFC surface and simultaneously induce formation of NFC-Ag(+) hydrogels, where Ag(+) was slowly reduced to Ag nanoparticles by hydroxyl groups on NFC without additional reducing agent. The NFC-Ag(+) hydrogel was initiated by strong association of carboxylate groups on NFC with Ag(+) and sufficient NFC surface charge reduction. The stiff hydrogel has a storage modulus leveled off at a plateau value of ~6800Pa. Porous aerogels and flat thin films comprising a continuous matrix of NFC were decorated with Ag nanoparticles through freeze-drying or solution-casting of NFC-Ag(+) dispersions with low contents of Ag(+), respectively, followed by UV reduction. The presence of Ag species on NFC reduced coalescence of nanofibrils in the film formation as revealed from AFM phase images.

  10. 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

  11. The role of hydrogels with tethered acetylcholine functionality on the adhesion and viability of hippocampal neurons and glial cells

    PubMed Central

    Zhou, Zhaoli; Yu, Panpan; Geller, Herbert M.; Ober, Christopher K.

    2012-01-01

    In neural tissue engineering, designing materials with the right chemical cues is crucial in providing a permissive microenvironment to encourage and guide neuronal cell attachment and differentiation. Modifying synthetic hydrogels with biologically active molecules has become an increasingly important route in this field to provide a successful biomaterial and cell interaction. This study presents a strategy of using the monomer 2-methacryloxyethyl trimethylammonium chloride (MAETAC) to provide tethered neurotransmitter acetylcholine-like functionality with a complete 2-acetoxy-N,N,N-trimethylethanaminium segment, thereby modifying the properties of commonly used, non-adhesive PEG-based hydrogels. The effect of the functional monomer concentration on the physical properties of the hydrogels was systematically studied, and the resulting hydrogels were also evaluated for mice hippocampal neural cell attachment and growth. Results from this study showed that MAETAC in the hydrogels promotes neuronal cell attachment and differentiation in a concentration-dependent manner, different proportions of MAETAC monomer in the reaction mixture produce hydrogels with different porous structures, swollen states, and mechanical strengths. Growth of mice hippocampal cells cultured on the hydrogels showed differences in number, length of processes and exhibited different survival rates. Our results indicate that chemical composition of the biomaterials is a key factor in neural cell attachment and growth, and integration of the appropriate amount of tethered neurotransmitter functionalities can be a simple and effective way to optimize existing biomaterials for neuronal tissue engineering applications. PMID:22196899

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

    PubMed

    Hacker, Michael C; Nawaz, Hafiz Awais

    2015-11-19

    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.

  13. 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

  14. 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

  15. Silk hydrogel for cartilage tissue engineering

    PubMed Central

    Chao, Pen-Hsiu Grace; Yodmuang, Supansa; Wang, Xiaoqin; Sun, Lin; Kaplan, David L.; Vunjak-Novakovic, Gordana

    2011-01-01

    Cartilage tissue engineering based on cultivation of immature chondrocytes in agarose hydrogel can yield tissue constructs with biomechanical properties comparable to native cartilage. However, agarose is immunogenic and non-degradable, and our capability to modify the structure, composition, and mechanical properties of this material is rather limited. In contrast, silk hydrogel is biocompatible and biodegradable, and it can be produced using a water-based method without organic solvents that enables precise control of structural and mechanical properties in a range of interest for cartilage tissue engineering. We observed that one particular preparation of silk hydrogel yielded cartilaginous constructs with biochemical content and mechanical properties matching constructs based on agarose. This finding and the possibility to vary the properties of silk hydrogel motivated this study of the factors underlying the suitability of hydrogels for cartilage tissue engineering. We present data resulting from a systematic variation of silk hydrogel properties, silk extraction method, gel concentration, and gel structure. Data suggest that silk hydrogel can be used as a tool for studies of the hydrogel-related factors and mechanisms involved in cartilage formation, as well as a tailorable and fully degradable scaffold for cartilage tissue engineering. PMID:20725950

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

    PubMed

    Thomas, Aline M; Gomez, Andrew J; Palma, Jaime L; Yap, Woon Teck; Shea, Lonnie D

    2014-10-01

    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

  17. 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

  18. 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

  19. 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

  20. Preparation and stability of agarose microcapsules containing BCG.

    PubMed

    Esquisabel, A; Hernandez, R M; Igartua, M; Gascón, A R; Calvo, B; Pedraz, J L

    2002-01-01

    An emulsification/internal gelation method of preparing small-sized agarose microcapsules containing Bacillus Calmette-Guerin (BCG) is reported. Agarose microcapsules have been prepared by the emulsification of the hydrogel within a vegetable oil followed by its gelation due to the cooling of the system. Four different oils (sesame, sweet almonds, camomile and jojoba) were assayed. The rheological analysis of the oils showed a Newtonian behaviour, with viscosity values of 37.7, 51.2, 59.3 and 67.1 mPa s for jojoba, camomile, sesame and sweet almonds oil, respectively. The particle size of the microcapsules obtained ranged from 23.1 microm for the microcapsules prepared with sweet almonds oil to 42.6 microm for those prepared with jojoba. The microcapsule particle size was found to be dependent on the viscosity of the oil used in the emulsification step. The encapsulated BCG was identified by the Difco TB stain set K, followed by observation under optical microscopy. Once prepared, microcapsules were freeze-dried using 5% trehalose as cryoprotectant and the stability of the microcapsules was assayed during 12 months storage at room temperature, observing that agarose microcapsules were stable after 12 months storage, since there was no evidence of alteration in the freeze-dried appearance, resuspension rate, observation under microscope, or particle size.

  1. Recovering DNA from agarose gels.

    PubMed

    Hegen, P N

    1994-09-01

    Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the internet. A commonly occurring theme on the net is the recovery of DNA, and this month's column discusses the pros and cons of various methods used to extract DNA fragments directly from agarose gels. For details on how to partake in the newsgroup, see the accompanying box. PMID:7985233

  2. Application of hydrogel prepared from ferrocene functionalized amino acid in the design of novel electrochemical immunosensing platform.

    PubMed

    Zhou, Miao; Sun, Zhifang; Shen, Congcong; Li, Zhengyuan; Zhang, Yi; Yang, Minghui

    2013-11-15

    A simple and novel supramolecular hydrogel was prepared from ferrocene (Fc) modified amino acid phenylalanine (F) and utilized as electrochemical immunosensing platform for the detection of human IgG. Scanning electron microscopy (SEM) characterization indicated that the hydrogel is composed of fibrils with diameter around 50-100 nm and length extend to 1mm. When the prepared hydrogel was reacted with H2O2, the Fc moieties on the amino acid was oxidized, leading to the disruption of the hydrogel structure and the decrease of its redox signal, which was characterized in detail by SEM and the electrochemical method. Regarding the redox current decrease upon the reaction of the hydrogel with H2O2, the hydrogel modified electrode was utilized as immunosensing interface. After the construction of the immunosensor based on the traditional sandwich protocol with glucose oxidase (GOx) functionalized carbon nanotube (CNT) as detection antibody label, the GOx attached onto electrode surface would catalyze glucose reaction to produce H2O2 and cause the decrease of redox current of the electrode. The current change is proportional to the concentration of IgG detected in the range from 0.1 to 100 pg/mL. The high sensitivity, wide linear range and good reproducibility of the immunosensor indicate this immunosensing platform can be easily extended to the detection of other protein biomarkers.

  3. Long-term three-dimensional neural tissue cultures in functionalized self-assembling peptide hydrogels, matrigel and collagen I.

    PubMed

    Koutsopoulos, Sotirios; Zhang, Shuguang

    2013-02-01

    Designer peptides with self-assembling properties form nanofibers which are further organized to form a hydrogel consisting of up to 99.5% water. We present here the encapsulation of neural stem cells into peptide nanofiber hydrogel scaffolds. This results in three-dimensional (3-D) neural tissue cultures in which neural stem cells differentiate into progenitor neural cells, neurons, astrocytes and oligodendrocytes when cultured in serum-free medium. Cell survival studies showed that neural cells in peptide hydrogels thrive for at least 5 months. In contrast, neural stem cells encapsulated in Collagen I were poorly differentiated and did not migrate significantly, thus forming clusters. We show that for culture periods of 1-2 weeks, neural stem cells proliferate and differentiate better in Matrigel. However, in long-term studies, the population of cells in Matrigel decreases whereas better cell survival rates are observed in neural tissue cultures in peptide hydrogels. Peptide functionalization with cell adhesion and cell differentiation motifs show superior cell survival and differentiation properties compared to those observed upon culturing neural cells in non-modified peptide hydrogels. These designed 3-D engineered tissue culturing systems have a potential use as tissue surrogates for tissue regeneration. The well-defined chemical and physical properties of the peptide nanofiber hydrogels and the use of serum-free medium allow for more realistic biological studies of neural cells in a biomimetic 3-D environment.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Functionalized, biodegradable hydrogels for control over sustained and localized siRNA delivery to incorporated and surrounding cells.

    PubMed

    Nguyen, Khanh; Dang, Phuong Ngoc; Alsberg, Eben

    2013-01-01

    Currently, the most severe limitation to applying RNA interference technology is delivery, including localizing the molecules to a specific site of interest to target a specific cell population and sustaining the presentation of these molecules for a controlled period of time. In this study, we engineered a functionalized, biodegradable system created by covalent incorporation of cationic linear polyethyleneimine (LPEI) into photocrosslinked dextran (DEX) hydrogels through a biodegradable ester linkage. The key innovation of this system is that control over the sustained release of short interference RNA (siRNA) was achieved, as LPEI could electrostatically interact with siRNA to maintain siRNA within the hydrogels and degradation of the covalent ester linkages between the LPEI and the hydrogels led to tunable release of LPEI/siRNA complexes over time. The covalent conjugation of LPEI did not affect the swelling or degradation properties of the hydrogels, and the addition of siRNA and LPEI had minimal effect on their mechanical properties. These hydrogels exhibited low cytotoxicity against human embryonic kidney 293 cells (HEK293). The release profiles could be tailored by varying DEX (8 and 12% w/w) and LPEI (0, 5, 10 μg/100 μl gel) concentrations with nearly 100% cumulative release achieved at day 9 (8% w/w gel) and day 17 (12% w/w gel). The released siRNA exhibited high bioactivity with cells surrounding and inside the hydrogels over an extended time period. This controllable and sustained siRNA delivery hydrogel system that permits tailored siRNA release profiles may be valuable to guide cell fate for regenerative medicine and other therapeutic applications such as cancer treatment.

  10. 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

  11. Magnetic hydrogels from alkyne/cobalt carbonyl-functionalized ABA triblock copolymers

    DOE PAGESBeta

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

    2016-03-09

    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. Furthermore, swelling tests, rheological studies and actuation tests demonstrated thatmore » the water capacity and modulus of the hydrogels were dependent upon the composition of the block copolymer precursors.« less

  12. Contemporary issues in hydrogels research

    SciTech Connect

    Peppas, N.A.

    1993-12-31

    The last ten years has seen an explosion in hydrogels research, the result of improved understanding of the structure and behavior of these water-swollen, crosslinked polymers. After the early developments of Flory And Katchalsky in the 1940s, the great Czechoslovakian researchers of the 1960s and Andrade, Hoffman, Ratner and Merrill of the early 1970s, hydrogels have again attracted significant research interest, especially through the imaginative research of Tanaka in the 1980s and others. Eight general areas of contemporary research in hydrogels are identified: (i) kinetic analysis of the copolymerization/crosslinking reactions used in hydrogel preparation; (ii) gelation and percolation theories; (iii) novel methods for tailor-made copolymers with desirable functional groups, or biodegradable chains; (iv) biomimetic hydrogels; (V) hydrogels of controlled porous structure; (vi) ultrapure hydrogels devoid of crosslinking agents, emulsifiers, etc.; (vii) critical phenomena in hydrogels; and (viii) behavior of anionic, cationic and amphiphilic hydrogels.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. Crosslinker effects on functional properties of alginate/N-succinylchitosan based hydrogels.

    PubMed

    Straccia, Maria Cristina; Romano, Ida; Oliva, Adriana; Santagata, Gabriella; Laurienzo, Paola

    2014-08-01

    In this paper, physico-chemical, mechanical and antimicrobial properties of hydrogels based on alginate/N-succinylchitosan blends crosslinked by calcium or zinc ions containing cellulose microfibers were investigated and discussed. With respect to plain alginate hydrogels, the addition of N-succinylchitosan significantly improved properties such as swelling degree and stability in saline solution. The water vapour transmission rate confirmed that all the hydrogels were able to assure a moist wound environment. Morphological analysis showed a good embedding of fibres within the zinc crosslinked hydrogels. In addition, zinc-crosslinked hydrogels evidenced antimicrobial activity against two common skin pathogenic bacteria, Staphylococcus aureus and Escherichia coli. Cytotoxicity assays proved that the amount of zinc released is slightly over the toxic level. Overall, the characteristics of the zinc-crosslinked hydrogels showed their potential interest as materials for wound dressing.

  2. 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

  3. The effect of matrix stiffness of injectable hydrogels on the preservation of cardiac function after a heart attack.

    PubMed

    Plotkin, Marian; Vaibavi, Srirangam Ramanujam; Rufaihah, Abdul Jalil; Nithya, Venkateswaran; Wang, Jing; Shachaf, Yonatan; Kofidis, Theo; Seliktar, Dror

    2014-02-01

    This study compares the effect of four injectable hydrogels with different mechanical properties on the post-myocardial infarction left ventricle (LV) remodeling process. The bioactive hydrogels were synthesized from Tetronic-fibrinogen (TF) and PEG-fibrinogen (PF) conjugates; each hydrogel was supplemented with two levels of additional cross-linker to increase the matrix stiffness as measured by the shear storage modulus (G'). Infarcts created by ligating the left anterior descending coronary artery in a rodent model were treated with the hydrogels, and all four treatment groups showed an increase in wall thickness, arterial density, and viable cardiac tissue in the peri-infarct areas of the LV. Echocardiography and hemodynamics data of the PF/TF treated groups showed significant improvement of heart function associated with the attenuated effects of the remodeling process. Multi-factorial regression analysis indicated that the group with the highest modulus exhibited the best rescue of heart function and highest neovascularization. The results of this study demonstrate that multiple properties of an injectable bioactive biomaterial, and notably the matrix stiffness, provide the multifaceted stimulation necessary to preserve cardiac function and prevent adverse remodeling following a heart attack.

  4. Functional elastic hydrogel as recyclable membrane for the adsorption and degradation of methylene blue.

    PubMed

    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 Pb(2+) than Cu(2+). 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

  5. Functional elastic hydrogel as recyclable membrane for the adsorption and degradation of methylene blue.

    PubMed

    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 Pb(2+) than Cu(2+). 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.

  6. 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

  7. 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

  8. 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.

  9. Lipid-coated hydrogel shapes as components of electrical circuits and mechanical devices

    NASA Astrophysics Data System (ADS)

    Sapra, K. Tanuj; Bayley, Hagan

    2012-11-01

    Recently, two-dimensional networks of aqueous droplets separated by lipid bilayers, with engineered protein pores as functional elements, were used to construct millimeter-sized devices such as a light sensor, a battery, and half- and full-wave rectifiers. Here, for the first time, we show that hydrogel shapes, coated with lipid monolayers, can be used as building blocks for such networks, yielding scalable electrical circuits and mechanical devices. Examples include a mechanical switch, a rotor driven by a magnetic field and painted circuits, analogous to printed circuit boards, made with centimeter-length agarose wires. Bottom-up fabrication with lipid-coated hydrogel shapes is therefore a useful step towards the synthetic biology of functional devices including minimal tissues.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. Potential of an injectable chitosan/starch/beta-glycerol phosphate hydrogel for sustaining normal chondrocyte function.

    PubMed

    Ngoenkam, Jatuporn; Faikrua, Atchariya; Yasothornsrikul, Sukkid; Viyoch, Jarupa

    2010-05-31

    An injectable hydrogel for chondrocyte delivery was developed by blending chitosan and starch derived from various sources with beta-glycerol phosphate (beta-GP) in the expectation that it would retain a liquid state at room temperature and gel at raised temperatures. Rheological investigation indicated that the system consisting of chitosan derived from crab shell and corn starch at 4:1 by weight ratio (1.53%, w/v of total polymers), and 6.0% (w/v) beta-GP (C/S/GP system) exhibited the sharpest sol-gel transition at 37+/-2 degrees C. The C/S/GP hydrogel was gradually degraded by 67% within 56 days in PBS containing 0.02 mg/ml lysozyme. The presence of starch in the system increased the water absorption of the hydrogel when compared to the system without starch. SEM observation revealed to the interior structure of the C/S/GP hydrogel having interconnected pore structure (average pore size 26.4 microm) whereas the pore size of the hydrogel without starch was 19.8 microm. The hydrogel also showed an ability to maintain chondrocyte phenotype as shown by cell morphology and expression of type II collagen mRNA and protein. In vivo study revealed that the gel was formed rapidly and localized at the injection site.

  18. Dual functionality of antimicrobial and antifouling of poly(N-hydroxyethylacrylamide)/salicylate hydrogels.

    PubMed

    Zhao, Chao; Li, Xiaosi; Li, Lingyan; Cheng, Gang; Gong, Xiong; Zheng, Jie

    2013-02-01

    The emergence and reemergence of microbial infection demand an urgent response to develop effective biomaterials that prevent biofilm formation and associated bacterial infection. In this work, we have synthesized and characterized hybrid poly(N-hydroxyethylacrylamide) (polyHEAA)/salicylate (SA) hydrogels with integrated antifouling and antimicrobial capacities. The antifouling efficacy of polyHEAA hydrogels was examined via exposure to proteins, cells, and bacteria, while the antimicrobial activity of SA-treated polyHEAA hydrogels was investigated against both gram-negative Escherichia coli RP437 and gram-positive Staphylococcus epidermidis. The results showed that polyHEAA/SA hydrogels exhibited high surface resistance to protein adsorption, cell adhesion, and bacteria attachment. The polyHEAA hydrogels were also characterized by their water content and state of water, revealing a strong ability to contain and retain high nonfreezable water content. This work demonstrates that the hybrid polyHEAA/SA hydrogels can be engineered to possess both antifouling and antimicrobial properties, which can be used for different in vitro and in vivo applications against bacterial infection.

  19. Protein crystallization in hydrogel beads.

    PubMed

    Willaert, Ronnie; Zegers, Ingrid; Wyns, Lode; Sleutel, Mike

    2005-09-01

    The use of hydrogel beads for the crystallization of proteins is explored in this contribution. The dynamic behaviour of the internal precipitant, protein concentration and relative supersaturation in a gel bead upon submerging the bead in a precipitant solution is characterized theoretically using a transient diffusion model. Agarose and calcium alginate beads have been used for the crystallization of a low-molecular-weight (14.4 kDa, hen egg-white lysozyme) and a high-molecular-weight (636.0 kDa, alcohol oxidase) protein. Entrapment of the protein in the agarose-gel matrix was accomplished using two methods. In the first method, a protein solution is mixed with the agarose sol solution. Gel beads are produced by immersing drops of the protein-agarose sol mixture in a cold paraffin solution. In the second method (which was used to produce calcium alginate and agarose beads), empty gel beads are first produced and subsequently filled with protein by diffusion from a bulk solution into the bead. This latter method has the advantage that a supplementary purification step is introduced (for protein aggregates and large impurities) owing to the diffusion process in the gel matrix. Increasing the precipitant, gel concentration and protein loading resulted in a larger number of crystals of smaller size. Consequently, agarose as well as alginate gels act as nucleation promoters. The supersaturation in a gel bead can be dynamically controlled by changing the precipitant and/or the protein concentration in the bulk solution. Manipulation of the supersaturation allowed the nucleation rate to be varied and led to the production of large crystals which were homogeneously distributed in the gel bead.

  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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

    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.

  2. 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

  3. 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

  4. 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.

  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.

  6. Promoting nerve cell functions on hydrogels grafted with poly(L-lysine).

    PubMed

    Cai, Lei; Lu, Jie; Sheen, Volney; Wang, Shanfeng

    2012-02-13

    We present a novel photopolymerizable poly(L-lysine) (PLL) and use it to modify polyethylene glycol diacrylate (PEGDA) hydrogels for creating a better, permissive nerve cell niche. Compared with their neutral counterparts, these PLL-grafted hydrogels greatly enhance pheochromocytoma (PC12) cell survival in encapsulation, proliferation, and neurite growth and also promote neural progenitor cell proliferation and differentiation capacity, represented by percentages of both differentiated neurons and astrocytes. The role of efficiently controlled substrate stiffness in regulating nerve cell behavior is also investigated and a polymerizable cationic small molecule, [2-(methacryloyloxy)ethyl]-trimethylammonium chloride (MTAC), is used to compare with this newly developed PLL. The results indicate that these PLL-grafted hydrogels are promising biomaterials for nerve repair and regeneration.

  7. A novel polyvinyl alcohol hydrogel functionalized with organic boundary lubricant for use as low-friction cartilage substitute: synthesis, physical/chemical, mechanical, and friction characterization.

    PubMed

    Blum, Michelle M; Ovaert, Timothy C

    2012-10-01

    A novel material design was developed by functionalizing polyvinyl alcohol hydrogel with an organic low-friction boundary lubricant (molar ratios of 0.2, 0.5, and 1.0 moles of lauroyl chloride). The hydrogels were fabricated using two different techniques. First, the boundary lubricant was initially functionalized to the polymer, then the hydrogels were created by physically crosslinking the reacted polymer. Second, hydrogels were initially created by crosslinking pure polyvinyl alcohol, with the functionalization reaction performed on the fully formed gel. After the reaction, Fourier transform infrared spectroscopy and attenuated total reflectance spectra revealed a clear ester peak, the diminishment of the alcohol peak, and the amplification of the alkyl peaks, which confirmed attachment of the hydrocarbon chains to the polymer. Additional chemical characterization occurred through elemental analysis where an average increase of 22% carbon and 40% hydrogen provided further confirmation of attachment. Physical characterization of the boundary lubricant functionalized hydrogels was performed by water content and contact angle measurements. Water content dependency showed that method 1 had a direct relationship with boundary lubricant concentration, and method 2 displayed an inverse relationship. The contact angle increased as boundary lubricant concentration increased for the pure matrix material for both processing methods, suggesting that the hydrocarbons produced surface properties that mimic natural cartilage, and contact behavior of the biphasic system was dependent on processing method. Friction tests demonstrated a significant decrease in friction coefficient, with a maximum decrease of 70% and a minimum decrease of 24% for boundary lubricant functionalized hydrogels compared with nonfunctionalized polyvinyl alcohol hydrogels.

  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. An agarose gel-based neurosphere culture system leads to enrichment of neuronal lineage cells in vitro.

    PubMed

    Park, Kyuhee; Nam, Yeonju; Choi, Yongmun

    2015-05-01

    Stem cell-based therapy holds great potential especially for neurological disorders. However, clinical applications await further understanding of many aspects of stem cell differentiation and development of technology enabling manipulation of stem cells into desired cell types in the central nervous system. Here, we developed a new method that leads to enrichment of neuronal lineage cells in neural stem cell cultures. The protocol involves cultivation of primary cells derived from the forebrains of rat E18 embryos above a layer of nonadhesive hard agarose gel in the form of neurospheres. In contrast to the neurospheres that were cultured above an anti-adhesive hydrogel layer, the primary cells that were cultured above a layer of agarose gel preferentially differentiated into β-III tubulin-positive neurons when allowed to undergo differentiation in vitro.In an effort to investigate the mechanism behind this observation, we found that the gene expression of a vertebrate neuronal determination gene (neurogenin1) was enhanced in the neurospheres that proliferated above a layer of agarose gel as compared with the control, and the gene expression level of neurogenin1 was quite well correlated with the rigidity of agarose gel. These results indicate that agarose gel can contribute, at least in part, to enrich neuronal progenitors and immature postmitotic neurons during neurosphere formation and may provide additional information to establish efficient protocols for the neural stem cell-based study.

  10. 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.

  11. 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

  12. 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

  13. Dynamic Compression of Chondrocyte-Agarose Constructs Reveals New Candidate Mechanosensitive Genes

    PubMed Central

    Bougault, Carole; Aubert-Foucher, Elisabeth; Paumier, Anne; Perrier-Groult, Emeline; Huot, Ludovic; Hot, David; Duterque-Coquillaud, Martine; Mallein-Gerin, Frédéric

    2012-01-01

    Articular cartilage is physiologically exposed to repeated loads. The mechanical properties of cartilage are due to its extracellular matrix, and homeostasis is maintained by the sole cell type found in cartilage, the chondrocyte. Although mechanical forces clearly control the functions of articular chondrocytes, the biochemical pathways that mediate cellular responses to mechanical stress have not been fully characterised. The aim of our study was to examine early molecular events triggered by dynamic compression in chondrocytes. We used an experimental system consisting of primary mouse chondrocytes embedded within an agarose hydrogel; embedded cells were pre-cultured for one week and subjected to short-term compression experiments. Using Western blots, we demonstrated that chondrocytes maintain a differentiated phenotype in this model system and reproduce typical chondrocyte-cartilage matrix interactions. We investigated the impact of dynamic compression on the phosphorylation state of signalling molecules and genome-wide gene expression. After 15 min of dynamic compression, we observed transient activation of ERK1/2 and p38 (members of the mitogen-activated protein kinase (MAPK) pathways) and Smad2/3 (members of the canonical transforming growth factor (TGF)-β pathways). A microarray analysis performed on chondrocytes compressed for 30 min revealed that only 20 transcripts were modulated more than 2-fold. A less conservative list of 325 modulated genes included genes related to the MAPK and TGF-β pathways and/or known to be mechanosensitive in other biological contexts. Of these candidate mechanosensitive genes, 85% were down-regulated. Down-regulation may therefore represent a general control mechanism for a rapid response to dynamic compression. Furthermore, modulation of transcripts corresponding to different aspects of cellular physiology was observed, such as non-coding RNAs or primary cilium. This study provides new insight into how chondrocytes respond

  14. 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.

  15. 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

  16. Agarose-assisted micro-contact printing for high-quality biomolecular micro-patterns.

    PubMed

    Jang, Min Jee; Nam, Yoonkey

    2015-05-01

    Micro-contact printing has been developed to print biomolecules, such as cell adhesive molecules, proteins, or DNAs, on a substrate, which can serve as experimental platforms for investigating biological issues and engineering biosensors. Despite the popularity of this method, it has been technically challenging to use a conventional stamp made of a hydrophobic polydimethoxysilane (PDMS) elastomer that often requires surface treatments to facilitate the inking and stamping of biomolecules. In this work, we proposed a new surface modification method for a PDMS stamp using agarose hydrogel and demonstrated the applications to the design of micro-patterned substrates with biomolecules. By using a simple bench-top dip-coating method with a commercial syringe pump to steadily pull out the stamp from boiled agarose solution, we coated an agarose layer on the stamp. It consequentially enhanced the transferability of ink molecules to the target substrate and the uniformity of printed patterns compared to the traditional methods for treating stamp surface such as surfactant coating and temporary oxidation with air plasma. In addition, this microstamping method was also used to produce patterns of proteins with the preservation of bioactivity, which could guide neuronal growth. Thus, we demonstrated the applicability to the interface designs of biochips and biosensors.

  17. Fabrication of micropatterned hydrogels for neural culture systems using dynamic mask projection photolithography.

    PubMed

    Curley, J Lowry; Jennings, Scott R; Moore, Michael J

    2011-01-01

    Increasingly, patterned cell culture environments are becoming a relevant technique to study cellular characteristics, and many researchers believe in the need for 3D environments to represent in vitro experiments which better mimic in vivo qualities. Studies in fields such as cancer research, neural engineering, cardiac physiology, and cell-matrix interaction have shown cell behavior differs substantially between traditional monolayer cultures and 3D constructs. Hydrogels are used as 3D environments because of their variety, versatility and ability to tailor molecular composition through functionalization. Numerous techniques exist for creation of constructs as cell-supportive matrices, including electrospinning, elastomer stamps, inkjet printing, additive photopatterning, static photomask projection-lithography, and dynamic mask microstereolithography. Unfortunately, these methods involve multiple production steps and/or equipment not readily adaptable to conventional cell and tissue culture methods. The technique employed in this protocol adapts the latter two methods, using a digital micromirror device (DMD) to create dynamic photomasks for crosslinking geometrically specific poly-(ethylene glycol) (PEG) hydrogels, induced through UV initiated free radical polymerization. The resulting "2.5D" structures provide a constrained 3D environment for neural growth. We employ a dual-hydrogel approach, where PEG serves as a cell-restrictive region supplying structure to an otherwise shapeless but cell-permissive self-assembling gel made from either Puramatrix or agarose. The process is a quick simple one step fabrication which is highly reproducible and easily adapted for use with conventional cell culture methods and substrates. Whole tissue explants, such as embryonic dorsal root ganglia (DRG), can be incorporated into the dual hydrogel constructs for experimental assays such as neurite outgrowth. Additionally, dissociated cells can be encapsulated in the

  18. 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

  19. Tissue Engineered, Hydrogel-Based Endothelial Progenitor Cell Therapy Robustly Revascularizes Ischemic Myocardium and Preserves Ventricular Function

    PubMed Central

    Atluri, Pavan; Miller, Jordan S; Emery, Robert J; Hung, George; Trubelja, Alen; Cohen, Jeffrey E; Lloyd, Kelsey; Han, Jason; Gaffey, Ann C; MacArthur, John W; Chen, Christopher S; Woo, Y Joseph

    2014-01-01

    Objective Cell based angiogenic therapy for ischemic heart failure has had limited clinical impact, likely related to very low cell retention (<1%) and dispersion. We developed a novel, tissue engineered, hydrogel based cell delivery strategy to overcome these limitations and provide prolonged regional retention of myocardial endothelial progenitor cells (EPC) at high cell dosage. Methods EPCs were isolated from Wistar Rats and encapsulated in fibrin gels. In vitro viability was quantified using a fluorescent live-dead stain of transgenic eGFP+ EPCs. EPC-laden constructs were implanted onto ischemic rat myocardium in a model of acute myocardial infarction (LAD ligation) for 4 weeks. Intramyocardial cell injection (IC, 2×106 EPCs), empty fibrin, and isolated LAD ligation groups served as controls. Hemodynamics were quantified using echocardiography, Doppler flow analysis, and intraventricular pressure-volume analysis. Vasculogenesis and ventricular geometry were quantified. EPC migration was analyzed by utilizing EPCs from transgenic eGFP+ rodents. Results EPCs demonstrated an overall 88.7% viability for all matrix and cell conditions investigated after 48 hours. Histologic assessment of 1-wk implants demonstrated significant migration of transgenic eGFP+ EPCs from the fibrin matrix to the infarcted myocardium as compared to IC (28±12.3 vs. 2.4±2.1cells/hpf, p=0.0001). We also observed a marked increase in vasculogenesis at the implant site. Significant improvements in ventricular hemodynamics and geometry were present following EPC-hydrogel therapy as compared to control. Conclusion We present a tissue engineered hydrogel-based EPC mediated therapy to enhance cell delivery, cell retention, vasculogenesis, and preservation of myocardial structure and function. PMID:25129603

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Hindered diffusion in agarose gels: test of effective medium model.

    PubMed Central

    Johnson, E M; Berk, D A; Jain, R K; Deen, W M

    1996-01-01

    The diffusivities of uncharged macromolecules in gels (D) are typically lower than in free solution (D infinity), because of a combination of hydrodynamic and steric factors. To examine these factors, we measured D and D infinity for dilute solutions of several fluorescein-labeled macromolecules, using an image-based fluorescence recovery after photobleaching technique. Test macromolecules with Stokes-Einstein radii (rs) of 2.1-6.2 nm, including three globular proteins (bovine serum albumin, ovalbumin, lactalbumin) and four narrow fractions of Ficoll, were studied in agarose gels with agarose volume fractions (phi) of 0.038-0.073. The gels were characterized by measuring the hydraulic permeability of supported agarose membranes, allowing calculation of the Darcy permeability (kappa) for each gel sample. It was found that kappa, which is a measure of the intrinsic hydraulic conductance of the gel, decreased by an order of magnitude as phi was increased over the range indicated. The diffusivity ratio D/D infinity, which varied from 0.20 to 0.63, decreased with increases in rs or phi. Thus as expected, diffusional hindrances were the most severe for large macromolecules and/or relatively concentrated gels. According to a recently proposed theory for hindered diffusion through fibrous media, the diffusivity ratio is given by the product of a hydrodynamic factor (F) and a steric factor (S). The functional form is D/D infinity = F(rs/k1/2) S(f), where f = [(rs+rf)/rf]2 phi and rf is the fiber radius. Values of D/D infinity calculated from this effective medium theory, without use of adjustable parameters, were in much better agreement with the measured values than were predictions based on other approaches. The strengths and limitations of the effective medium theory for predicting diffusivities in gels are discussed. PMID:8789119

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. Neovascularization within porous PEG hydrogels

    NASA Astrophysics Data System (ADS)

    Chiu, Yu-Chieh

    The goal of this work described was to develop techniques that can be used to enhance vascularized tissue formation in PEG-based hydrogels. In the first part of the study a technique was developed to generate porous PEG hydrogels using a salt leaching technique. This technique was then used to examine the role of pore size on vascularization and tissue remodeling in porous PEG hydrogel in vitro and in vitro. Both in vitro and in vivo studies showed that vessel invasion was pore size dependent. In addition, a thin layer of inflammatory tissue was observed between PEG hydrogel and blood vessels that formed within the gels. The porous PEG hydrogels were very stable in vitro and in vivo and did not exhibit any signs of degradation. Hydrogels used in tissue engineering need to exhibit controlled degradation. In order to address the stability of PEG hydrogels, porous hydrogels were rendered using degradable PEG-co-(L-Lactic acid) diacrylate PEG-PLLA-DA. This polymer is degraded via hydrolysis of the PLLA chains. The hydrogels were found to exhibit autofluorescence that allowed for the unique ability to nondestructively image hydrogel structure under fully swelled conditions using confocal microscopy. Interestingly, pore size remained stable though out the study, and was not a function of degradation. In addition, degradation time of porous PEG-LLA-DA hydrogels was influenced by polymer concentration. Compressive modulus was a function of polymer concentration and pore size and decreased during hydrogel degradation. The incorporation of cell adhesion sequences into the hydrogel showed that they can support cell adhesion with morphology varying with pore size. This technique could be used to tailor porous biodegradable scaffolds for tissue engineering applications. In the final portion of this thesis a poly-lysine (PLL) molecule was synthesized in order to allow clustering of adhesion sequences in PEG hydrogels. Clusters of peptide sequences have been shown to enhance cell

  12. 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.

  13. Microstructured polyacrylamide hydrogels made with hydrophobic nanoparticles.

    PubMed

    Nuño-Donlucas, S M; Sánchez-Díaz, J C; Rabelero, M; Cortés-Ortega, J; Luhrs-Olmos, C C; Fernández-Escamilla, V V; Mendizábal, E; Puig, J E

    2004-02-01

    Poly(methyl methacrylate) nanosize particles, made by microemulsion polymerization, were dispersed in an acrylamide aqueous solution, which was polymerized in the presence of a cross-linking agent to yield microstructured hydrogels. The kinetics of swelling and the mechanical properties of these hydrogels were investigated as a function of concentration of particles. The microstructured hydrogels exhibit higher equilibrium swelling and larger Young modulus than conventional (that is, without particles) polyacrylamide hydrogel. The morphology of the microstructured hydrogels was examined by transmission electron microscopy.

  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. Self-assembled rosette nanotubes and poly(2-hydroxyethyl methacrylate) hydrogels promote skin cell functions.

    PubMed

    Sun, Linlin; Li, Dongni; Hemraz, Usha D; Fenniri, Hicham; Webster, Thomas J

    2014-10-01

    The next generation skin of wound healing materials should stimulate skin regeneration by actively promoting appropriate cellular adhesion and proliferation. As materials with novel self-assembling and solidification properties when transitioning from room to body temperatures, rosette nanotubes (RNTs) may be such a proactive material. RNTs resemble naturally occurring nanostructures in the skin (such as collagen and keratin) assembling with noncovalent forces in physiological environments. Presenting desirable bioactive properties, RNTs have been used for various tissue engineering applications including increasing in vivo bone and cartilage regeneration. The objective of the current in vitro study was, for the first time, to improve properties of a commonly used hydrogel (poly(2-hydroxyethyl methacrylate) or pHEMA) for skin regeneration by incorporating one type of novel self-assembled RNTs, called TBL. Results showed for the first time increased keratinocyte and fibroblast proliferation on hydrogels coated with TBLs compared to those not coated with TBL. In this manner, this study provides the first evidence that TBL RNTs are promising for wound healing applications due to their optimal cytocompatibility, solidification, and mechanical properties and, thus, should be further studied for such applications.

  16. Antiseptic cyclodextrin-functionalized hydrogels and gauzes for loading and delivery of benzalkonium chloride.

    PubMed

    Garcia-Fernandez, Maria José; Brackman, Gilles; Coenye, Tom; Concheiro, Angel; Alvarez-Lorenzo, Carmen

    2013-01-01

    Prevention and management of wound infections receive a lot of attention, since the presence of micro-organisms interferes with the wound-healing process. The aim of this work was to use cyclodextrins (CDs) to endow hydrogels and gauzes with the ability to take up antiseptics and sustain their delivery for several hours. Benzalkonium chloride (BzCl) can form inclusion complexes with cross-linked CDs that regulate the release through an affinity-driven mechanism. Grafting of CDs to cotton gauzes using citric acid as the linker, at 190 °C and for 15 min, led to grafting yields of about 148%, much larger than those obtained at 180 °C or with shorter reaction times. Microbiological tests revealed that the BzCl-loaded networks can inhibit the growth of Staphylococcus epidermidis and Escherichia coli both on agar plates and in liquid medium. Furthermore, the antiseptic-loaded gauzes were able to inhibit biofilm formation by Staphylococcus aureus RN1HG pMV158GFP when applied in early stages of biofilm formation and could reduce the number of living cells in preformed biofilms grown in a chronic wound biofilm model. These findings highlight the role of CDs as main components of hydrogels and gauzes for the efficient delivery of antiseptics.

  17. 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

  18. Multilayer microfluidic PEGDA hydrogels.

    PubMed

    Cuchiara, Michael P; Allen, Alicia C B; Chen, Theodore M; Miller, Jordan S; West, Jennifer L

    2010-07-01

    Development of robust 3D tissue analogs in vitro is limited by passive, diffusional mass transport. Perfused microfluidic tissue engineering scaffolds hold the promise to improve mass transport limitations and promote the development of complex, metabolically dense, and clinically relevant tissues. We report a simple and robust multilayer replica molding technique in which poly(dimethylsiloxane) (PDMS) and poly(ethylene glycol) diacrylate (PEGDA) are serially replica molded to develop microfluidic PEGDA hydrogel networks embedded within independently fabricated PDMS housings. We demonstrate the ability to control solute-scaffold effective diffusivity as a function of solute molecular weight and hydrogel concentration. Within cell laden microfluidic hydrogels, we demonstrate increased cellular viability in perfused hydrogel systems compared to static controls. We observed a significant increase in cell viability at all time points greater than zero at distances up to 1 mm from the perfused channel. Knowledge of spatiotemporal mass transport and cell viability gradients provides useful engineering design parameters necessary to maximize overall scaffold viability and metabolic density. This work has applications in the development of hydrogels as in vitro diagnostics and ultimately as regenerative medicine based therapeutics.

  19. 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.

  20. 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

  1. Variably elastic hydrogel patterned via capillary action in microchannels.

    PubMed

    Dong, Rui; Jensen, Tor W; Engberg, Kristin; Nuzzo, Ralph G; Leckband, Deborah E

    2007-01-30

    Agarose hydrogels of varied elastic modulus can be patterned into 100-microm-wide channels with wall heights of 60 microm. After modifying the hydrogels with chloroacetic acid (acid gels), they are amenable to modification with amine-containing ligands using EDC-NHS chemistry. Using both rheometry and atomic force microscopy (AFM) nanoindentation measurements, the elastic modulus of unmodified hydrogels increases linearly from 3.6 +/- 0.5 kPa to 45.2 +/- 5.5 kPa for 0.5 to 2.0 wt/vol % hydrogel, respectively. The elastic modulus of acid gels is 2.2 +/- 0.3 kPa to 16.2 +/- 1.6 kPa for 0.5 to 2.0 wt/vol %, respectively. No further changes were measured after further modifying the acid gels with fibronectin. Confocal images of rhodamine-modified acid gels show that the optimal filling viscosity of the agarose solutions is between 1 and 4 cP. This new method of patterning allows for the creation of substrates that take advantage of both micron-scale patterns and variably elastic hydrogels.

  2. 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

  3. 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

  4. Hydrogel with chains functionalized with carboxyl groups as universal 3D platform in DNA biosensors.

    PubMed

    Kowalczyk, Agata; Fau, Michal; Karbarz, Marcin; Donten, Mikolaj; Stojek, Zbigniew; Nowicka, Anna M

    2014-04-15

    Application of hydrogel based on N-isopropylacrylamide with carboxyl groups grafted to the chains enabled the immobilization of DNA at an extent exceeding that for flat surfaces by at least one order of magnitude. The probe DNA strands in the 3D platform were fully available for the hybridization process. The examination of the gels containing different amounts of grafted carboxyl groups (1-10%) was done using quartz crystal microbalance, electrochemical impedance spectroscopy, chronoamperometry and ionic coupled plasma with laser ablation. The optimal carboxyl group content was determined to be 5%. A very good agreement of the data obtained with independent techniques on content of DNA in the gel was obtained. In comparison to the other methods of immobilization of DNA the new platform enabled complete removal of DNA after the measurements and analysis and, therefore, could be used many times. After a 10-fold exchange of the DNA-sensing layer the efficiency of hybridization and analytical signal did not change by more than 5%. The sensor response increased linearly with logarithm of concentration of target DNA in the range 1×10(-13)-1×10(-6) M. The obtained detection limit was circa 8×10(-13) M of target DNA in the sample which is a substantial improvement over the planar sensing layers. PMID:24287408

  5. 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

  6. Continuous superporous agarose beds for chromatography and electrophoresis.

    PubMed

    Gustavsson, P E; Larsson, P O

    1999-02-01

    Continuous agarose beds (monoliths) were prepared by casting agarose emulsions designed to generate superporous agarose. The gel structures obtained were transected by superpores (diameters could be varied in the range 20-200 microns) through which liquids could be pumped. The pore structure and the basic properties of the continuous gel were investigated by microscopy and size exclusion chromatography. The chromatographic behaviour was approximately the same as for beds packed with homogeneous agarose beads with a particle diameter equivalent to the distance between the superpores. In one application, the superporous continuous agarose bed was derivatized with a NAD+ analogue and used in the affinity purification of bovine lactate dehydrogenase from a crude extract. In another application, a new superporous composite gel material was prepared by adding hydroxyapatite particles to the agarose phase. The composite bed was used to separate a protein mixture by hydroxyapatite chromatography. In a third application, the continuous superporous agarose material was used as an electrophoresis gel. Here, a water-immiscible organic liquid was pumped through the superpores to dissipate the joule heat evolved, thus allowing high current densities.

  7. Hydrogels for Delivery of Bioactive Agents: A Historical Perspective

    PubMed Central

    Lee, Sang Cheon; Kwon, Il Keun; Park, Kinam

    2012-01-01

    Since 1960 when the history of modern hydrogels began significant progresses have been made in the field of controlled drug delivery. In particular, recent advances in the so-called smart hydrogels have made it possible to design highly sophisticated formulations, e.g., self-regulated drug delivery systems. Despite intensive efforts, clinical applications of smart hydrogels have been limited. Smart hydrogels need to be even smarter to execute functions necessary for achieving desired clinical functions. It is necessary to develop novel hydrogels that meet the requirements of the intended, specific applications, rather than finding applications of newly developed hydrogels. Furthermore, developing smarter hydrogels that can mimic natural systems is necessary, but the fundamental differences between natural and synthetic systems need to be understood. Such understanding will allow us to develop novel hydrogels with new, multiple functions we are looking for. PMID:22906864

  8. Fluorescence spectroscopy and confocal microscopy of the mycotoxin citrinin in condensed phase and hydrogel films.

    PubMed

    Lauer, Milena H; Gehlen, Marcelo H; de Jesus, Karen; Berlinck, Roberto G S

    2014-05-01

    The emission spectra, quantum yields and fluorescence lifetimes of citrinin in organic solvents and hydrogel films have been determined. Citrinin shows complex fluorescence decays due to the presence of two tautomers in solution and interconversion from excited-state double proton transfer (ESDPT) process. The fluorescence decay times associated with the two tautomers have values near 1 and 5 ns depending on the medium. In hydrogel films of agarose and alginate, fluorescence imaging showed that citrinin is not homogeneously dispersed and highly emissive micrometer spots may be formed. Fluorescence spectrum and decay analysis are used to recognize the presence of citrinin in hydrogel films using confocal fluorescence microscopy and spectroscopy.

  9. Evaluation of apparent fracture toughness of articular cartilage and hydrogels

    PubMed Central

    Xiao, Yinghua; Rennerfeldt, Deena A.; Friis, Elizabeth A.; Gehrke, Stevin H.; Detamore, Michael S.

    2014-01-01

    Recently, biomaterials-based tissue-engineering strategies, including the use of hydrogels, have offered great promise for repairing articular cartilage. Mechanical failure testing in outcome analyses is of crucial clinical importance to the success of engineered constructs. Interpenetrating networks (IPNs) are gaining more attention, due to their superior mechanical integrity. This study provided a combination testing method of apparent fracture toughness, which was applied to both articular cartilage and hydrogels. The apparent fracture toughnesses of two groups, hydrogels and articular cartilage, were evaluated based on the modified single-edge notch test and ASTM standards on the single-edge notch test and compact tension test. The results demonstrated that the toughness for articular cartilage (348 ± 43 MPa/mm½) was much higher than that for hydrogels. With a toughness value of 10.8 ± 1.4 MPa/mm½, IPNs of agarose and poly(ethylene glycol) diacrylate (PEG-DA) looked promising. The IPNs were 1.4 times tougher than PEG-DA alone, although still over an order of magnitude less tough than cartilage. A new method was developed to evaluate hydrogels and cartilage in a manner that enabled a more relevant direct comparison for fracture testing of hydrogels for cartilage tissue engineering. Moreover, a target toughness value for cartilage of using this direct comparison method has been identified (348 ± 43 MPa/mm½), and the toughness discrepancy to be overcome between hydrogels and cartilage has been quantified. PMID:24700577

  10. The functional behavior of a macrophage/fibroblast co-culture model derived from normal and diabetic mice with a marine gelatin-oxidized alginate hydrogel.

    PubMed

    Zeng, Qiong; Chen, Weiliam

    2010-08-01

    Tissues/cells-mediated biodegradable material degradation is epitomized by the constantly changing tissues/cell-implant interface, implicating the constant adaptation of the tissues/cells. Macrophages and fibroblasts are multi-functional cells highly involved in the interactions; the two cell types modulates the behaviors of each other, but their combinatorial functional behavior in the presence of interactive bioactive wound dressings has not been adequately examined. The activity is further complicated by the implantation of biodegradable materials, such as hydrogels commonly utilized as wound dressings, in a pathological environment and this is exemplified by the macrophages with a diabetic pathology producing an alternative cytokine profile which is implicated in wound healing delay. In this study, an in situ gelable formable/conformable hydrogel formulated from modified alginate and marine gelatin was used as a model biodegradable interactive wound dressing to elucidate the combinatorial behavior of macrophages/fibroblasts derived from both normal and diabetic hosts. Cell proliferation, migration and distribution were first characterized; this was followed by simultaneous quantitative detection of 40 inflammatory cytokines and chemokines by a protein microarray. The results showed that the macrophages/fibroblasts co-culture promoted fibroblasts proliferation and migration in the presence of the hydrogel; moreover, the expressions of inflammatory cytokines and chemokines were altered when compared with the corresponding fibroblasts or macrophages monocultures. The inflammatory cytokines patterns between the normal and diabetic hosts were considerably different.

  11. The functional behavior of a macrophage/fibroblast co-culture model derived from normal and diabetic mice with a marine gelatin-oxidized alginate hydrogel.

    PubMed

    Zeng, Qiong; Chen, Weiliam

    2010-08-01

    Tissues/cells-mediated biodegradable material degradation is epitomized by the constantly changing tissues/cell-implant interface, implicating the constant adaptation of the tissues/cells. Macrophages and fibroblasts are multi-functional cells highly involved in the interactions; the two cell types modulates the behaviors of each other, but their combinatorial functional behavior in the presence of interactive bioactive wound dressings has not been adequately examined. The activity is further complicated by the implantation of biodegradable materials, such as hydrogels commonly utilized as wound dressings, in a pathological environment and this is exemplified by the macrophages with a diabetic pathology producing an alternative cytokine profile which is implicated in wound healing delay. In this study, an in situ gelable formable/conformable hydrogel formulated from modified alginate and marine gelatin was used as a model biodegradable interactive wound dressing to elucidate the combinatorial behavior of macrophages/fibroblasts derived from both normal and diabetic hosts. Cell proliferation, migration and distribution were first characterized; this was followed by simultaneous quantitative detection of 40 inflammatory cytokines and chemokines by a protein microarray. The results showed that the macrophages/fibroblasts co-culture promoted fibroblasts proliferation and migration in the presence of the hydrogel; moreover, the expressions of inflammatory cytokines and chemokines were altered when compared with the corresponding fibroblasts or macrophages monocultures. The inflammatory cytokines patterns between the normal and diabetic hosts were considerably different. PMID:20452666

  12. The Functional Behavior of a Macrophage/Fibroblast Co-culture Model Derived from Normal and Diabetic Mice with a Marine Gelatin - Oxidized Alginate Hydrogel

    PubMed Central

    Zeng, Qiong; Chen, Weiliam

    2010-01-01

    Tissues/cells-mediated biodegradable material degradation is epitomized by the constantly changing tissues/cell-implant interface, implicating the constant adaptation of the tissues/cells. Macrophages and fibroblasts are multi-functional cells highly involved in the interactions; the two cell types modulates the behaviors of each other, but their combinatorial functional behavior in the presence of interactive bioactive wound dressings has not been adequately examined. The activity is further complicated by the implantation of biodegradable materials, such as hydrogels commonly utilized as wound dressings, in a pathological environment and this is exemplified by the macrophages with a diabetic pathology producing an alternative cytokine profile which is implicated in wound healing delay. In this study, an in situ gelable formable/conformable hydrogel formulated from modified alginate and marine gelatin was used as a model biodegradable interactive wound dressing to elucidate the combinatorial behavior of macrophages/fibroblasts derived from both normal and diabetic hosts. Cell proliferation, migration and distribution were first characterized; this was followed by simultaneous quantitative detection of 40 inflammatory cytokines and chemokines by a protein microarray. The results showed that the macrophages/fibroblasts co-culture promoted fibroblasts proliferation and migration in the presence of the hydrogel; moreover, the expressions of inflammatory cytokines and chemokines were altered when compared with the corresponding fibroblasts or macrophages monocultures. The inflammatory cytokines patterns between the normal and diabetic hosts were considerably different. PMID:20452666

  13. Pericellular hydrogel/nanonets inhibit cancer cells.

    PubMed

    Kuang, Yi; Shi, Junfeng; Li, Jie; Yuan, Dan; Alberti, Kyle A; Xu, Qiaobing; Xu, Bing

    2014-07-28

    Fibrils formed by proteins are vital components for cells. However, selective formation of xenogenous nanofibrils of small molecules on mammalian cells has yet to be observed. Here we report an unexpected observation of hydrogel/nanonets of a small D-peptide derivative in pericellular space. Surface and secretory phosphatases dephosphorylate a precursor of a hydrogelator to trigger the self-assembly of the hydrogelator and to result in pericellular hydrogel/nanonets selectively around the cancer cells that overexpress phosphatases. Cell-based assays confirm that the pericellular hydrogel/nanonets block cellular mass exchange to induce apoptosis of cancer cells, including multidrug-resistance (MDR) cancer cells, MES-SA/Dx5. Pericellular hydrogel/nanonets of small molecules to exhibit distinct functions illustrates a fundamentally new way to engineer molecular assemblies spatiotemporally in cellular microenvironment for inhibiting cancer cell growth and even metastasis.

  14. Shock Absorbing Function Study on Denucleated Intervertebral Disc with or without Hydrogel Injection through Static and Dynamic Biomechanical Tests In Vitro

    PubMed Central

    Zhou, Zhiyu; Wei, Fuxin; Liang, Jiabi; Deng, Wenbin; Dai, Xuejun; Zhou, Guangqian

    2014-01-01

    Hydrogel injection has been recently proposed as a novel therapy for disc degenerative diseases, with the potential to restore the spine motion and the intervertebral disc height. However, it remains unknown whether the new technique could also maintain the shock absorbing property of the treated intervertebral disc. In this study, 18 porcine lumbar bone-disc-bone specimens were collected and randomly divided into three groups: the normal with intact intervertebral discs, the mimic for the injection of disulfide cross-linked hyaluronan hydrogels following discectomy, and the control disc with discectomy only. In the static compression test, specimens in the mimic group exhibited displacements similar to those in the normal discs, whereas the control group showed a significantly larger displacement range in the first two steps (P < 0.05). With the frequency increasing, all specimens generally displayed an increasing storage modulus, decreasing loss modulus, and tanδ. At any frequency point, the control group exhibited the largest value in all the three parameters among three groups while the normal group was the lowest, with the mimic group being mostly close to the normal group. Therefore, the hydrogel injection into the intervertebral discs greatly restored their shock absorbing function, suggesting that the technique could serve as an effective approach to maintaining biomechanical properties of the degenerative intervertebral disc. PMID:25045680

  15. 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.

  16. Enzyme-sensing chitosan hydrogels.

    PubMed

    Sadat Ebrahimi, Mir Morteza; Schönherr, Holger

    2014-07-01

    We report on a chitosan hydrogel-based platform for the detection of enzymes, which is compatible with the implementation in infection-sensing wound dressings. Thin films of the established wound dressing biopolymer chitosan were functionalized with a fluorogenic substrate, which is released upon enzymatic degradation, resulting in a pronounced increase in fluorescence emission intensity. In this first model study, the fluorogenic substrate alanyl-alanyl-phenylalanine-7-amido-4-methylcoumarin (AAP-AMC) was covalently conjugated via amide bond formation to chitosan and was shown to facilitate the detection of the serine protease α-chymotrypsin. Systematic investigations established the dependence of hydrogel thickness and substrate loading on the hydrogel preparation conditions, as well as the dependence of the rate of the reaction on the initial enzyme concentration and the loading of AAP-AMC in the hydrogel. The initial release rate of the fluorophore 7-AMC was found to be linear with enzyme concentration and substrate loading and was independent of hydrogel thickness. Under optimized conditions the hydrogel reports the presence of α-chymotrypsin in <5 min with a limit of detection of ≤10 nM. This generic approach, which can be adapted to detect different kinds of enzymes by using appropriate fluorogenic or chromogenic substrates, is highly interesting for targeting the detection of specific pathogenic bacteria, e.g., in wound dressings. PMID:24914451

  17. 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.

  18. 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

  19. Gelatin Hydrogel Enhances the Engraftment of Transplanted Cardiomyocytes and Angiogenesis to Ameliorate Cardiac Function after Myocardial Infarction.

    PubMed

    Nakajima, Kazuaki; Fujita, Jun; Matsui, Makoto; Tohyama, Shugo; Tamura, Noriko; Kanazawa, Hideaki; Seki, Tomohisa; Kishino, Yoshikazu; Hirano, Akinori; Okada, Marina; Tabei, Ryota; Sano, Motoaki; Goto, Shinya; Tabata, Yasuhiko; Fukuda, Keiichi

    2015-01-01

    Cell transplantation therapy will mean a breakthrough in resolving the donor shortage in cardiac transplantation. Cardiomyocyte (CM) transplantation, however, has been relatively inefficient in restoring cardiac function after myocardial infarction (MI) due to low engraftment of transplanted CM. In order to ameliorate engraftment of CM, the novel transplantation strategy must be invented. Gelatin hydrogel (GH) is a biodegradable water-soluble polymer gel. Gelatin is made of collagen. Although we observed that collagen strongly induced the aggregation of platelets to potentially cause coronary microembolization, GH did not enhance thrombogenicity. Therefore, GH is a suitable biomaterial in the cell therapy after heart failure. To assess the effect of GH on the improvement of cardiac function, fetal rat CM (5×10(6) or 1x10(6) cells) were transplanted with GH (10 mg/ml) to infarcted hearts. We compared this group with sham operated rats, CM in phosphate buffered saline (PBS), only PBS, and only GH-transplanted groups. Three weeks after transplantation, cardiac function was evaluated by echocardiography. The echocardiography confirmed that transplantation of 5×10(6) CM with GH significantly improved cardiac systolic function, compared with the CM+PBS group (fractional area change: 75.1±3.4% vs. 60.7±5.9%, p<0.05), only PBS, and only GH groups (60.1±6.5%, 65.0±2.8%, p<0.05). Pathological analyses demonstrated that in the CM+GH group, CM were efficiently engrafted in infarcted myocardium (p<0.01) and angiogenesis was significantly enhanced (p<0.05) in both central and peripheral areas of the scar. Moreover, quantitative RT-PCR revealed that angiogenic cytokines, such as basic fibroblast growth factor, vascular endothelial growth factor, and hepatocyte growth factor, were significantly enriched in the CM+GH group (p<0.05). Here, we report that GH confined the CM effectively in infarcted myocardium after transplantation, and that CM transplanted with GH improved

  20. Gelatin Hydrogel Enhances the Engraftment of Transplanted Cardiomyocytes and Angiogenesis to Ameliorate Cardiac Function after Myocardial Infarction

    PubMed Central

    Nakajima, Kazuaki; Fujita, Jun; Matsui, Makoto; Tohyama, Shugo; Tamura, Noriko; Kanazawa, Hideaki; Seki, Tomohisa; Kishino, Yoshikazu; Hirano, Akinori; Okada, Marina; Tabei, Ryota; Sano, Motoaki; Goto, Shinya; Tabata, Yasuhiko; Fukuda, Keiichi

    2015-01-01

    Cell transplantation therapy will mean a breakthrough in resolving the donor shortage in cardiac transplantation. Cardiomyocyte (CM) transplantation, however, has been relatively inefficient in restoring cardiac function after myocardial infarction (MI) due to low engraftment of transplanted CM. In order to ameliorate engraftment of CM, the novel transplantation strategy must be invented. Gelatin hydrogel (GH) is a biodegradable water-soluble polymer gel. Gelatin is made of collagen. Although we observed that collagen strongly induced the aggregation of platelets to potentially cause coronary microembolization, GH did not enhance thrombogenicity. Therefore, GH is a suitable biomaterial in the cell therapy after heart failure. To assess the effect of GH on the improvement of cardiac function, fetal rat CM (5×106 or 1x106 cells) were transplanted with GH (10 mg/ml) to infarcted hearts. We compared this group with sham operated rats, CM in phosphate buffered saline (PBS), only PBS, and only GH-transplanted groups. Three weeks after transplantation, cardiac function was evaluated by echocardiography. The echocardiography confirmed that transplantation of 5×106 CM with GH significantly improved cardiac systolic function, compared with the CM+PBS group (fractional area change: 75.1±3.4% vs. 60.7±5.9%, p<0.05), only PBS, and only GH groups (60.1±6.5%, 65.0±2.8%, p<0.05). Pathological analyses demonstrated that in the CM+GH group, CM were efficiently engrafted in infarcted myocardium (p<0.01) and angiogenesis was significantly enhanced (p<0.05) in both central and peripheral areas of the scar. Moreover, quantitative RT-PCR revealed that angiogenic cytokines, such as basic fibroblast growth factor, vascular endothelial growth factor, and hepatocyte growth factor, were significantly enriched in the CM+GH group (p<0.05). Here, we report that GH confined the CM effectively in infarcted myocardium after transplantation, and that CM transplanted with GH improved cardiac

  1. 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

  2. Fewer Bacteria Adhere to Softer Hydrogels.

    PubMed

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

    2015-09-01

    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 20 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 h 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 h incubation period, there were 52 and 82% fewer 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 h incubation on the soft versus intermediate and stiff PEGDMA hydrogels. We suggest that hydrogel stiffness is an easily tunable variable that could potentially be used synergistically with traditional antimicrobial strategies to reduce early bacterial adhesion and therefore the occurrence of biofilm-associated infections.

  3. 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

  4. A facile one-step approach to functionalized graphene oxide-based hydrogels used as effective adsorbents toward anionic dyes

    NASA Astrophysics Data System (ADS)

    Wang, Xinpeng; Liu, Zhiming; Ye, Xiangping; Hu, Kun; Zhong, Huiqing; Yu, Jianfeng; Jin, Mei; Guo, Zhouyi

    2014-07-01

    Herein, we used a facile method mainly through self-assemble, hydrogen bonding and electrostatic interaction to synthesize poly(diallyldimethylammonium chloride)/graphene oxide (PDDA/GO) hydrogels, which can be easily used as adsorbents to eliminate anionic dyes. The as-prepared PDDA/GO hydrogels were characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopy. In order to research the adsorption kinetics for the removal of anion dyes from water pollution, we further investigated that the effect of concentration, temperature, pH, ionic strength or cycle number on the removal process. The results indicated that due to the strong π-π stacking and anion-cation interaction, there were high removal efficiencies for both ponceau S (PS) and trypan blue (TB). The equilibrium time of adsorption is 30 min and 120 min for PS and TB, respectively, at which the solution could be decolorized to nearly colorless. Meanwhile, the adsorption process was more according with the pseudo-second-order model than the pseudo-first-order model. The hydrogels exhibited high removal efficiency for those two anionic dyes after four repeated adsorption and desorption treatments. It was demonstrated that PDDA/GO hydrogels would have great potential as a freestanding and reusable adsorbent for the practical application in water purification.

  5. Superporous agarose beads as a hydrophobic interaction chromatography support.

    PubMed

    Gustavsson, P E; Axelsson, A; Larsson, P O

    1999-01-15

    Superporous agarose beads were used as a support for hydrophobic interaction chromatography. These beads have large connecting flow pores in addition to their normal diffusion pores. The flow pores, which are approximately one fifth of the overall diameter of the superporous agarose beads, were earlier shown to give the beads improved mass transfer properties relative to homogeneous agarose beads (Gustavsson and Larsson, J. Chromatogr. A, 734 (1996) 231-240). Superporous agarose beads and homogeneous agarose beads of the same particle size range (106-180 microns) were derivatized with phenyl groups. The properties of the superporous beads were then compared with the homogeneous beads in the separation of a mixture of three model proteins (ribonuclease A, lysozyme and bovine serum albumin) at various superficial flow velocities from 30 to 600 cm/h. The superporous beads gave satisfactory separation at flow velocities five times higher than was possible for homogeneous beads. The performance of the two types of beads was also compared in the purification of lactate dehydrogenase from a beef heart extract at a superficial flow velocity of 150 cm/h. The superporous beads performed considerably better, leading to twice the purification factor and twice the concentration of the desired product. The results were interpreted using the theoretical treatment given by Carta and Rodrigues (Carta and Rodrigues, Chem. Eng. Sci., 48 (1993) 3927).

  6. 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

  7. An Injectable, Self-Healing Hydrogel to Repair the Central Nervous System.

    PubMed

    Tseng, Ting-Chen; Tao, Lei; Hsieh, Fu-Yu; Wei, Yen; Chiu, Ing-Ming; Hsu, Shan-hui

    2015-06-17

    An injectable, self-healing hydrogel (≈1.5 kPa) is developed for healing nerve-system deficits. Neurosphere-like progenitors proliferate in the hydrogel and differentiate into neuron-like cells. In the zebrafish injury model, the central nervous system function is partially rescued by injection of the hydrogel and significantly rescued by injection of the neurosphere-laden hydrogel. The self-healing hydrogel may thus potentially repair the central nervous system.

  8. Stable environmentally sensitive cationic hydrogels for controlled delivery applications.

    PubMed

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

    2010-01-01

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

  9. 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.

  10. 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

  11. Monolithic cryogels made of agarose-chitosan composite and loaded with agarose beads for purification of immunoglobulin G.

    PubMed

    Sun, Sijuan; Tang, Yuhai; Fu, Qiang; Liu, Xuan; Guo, Li'an; Zhao, Yanding; Chang, Chun

    2012-05-01

    In order to obtain a novel absorbent with high adsorption capacity for the purification of immunoglobulin G (IgG), continuous supermacroporous agarose beads embedded agarose-chitosan composite monolithic cryogels (agarose-chitosan cryogels) were prepared by cryo-copolymerization of agarose-chitosan blend solutions with glutaraldehyde as the crosslinker in the presence of agarose beads. After coupling 2-mercaptopyridine onto divinylsulfone-activated matrix, the obtained cryogels were used for the purification of IgG. The microstructure morphologies of the cryogels were analyzed by scanning electron microscopy. The results showed that the obtained cryogels possess interconnected pores of 10-100 μm size. The specific surface area was 350 m(2)/g with maximum adsorption capacity of IgG 71.4 mg/g. The cryogels showed workable stability, and can be reused at least 15 times without significant loss in adsorption capacity. IgG purity after one-step purification from human plasma was monitored by electrophoresis and the average recovery was estimated to be 90%.

  12. Hydrogels dispersed by doped rare earth fluoride nanocrystals: ionic liquid dispersion and down/up-conversion luminescence.

    PubMed

    Yan, Zhi-Yuan; Jia, Li-Ping; Yan, Bing

    2014-01-01

    Two typical kinds of rare earth fluoride nanocrystals codoped with rare earth ions (Eu(3+) and Tm(3+)/Er(3+),Yb(3+)) are synthesized and dispersed in ionic liquid compound (1-chlorohexane-3-methylimidazolium chloride, abbreviated as [C6mim][Cl]). Assisted by agarose, the luminescent hydrogels are prepared homogeneously. The down/up-conversion luminescence of these hydrogels can be realized for the dispersed rare earth fluoride nanocrystals. The results provide a strategy to prepare luminescent (especially up-conversion luminescent) hydrogels with ionic liquid to disperse rare earth fluoride nanocrystals.

  13. Properties of cellulase immobilized on agarose gel with spacer

    SciTech Connect

    Chim-anage, P.; Kashiwagi, Y.; Magae, Y.; Ohta, T.; Sasaki, T.

    1986-12-01

    Cellulase produced by fungus Trichoderma viride was immobilized on agarose beads (Sepharose 4B) activated by cyanogen bromide and also on activated agarose beads that contained spacer arm (activated Ch-Sepharose 4B and Affi-Gel 15). The CMCase activity retained by immobilized cellulase on activated Sepharose containing the spacer tended to be higher than that immobilized without spacer, although the extent of protein immobilization was lower. Also, the higher substrate specificity for cellulase immobilized on beads with spacer was obtained for cellobiose, acid-swollen cellulose, or cellulose powder. The hydrolysis product from their substrates was mainly glucose. 10 references.

  14. 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

  15. 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.

  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. 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

  18. 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.

  19. Agarose coated spherical micro resonator for humidity measurements.

    PubMed

    Mallik, Arun Kumar; Liu, Dejun; Kavungal, Vishnu; Wu, Qiang; Farrell, Gerald; Semenova, Yuliya

    2016-09-19

    A new type of fiber optic relative humidity (RH) sensor based on an agarose coated silica microsphere resonator is proposed and experimentally demonstrated. Whispering gallery modes (WGMs) in the micro resonator are excited by evanescent coupling using a tapered fiber with ~3.3 µm waist diameter. A change in the relative humidity of the surrounding the resonator air induces changes in the refractive index (RI) and thickness of the Agarose coating layer. These changes in turn lead to a spectral shift of the WGM resonances, which can be related to the RH value after a suitable calibration. Studies of the repeatability, long-term stability, measurement accuracy and temperature dependence of the proposed sensor are carried out. The RH sensitivity of the proposed sensor depends on the concentration of the agarose gel which determines the initial thickness of the deposited coating layer. Studies of the micro- resonators with coating layers fabricated from gels with three different Agarose concentrations of 0.5%, 1.125% and 2.25 wt./vol.% showed that an increase in the initial thickness of the coating material results in an increase in sensitivity but also leads to a decrease of quality factor (Q) of the micro resonator. The highest sensitivity achieved in our experiments was 518 pm/%RH in the RH range from 30% to 70%. The proposed sensor offers the advantages of a very compact form factor, low hysteresis, good repeatability, and low cross sensitivity to temperature. PMID:27661866

  20. 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.

  1. 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

  2. Agarose gel investigation of quantum dots conjugated with short ssDNA.

    PubMed

    Wu, Tsai-Chin; Dutta, Mitra; Stroscio, Michael A

    2013-12-01

    Herein, we investigate the migration distance of quantum-dot-functionalized complexes in electrophoresis. The quantitative study of these moving particles in an electrophoretic environment is modeled using an extended Smoluchowski equation. An extended Smoluchowski equation is proposed to addressed the D(m) to Ln(N) plot slope variation issue present in previous work and agreement between experiment and theory is found. The procedures underlying this work then discusses the potential of using agarose electrophoresis as a mean of monitoring the composition of nano-complexes consisting of quantum dots functionalized with differing numbers of DNA molecules.

  3. 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

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

    PubMed

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

    2009-01-01

    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 Ca(2+). We found that human SAP binds to an agarose with a K(D) of 7 x 10(-8) M and a B(max) of 2.1 microg SAP/mg wet weight agarose. Mixing this agarose 1 : 5 w/v with 30 microg/mL human SAP (the average SAP concentration in normal serum) in a buffer containing 2 mM Ca(2+) reduced the free SAP concentration to approximately 0.02 microg/mL, well below the concentration that inhibits fibrocyte differentiation. Compared with a hydrogel dressing and a foam dressing, dressings containing this agarose and Ca(2+) significantly increased the speed of wound healing in partial thickness wounds in pigs. This suggests that agarose/Ca(2+) dressings may be beneficial for wound healing in humans. PMID:19660048

  5. 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

  6. 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.

  7. 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

  8. 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

  9. The synthesis and study of telechelic polyelectrolytes for hydrogel formation

    NASA Astrophysics Data System (ADS)

    Hunt, Jasmine N.

    Polymeric hydrogels comprised of oppositely charged ABA triblock copolymer polyelectrolytes based upon poly(allyl glycidyl ether-b-ethylene glycol-ballyl glycidyl ether), P(AGE-b-EG-b-AGE), with functionalized ionic 'A'-endblocks and a neutral, hydrophilic 'B'-block were synthesized. Aqueous solutions of poly-cations and -anions were mixed at room temperature, producing hydrogels through co-assembly driven by electrostatic interactions between the endblocks. Due the ease and modular nature of the synthesis and hydrogel formation, polymeric libraries differing in relative block lengths and ionic functionalization were created and the affects of polymer composition on the hydrogel's mechanical and structural properties were examined.

  10. 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.

  11. 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

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

    PubMed

    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. PMID:19433871

  13. 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.

  14. 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

  15. Environmentally Responsive Hydrogels

    NASA Astrophysics Data System (ADS)

    Schueneman, Susan M.; Chen, Wei

    2002-07-01

    A hydrogel experimental module was designed for an undergraduate upper-level laboratory course. Cross-linked poly(N-isopropylacrylamide) (PIPAM) is a thermo-sensitive hydrogel; it undergoes a volume collapse driven by hydrophobic interactions in pure water as the temperature increases to 32 °C. The extent and temperature of the volume transition are two critical parameters in its applications ranging from pharmaceutics to biotechnology and they can be controlled by incorporating ionic components in the PIPAM system. In this experiment, linear PIPAM, cross-linked neutral PIPAM gel, and cross-linked ionic PIPAM gel were prepared by radical polymerization. Viscosity, molecular weight, and thermal transition (cloud point) of linear PIPAM were determined. Volume collapses of the neutral and ionic PIPAM gels as a function of temperature were examined and compared. In this module, students were exposed to original literature and contemporary chemical research in polymer chemistry and they learned to integrate concepts from different disciplines of chemistry into a unified experimental approach to problem solving. This module could also be used for polymer chemistry or physical chemistry laboratory courses.

  16. 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

  17. Diffusivity of ions in agarose gels and intervertebral disc: effect of porosity.

    PubMed

    Gu, Wei Yong; Yao, Hai; Vega, Adriana L; Flagler, Daniel

    2004-12-01

    The effect of tissue porosity on ion (sodium, potassium, and chloride) diffusivity in agarose gels and porcine intervertebral disc tissues was investigated using an electrical conductivity method. An empirical, constitutive model for diffusivity (D) of solutes in porous fibrous media was proposed: D/Do = exp[-alpha(r(s)/k(1/2))beta] where r(s) is the Stokes radius of a solute, kappa is the Darcy permeability of the porous medium, Do is the diffusivity in free solution, alpha and beta are two positive parameters whose values depend on material structure. It is found that alpha = 1.25 +/- 0.138, beta = 0.681 +/- 0.059 (95% confidence interval, R2 = 0.92, n = 72) for agarose gels and alpha = 1.29 +/- 0.171 and beta = 0.372 +/- 0.088 (95% confidence interval, R2 = 0.88, n = 86) for porcine annulus fibrosus. The functional relationship between solute diffusivity and tissue deformation was derived. Comparisons of our model prediction with experimental data on diffusion coefficients of macromolecules (proteins, dextrans, polymer beads) in agarose gels in the literature were made. Our results were also compared to the data on ion diffusivity in charged gels and in cartilaginous tissues reported in the literature. There was a good agreement between our model prediction and the data in the literature. The present study provides additional information on solute diffusivity in uncharged gels and charged tissues, and is important for understanding nutritional transport in avascular cartilaginous tissues under different mechanical loading conditions.

  18. Low friction hydrogel for articular cartilage repair: evaluation of mechanical and tribological properties in comparison with natural cartilage tissue.

    PubMed

    Blum, Michelle M; Ovaert, Timothy C

    2013-10-01

    The mechanical and tribological properties of a novel biomaterial, a boundary lubricant functionalized hydrogel, were investigated and compared to natural cartilage tissue. This low friction hydrogel material was developed for use as a synthetic replacement for focal defects in articular cartilage. The hydrogel was made by functionalizing the biocompatible polymer polyvinyl alcohol with a carboxylic acid derivative boundary lubricant molecule. Two different gel processing techniques were used to create the hydrogels. The first method consisted of initially functionalizing the boundary lubricant to the polyvinyl alcohol and then creating hydrogels by physically crosslinking the reacted polymer. The second method consisted of creating non-functionalized polyvinyl alcohol hydrogels and then performing the functionalization reaction on the fully formed gel. Osteochondral bovine samples were collected and replicate experiments were conducted to compare the mechanical and tribological performance of the boundary lubricant functionalized hydrogels to non-functionalized hydrogels and native cartilage. Friction experiments displayed a maximum decrease in friction coefficient of 70% for the functionalized hydrogels compared to neat polyvinyl alcohol. Indentation investigated the elastic modulus of the hydrogels, demonstrating that stability of the hydrogel was affected by processing method. Hydrogel performance was within the lower ranges of natural cartilage tested under the exact same conditions, showing the potential of the boundary lubricant functionalized hydrogels to perform as a biomimetic synthetic articular cartilage replacement.

  19. 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

  20. An Efficient, Recyclable, and Stable Immobilized Biocatalyst Based on Bioinspired Microcapsules-in-Hydrogel Scaffolds.

    PubMed

    Zhang, Shaohua; Jiang, Zhongyi; Shi, Jiafu; Wang, Xueyan; Han, Pingping; Qian, Weilun

    2016-09-28

    Design and preparation of high-performance immobilized biocatalysts with exquisite structures and elucidation of their profound structure-performance relationship are highly desired for green and sustainable biotransformation processes. Learning from nature has been recognized as a shortcut to achieve such an impressive goal. Loose connective tissue, which is composed of hierarchically organized cells by extracellular matrix (ECM) and is recognized as an efficient catalytic system to ensure the ordered proceeding of metabolism, may offer an ideal prototype for preparing immobilized biocatalysts with high catalytic activity, recyclability, and stability. Inspired by the hierarchical structure of loose connective tissue, we prepared an immobilized biocatalyst enabled by microcapsules-in-hydrogel (MCH) scaffolds via biomimetic mineralization in agarose hydrogel. In brief, the in situ synthesized hybrid microcapsules encapsulated with glucose oxidase (GOD) are hierarchically organized by the fibrous framework of agarose hydrogel, where the fibers are intercalated into the capsule wall. The as-prepared immobilized biocatalyst shows structure-dependent catalytic performance. The porous hydrogel permits free diffusion of glucose molecules (diffusion coefficient: ∼6 × 10(-6) cm(2) s(-1), close to that in water) and retains the enzyme activity as much as possible after immobilization (initial reaction rate: 1.5 × 10(-2) mM min(-1)). The monolithic macroscale of agarose hydrogel facilitates the easy recycling of the immobilized biocatalyst (only by using tweezers), which contributes to the nonactivity decline during the recycling test. The fiber-intercalating structure elevates the mechanical stability of the in situ synthesized hybrid microcapsules, which inhibits the leaching and enhances the stability of the encapsulated GOD, achieving immobilization efficiency of ∼95%. This study will, therefore, provide a generic method for the hierarchical organization of (bio

  1. An Efficient, Recyclable, and Stable Immobilized Biocatalyst Based on Bioinspired Microcapsules-in-Hydrogel Scaffolds.

    PubMed

    Zhang, Shaohua; Jiang, Zhongyi; Shi, Jiafu; Wang, Xueyan; Han, Pingping; Qian, Weilun

    2016-09-28

    Design and preparation of high-performance immobilized biocatalysts with exquisite structures and elucidation of their profound structure-performance relationship are highly desired for green and sustainable biotransformation processes. Learning from nature has been recognized as a shortcut to achieve such an impressive goal. Loose connective tissue, which is composed of hierarchically organized cells by extracellular matrix (ECM) and is recognized as an efficient catalytic system to ensure the ordered proceeding of metabolism, may offer an ideal prototype for preparing immobilized biocatalysts with high catalytic activity, recyclability, and stability. Inspired by the hierarchical structure of loose connective tissue, we prepared an immobilized biocatalyst enabled by microcapsules-in-hydrogel (MCH) scaffolds via biomimetic mineralization in agarose hydrogel. In brief, the in situ synthesized hybrid microcapsules encapsulated with glucose oxidase (GOD) are hierarchically organized by the fibrous framework of agarose hydrogel, where the fibers are intercalated into the capsule wall. The as-prepared immobilized biocatalyst shows structure-dependent catalytic performance. The porous hydrogel permits free diffusion of glucose molecules (diffusion coefficient: ∼6 × 10(-6) cm(2) s(-1), close to that in water) and retains the enzyme activity as much as possible after immobilization (initial reaction rate: 1.5 × 10(-2) mM min(-1)). The monolithic macroscale of agarose hydrogel facilitates the easy recycling of the immobilized biocatalyst (only by using tweezers), which contributes to the nonactivity decline during the recycling test. The fiber-intercalating structure elevates the mechanical stability of the in situ synthesized hybrid microcapsules, which inhibits the leaching and enhances the stability of the encapsulated GOD, achieving immobilization efficiency of ∼95%. This study will, therefore, provide a generic method for the hierarchical organization of (bio

  2. In-gel expression and in situ immobilization of proteins for generation of three dimensional protein arrays in a hydrogel matrix.

    PubMed

    Byun, Ju-Young; Lee, Kyung-Ho; Lee, Ka-Young; Kim, Min-Gon; Kim, Dong-Myung

    2013-03-01

    A method has been developed for the direct conversion of DNA arrays into three dimensional protein arrays on a hydrogel matrix. An agarose gel embedded with bacterial protein synthesis machinery was used as the DNA-programmable expression gel matrix for the in situ translation of genes on a DNA array. Upon incubation of the expression gel matrix cast on a DNA array, protein synthesis took place at the interface of the two surfaces and the cell-free synthesized proteins were deposited on the gel matrix surrounding the corresponding DNA spots. Diffusional dilution of the expressed proteins was minimized by modifying the agarose with Ni-NTA moieties. This procedure resulted in the generation of localized protein spots with confined radii. The developed approach not only simplifies the procedures typically used for the preparation of protein arrays but it also provides conditions for the loading of higher amounts of proteins on the array while retaining their structural integrity and functionality over extended time periods.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. Cell-laden microengineered gelatin methacrylate hydrogels

    PubMed Central

    Nichol, Jason W.; Koshy, Sandeep; Bae, Hojae; Hwang, Chang Mo; Yamanlar, Seda; Khademhosseini, Ali

    2010-01-01

    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 to the methacrylation degree and gel concentration. Pattern fidelity and resolution of GelMA was 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 requires cell-responsive microengineered hydrogels. PMID:20417964

  8. 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

  9. 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.

  10. Bisphosphonate-linked hyaluronic acid hydrogel sequesters and enzymatically releases active bone morphogenetic protein-2 for induction of osteogenic differentiation.

    PubMed

    Hulsart-Billström, Gry; Yuen, Pik Kwan; Marsell, Richard; Hilborn, Jöns; Larsson, Sune; Ossipov, Dmitri

    2013-09-01

    Regeneration of bone by delivery of bone morphogenetic proteins (BMPs) from implantable scaffolds is a promising alternative to the existing autologous bone grafting procedures. Hydrogels are used extensively in biomaterials as delivery systems for different growth factors. However, a controlled release of the growth factors is necessary to induce bone formation, which can be accomplished by various chemical functionalities. Herein we demonstrate that functionalization of a hyaluronan (HA) hydrogel with covalently linked bisphosphonate (BP) ligands provides efficient sequestering of BMP-2 in the resulting HA-BP hydrogel. The HA-BP hydrogel was investigated in comparison with its analogue lacking BP groups (HA hydrogel). While HA hydrogel released 100% of BMP-2 over two weeks, less than 10% of BMP-2 was released from the HA-BP hydrogel for the same time. We demonstrate that the sequestered growth factor can still be released by enzymatic degradation of the HA-BP hydrogel. Most importantly, entrapment of BMP-2 in HA-BP hydrogel preserves the growth factor bioactivity, which was confirmed by induction of osteogenic differentiation of mesenchymal stem cells (MSCs) after the cells incubation with the enzymatic digest of the hydrogel. At the same time, the hydrogels degradation products were not toxic to MSCs and osteoblasts. Furthermore, BP-functionalization of HA hydrogels promotes adhesion of the cells to the surface of HA hydrogel. Altogether, the present findings indicate that covalent grafting of HA hydrogel with BP groups can alter the clinical effects of BMPs in bone tissue regeneration.

  11. 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.

  12. Processing Techniques and Applications of Silk Hydrogels in Bioengineering.

    PubMed

    Floren, Michael; Migliaresi, Claudio; Motta, Antonella

    2016-01-01

    Hydrogels are an attractive class of tunable material platforms that, combined with their structural and functional likeness to biological environments, have a diversity of applications in bioengineering. Several polymers, natural and synthetic, can be used, the material selection being based on the required functional characteristics of the prepared hydrogels. Silk fibroin (SF) is an attractive natural polymer for its excellent processability, biocompatibility, controlled degradation, mechanical properties and tunable formats and a good candidate for the fabrication of hydrogels. Tremendous effort has been made to control the structural and functional characteristic of silk hydrogels, integrating novel biological features with advanced processing techniques, to develop the next generation of functional SF hydrogels. Here, we review the several processing methods developed to prepare advanced SF hydrogel formats, emphasizing a bottom-up approach beginning with critical structural characteristics of silk proteins and their behavior under specific gelation environments. Additionally, the preparation of SF hydrogel blends and other advanced formats will also be discussed. We conclude with a brief description of the attractive utility of SF hydrogels in relevant bioengineering applications. PMID:27649251

  13. Step-Index Optical Fiber Made of Biocompatible Hydrogels.

    PubMed

    Choi, Myunghwan; Humar, Matjaž; Kim, Seonghoon; Yun, Seok-Hyun

    2015-07-15

    A biocompatible step-index optical fiber made of poly(ethylene glycol) and alginate hydrogels is demonstrated. The fabricated fiber exhibits excellent light-guiding efficiency in biological tissues. Moreover, the core of hydrogel fibers can be easily doped with functional molecules and nanoparticles for localized light emission, sensing, and therapy.

  14. Processing Techniques and Applications of Silk Hydrogels in Bioengineering

    PubMed Central

    Floren, Michael; Migliaresi, Claudio; Motta, Antonella

    2016-01-01

    Hydrogels are an attractive class of tunable material platforms that, combined with their structural and functional likeness to biological environments, have a diversity of applications in bioengineering. Several polymers, natural and synthetic, can be used, the material selection being based on the required functional characteristics of the prepared hydrogels. Silk fibroin (SF) is an attractive natural polymer for its excellent processability, biocompatibility, controlled degradation, mechanical properties and tunable formats and a good candidate for the fabrication of hydrogels. Tremendous effort has been made to control the structural and functional characteristic of silk hydrogels, integrating novel biological features with advanced processing techniques, to develop the next generation of functional SF hydrogels. Here, we review the several processing methods developed to prepare advanced SF hydrogel formats, emphasizing a bottom-up approach beginning with critical structural characteristics of silk proteins and their behavior under specific gelation environments. Additionally, the preparation of SF hydrogel blends and other advanced formats will also be discussed. We conclude with a brief description of the attractive utility of SF hydrogels in relevant bioengineering applications. PMID:27649251

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Superporous agarose beads as a solid support for microfluidic immunoassay.

    PubMed

    Yang, Yoonsun; Nam, Seong-Won; Lee, Nae Yoon; Kim, Youn Sang; Park, Sungsu

    2008-09-01

    We demonstrate here with the feasibility of superporous agarose (SA) beads as a solid support in microfluidic immunoassay by detecting goat IgG. In our procedure, SA beads containing superpores were covalently conjugated to protein A. The conjugated beads were introduced into a polydimethyl siloxane microfluidic device. The sandwich immunoassay was performed in the microfluidic device by subsequently introducing anti-goat IgG as the primary antibodies, goat IgG as analytes, alkaline phosphatase-conjugated F(ab')2 anti-goat IgG as detection antibodies, and 5-bromo-4-chloro-3-indolylphosphate/nitroblue tetrazolium as substrate in a flow. Depending on the goat IgG concentration, dark and pinky precipitates appeared inside the microchannel immediately after the introduction of all the reagents. The minimum detection limit, 100 pg goat IgG/mL in PBS, was achieved with the naked eye. This enhanced sensitivity is mainly because analytical reagents were allowed to access the outer surface as well as the inner matrices of the beads. This is supported by the facts that the binding of fluorescein isothiocyanate IgG happened throughout the inside matrices of protein A-conjugated SA beads but was limited to the outer surface of protein A-conjugated homogeneous agarose beads. These results suggest that SA beads are highly suitable as a solid support for microfluidic immunoassays.

  1. Survival of different cell lines in alginate-agarose microcapsules.

    PubMed

    Orive, G; Hernández, R M; Gascón, A R; Igartua, M; Pedraz, J L

    2003-01-01

    Cell microencapsulation has emerged as a promising therapeutic strategy to treat a wide range of diseases. The optimisation of this technology depends on several critical issues such as the careful selection of the cell line, the controlled manufacture of microcapsules and the suitable adaptation of the construct design to the selected cell line. In this work, we studied the behavior of hybridoma cells once enclosed in solid and liquefied core alginate-agarose beads. Results show that hybridoma cells presented a better growing pattern and improved their viability and antibody production within liquefied beads. However, when these beads were evaluated with a compression resistance study, they were found to be mechanically more fragile than solid ones. To address this problem, we entrapped non-autologous cells (BHK fibroblast and C2C12 myoblast) in solid alginate-agarose beads and observed that they showed an improved growing profile and prolonged their viability up to 70 days in comparison to the 15 days seen for the hybridoma cells.

  2. 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

  3. 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

  4. 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.

  5. Hydrogel microparticles for biosensing

    PubMed Central

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

    2015-01-01

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

  6. 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.

  7. 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

  8. Use of Cross-Linked Poly(ethylene glycol)-Based Hydrogels for Protein Crystallization

    PubMed Central

    2015-01-01

    Poly(ethylene glycol) (PEG) hydrogels are highly biocompatible materials extensively used for biomedical and pharmaceutical applications, controlled drug release, and tissue engineering. In this work, PEG cross-linked hydrogels, synthesized under various conditions, were used to grow lysozyme crystals by the counterdiffusion technique. Crystallization experiments were conducted using a three-layer arrangement. Results demonstrated that PEG fibers were incorporated within lysozyme crystals controlling the final crystal shape. PEG hydrogels also induced the nucleation of lysozyme crystals to a higher extent than agarose. PEG hydrogels can also be used at higher concentrations (20–50% w/w) as a separation chamber (plug) in counterdiffusion experiments. In this case, PEG hydrogels control the diffusion of the crystallization agent and therefore may be used to tailor the supersaturation to fine-tune crystal size. As an example, insulin crystals were grown in 10% (w/w) PEG hydrogel. The resulting crystals were of an approximate size of 500 μm. PMID:25383049

  9. A Molecular Chaperone for G4-Quartet Hydrogels.

    PubMed

    Peters, Gretchen Marie; Skala, Luke P; Davis, Jeffery T

    2016-01-13

    Thioflavin T (ThT) functions as a molecular chaperone for gelation of water by guanosine and lithium borate. Substoichiometric ThT (1 mol % relative to hydrogelator) results in faster hydrogelation as monitored by (1)H NMR and visual comparison. Vial-inversion tests and rheology show that ThT increases the stiffness of the Li(+) guanosine-borate (GB) hydrogel. In addition, the dye promotes relatively rapid and complete repair of a Li(+) GB hydrogel destroyed by shearing. We used rheology to show that other planar aromatics, some cationic and one neutral dye (methylene violet), also stiffened the Li(+) GB hydrogel. Data from powder X-ray diffraction, UV, and circular dichroism spectroscopy and ThT fluorescence indicate that G4 quartets are formed by the Li(+) GB system. We observed a species in solution by (1)H NMR that was intermediate in size between monomeric gelator and NMR-invisible hydrogel. The concentration of this intermediate decreased much faster when ThT was present in solution, again showing that the dye can accelerate hydrogel formation. We propose that ThT functions as a molecular chaperone by end stacking on terminal G4-quartets and promoting the assembly of these smaller fragments into longer G4-based structures that can then provide more cross-linking sites needed for hydrogelation.

  10. Ultrathin sP(EO-stat-PO) hydrogel coatings are biocompatible and preserve functionality of surface bound growth factors in vivo.

    PubMed

    Neuerburg, Carl; Recknagel, Stefan; Fiedler, Jörg; Groll, Jürgen; Moeller, Martin; Bruellhoff, Kristina; Reichel, Heiko; Ignatius, Anita; Brenner, Rolf E

    2013-10-01

    Hydrogel coatings prepared from reactive star shaped polyethylene oxide based prepolymers (NCO-sP(EO-stat-PO)) minimize unspecific protein adsorption in vitro, while proteins immobilized on NCO-sP(EO-stat-PO) coatings retain their structure and biological function. The aim of the present study was to assess biocompatibility and the effect on early osseointegrative properties of a NCO-sP(EO-stat-PO) coating with additional RGD-peptides and augmentation with bone morphogenetic protein-4 (BMP) used on a medical grade high-density polyethylene (HDPE) base under in vivo circumstances. For testing of biocompatibility dishes with large amounts of bulk NCO-sP(EO-stat-PO) were implanted subcutaneously into 14 Wistar rats. In a second set-up functionalization of implants with ultrathin surface layers by coating ammonia-plasma treated HDPE with NCO-sP(EO-stat-PO), functionalization with linear RGD-peptides, and augmentation with RGD and BMP-4 was analyzed. Therefore, implants were placed subcutaneously in the paravertebral tissue and transcortically in the distal femur of another 14 Wistar rats. Both tests revealed no signs of enhanced inflammation of the surrounding tissue analyzed by CD68, IL-1ß-/TNF-α-antibody staining, nor systemic toxic reactions according to histological analysis of various organs. The mean thickness of the fibrous tissue surrounding the femoral implants was highest in native HDPE-implants and tended to be lower in all NCO-sP(EO-stat-PO) modified implants. Micro-CT analysis revealed a significant increase of peri-implant bone volume in RGD/BMP-4 coated samples. These results demonstrate that even very low amounts of surface bound growth factors do have significant effects when immobilized in an environment that retains their biological function. Hence, NCO-sP(EO-stat-PO)-coatings could offer an attractive platform to improve integration of orthopedic implants.

  11. Sustained release of hepatocyte growth factor by cationic self-assembling peptide/heparin hybrid hydrogel improves β-cell survival and function through modulating inflammatory response

    PubMed Central

    Liu, Shuyun; Zhang, Lanlan; Cheng, Jingqiu; Lu, Yanrong; Liu, Jingping

    2016-01-01

    Inflammatory response is a major cause of grafts dysfunction in islet transplantation. Hepatocyte growth factor (HGF) had shown anti-inflammatory activity in multiple diseases. In this study, we aim to deliver HGF by self-assembling peptide/heparin (SAP/Hep) hybrid gel to protect β-cell from inflammatory injury. The morphological and slow release properties of SAPs were analyzed. Rat INS-1 β-cell line was treated with tumor necrosis factor α in vitro and transplanted into rat kidney capsule in vivo, and the viability, apoptosis, function, and inflammation of β-cells were evaluated. Cationic KLD1R and KLD2R self-assembled to nanofiber hydrogel, which showed higher binding affinity for Hep and HGF because of electrostatic interaction. Slow release of HGF from cationic SAP/Hep gel is a two-step mechanism involving binding affinity with Hep and molecular diffusion. In vitro and in vivo results showed that HGF-loaded KLD2R/Hep gel promoted β-cell survival and insulin secretion, and inhibited cell apoptosis, cytokine release, T-cell infiltration, and activation of NFκB/p38 MAPK pathways in β-cells. This study suggested that SAP/Hep gel is a promising carrier for local delivery of bioactive proteins in islet transplantation. PMID:27729786

  12. Extraction and identification of electroimmunoprecipitated proteins from agarose gels.

    PubMed

    Beyer, Natascha Helena; Schou, Christian; Houen, Gunnar; Heegaard, Niels H H

    2008-01-31

    A method for the identification of protein antigens captured in electroimmunoprecipitates was developed. Different antigen-antibody precipitates were generated by agarose gel immunoelectrophoresis. The immunoprecipitates were excised and various methods for extracting and dissociating the precipitates were systematically studied by analyzing for protein components of the extracts using peptide mass fingerprinting after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The optimal recovery of antigen was obtained by 24-h extraction at 37 degrees C using a minimal volume of 0.06 M Tris-HCl, 10% SDS (pH 7). This simple and robust method is useful for the characterization of antibody specificity. It can also be used to identify antigens generating unknown precipitates in crossed immunoelectrophoresis with polyspecific antisera, including human IgG-antigen complexes electroimmunoprecipitated by secondary antibodies. Thus, the method may prove useful as an additional technique in biomarker discovery.

  13. Direct measurement of intraparticle fluid velocity in superporous agarose beads.

    PubMed

    Larsson, P O; Gustavsson, P E; Axelsson, A

    1998-01-01

    Superporous agarose beads contain both normal diffusion pores and special, very wide superpores through which part of the chromatographic flow is transported, a situation that may greatly improve the chromatographic performance. For the first time such pore flow was measured directly by following the movement of microparticles (dyed yeast cells) through superporous beads packed in a chromatographic bed. The passage of the microparticles through the superpores and through the interstitial pores was recorded by a microscope/video camera. The video recordings were subsequently used to determine flow paths as well as the convective fluid velocities in both the superpores and the interstitial pores. The superpore fluid velocity was found to be proportional to the ratio between the squares of the respective pore diameters, which is in agreement with the Kozeny-Carman equation. Values for two-dimensional and three-dimensional tortuosity of the flow paths were measured and calculated respectively.

  14. Analysis of cell surface properties using derivatized agarose beads.

    PubMed

    Salbilla, B A; Vaghefi, H; Chhabra, P; Hall, G; Brown, D; Sadoughi, F; Francisco, E; Attas, L; Walker, S L; Nguyen, B N; Oppenheimer, S B

    1999-07-01

    An assay has been developed to analyse cell surface properties using agarose beads derivatized with amino acids, sugars, proteins, and other molecules. The assay is simple and rapid and is useful to identify new cell surface markers. Various species and strains of yeast, paramecium, and Euglena were tested for their ability to bind to over 100 types of derivatized beads. A variety of specificity studies were performed in order to understand the nature of cell-bead binding. Our results indicate that cell-bead binding is often specific enough to distinguish between configurational isomers and spacer sizes and can be blocked by addition of specific molecules to the incubation medium. In some cases, different species or strains differed only by their binding to a single bead type. This simple and rapid assay may help to uncover new cell surface receptors and may lead to the development of clinically useful compounds for therapeutic applications.

  15. In vitro refolding of porcine pepsin immobilized on agarose beads.

    PubMed

    Kurimoto, E; Harada, T; Akiyama, A; Sakai, T; Kato, K

    2001-08-01

    Since in vitro refolding of pepsin has long been attempted without success, it has been suspected that pepsin has no intrinsic refolding ability. In the present study, in order to eliminate unfavorable intermolecular interactions bringing about aggregation and autoproteolysis, we immobilized pepsin onto agarose beads. This technique enabled us to search extensively for appropriate refolding conditions without limitation of the refolding period. Renaturation of immobilized pepsin was observed exclusively at pH 3-5. This process was extremely slow and reached equilibrium after 300 h. Sixty percent of the proteolytic activity was recovered at pH 5. Addition of salts raised the recovery to 80% but had no significant effect on the refolding rate, suggesting that the salts mainly stabilize the native state of pepsin. This is the first report on the successful in vitro refolding of pepsin.

  16. Refolding of firefly luciferase immobilized on agarose beads.

    PubMed

    Zako, T; Deguchi, H; Kitayama, A; Ueda, H; Nagamune, T

    2000-03-01

    The renaturation yield of the denatured firefly luciferase decreased strongly with increasing protein concentration in a renaturation buffer, because of aggregation. In this study, firefly luciferase was immobilized on agarose beads at a high concentration. Although the protein concentration was extremely high (about 100-fold) compared to that of soluble luciferase, the renaturation yield was comparable with that for the soluble one. Thus, immobilization was shown to be effective for avoiding aggregation of firefly luciferase. It was also shown that the optimum buffer conditions for renaturation of the immobilized luciferase were the same as those for the renaturation in solution. Also, it was indicated that electrostatic interactions between a protein and the matrix have a negative effect on renaturation of the immobilized luciferase since the renaturation yield decreased at acidic pH only for the immobilized luciferase. These novel observations are described in detail in this paper.

  17. 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

  18. Aromatic-aromatic interactions enhance interfiber contacts for enzymatic formation of a spontaneously aligned supramolecular hydrogel.

    PubMed

    Zhou, Jie; Du, Xuewen; Gao, Yuan; Shi, Junfeng; Xu, Bing

    2014-02-26

    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.

  19. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

    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.

  1. 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.

  2. 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.

  3. 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

  4. Controlling the Porosity and Microarchitecture of Hydrogels for Tissue Engineering

    PubMed Central

    Annabi, Nasim; Nichol, Jason W.; Zhong, Xia; Ji, Chengdong; Koshy, Sandeep; Khademhosseini, Ali

    2010-01-01

    Tissue engineering holds great promise for regeneration and repair of diseased tissues, making the development of tissue engineering scaffolds a topic of great interest in biomedical research. Because of their biocompatibility and similarities to native extracellular matrix, hydrogels have emerged as leading candidates for engineered tissue scaffolds. However, precise control of hydrogel properties, such as porosity, remains a challenge. Traditional techniques for creating bulk porosity in polymers have demonstrated success in hydrogels for tissue engineering; however, often the conditions are incompatible with direct cell encapsulation. Emerging technologies have demonstrated the ability to control porosity and the microarchitectural features in hydrogels, creating engineered tissues with structure and function similar to native tissues. In this review, we explore the various technologies for controlling the porosity and microarchitecture within hydrogels, and demonstrate successful applications of combining these techniques. PMID:20121414

  5. Hybrid supramolecular and colloidal hydrogels that bridge multiple length scales.

    PubMed

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

    2015-04-27

    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.

  6. 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

  7. 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

  8. High-quality substrate for fluorescence enhancement using agarose-coated silica opal film.

    PubMed

    Xu, Ming; Li, Juan; Sun, Liguo; Zhao, Yuanjin; Xie, Zhuoying; Lv, Linli; Zhao, Xiangwei; Xiao, Pengfeng; Hu, Jing; Lv, Mei; Gu, Zhongze

    2010-08-01

    To improve the sensitivity of fluorescence detection in biochip, a new kind of substrates was developed by agarose coating on silica opal film. In this study, silica opal film was fabricated on glass substrate using the vertical deposition technique. It can provide stronger fluorescence signals and thus improve the detection sensitivity. After coating with agarose, the hybrid film could provide a 3D support for immobilizing sample. Comparing with agarose-coated glass substrate, the agarose-coated opal substrates could selectively enhance particular fluorescence signals with high sensitivity when the stop band of the silica opal film in the agarose-coated opal substrate overlapped the fluorescence emission wavelength. A DNA hybridization experiment demonstrated that fluorescence intensity of special type of agarose-coated opal substrates was about four times that of agarose-coated glass substrate. These results indicate that the optimized agarose-coated opal substrate can be used for improving the sensitivity of fluorescence detection with high quality and selectivity.

  9. 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

  10. 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

  11. 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

  12. Preparation of gold nanoparticles-agarose gel composite and its application in SERS detection

    NASA Astrophysics Data System (ADS)

    Ma, Xiaoyuan; Xia, Yu; Ni, Lili; Song, Liangjing; Wang, Zhouping

    2014-03-01

    Agarose gel/gold nanoparticles hybrid was prepared by adding gold nanoparticles to preformed agarose gel. Nanocomposite structures and properties were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and UV-Vis-NIR absorption spectroscopy. Based on the swelling-contraction characteristics of agarose gel and the adjustable localized surface plasmon resonance (LSPR) of the gold nanoparticles, the nanocomposites were used as surface enhanced Raman scattering (SERS) substrate to detect the Raman signal molecules (NBA, MBA, 1NAT). Results revealed that the porous structure of the agarose gel provided a good carrier for the enrichment of the gold nanoparticles. The gold nanoparticles dynamic hot-spot effect arising from the agarose gel contraction loss of water in the air greatly enhanced the Raman signal. Furthermore, the gel could be cleaned with washing solution and recycling could be achieved for Raman detection.

  13. Agarose droplet microfluidics for highly parallel and efficient single molecule emulsion PCR.

    PubMed

    Leng, Xuefei; Zhang, Wenhua; Wang, Chunming; Cui, Liang; Yang, Chaoyong James

    2010-11-01

    An agarose droplet method was developed for highly parallel and efficient single molecule emulsion PCR. The method capitalizes on the unique thermoresponsive sol-gel switching property of agarose for highly efficient DNA amplification and amplicon trapping. Uniform agarose solution droplets generated via a microfluidic chip serve as robust and inert nanolitre PCR reactors for single copy DNA molecule amplification. After PCR, agarose droplets are gelated to form agarose beads, trapping all amplicons in each reactor to maintain the monoclonality of each droplet. This method does not require cocapsulation of primer labeled microbeads, allows high throughput generation of uniform droplets and enables high PCR efficiency, making it a promising platform for many single copy genetic studies.

  14. 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

  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.

  16. 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

  17. Hydrogel Biomaterials: A Smart Future?

    PubMed Central

    Kopeček, Jindřich

    2007-01-01

    Hydrogels were the first biomaterials developed for human use. The state-of-the-art and potential for the future are discussed. Recently, new designs have produced mechanically strong synthetic hydrogels. Protein based hydrogels and hybrid hydrogels containing protein domains present a novel advance; such biomaterials may self-assemble from block or graft copolymers containing biorecognition domains. One of the domains, the coiled-coil, ubiquitously found in nature, has been used as an example to demonstrate the developments in the design of smart hydrogels. The application potential of synthetic, protein-based, DNA-based, and hybrid hydrogels bodes well for the future of this class of biomaterials. PMID:17697712

  18. 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

  19. Anion-Responsive Metallopolymer Hydrogels for Healthcare Applications.

    PubMed

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

    2015-07-23

    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.

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

    PubMed

    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.

  1. 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

  2. Injectable and Glucose-Responsive Hydrogels Based on Boronic Acid-Glucose Complexation.

    PubMed

    Dong, Yizhou; Wang, Weiheng; Veiseh, Omid; Appel, Eric A; Xue, Kun; Webber, Matthew J; Tang, Benjamin C; Yang, Xi-Wen; Weir, Gordon C; Langer, Robert; Anderson, Daniel G

    2016-08-30

    Injectable hydrogels have been widely used for a number of biomedical applications. Here, we report a new strategy to form an injectable and glucose-responsive hydrogel using the boronic acid-glucose complexation. The ratio of boronic acid and glucose functional groups is critical for hydrogel formation. In our system, polymers with 10-60% boronic acid, with the balance being glucose-modified, are favorable to form hydrogels. These hydrogels are shear-thinning and self-healing, recovering from shear-induced flow to a gel state within seconds. More importantly, these polymers displayed glucose-responsive release of an encapsulated model drug. The hydrogel reported here is an injectable and glucose-responsive hydrogel constructed from the complexation of boronic acid and glucose within a single component polymeric material.

  3. Polymer hydrogels: Chaperoning vaccines

    NASA Astrophysics Data System (ADS)

    Staats, Herman F.; Leong, Kam W.

    2010-07-01

    A cationic nanosized hydrogel (nanogel) shows controlled antigen delivery in vivo following intranasal administration and hence holds promise for a clinically effective adjuvant-free and needle-free vaccine system.

  4. 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

  5. A new simplified procedure for C1 inhibitor purification. A novel use for jacalin-agarose.

    PubMed

    Pilatte, Y; Hammer, C H; Frank, M M; Fries, L F

    1989-06-01

    C1 inhibitor (C1-INH), the major regulatory protein of the classical pathway of complement activation, is also involved in the regulation of several other plasma proteolytic systems including the coagulation, fibrinolytic and contact systems. All the previously published methods for the purification of C1-INH are time-consuming and some do not yield highly pure protein. Recently, it was reported that Jack fruit (Artocarpus integrifolia) lectin, also called jacalin, binds C1-INH. Since jacalin binds only a small number of human serum proteins it appeared that jacalin-agarose affinity chromatography would constitute a very selective early step for the purification of C1-INH. Consequently we have designed a new, simplified three-step procedure for the purification of C1-INH which includes PEG fractionation, jacalin-agarose chromatography and hydrophobic interaction chromatography on phenyl-Sepharose which takes advantage of the marked hydrophilicity of the inhibitor. This procedure has three major advantages over those which have been the most frequently used. Firstly, it includes only two fast chromatographic steps. Secondly, because the C1-INH pool is cleanly and predictably separated from the unwanted proteins by differential elution conditions in both chromatographic steps, no antigenic or functional assays are required to define the desired peaks. Thirdly, only the final product is dialyzed while all other methods required several buffer changes. For these reasons this procedure is much faster and simpler than the previously published methods. About 10-12 mg of highly purified and fully active C1-INH can be obtained within 1 day from 120 ml of plasma giving an average yield of 40-45%. This method may thus be highly adaptable to bulk purification for clinical use or for preparation of genetically or pathologically altered C1-INH from clinical specimens.

  6. 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

  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. Collagen and chondrocyte concentrations control ultrasound scattering in agarose scaffolds.

    PubMed

    Inkinen, S; Liukkonen, J; Ylärinne, J H; Puhakka, P H; Lammi, M J; Virén, T; Jurvelin, J S; Töyräs, J

    2014-09-01

    Ultrasound imaging has been proposed for diagnostics of osteoarthritis and cartilage injuries in vivo. However, the specific contribution of chondrocytes and collagen to ultrasound scattering in articular cartilage has not been systematically studied. We investigated the role of these tissue structures by measuring ultrasound scattering in agarose scaffolds with varying collagen and chondrocyte concentrations. Ultrasound catheters with center frequencies of 9 MHz (7.1-11.0 MHz, -6 dB) and 40 MHz (30.1-45.3 MHz, -6 dB) were applied using an intravascular ultrasound device. Ultrasound backscattering quantified in a region of interest starting right below sample surface differed significantly (p < 0.05) with the concentrations of collagen and chondrocytes. An ultrasound frequency of 40 MHz, as compared with 9 MHz, was more sensitive to variations in collagen and chondrocyte concentrations. The present findings may improve diagnostic interpretation of arthroscopic ultrasound imaging and provide information necessary for development of models describing ultrasound propagation within cartilage. PMID:24972499

  9. Immobilization of angiotensin-converting enzyme on glyoxyl-agarose.

    PubMed

    Megías, Cristina; Pedroche, Justo; del Mar Yust, María; Alaiz, Manuel; Girón-Calle, Julio; Millán, Francisco; Vioque, Javier

    2006-06-28

    The assay of angiotensin-converting enzyme (ACE) inhibition by food-derived peptides is usually carried out by using soluble ACE in a batch process. The purification of this enzyme from tissues is not an easy task, and the resulting preparation loses activity very fast. In addition, ACE commercial preparations are very expensive. In this work the immobilization of ACE, through lysine amino groups, to 4% beads cross-linked (4 BCL) glyoxyl-agarose is described. The amount of immobilized enzyme increased with increasing concentrations of enzyme and with incubation time until a saturation point was reached at 50 mg protein/mL gel and 3.5 hours, respectively. The IC50 values for a noncompetitive sunflower peptide inhibitor were similar for the soluble (30.56 microM) and immobilized (32.7 microM) enzymes. An immobilized derivative was obtained that was 60 times more stable than the soluble enzyme at 60 degrees C. This procedure yields a derivative that can be reused and has increased thermal stability compared to that of the soluble enzyme. Thus, ACE immobilization is a good alternative to using soluble freshly prepared or commercial preparations because of economical and practical reasons.

  10. Removal of digoxin from plasma using monoclonal anti-digoxin antibodies immobilized on agarose

    SciTech Connect

    Brizgys, M.; Pincus, S.; Rollins, D.E.

    1986-05-01

    Monoclonal anti-digoxin antibodies (dig-Ab) have been covalently coupled to agarose supports to evaluate them as part of an extracorporeal device for removal of digoxin from the circulation. The agarose supports studied were Sepharose CL-6B, agarose-polyacrolein microsphere (APAM) beads, Bio Gel A-5m and Affi-gel 15 (Bio-Rad). Antibody concentrations between 2 and 4 mg/g gel were coupled to the agarose beads which were then placed in glass columns. Bovine ..cap alpha..-globulin coupled to the agarose supports was used as a control. Binding capacity and affinity of the immobilized antibody were determined by perfusing the dig-Ab agarose beads with a plasma solution containing /sup 3/H-digoxin and various concentrations of digoxin. The binding capacity of the immobilized dig-Ab was 30% of the theoretical value for Sepharose, Bio Gel and Affigel, and 10% of the theoretical value for dig-Ab coupled to APAM beads. The affinity of the immobilized dig-Ab was 10-100 fold less than non-immobilized Ab (3.4 x 10/sup 8/M/sup -1/. The APAM beads showed a significant decrease in binding of digoxin as the flow rate was increased from 0.5 to 5.0 ml/min. These data demonstrate that dig-Ab coupled to agarose and incorporated into a column can be used to remove digoxin from plasma in vitro.

  11. Evaluation of an In Situ Gelable and Injectable Hydrogel Treatment to Preserve Human Disc Mechanical Function Undergoing Physiologic Cyclic Loading Followed by Hydrated Recovery.

    PubMed

    Showalter, Brent L; Elliott, Dawn M; Chen, Weiliam; Malhotra, Neil R

    2015-08-01

    Despite the prevalence of disc degeneration and its contributions to low back problems, many current treatments are palliative only and ultimately fail. To address this, nucleus pulposus replacements are under development. Previous work on an injectable hydrogel nucleus pulposus replacement composed of n-carboxyethyl chitosan, oxidized dextran, and teleostean has shown that it has properties similar to native nucleus pulposus, can restore compressive range of motion in ovine discs, is biocompatible, and promotes cell proliferation. The objective of this study was to determine if the hydrogel implant will be contained and if it will restore mechanics in human discs undergoing physiologic cyclic compressive loading. Fourteen human lumbar spine segments were tested using physiologic cyclic compressive loading while intact, following nucleotomy, and again following treatment of injecting either phosphate buffered saline (PBS) (sham, n = 7) or hydrogel (implant, n = 7). In each compressive test, mechanical parameters were measured immediately before and after 10,000 cycles of compressive loading and following a period of hydrated recovery. The hydrogel implant was not ejected from the disc during 10,000 cycles of physiological compression testing and appeared undamaged when discs were bisected following all mechanical tests. For sham samples, creep during cyclic loading increased (+15%) from creep during nucleotomy testing, while for implant samples creep strain decreased (-3%) toward normal. There was no difference in compressive modulus or compressive strains between implant and sham samples. These findings demonstrate that the implant interdigitates with the nucleus pulposus, preventing its expulsion during 10,000 cycles of compressive loading and preserves disc creep within human L5-S1 discs. This and previous studies provide a solid foundation for continuing to evaluate the efficacy of the hydrogel implant.

  12. [Modification of seaweed polysaccharide-agarose and its application as skin dressing (III)--skin regeneration with agarose grafting hyaluronic acid sponge].

    PubMed

    Huang, Jianyan; Zhang, Lingmin; Chu, Bin; Chen, Peng; Tang, Shunqing

    2011-02-01

    In this paper, a kind of skin dressing, agarose- grafting- hyaluronic acid (Ag-g-HA) sponge was applied to test the modified agarose based scaffold for skin regeneration. The bFGF loading agarose-grafting hyaluronan scaffold had homogenous porosities, and the loaded bFGF was bioactive in 2 weeks. The Ag-g-HA sponge was applied into skin of mice, and it was found that the dressing promoted skin regeneration and no infection and leakage in lesion site took place. H&E staining results showed that the repaired skin was similar to autologous skin. These demonstrate that Ag-g-HA sponge has a promise in skin regeneration.

  13. Fast contact of solid-liquid interface created high strength multi-layered cellulose hydrogels with controllable size.

    PubMed

    He, Meng; Zhao, Yanteng; Duan, Jiangjiang; Wang, Zhenggang; Chen, Yun; Zhang, Lina

    2014-02-12

    Novel onion-like and multi-layered tubular cellulose hydrogels were constructed, for the first time, from the cellulose solution in a 7% NaOH/12% urea aqueous solvent by changing the shape of the gel cores. In our findings, the contacting of the cellulose solution with the surface of the agarose gel rod or sphere loaded with acetic acid led to the close chain packing to form immediately a gel layer, as a result of the destruction of the cellulose inclusion complex by acid through inducing the cellulose self-aggregation. Subsequently, multi-layered cellulose hydrogels were fabricated via a multi-step interrupted gelation process. The size, layer thickness and inter-layer space of the multi-layered hydrogels could be controlled by adjusting the cellulose concentrations, the gel core diameter and the contacting time of the solid-liquid interface. The multi-layered cellulose hydrogels displayed good architectural stability and solvent resistance. Moreover, the hydrogels exhibited high compressive strength and excellent biocompatibility. L929 cells could adhere and proliferate on the surface of the layers and in interior space, showing great potential as tissue engineering scaffolds and cell culture carrier. This work opens up a new avenue for the construction of the high strength multi-layered cellulose hydrogels formed from inner to outside via a fast contact of solid-liquid interface. PMID:24405277

  14. Direct measurements of convective fluid velocities in superporous agarose beads.

    PubMed

    Gustavsson, P E; Axelsson, A; Larsson, P O

    1998-02-01

    Superporous agarose beads contain two sets of pores, diffusion pores and so-called superpores or flow pores, in which the chromatographic flow can transport substances to the interior of each individual bead [Gustavsson and Larsson, J. Chromatogr. A 734 (1996) 231]. The existence of pore flow may be proven indirectly by the chromatographic performance of beads but it has never been directly demonstrated in a chromatographic bed. In this report, pore flow was directly measured by following the movement of micro-particles (dyed yeast cells) in a packed bed. The passage of the micro-particles through the superpores and through the interstitial pores was followed by a microscope/video camera focused on beads which were situated four layers from the glass wall. The video recordings were subsequently used to determine the convective fluid velocities in both the superpores and the interstitial pores. Experiments were carried out with three different bead size ranges, all of which contained superporous beads having an average superpore diameter of 30 microns. The superpore fluid velocity as % of interstitial fluid velocity was determined to be 2-5% for columns packed with 300-500-micron beads (3% average value), 6-12% for columns packed with 180-300-micron beads (7% average value) and 11-24% for columns packed with 106-180-micron beads (17% average value). These data were compared to and found to agree with theoretically calculated values based on the Kozeny-Carman equation. In order to observe and accurately measure fluid velocities within a chromatographic bed, special techniques were adopted. Also, precautions were made to ensure that the experimental conditions used were representative of normal chromatography runs.

  15. Hierarchical nanostructured conducting polymer hydrogel with high electrochemical activity

    PubMed Central

    Pan, Lijia; Yu, Guihua; Zhai, Dongyuan; Lee, Hye Ryoung; Zhao, Wenting; Liu, Nian; Wang, Huiliang; Tee, Benjamin C.-K.; Shi, Yi; Cui, Yi; Bao, Zhenan

    2012-01-01

    Conducting polymer hydrogels represent a unique class of materials that synergizes the advantageous features of hydrogels and organic conductors and have been used in many applications such as bioelectronics and energy storage devices. They are often synthesized by polymerizing conductive polymer monomer within a nonconducting hydrogel matrix, resulting in deterioration of their electrical properties. Here, we report a scalable and versatile synthesis of multifunctional polyaniline (PAni) hydrogel with excellent electronic conductivity and electrochemical properties. With high surface area and three-dimensional porous nanostructures, the PAni hydrogels demonstrated potential as high-performance supercapacitor electrodes with high specific capacitance (∼480 F·g-1), unprecedented rate capability, and cycling stability (∼83% capacitance retention after 10,000 cycles). The PAni hydrogels can also function as the active component of glucose oxidase sensors with fast response time (∼0.3 s) and superior sensitivity (∼16.7 μA·mM-1). The scalable synthesis and excellent electrode performance of the PAni hydrogel make it an attractive candidate for bioelectronics and future-generation energy storage electrodes. PMID:22645374

  16. Dynamic Manipulation of Hydrogels to Control Cell Behavior: A Review

    PubMed Central

    Vats, Kanika

    2013-01-01

    For many tissue engineering applications and studies to understand how materials fundamentally affect cellular functions, it is important to have the ability to synthesize biomaterials that can mimic elements of native cell–extracellular matrix interactions. Hydrogels possess many properties that are desirable for studying cell behavior. For example, hydrogels are biocompatible and can be biochemically and mechanically altered by exploiting the presentation of cell adhesive epitopes or by changing hydrogel crosslinking density. To establish physical and biochemical tunability, hydrogels can be engineered to alter their properties upon interaction with external driving forces such as pH, temperature, electric current, as well as exposure to cytocompatible irradiation. Additionally, hydrogels can be engineered to respond to enzymes secreted by cells, such as matrix metalloproteinases and hyaluronidases. This review details different strategies and mechanisms by which biomaterials, specifically hydrogels, can be manipulated dynamically to affect cell behavior. By employing the appropriate combination of stimuli and hydrogel composition and architecture, cell behavior such as adhesion, migration, proliferation, and differentiation can be controlled in real time. This three-dimensional control in cell behavior can help create programmable cell niches that can be useful for fundamental cell studies and in a variety of tissue engineering applications. PMID:23541134

  17. Effect of initial total monomer concentration on the swelling behavior of cationic acrylamide-based hydrogels

    SciTech Connect

    Baker, J.P.; Hong, L.H.; Blanch, H.W.; Prausnitz, J.M. . Dept. of Chemical Engineering Lawrence Berkeley Lab., CA . Chemical Sciences Div.)

    1994-03-14

    The aqueous equilibrium swelling properties of a series of lightly-cross-linked cationic hydrogels based on acrylamide and [(methacrylamido) propyl] trimethylammonium chloride (MAPTAC) were measured as a function of initial total monomer concentration % T (w/v) and ionic strength. Swelling is a strong decreasing function of rising % T; the 10 % T hydrogel obtained a 17-fold larger swelling ratio (g of swollen hydrogel/g of dry hydrogel) in pure water compared to the 40 % T hydrogel. Good agreement is obtained between measured swelling equilibria in aqueous sodium chloride and that calculated from a Flory-type swelling model including ideal Donnan equilibria provided that an adjustable parameter is introduced into the swelling model for hydrogels in pure water. The experimental results presented here indicate that network-chain interpenetration increases with rising % T.

  18. Hydrogels in Regenerative Medicine

    PubMed Central

    Slaughter, Brandon V.; Khurshid, Shahana S.; Fisher, Omar Z.; Khademhosseini, Ali

    2015-01-01

    Hydrogels, due to their unique biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics, have been the material of choice for many applications in regenerative medicine. They can serve as scaffolds that provide structural integrity to tissue constructs, control drug and protein delivery to tissues and cultures, and serve as adhesives or barriers between tissue and material surfaces. In this work, the properties of hydrogels that are important for tissue engineering applications and the inherent material design constraints and challenges are discussed. Recent research involving several different hydrogels polymerized from a variety of synthetic and natural monomers using typical and novel synthetic methods are highlighted. Finally, special attention is given to the microfabrication techniques that are currently resulting in important advances in the field. PMID:20882499

  19. 25th anniversary article: Engineering hydrogels for biofabrication.

    PubMed

    Malda, Jos; Visser, Jetze; Melchels, Ferry P; Jüngst, Tomasz; Hennink, Wim E; Dhert, Wouter J A; Groll, Jürgen; Hutmacher, Dietmar W

    2013-09-25

    With advances in tissue engineering, the possibility of regenerating injured tissue or failing organs has become a realistic prospect for the first time in medical history. Tissue engineering - the combination of bioactive materials with cells to generate engineered constructs that functionally replace lost and/or damaged tissue - is a major strategy to achieve this goal. One facet of tissue engineering is biofabrication, where three-dimensional tissue-like structures composed of biomaterials and cells in a single manufacturing procedure are generated. Cell-laden hydrogels are commonly used in biofabrication and are termed "bioinks". Hydrogels are particularly attractive for biofabrication as they recapitulate several features of the natural extracellular matrix and allow cell encapsulation in a highly hydrated mechanically supportive three-dimensional environment. Additionally, they allow for efficient and homogeneous cell seeding, can provide biologically-relevant chemical and physical signals, and can be formed in various shapes and biomechanical characteristics. However, despite the progress made in modifying hydrogels for enhanced bioactivation, cell survival and tissue formation, little attention has so far been paid to optimize hydrogels for the physico-chemical demands of the biofabrication process. The resulting lack of hydrogel bioinks have been identified as one major hurdle for a more rapid progress of the field. In this review we summarize and focus on the deposition process, the parameters and demands of hydrogels in biofabrication, with special attention to robotic dispensing as an approach that generates constructs of clinically relevant dimensions. We aim to highlight this current lack of effectual hydrogels within biofabrication and initiate new ideas and developments in the design and tailoring of hydrogels. The successful development of a "printable" hydrogel that supports cell adhesion, migration, and differentiation will significantly advance

  20. Bioactive Nanocomposite Poly (Ethylene Glycol) Hydrogels Crosslinked by Multifunctional Layered Double Hydroxides Nanocrosslinkers.

    PubMed

    Huang, Heqin; Xu, Jianbin; Wei, Kongchang; Xu, Yang J; Choi, Chun Kit K; Zhu, Meiling; Bian, Liming

    2016-07-01

    Poly (ethylene glycol) (PEG) based hydrogels have been widely used in many biomedical applications such as regenerative medicine due to their good biocompatibility and negligible immunogenicity. However, bioactivation of PEG hydrogels, such as conjugation of bioactive biomolecules, is usually necessary for cell-related applications. Such biofunctionalization of PEG hydrogels generally involves complicated and time-consuming bioconjugation procedures. Herein, we describe the facile preparation of bioactive nanocomposite PEG hydrogel crosslinked by the novel multifunctional nanocrosslinkers, namely polydopamine-coated layered double hydroxides (PD-LDHs). The catechol-rich PD-LDH nanosheets not only act as effective nanocrosslinkers reinforcing the mechanical strength of the hydrogel, but also afford the hydrogels with robust bioactivity and bioadhesion via the cortical-mediated couplings. The obtained nanocomposite PEG hydrogels with the multifunctional PD-LDH crosslinking domains show tunable mechanical properties, self-healing ability, and bioadhesion to biological tissues. Furthermore, these hydrogels also promote the sequestration of proteins and support the osteogenic differentiation of human mesenchymal stem cells without any further bio-functionalization. Such facile preparation of bioactive and bioadhesive PEG hydrogels have rarely been achieved and may open up a new avenue for the design of nanocomposite PEG hydrogels for biomedical applications. PMID:27061462

  1. Hydrogel formulation determines cell fate of fetal and adult neural progenitor cells.

    PubMed

    Aurand, Emily R; Wagner, Jennifer L; Shandas, Robin; Bjugstad, Kimberly B

    2014-01-01

    Hydrogels provide a unique tool for neural tissue engineering. These materials can be customized for certain functions, i.e. to provide cell/drug delivery or act as a physical scaffold. Unfortunately, hydrogel complexities can negatively impact their biocompatibility, resulting in unintended consequences. These adverse effects may be combated with a better understanding of hydrogel chemical, physical, and mechanical properties, and how these properties affect encapsulated neural cells. We defined the polymerization and degradation rates and compressive moduli of 25 hydrogels formulated from different concentrations of hyaluronic acid (HA) and poly(ethylene glycol) (PEG). Changes in compressive modulus were driven primarily by the HA concentration. The in vitro biocompatibility of fetal-derived (fNPC) and adult-derived (aNPC) neural progenitor cells was dependent on hydrogel formulation. Acute survival of fNPC benefited from hydrogel encapsulation. NPC differentiation was divergent: fNPC differentiated into mostly glial cells, compared with neuronal differentiation of aNPC. Differentiation was influenced in part by the hydrogel mechanical properties. This study indicates that there can be a wide range of HA and PEG hydrogels compatible with NPC. Additionally, this is the first study comparing hydrogel encapsulation of NPC derived from different aged sources, with data suggesting that fNPC and aNPC respond dissimilarly within the same hydrogel formulation.

  2. Poly(N-isopropylacrylamide) hydrogels with interpenetrating multiwalled carbon nanotubes for cell sheet engineering.

    PubMed

    Chen, Yu-Shuan; Tsou, Pei-Chun; Lo, Jem-Mau; Tsai, Hsieh-Chih; Wang, Yan-Zhen; Hsiue, Ging-Ho

    2013-10-01

    Hydrogels have been developed as artificial extracellular matrixes (ECMs) to mimic native tissue microenvironments for various applications. Unfortunately, poly(N-isopropylacrylamide) (PNIPAAM)-based hydrogels are not suitable for cell culturing and cell sheet preparation. Carbon nanotubes (CNTs), with their mechanical strength and electrical conductivity, have been considered as additives to increase the applicability of hydrogels to cell encapsulation and advance cardiac electrophysiological functions. A simple method for fabrication of PNIPAAM hydrogels interpenetrated with multiwalled CNTs (MWCNTs) as substrates for cell sheet preparation is reported. The results demonstrate that PNIPAAM hydrogels with interpenetrating MWCNTs still exhibit thermosensitive behavior. It is also found that epithelial Madin-Darby canine kidney (MDCK) cells can only attach and proliferate on MWCNT-interpenetrated PNIPAAM hydrogels. Furthermore, the PNIPAAM hydrogels with MWCNTs possess higher elastic moduli and hydrophobicities than those without MWCNTs, suggesting these two characteristics are necessary for the cells to attach to the hydrogel surfaces. Moreover, cell sheets can only be harvested from PNIPAAM hydrogels with MWCNTs because of their high ratio of cell attachment. Thus, this simple method provides sufficient mechanical strength to PNIPAAM hydrogels so that anchorage-dependent cells can be cultivated and provides a superior system for preparing cell sheets.

  3. Poly(ethylene glycol) hydrogels with cell cleavable groups for autonomous cell delivery.

    PubMed

    Kar, Mrityunjoy; Vernon Shih, Yu-Ru; Velez, Daniel Ortiz; Cabrales, Pedro; Varghese, Shyni

    2016-01-01

    Cell-responsive hydrogels hold tremendous potential as cell delivery devices in regenerative medicine. In this study, we developed a hydrogel-based cell delivery vehicle, in which the encapsulated cell cargo control its own release from the vehicle in a protease-independent manner. Specifically, we have synthesized a modified poly(ethylene glycol) (PEG) hydrogel that undergoes degradation responding to cell-secreted molecules by incorporating disulfide moieties onto the backbone of the hydrogel precursor. Our results show the disulfide-modified PEG hydrogels disintegrate seamlessly into solution in presence of cells without any external stimuli. The rate of hydrogel degradation, which ranges from hours to months, is found to be dependent upon the type of encapsulated cells, cell number, and fraction of disulfide moieties present in the hydrogel backbone. The differentiation potential of human mesenchymal stem cells released from the hydrogels is maintained in vitro. The in vivo analysis of these cell-laden hydrogels, through a dorsal window chamber and intramuscular implantation, demonstrated autonomous release of cells to the host environment. The hydrogel-mediated implantation of cells resulted in higher cell retention within the host tissue when compared to that without a biomaterial support. Biomaterials that function as a shield to protect cell cargos and assist their delivery in response to signals from the encapsulated cells could have a wide utility in cell transplantation and could improve the therapeutic outcomes of cell-based therapies. PMID:26606444

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

    NASA Astrophysics Data System (ADS)

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

    2008-06-01

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

  5. Swelling equilibria for cationic 2-hydroxyethyl methacrylate (HEMA)-based hydrogels

    SciTech Connect

    Baker, J.P.; Blanch, H.W.; Prausnitz, J.M.

    1993-08-01

    Cationic HEMA-based hydrogels were synthesized by copolymerizing HEMA with [(methacrylamido)propyl]trimethylammonium chloride (MAPTAC). Swelling equilibria were measured in pure water an in aqueous sodium chloride solutions. Hydrogel swelling is an increasing function of the MAPTAC content. A Flory-type swelling model using a concentration-dependent Flory {Chi} parameter semi-qualitatively describes poly(HEMA co-MAPTAC) hydrogel swelling in aqueous sodium chloride.

  6. Adhesion in hydrogel contacts

    NASA Astrophysics Data System (ADS)

    Torres, J. R.; Jay, G. D.; Kim, K.-S.; Bothun, G. D.

    2016-05-01

    A generalized thermomechanical model for adhesion was developed to elucidate the mechanisms of dissipation within the viscoelastic bulk of a hyperelastic hydrogel. Results show that in addition to the expected energy release rate of interface formation, as well as the viscous flow dissipation, the bulk composition exhibits dissipation due to phase inhomogeneity morphological changes. The mixing thermodynamics of the matrix and solvent determines the dynamics of the phase inhomogeneities, which can enhance or disrupt adhesion. The model also accounts for the time-dependent behaviour. A parameter is proposed to discern the dominant dissipation mechanism in hydrogel contact detachment.

  7. VEGF-conjugated alginate hydrogel prompt angiogenesis and improve pancreatic islet engraftment and function in type 1 diabetes.

    PubMed

    Yin, Nina; Han, Yongming; Xu, Hanlin; Gao, Yisen; Yi, Tao; Yao, Jiale; Dong, Li; Cheng, Dejun; Chen, Zebin

    2016-02-01

    Type 1 diabetes was a life-long disease that affected numerous people around the world. Insulin therapy has its limitations that may involve hyperglycemia and heavy burden of patient by repeated dose. Islet transplantation emerged as a promising approach to reach periodical reverse of diabetes, however, transplanted islets suffer from foreign body reaction and lack of nutrition and oxygen supply, especially in the blood-vessel-shortage subcutaneous site which was preferred by patient and surgeon. In this study, we designed and synthesized a vascular endothelial growth factor (VEGF) conjugated alginate material to encapsulate the transplanted islets via 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) reaction, and successful conjugation was confirmed by Nuclear Magnetic Resonance H1 spectrum. The best VEGF concentration (100ng/ml) was determined by the combined studies of the mechanical property and endothelial cell growth assay. In vivo study, conjugated VEGF on alginate exhibited sustained promoting angiogenesis property after subcutaneous transplantation by histology study and islets encapsulated in this material achieved long term therapeutic effect (up to 50days) in the diabetic mice model. In conclusion, this study establishes a simple biomaterial strategy for islet transplantation to enhance islet survival and function, which could be a feasible therapeutic alternative for type 1 diabetes. PMID:26652453

  8. Hydrogels for the Repair of Articular Cartilage Defects

    PubMed Central

    Maher, Suzanne A.; Lowman, Anthony M.

    2011-01-01

    The repair of articular cartilage defects remains a significant challenge in orthopedic medicine. Hydrogels, three-dimensional polymer networks swollen in water, offer a unique opportunity to generate a functional cartilage substitute. Hydrogels can exhibit similar mechanical, swelling, and lubricating behavior to articular cartilage, and promote the chondrogenic phenotype by encapsulated cells. Hydrogels have been prepared from naturally derived and synthetic polymers, as cell-free implants and as tissue engineering scaffolds, and with controlled degradation profiles and release of stimulatory growth factors. Using hydrogels, cartilage tissue has been engineered in vitro that has similar mechanical properties to native cartilage. This review summarizes the advancements that have been made in determining the potential of hydrogels to replace damaged cartilage or support new tissue formation as a function of specific design parameters, such as the type of polymer, degradation profile, mechanical properties and loading regimen, source of cells, cell-seeding density, controlled release of growth factors, and strategies to cause integration with surrounding tissue. Some key challenges for clinical translation remain, including limited information on the mechanical properties of hydrogel implants or engineered tissue that are necessary to restore joint function, and the lack of emphasis on the ability of an implant to integrate in a stable way with the surrounding tissue. Future studies should address the factors that affect these issues, while using clinically relevant cell sources and rigorous models of repair. PMID:21510824

  9. Hyaluronic acid/chondroitin sulfate-based hydrogel prepared by gamma irradiation technique.

    PubMed

    Zhao, Linlin; Gwon, Hui-Jeong; Lim, Youn-Mook; Nho, Young-Chang; Kim, So Yeon

    2014-02-15

    Gamma-ray irradiation of novel hydrogels was used to develop a biocompatible hydrogel system for skin tissue engineering. These novel hydrogels are composed of natural polymers including hyaluronic acid (HA) and chondroitin sulfate (CS), and the synthetic polymer, poly(vinyl alcohol) (PVA). The γ-ray irradiation method has advantages, such as relatively simple manipulation without need of any extra reagents for polymerization and cross-linking. We synthesized HA and CS derivatives with polymerizable residues. The HA/CS/PVA hydrogels with various compositions were prepared by using γ-ray irradiation technique and their physicochemical properties were investigated to evaluate the feasibility of their use as artificial skin substitutes. HA/CS/PVA hydrogels showed an 85-88% degree of gelation under 15 kGy radiation. All HA/CS/PVA hydrogels exhibited more than 90% water content and reached an equilibrium swelling state within 24h. Hydrogels with higher concentrations of hyaluronidase solution and HA/CS content had proportionally higher enzymatic degradation rates. The drug release behaviors from HA/CS/PVA hydrogels were influenced by the composition of the hydrogel and drug properties. Exposure of human keratinocyte (HaCaT) culture to the extracts of HA/CS/PVA hydrogels did not significantly affect the cell viability. All HaCaT cell cultures exposed to the extracts of HA/CS/PVA hydrogels exhibited greater than 92% cell viability. The HaCaT growth in HA/CS/PVA hydrogels gradually increased as a function of culture time. After 7 days, the HaCaT cells in all HA/CA/PVA hydrogels exhibited more than 80% viability compared to the control group HaCaT culture on a culture plate. PMID:24507324

  10. Adhesion in hydrogels and model glassy polymers

    NASA Astrophysics Data System (ADS)

    Guvendiren, Murat

    Two main topics are addressed in this dissertation: (1) adhesion in hydrogels; (2) interfacial interactions between model glassy polymers. A self-assembly technique for the formation of hydrogels from acrylic triblock copolymer solutions was developed, based on vapor phase solvent exchange. Structure formation in the gels was characterized by small angle X-ray scattering, and swelling was measured in controlled pH buffer solutions. Strong gels are formed with polymer weight fractions between 0.01 and 0.15, and with shear moduli between 0.6 kPa and 3.5 kPa. Adhesive functionality, based on 3,4-dihydroxy-L-phenylalanine (DOPA) was also incorporated into the triblock copolymers. The effect of DOPA concentration on gel formation and swelling was investigated in detail. The adhesive properties of DOPA-functionalized hydrogels on TiO2 were investigated with an axisymmetric adhesion method. It was shown that the presence of DOPA enhances the adhesive properties of the hydrogels, but that the effect is minimized at pH values below 10, where the DOPA groups are hydrophobic. Thin film membranes were produced in order to study the specific interactions between DOPA and TiO2 and DOPA and tissue, using a membrane inflation method. The presence of DOPA in the membranes enhances the adhesion on TiO 2 and tissue, although adhesion to tissue requires that the DOPA groups be oxidized while in contact with the tissue of interest. Porous hydrogel scaffolds for tissue engineering applications were formed by adding salt crystals to the triblock copolymer solution prior to solvent exchange. Salt was then leached out by immersing the gel into water. Structures of the porous hydrogels were characterized by confocal laser scanning microscopy. These hydrogels were shown to be suitable for tissue regeneration and drug delivery applications. Diffusion-mediated adhesion between two component miscible polymer systems having very different glassy temperatures was also investigated. Axisymmetric

  11. Repairable, nanostructured biomimetic hydrogels

    NASA Astrophysics Data System (ADS)

    Firestone, M.; Brombosz, S.; Grubjesic, S.

    2013-03-01

    Proteins facilitate many key cellular processes, including signal recognition and energy transduction. The ability to harness this evolutionarily-optimized functionality could lead to the development of protein-based systems useful for advancing alternative energy storage and conversion. The future of protein-based, however, requires the development of materials that will stabilize, order and control the activity of the proteins. Recently we have developed a synthetic approach for the preparation of a durable biomimetic chemical hydrogel that can be reversibly swollen in water. The matrix has proven ideal for the stable encapsulation of both water- and membrane-soluble proteins. The material is composed of an aqueous dispersion of a diacrylate end-derivatized PEO-PPO-PEO macromer, a saturated phospholipid and a zwitterionic co-surfactant that self-assembles into a nanostructured physical gel at room temperature as determined by X-ray scattering. The addition of a water soluble PEGDA co-monomer and photoinitator does not alter the self-assembled structure and UV irradiation serves to crosslink the acrylate end groups on the macromer with the PEGDA forming a network within the aqueous domains as determined by FT-IR. More recently we have begun to incorporate reversible crosslinks employing Diels-Alder chemistry, allowing for the extraction and replacement of inactive proteins. The ability to replenish the materials with active, non-denatured forms of protein is an important step in advancing these materials for use in nanostructured devices This work was supported by the Office of Basic Energy Sciences, Division of Materials Sciences, USDoE under Contract No. DE-AC02-06CH11357.

  12. Environmentally Responsive Hydrogels: Development and Integration with Hard Materials

    NASA Astrophysics Data System (ADS)

    Chatterjee, Prithwish

    Environmentally responsive hydrogels are one interesting class of soft materials. Due to their remarkable responsiveness to stimuli such as temperature, pH, or light, they have attracted widespread attention in many fields. However, certain functionality of these materials alone is often limited in comparison to other materials such as silicon; thus, there is a need to integrate soft and hard materials for the advancement of environmentally responsive materials. Conventional hydrogels lack good mechanical properties and have inherently slow response time, important characteristics which must be improved before the hydrogels can be integrated with silicon. In the present dissertation work, both these important attributes of a temperature responsive hydrogel, poly(N-isopropylacrylamide) (PNIPAAm), were improved by adopting a low temperature polymerization process and adding a silicate compound, tetramethyl orthosilicate. Furthermore, the transition temperature was modulated by adjusting the media quality in which the hydrogels were equilibrated, e.g. by adding a co-solvent (methanol) or an anionic surfactant (sodium dodecyl sulfate). Interestingly, the results revealed that, based on the hydrogels' porosity, there were appreciable differences when the PNIPAAm hydrogels interacted with the media molecules. Next, an adhesion mechanism was developed in order to transfer silicon thin film onto the hydrogel surface. This integration provided a means of mechanical buckling of the thin silicon film due to changes in environmental stimuli (e.g., temperature, pH). We also investigated how novel transfer printing techniques could be used to generate patterned deformation of silicon thin film when integrated on a planar hydrogel substrate. Furthermore, we explore multilayer hybrid hydrogel structures formed by the integration of different types of hydrogels that have tunable curvatures under the influence of different stimuli. Silicon thin film integration on such tunable

  13. A practical guide to hydrogels for cell culture.

    PubMed

    Caliari, Steven R; Burdick, Jason A

    2016-04-28

    There is growing appreciation of the role that the extracellular environment plays in regulating cell behavior. Mechanical, structural, and compositional cues, either alone or in concert, can drastically alter cell function. Biomaterials, and particularly hydrogels, have been developed and implemented to present defined subsets of these cues for investigating countless cellular processes as a means of understanding morphogenesis, aging, and disease. Although most scientists concede that standard cell culture materials (tissue culture plastic and glass) do a poor job of recapitulating native cellular milieus, there is currently a knowledge barrier for many researchers in regard to the application of hydrogels for cell culture. Here, we introduce hydrogels to those who may be unfamiliar with procedures to culture and study cells with these systems, with a particular focus on commercially available hydrogels.

  14. Skeletal tissue regeneration: where can hydrogels play a role?

    PubMed

    Moreira Teixeira, Liliana S; Patterson, Jennifer; Luyten, Frank P

    2014-09-01

    The emerging field of tissue engineering reveals promising approaches for the repair and regeneration of skeletal tissues including the articular cartilage, bone, and the entire joint. Amongst the myriad of biomaterials available to support this strategy, hydrogels are highly tissue mimicking substitutes and thus of great potential for the regeneration of functional tissues. This review comprises an overview of the novel and most promising hydrogels for articular cartilage, osteochondral and bone defect repair. Chondro- and osteo-conductive and -instructive hydrogels are presented, highlighting successful combinations with inductive signals and cell sources. Moreover, advantages, drawbacks, and future perspectives of the role of hydrogels in skeletal regeneration are addressed, pointing out the current state of this rising approach. PMID:24968789

  15. Nanostructured conducting polymer hydrogels for energy storage applications.

    PubMed

    Shi, Ye; Peng, Lele; Yu, Guihua

    2015-08-14

    Conducting polymer hydrogels are emerging as a promising class of polymeric materials for various technological applications, especially for energy storage devices due to their unique combination of advantageous features of conventional polymers and organic conductors. To overcome the drawbacks of conventional synthesis, new synthetic routes in which acid molecules are adopted as both crosslinkers and dopants have been developed for conducting polymer hydrogels with unique 3D hierarchical porous nanostructures, resulting in high electrical conductivity, large surface area, structural tunability and hierarchical porosity for rapid mass/charge transport. The newly developed conducting polymer hydrogels exhibit high performance when applied as active electrode materials for electrochemical capacitors or as functional binder materials for high-energy lithium-ion batteries. This feature article summarizes the synthesis of conducting polymer hydrogels, presents their applications in energy storage, and discusses further opportunities and challenges.

  16. Opportunities for Multicomponent Hybrid Hydrogels in Biomedical Applications

    PubMed Central

    2015-01-01

    Hydrogels provide mechanical support and a hydrated environment that offer good cytocompatibility and controlled release of molecules, and myriad hydrogels thus have been studied for biomedical applications. In the past few decades, research in these areas has shifted increasingly to multicomponent hydrogels that better capture the multifunctional nature of native biological environments and that offer opportunities to selectively tailor materials properties. This review summarizes recent approaches aimed at producing multicomponent hydrogels, with descriptions of contemporary chemical and physical approaches for forming networks, and of the use of both synthetic and biologically derived molecules to impart desired properties. Specific multicomponent materials with enhanced mechanical properties are presented, as well as materials in which multiple biological functions are imparted for applications in tissue engineering, cancer treatment, and gene therapies. The progress in the field suggests significant promise for these approaches in the development of biomedically relevant materials. PMID:25426888

  17. The rational design of a peptide-based hydrogel responsive to H2S.

    PubMed

    Peltier, Raoul; Chen, Ganchao; Lei, Haipeng; Zhang, Mei; Gao, Liqian; Lee, Su Seong; Wang, Zuankai; Sun, Hongyan

    2015-12-18

    The development of hydrogels that are responsive to external stimuli in a well-controlled manner is important for numerous biomedical applications. Herein we reported the first example of a hydrogel responsive to hydrogen sulphide (H2S). H2S is an important gasotransmitter whose deregulation has been associated with a number of pathological conditions. Our hydrogel design is based on the functionalization of an ultrashort hydrogelating peptide sequence with an azidobenzyl moiety, which was reported to react with H2S selectively under physiological conditions. The resulting peptide was able to produce hydrogels at a concentration as low as 0.1 wt%. It could then be fully degraded in the presence of excess H2S. We envision that the novel hydrogel developed in this study may provide useful tools for biomedical research. PMID:26463661

  18. Facile One-step Micropatterning Using Photodegradable Methacrylated Gelatin Hydrogels for Improved Cardiomyocyte Organization and Alignment

    PubMed Central

    Tsang, Kelly M.C.; Annabi, Nasim; Ercole, Francesca; Zhou, Kun; Karst, Daniel; Li, Fanyi; Haynes, John M.; Evans, Richard A.; Thissen, Helmut

    2015-01-01

    Hydrogels are often employed as temporary platforms for cell proliferation and tissue organization in vitro. Researchers have incorporated photodegradable moieties into synthetic polymeric hydrogels as a means of achieving spatiotemporal control over material properties. In this study protein-based photodegradable hydrogels composed of methacrylated gelatin (GelMA) and a crosslinker containing o-nitrobenzyl ester groups have been developed. The hydrogels are able to degrade rapidly and specifically in response to UV light and can be photopatterned to a variety of shapes and dimensions in a one-step process. Micropatterned photodegradable hydrogels are shown to improve cell distribution, alignment and beating regularity of cultured neonatal rat cardiomyocytes. Overall this work introduces a new class of photodegradable hydrogel based on natural and biofunctional polymers as cell culture substrates for improving cellular organization and function. PMID:26327819

  19. Injectable Hydrogel Composite Based Gelatin-PEG and Biphasic Calcium Phosphate Nanoparticles for Bone Regeneration

    NASA Astrophysics Data System (ADS)

    Van, Thuy Duong; Tran, Ngoc Quyen; Nguyen, Dai Hai; Nguyen, Cuu Khoa; Tran, Dai Lam; Nguyen, Phuong Thi

    2016-05-01

    Gelatin hydrogels have recently attracted much attention for tissue regeneration because of their biocompatibility. In this study, we introduce poly-ethylene glycol (PEG)—grafted gelatin containing tyramine moieties which have been utilized for in situ enzyme-mediated hydrogel preparation. The hydrogel can be used to load nanoparticles of biphasic calcium phosphate, a mixture of hydroxyapatite and β-tricalcium phosphate, and forming injectable bio-composites. Proton nuclear magnetic resonance (1H NMR) spectra indicated that tyramine-functionalized polyethylene glycol-nitrophenyl carbonate ester was conjugated to the gelatin. The hydrogel composite was rapidly formed in situ (within a few seconds) in the presence of horseradish peroxidase and hydrogen peroxide. In vitro experiments with bio-mineralization on the hydrogel composite surfaces was well-observed after 2 weeks soaking in simulated body fluid solution. The obtained results indicated that the hydrogel composite could be a potential injectable material for bone regeneration.

  20. A new strategy for electrochemical immunoassay based on enzymatic silver deposition on agarose beads.

    PubMed

    Luo, Yan; Mao, Xun; Peng, Zhao-Feng; Jiang, Jian-Hui; Shen, Guo-Li; Yu, Ru-Qin

    2008-02-15

    A novel, sensitive electrochemical immunoassay in a homogeneously dispersed medium is described herein based on the unique features of agarose beads and the special amplified properties of biometallization. The immunochemical recognition event between human immunoglobulin G (IgG) and goat anti-human IgG antibody is chosen as the model system to demonstrate the proposed immunoassay approach. Avidin-agarose beads rapidly react with the biotinylated goat anti-human IgG antibody to form agarose beads-goat anti-human IgG conjugate (agarose bead-Ab). Agarose bead-Ab, alkaline phosphatase conjugated goat anti-human IgG antibody (ALP-Ab) and the human IgG analyte are mixed to form sandwich-type immunocomplex followed by the addition of the enzymatic silver deposition solution to deposit silver onto the surface of proteins and agarose beads. The silver deposited are dissolved and quantified by anodic stripping voltammetry. The influence of relevant experimental variables was examined and optimized. The logarithm of the anodic stripping peak current depended linearly on the logarithm of the concentration of human IgG in the range from 1 to 1000ng/ml. A detection limit as low as 0.5ng/ml human IgG was attained by 3sigma-rule. The R.S.D. of the approach is 9.65% for eight times determination of 10ng/ml human IgG under same conditions. Optical microscope and TEM graphs were also utilized to characterize agarose beads and silver nanoparticles formed.

  1. Osteochondral defect repair using a polyvinyl alcohol-polyacrylic acid (PVA-PAAc) hydrogel.

    PubMed

    Bichara, David A; Bodugoz-Sentruk, Hatice; Ling, Doris; Malchau, Erik; Bragdon, Charles R; Muratoglu, Orhun K

    2014-08-01

    Poly(vinyl alcohol) (PVA) hydrogels can be candidates for articular cartilage repair due to their high water content. We synthesized a PVA-poly(acrylic acid) (PAAc) hydrogel formulation and determined its ability to function as a treatment option for condylar osteochondral (OC) defects in a New Zealand white rabbit (NZWR) model for 12 weeks and 24 weeks. In addition to hydrogel OC implants, tensile bar-shaped hydrogels were also implanted subcutaneously to evaluate changes in mechanical properties as a function of in vivo duration. There were no statistically significant differences (p > 0.05) in the water content measured in the OC hydrogel implant that was harvested after 12 weeks and 24 weeks, and non-implanted controls. There were no statistically significant differences (p > 0.05) in the break stress, strain at break or modulus of the tensile bars either between groups. Histological analysis of the OC defect, synovial capsule and fibrous tissue around the tensile bars determined hydrogel biocompatibility. Twelve-week hydrogels were found to be in situ flush with the articular cartilage; meniscal tissue demonstrated an intact surface. Twenty-four week hydrogels protruded from the defect site due to lack of integration with subchondral tissue, causing fibrillation to the meniscal surface. Condylar micro-CT scans ruled out osteolysis and bone cysts of the subchondral bone, and no PVA-PAAc hydrogel contents were found in the synovial fluid. The PVA-PAAc hydrogel was determined to be fully biocompatible, maintained its properties over time, and performed well at the 12 week time point. Physical fixation of the PVA-PAAc hydrogel to the subchondral bone is required to ensure long-term performance of hydrogel plugs for OC defect repair.

  2. Periodontal Tissue Regeneration Using Enzymatically Solidified Chitosan Hydrogels With or Without Cell Loading

    PubMed Central

    Yan, Xiang-Zhen; van den Beucken, Jeroen J.J.P.; Cai, Xinjie; Yu, Na; Jansen, John A.

    2015-01-01

    This study is aimed to evaluate the in vivo biocompatibility and periodontal regenerative potential of enzymatically solidified chitosan hydrogels with or without incorporated periodontal ligament cells (PDLCs). To this end, chitosan hydrogels, with (n=8; CHIT+CELL) or without (n=8; CHIT) fluorescently labeled PDLCs, were prepared and transplanted into rat intrabony periodontal defects; untreated defects were used as empty controls (n=8; EMPTY). After 4 weeks, maxillae were harvested, decalcified, and used for histological, histomorphometrical, and immunohistochemical assessments. The results showed that PDLCs remained viable upon encapsulation within chitosan hydrogels before transplantation. Histological analysis demonstrated that the chitosan hydrogels were largely degraded after 4 weeks of implantation, without any adverse reaction in the surrounding tissue. In terms of periodontal regeneration, alveolar bone height, alveolar bone area, and epithelial downgrowth were comparable for CHIT, CHIT+CELL, as well as EMPTY groups. In contrast, both CHIT and CHIT+CELL showed a significant increase in functional ligament length compared with EMPTY. From a cellular perspective, the contribution of chitosan hydrogel-incorporated cells to the periodontal regeneration could not be ascertained, as no signal from transplanted PDLCs could be detected at 4 weeks posttransplantation. The results demonstrated that enzymatically solidified chitosan hydrogels are highly biocompatible and biodegradable. Moreover, chitosan hydrogels without cell loading can improve periodontal regeneration in terms of functional ligament length, indicating the great potential of this hydrogel in clinical applications. Further work on the use of chitosan hydrogels as cell carriers is required. PMID:25345525

  3. Cyclodextrin Inclusion Polymers Forming Hydrogels

    NASA Astrophysics Data System (ADS)

    Li, Jun

    This chapter reviews the advances in the developments of supramolecular hydrogels based on the polypseudorotaxanes and polyrotaxanes formed by inclusion complexes of cyclodextrins threading onto polymer chains. Both physical and chemical supramolecular hydrogels of many different types are discussed with respect to their preparation, structure, property, and gelation mechanism. A large number of physical supramolecular hydrogels were formed induced by self-assembly of densely packed cyclodextrin rings threaded on polymer or copolymer chains acting as physical crosslinking points. The thermo-reversible and thixotropic properties of these physical supramolecular hydrogels have inspired their applications as injectable drug delivery systems. Chemical supramolecular hydrogels synthesized from polypseudorotaxanes and polyrotaxanes were based on the chemical crosslinking of either the cyclodextrin molecules or the included polymer chains. The chemical supramolecular hydrogels were often made biodegradable through incorporation of hydrolyzable threading polymers, end caps, or crosslinkers, for their potential applications as biomaterials.

  4. Nondestructive evaluation of hydrogel mechanical properties using ultrasound

    PubMed Central

    Walker, Jason M.; Myers, Ashley M.; Schluchter, Mark D.; Goldberg, Victor M.; Caplan, Arnold I.; Berilla, Jim A.; Mansour, Joseph M.; Welter, Jean F.

    2012-01-01

    The feasibility of using ultrasound technology as a noninvasive, nondestructive method for evaluating the mechanical properties of engineered weight-bearing tissues was evaluated. A fixture was designed to accurately and reproducibly position the ultrasound transducer normal to the test sample surface. Agarose hydrogels were used as phantoms for cartilage to explore the feasibility of establishing correlations between ultrasound measurements and commonly used mechanical tissue assessments. The hydrogels were fabricated in 1–10% concentrations with a 2–10 mm thickness. For each concentration and thickness, six samples were created, for a total of 216 gel samples. Speed of sound was determined from the time difference between peak reflections and the known height of each sample. Modulus was computed from the speed of sound using elastic and poroelastic models. All ultrasonic measurements were made using a 15 MHz ultrasound transducer. The elastic modulus was also determined for each sample from a mechanical unconfined compression test. Analytical comparison and statistical analysis of ultrasound and mechanical testing data was carried out. A correlation between estimates of compressive modulus from ultrasonic and mechanical measurements was found, but the correlation depended on the model used to estimate the modulus from ultrasonic measurements. A stronger correlation with mechanical measurements was found using the poroelastic rather than the elastic model. Results from this preliminary testing will be used to guide further studies of native and engineered cartilage. PMID:21773854

  5. Hydrogels for central nervous system therapeutic strategies.

    PubMed

    Russo, Teresa; Tunesi, Marta; Giordano, Carmen; Gloria, Antonio; Ambrosio, Luigi

    2015-12-01

    The central nervous system shows a limited regenerative capacity, and injuries or diseases, such as those in the spinal, brain and retina, are a great problem since current therapies seem to be unable to achieve good results in terms of significant functional recovery. Different promising therapies have been suggested, the aim being to restore at least some of the lost functions. The current review deals with the use of hydrogels in developing advanced devices for central nervous system therapeutic strategies. Several approaches, involving cell-based therapy, delivery of bioactive molecules and nanoparticle-based drug delivery, will be first reviewed. Finally, some examples of injectable hydrogels for the delivery of bioactive molecules in central nervous system will be reported, and the key features as well as the basic principles in designing multifunctional devices will be described.

  6. Direct printing of silver nanoparticles by an agarose stamp on planar and patterned substrates.

    PubMed

    Kao, Yu-Chih; Hong, Franklin Chau-Nan

    2011-05-01

    In this study, we have used an agarose stamp to conduct direct printing of silver nanoparticles, nanowires and nanoplates on both planar and structured substrates. Nanoparticle solution could be first coated on an agarose stamp, and then transferred to a planar substrate. Micro-patterns comprising metal nanoparticles could be printed on planar substrates without the formation of residual layers. Thus a three-dimensional metal microstructure could be easily fabricated. The patterning of electrodes by printing Ag nanowires directly on TiO(2) was also demonstrated to fabricate resistive random access memory (RRAM) devices by all-solution-processing methods. By using a flat agarose stamp, the patterns printed on the microstructured substrates were quite different from those on the nanostructured substrates. On the microstructured substrates, direct printing could print silver nanoparticles onto the protrusion surface, and could print silver layers as thick as several microns, useful for high conductivity electrodes. On the substrates with nanostructures such as photonic crystals or nano-gratings, direct printing could transfer nanoparticles into the grooves or cavities only due to the contact of the agarose stamp with the groove or concavity surface. A new approach to fabricate metal wire grid polarizers was further demonstrated. A nanoporous agarose stamp has a good potential for printing using nanoparticle suspension.

  7. Rapid agarose gel electrophoretic mobility shift assay for quantitating protein: RNA interactions.

    PubMed

    Ream, Jennifer A; Lewis, L Kevin; Lewis, Karen A

    2016-10-15

    Interactions between proteins and nucleic acids are frequently analyzed using electrophoretic mobility shift assays (EMSAs). This technique separates bound protein:nucleic acid complexes from free nucleic acids by electrophoresis, most commonly using polyacrylamide gels. The current study utilizes recent advances in agarose gel electrophoresis technology to develop a new EMSA protocol that is simpler and faster than traditional polyacrylamide methods. Agarose gels are normally run at low voltages (∼10 V/cm) to minimize heating and gel artifacts. In this study we demonstrate that EMSAs performed using agarose gels can be run at high voltages (≥20 V/cm) with 0.5 × TB (Tris-borate) buffer, allowing for short run times while simultaneously yielding high band resolution. Several parameters affecting band and image quality were optimized for the procedure, including gel thickness, agarose percentage, and applied voltage. Association of the siRNA-binding protein p19 with its target RNA was investigated using the new system. The agarose gel and conventional polyacrylamide gel methods generated similar apparent binding constants in side-by-side experiments. A particular advantage of the new approach described here is that the short run times (5-10 min) reduce opportunities for dissociation of bound complexes, an important concern in non-equilibrium nucleic acid binding experiments. PMID:27495142

  8. Isolation and restriction endonuclease cleavage of Anaplasma marginale DNA in situ in agarose.

    PubMed Central

    Krueger, C M; Buening, G M

    1988-01-01

    Bacterial restriction endonucleases were used to produce DNA cleavage patterns that could be useful as tools to study the relatedness among Anaplasma marginale isolates. Bovine erythrocytes infected with A. marginale were lysed, washed, and embedded in agarose. The embedded erythrocytes and bacterial pathogens were partially digested by sequential infiltration of the agarose with acetone, lysozyme, sodium dodecyl sulfate, and proteinase K. The unfragmented genomic DNA was left supported and protected in a porous matrix. The DNA was digested in situ in agarose under the following conditions: (i) brief treatment with phenol, (ii) brief washing with distilled water, and (iii) adjustment of restriction enzyme digestion mixture to compensate for the volume of the agarose. The cleaved DNA was electrophoresed horizontally to produce a DNA cleavage pattern. Of 19 restriction enzymes screened, 12 produced distinct DNA bands from the genomes of each of the five A. marginale isolates examined. The DNA cleavage pattern produced from each isolate with a given restriction enzyme was reproducible. However, the DNA cleavage patterns produced from different isolates with a given restriction enzyme were not necessarily identical. This procedure could be modified for general bacterial DNA isolation, in situ agarose digestion, and manipulations. Images PMID:2838504

  9. Recent advances in clay mineral-containing nanocomposite hydrogels.

    PubMed

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

    2015-12-28

    Clay mineral-containing nanocomposite hydrogels have been proven to have exceptional composition, properties, and applications, and consequently have attracted a significant amount of research effort over the past few years. The objective of this paper is to summarize and evaluate scientific advances in clay mineral-containing nanocomposite hydrogels in terms of their specific preparation, formation mechanisms, properties, and applications, and to identify the prevailing challenges and future directions in the field. The state-of-the-art of existing technologies and insights into the exfoliation of layered clay minerals, in particular montmorillonite and LAPONITE®, are discussed first. The formation and structural characteristics of polymer/clay nanocomposite hydrogels made from in situ free radical polymerization, supramolecular assembly, and freezing-thawing cycles are then examined. Studies indicate that additional hydrogen bonding, electrostatic interactions, coordination bonds, hydrophobic interaction, and even covalent bonds could occur between the clay mineral nanoplatelets and polymer chains, thereby leading to the formation of unique three-dimensional networks. Accordingly, the hydrogels exhibit exceptional optical and mechanical properties, swelling-deswelling behavior, and stimuli-responsiveness, reflecting the remarkable effects of clay minerals. With the pivotal roles of clay minerals in clay mineral-containing nanocomposite hydrogels, the nanocomposite hydrogels possess great potential as superabsorbents, drug vehicles, tissue scaffolds, wound dressing, and biosensors. Future studies should lay emphasis on the formation mechanisms with in-depth insights into interfacial interactions, the tactical functionalization of clay minerals and polymers for desired properties, and expanding of their applications. PMID:26435008

  10. Recent advances in clay mineral-containing nanocomposite hydrogels.

    PubMed

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

    2015-12-28

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

  11. MWNT-hybrided supramolecular hydrogel for hydrophobic camptothecin delivery.

    PubMed

    Mu, Shansong; Liang, Yuanyuan; Chen, Shuaijun; Zhang, Liming; Liu, Tao

    2015-05-01

    To encapsulate the hydrophobic camptothecin (CPT) into hydrogel matrix with a high loading amount, a supramolecular hydrogel hybrided with multi-walled carbon nanotubes (MWNTs) was developed by the host-guest interactions and used for loading and delivering CPT. Firstly, carboxylated MWNTs were modified by polyethylene glycol monomethyl ether (MPEG), which resulted in the water-dispersed MPEG-MWNTs. Then α-cyclodextrin (α-CD) was mixed with MPEG-MWNTs and the hybrid supramolecular hydrogel was fabricated by the inclusion interactions between α-CD and MPEG. The used MPEG not only dispersed MWNTs in aqueous solution, but also functioned as hydrogel matrix by interacting with α-CD. The gelation time for the sol-gel transition and rheological properties of the resultant hydrogels were studied. Due to the excellent application of MWNTs in drug delivery, hydrophobic CPT could be loaded into the hydrogel matrix by a higher amount compared with micelles. By in vitro release and cell viability tests, it was found that the encapsulated CPT could exhibit a controlled and sustained release behavior as well as sustained antitumor efficacy.

  12. Decellularized myocardial matrix hydrogels: In basic research and preclinical studies.

    PubMed

    Wang, Raymond M; Christman, Karen L

    2016-01-15

    A variety of decellularized materials have been developed that have demonstrated potential for treating cardiovascular diseases and improving our understanding of cardiac development. Of these biomaterials, decellularized myocardial matrix hydrogels have shown great promise for creating cellular microenvironments representative of the native cardiac tissue and treating the heart after a myocardial infarction. Decellularized myocardial matrix hydrogels derived from porcine cardiac tissue form a nanofibrous hydrogel once thermally induced at physiological temperatures. Use of isolated cardiac extracellular matrix in 2D and 3D in vitro platforms has demonstrated the capability to provide tissue specific cues for cardiac cell growth and differentiation. Testing of the myocardial matrix hydrogel as a therapy after myocardial infarction in both small and large animal models has demonstrated improved left ventricular function, increased cardiac muscle, and cellular recruitment into the treated infarct. Based on these results, steps are currently being taken to translate these hydrogels into a clinically used injectable biomaterial therapy. In this review, we will focus on the basic science and preclinical studies that have accelerated the development of decellularized myocardial matrix hydrogels into an emerging novel therapy for treating the heart after a myocardial infarction.

  13. Engineering Protein Hydrogels Using SpyCatcher-SpyTag Chemistry.

    PubMed

    Gao, Xiaoye; Fang, Jie; Xue, Bin; Fu, Linglan; Li, Hongbin

    2016-09-12

    Constructing hydrogels from engineered proteins has attracted significant attention within the material sciences, owing to their myriad potential applications in biomedical engineering. Developing efficient methods to cross-link tailored protein building blocks into hydrogels with desirable mechanical, physical, and functional properties is of paramount importance. By making use of the recently developed SpyCatcher-SpyTag chemistry, we successfully engineered protein hydrogels on the basis of engineered tandem modular elastomeric proteins. Our resultant protein hydrogels are soft but stable, and show excellent biocompatibility. As the first step, we tested the use of these hydrogels as a drug carrier, as well as in encapsulating human lung fibroblast cells. Our results demonstrate the robustness of the SpyCatcher-SpyTag chemistry, even when the SpyTag (or SpyCatcher) is flanked by folded globular domains. These results demonstrate that SpyCatcher-SpyTag chemistry can be used to engineer protein hydrogels from tandem modular elastomeric proteins that can find applications in tissue engineering, in fundamental mechano-biological studies, and as a controlled drug release vehicle. PMID:27477779

  14. Engineering Protein Hydrogels Using SpyCatcher-SpyTag Chemistry.

    PubMed

    Gao, Xiaoye; Fang, Jie; Xue, Bin; Fu, Linglan; Li, Hongbin

    2016-09-12

    Constructing hydrogels from engineered proteins has attracted significant attention within the material sciences, owing to their myriad potential applications in biomedical engineering. Developing efficient methods to cross-link tailored protein building blocks into hydrogels with desirable mechanical, physical, and functional properties is of paramount importance. By making use of the recently developed SpyCatcher-SpyTag chemistry, we successfully engineered protein hydrogels on the basis of engineered tandem modular elastomeric proteins. Our resultant protein hydrogels are soft but stable, and show excellent biocompatibility. As the first step, we tested the use of these hydrogels as a drug carrier, as well as in encapsulating human lung fibroblast cells. Our results demonstrate the robustness of the SpyCatcher-SpyTag chemistry, even when the SpyTag (or SpyCatcher) is flanked by folded globular domains. These results demonstrate that SpyCatcher-SpyTag chemistry can be used to engineer protein hydrogels from tandem modular elastomeric proteins that can find applications in tissue engineering, in fundamental mechano-biological studies, and as a controlled drug release vehicle.

  15. A new three dimensional biomimetic hydrogel to deliver factors secreted by human mesenchymal stem cells in spinal cord injury.

    PubMed

    Caron, Ilaria; Rossi, Filippo; Papa, Simonetta; Aloe, Rossella; Sculco, Marika; Mauri, Emanuele; Sacchetti, Alessandro; Erba, Eugenio; Panini, Nicolò; Parazzi, Valentina; Barilani, Mario; Forloni, Gianluigi; Perale, Giuseppe; Lazzari, Lorenza; Veglianese, Pietro

    2016-01-01

    Stem cell therapy with human mesenchymal stem cells (hMSCs) represents a promising strategy in spinal cord injury (SCI). However, both systemic and parenchymal hMSCs administrations show significant drawbacks as a limited number and viability of stem cells in situ. Biomaterials able to encapsulate and sustain hMSCs represent a viable approach to overcome these limitations potentially improving the stem cell therapy. In this study, we evaluate a new agarose/carbomer based hydrogel which combines different strategies to optimize hMSCs viability, density and delivery of paracrine factors. Specifically, we evaluate a new loading procedure on a lyophilized scaffold (soaked up effect) that reduces mechanical stress in encapsulating hMSCs into the hydrogel. In addition, we combine arginine-glycine-aspartic acid (RGD) tripeptide and 3D extracellular matrix deposition to increase the capacity to attach and maintain healthy hMSCs within the hydrogel over time. Furthermore, the fluidic diffusion from the hydrogel toward the injury site is improved by using a cling film that oriented efficaciously the delivery of paracrine factors in vivo. Finally, we demonstrate that an improved combination as here proposed of hMSCs and biomimetic hydrogel is able to immunomodulate significantly the pro-inflammatory environment in a SCI mouse model, increasing M2 macrophagic population and promoting a pro-regenerative environment in situ.

  16. A new three dimensional biomimetic hydrogel to deliver factors secreted by human mesenchymal stem cells in spinal cord injury.

    PubMed

    Caron, Ilaria; Rossi, Filippo; Papa, Simonetta; Aloe, Rossella; Sculco, Marika; Mauri, Emanuele; Sacchetti, Alessandro; Erba, Eugenio; Panini, Nicolò; Parazzi, Valentina; Barilani, Mario; Forloni, Gianluigi; Perale, Giuseppe; Lazzari, Lorenza; Veglianese, Pietro

    2016-01-01

    Stem cell therapy with human mesenchymal stem cells (hMSCs) represents a promising strategy in spinal cord injury (SCI). However, both systemic and parenchymal hMSCs administrations show significant drawbacks as a limited number and viability of stem cells in situ. Biomaterials able to encapsulate and sustain hMSCs represent a viable approach to overcome these limitations potentially improving the stem cell therapy. In this study, we evaluate a new agarose/carbomer based hydrogel which combines different strategies to optimize hMSCs viability, density and delivery of paracrine factors. Specifically, we evaluate a new loading procedure on a lyophilized scaffold (soaked up effect) that reduces mechanical stress in encapsulating hMSCs into the hydrogel. In addition, we combine arginine-glycine-aspartic acid (RGD) tripeptide and 3D extracellular matrix deposition to increase the capacity to attach and maintain healthy hMSCs within the hydrogel over time. Furthermore, the fluidic diffusion from the hydrogel toward the injury site is improved by using a cling film that oriented efficaciously the delivery of paracrine factors in vivo. Finally, we demonstrate that an improved combination as here proposed of hMSCs and biomimetic hydrogel is able to immunomodulate significantly the pro-inflammatory environment in a SCI mouse model, increasing M2 macrophagic population and promoting a pro-regenerative environment in situ. PMID:26497428

  17. Understanding the adhesion phenomena in carbohydrate-hydrogel-based systems: Water up-take, swelling and elastic detachment.

    PubMed

    Caccavo, Diego; Lamberti, Gaetano; Cascone, Sara; Barba, Anna Angela; Larsson, Anette

    2015-10-20

    The bio-adhesion is a complex phenomenon which takes place when two materials (at least one of biological nature, the other usually is a polymeric one) are held together for extended periods of time, usually for local drug delivery purposes. Despite bio-adhesion is widely exploited in commercial pharmaceuticals such as the buccal patches, the underlying phenomena of the process are not completely clarified yet. In this study experimental tests, in which the role of biological membranes is played by a water-rich agarose gel whereas patches are mimicked by hydrogel tablets (made of Carbopol or of Carbopol added with NaCl), have been used to analyze the behavior of the model system above described. Tablets have been forced to adhere on the agarose gel, and after a given contact time they have been detached, recording the required forces. Furthermore weight gain of the tablets (the water transported from the agarose gel toward the tablet) has been quantified. Water transport (during the time in which the contact between tablet and agarose gel is held) and elastic part of mechanical response during the detachment are modelled to achieve a better understanding of the adhesion process. Both the two sub-models nicely reproduce, respectively, the weight gain as well as the swelling of the Carbopol tablets, and the point at which the mechanical response ceases to be purely elastic. PMID:26256158

  18. Linear and fast hydrogel glucose sensor materials enabled by volume resetting agents.

    PubMed

    Zhang, Chunjie; Cano, Gerry G; Braun, Paul V

    2014-08-27

    A volume resetting agent is incorporated into a boronic acid functionalized hydrogel containing an embedded photonic crystal, yielding a glucose sensor material with a linear and fast response, minimal hysteresis, and good stability under simulated physiological conditions. The hydrogel can be tuned to modulate both the sensitivity and kinetics. PMID:25042106

  19. Cartilage Tissue Engineering Application of Injectable Gelatin Hydrogel with In Situ Visible-Light-Activated Gelation Capability in Both Air and Aqueous Solution

    PubMed Central

    Lin, Hang; Cheng, Anthony Wai-Ming; Alexander, Peter G.; Beck, Angela M.

    2014-01-01

    Chondroprogenitor cells encapsulated in a chondrogenically supportive, three-dimensional hydrogel scaffold represents a promising, regenerative approach to articular cartilage repair. In this study, we have developed an injectable, biodegradable methacrylated gelatin (mGL)–based hydrogel capable of rapid gelation via visible light (VL)–activated crosslinking in air or aqueous solution. The mild photocrosslinking conditions permitted the incorporation of cells during the gelation process. Encapsulated human-bone-marrow-derived mesenchymal stem cells (hBMSCs) showed high, long-term viability (up to 90 days) throughout the scaffold. To assess the applicability of the mGL hydrogel for cartilage tissue engineering, we have evaluated the efficacy of chondrogenesis of the encapsulated hBMSCs, using hBMSCs seeded in agarose as control. The ability of hBMSC-laden mGL constructs to integrate with host tissues after implantation was further investigated utilizing an in vitro cartilage repair model. The results showed that the mGL hydrogel, which could be photopolymerized in air and aqueous solution, supports hBMSC growth and TGF-β3-induced chondrogenesis. Compared with agarose, mGL constructs laden with hBMSCs are mechanically stronger with time, and integrate well with native cartilage tissue upon implantation based on push-out mechanical testing. VL-photocrosslinked mGL scaffold thus represents a promising scaffold for cell-based repair and resurfacing of articular cartilage defects. PMID:24575844

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  1. Thermal-Responsive Behavior of a Cell Compatible Chitosan/Pectin Hydrogel.

    PubMed

    Birch, Nathan P; Barney, Lauren E; Pandres, Elena; Peyton, Shelly R; Schiffman, Jessica D

    2015-06-01

    Biopolymer hydrogels are important materials for wound healing and cell culture applications. While current synthetic polymer hydrogels have excellent biocompatibility and are nontoxic, they typically function as a passive matrix that does not supply any additional bioactivity. Chitosan (CS) and pectin (Pec) are natural polymers with active properties that are desirable for wound healing. Unfortunately, the synthesis of CS/Pec materials have previously been limited by harsh acidic synthesis conditions, which further restricted their use in biomedical applications. In this study, a zero-acid hydrogel has been synthesized from a mixture of chitosan and pectin at biologically compatible conditions. For the first time, we demonstrated that salt could be used to suppress long-range electrostatic interactions to generate a thermoreversible biopolymer hydrogel that has temperature-sensitive gelation. Both the hydrogel and the solution phases are highly elastic, with a power law index of close to -1. When dried hydrogels were placed into phosphate buffered saline solution, they rapidly rehydrated and swelled to incorporate 2.7× their weight. As a proof of concept, we removed the salt from our CS/Pec hydrogels, thus, creating thick and easy to cast polyelectrolyte complex hydrogels, which proved to be compatible with human marrow-derived stem cells. We suggest that our development of an acid-free CS/Pec hydrogel system that has excellent exudate uptake, holds potential for wound healing bandages.

  2. Spermidine cross-linked hydrogels as a controlled release biomimetic approach for cloxacillin.

    PubMed

    López-Cebral, Rita; Romero-Caamaño, Vanessa; Seijo, Begoña; Alvarez-Lorenzo, Carmen; Martín-Pastor, Manuel; Concheiro, Ángel; Landin, Mariana; Sanchez, Alejandro

    2014-07-01

    The intrinsic ability of albumin to bind active substances in the physiological fluids has been explored to endow hydrogels with improved capability to regulate drug release. To develop such biomimetic-functional hydrogels, it is critical that albumin conformation is not altered and that the protein remains retained inside the hydrogel keeping its conformational freedom, i.e., it should be not chemically cross-linked. Thus, the hydrogels were prepared with various proportions of albumin by physical cross-linking of anionic polysaccharides (gellan gum and chondroitin sulfate) with the cationic endogen polyamine spermidine under mild conditions in order to prevent albumin denaturation. Texture and swelling properties of hydrogels with various compositions were recorded, and the effect of the preparation variables was evaluated applying neurofuzzy logic tools for hydrogels prepared with and without albumin and associating the antibiotic cloxacillin. Developed hydrogel systems were extensively analyzed by means of nuclear magnetic resonance (NMR) to determine weak-to-medium and strong binding modes and the equilibrium constants of the albumin-cloxacillin association. NMR techniques were also employed to demonstrate the successful modulation of the cloxacillin release from the albumin-containing hydrogels. In vitro microbiological tests carried out with Staphylococcus aureus and Staphylococcus epidermidis confirmed the interest of the albumin-containing hydrogels as efficient platforms for cloxacillin release in its bioactive form.

  3. Spermidine cross-linked hydrogels as a controlled release biomimetic approach for cloxacillin.

    PubMed

    López-Cebral, Rita; Romero-Caamaño, Vanessa; Seijo, Begoña; Alvarez-Lorenzo, Carmen; Martín-Pastor, Manuel; Concheiro, Ángel; Landin, Mariana; Sanchez, Alejandro

    2014-07-01

    The intrinsic ability of albumin to bind active substances in the physiological fluids has been explored to endow hydrogels with improved capability to regulate drug release. To develop such biomimetic-functional hydrogels, it is critical that albumin conformation is not altered and that the protein remains retained inside the hydrogel keeping its conformational freedom, i.e., it should be not chemically cross-linked. Thus, the hydrogels were prepared with various proportions of albumin by physical cross-linking of anionic polysaccharides (gellan gum and chondroitin sulfate) with the cationic endogen polyamine spermidine under mild conditions in order to prevent albumin denaturation. Texture and swelling properties of hydrogels with various compositions were recorded, and the effect of the preparation variables was evaluated applying neurofuzzy logic tools for hydrogels prepared with and without albumin and associating the antibiotic cloxacillin. Developed hydrogel systems were extensively analyzed by means of nuclear magnetic resonance (NMR) to determine weak-to-medium and strong binding modes and the equilibrium constants of the albumin-cloxacillin association. NMR techniques were also employed to demonstrate the successful modulation of the cloxacillin release from the albumin-containing hydrogels. In vitro microbiological tests carried out with Staphylococcus aureus and Staphylococcus epidermidis confirmed the interest of the albumin-containing hydrogels as efficient platforms for cloxacillin release in its bioactive form. PMID:24921673

  4. Improved lectin-mediated immobilization of human red blood cells in superporous agarose beads.

    PubMed

    Gottschalk, Ingo; Gustavsson, Per Erik; Ersson, Bo; Lundahl, Per

    2003-01-25

    A new type of agarose bead, superporous agarose, was used as a gel support for immobilization of human red blood cells (RBCs) mediated by wheat germ lectin. The number of immobilized cells was similar to that obtained with commercial wheat germ lectin-agarose but the cell stability appeared to be superior. This allowed improved frontal affinity chromatographic analyses of cytochalasin B (CB)-binding to the glucose transporter GLUT1 which established a ratio of one CB-binding site per GLUT1 dimer for both plain RBCs or those treated with different poly amino acids. The measured dissociation constants, 70+/-14 nM for CB and 12+/-3 mM for glucose binding to GLUT1, are similar to those reported earlier.

  5. Quantitative determination of glycine in aqueous solution using glutamate dehydrogenase-immobilized glyoxal agarose beads.

    PubMed

    Keskin, Semra Yilmazer; Keskin, Can Serkan

    2014-01-01

    In this study, an enzymatic procedure for the determination of glycine (Gly) was developed by using a column containing immobilized glutamate dehydrogenase (GDH) on glyoxal agarose beads. Ammonia is produced from the enzymatic reactions between Gly and GDH with NAD(+) in phosphate buffer medium. The indophenol blue method was used for ammonia detection based on the spectrophotometric measurements of blue-colored product absorbing at 640 nm. The calibration graph is linear in the range of 0.1-10 mM of Gly concentrations. The effect of pH, temperature, and time interval was studied to find column stability, and also the interference effects of other amino acids was investigated. The interaction between GDH and glyoxal agarose beads was analyzed by Fourier transform infrared (FTIR) spectroscopy. The morphology of the immobilized and non-immobilized agarose beads were characterized by atomic force microscopy (AFM).

  6. Agarose- and alginate-based biopolymers for sample preparation: Excellent green extraction tools for this century.

    PubMed

    Sanagi, Mohd Marsin; Loh, Saw Hong; Wan Ibrahim, Wan Nazihah; Pourmand, Neda; Salisu, Ahmed; Wan Ibrahim, Wan Aini; Ali, Imran

    2016-03-01

    Recently, there has been considerable interest in the use of miniaturized sample preparation techniques before the chromatographic monitoring of the analytes in unknown complex compositions. The use of biopolymer-based sorbents in solid-phase microextraction techniques has achieved a good reputation. A great variety of polysaccharides can be extracted from marine plants or microorganisms. Seaweeds are the major sources of polysaccharides such as alginate, agar, agarose, as well as carrageenans. Agarose and alginate (green biopolymers) have been manipulated for different microextraction approaches. The present review is focused on the classification of biopolymer and their applications in multidisciplinary research. Besides, efforts have been made to discuss the state-of-the-art of the new microextraction techniques that utilize commercial biopolymer interfaces such as agarose in liquid-phase microextraction and solid-phase microextraction.

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

    PubMed

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

    2015-11-01

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

  8. A 3D printed microfluidic device for production of functionalized hydrogel microcapsules for culture and differentiation of human Neuronal Stem Cells (hNSC).

    PubMed

    Alessandri, Kevin; Feyeux, Maxime; Gurchenkov, Basile; Delgado, Christophe; Trushko, Anastasiya; Krause, Karl-Heinz; Vignjević, Daniela; Nassoy, Pierre; Roux, Aurélien

    2016-04-26

    We present here a microfluidic device that generates sub-millimetric hollow hydrogel spheres, encapsulating cells and coated internally with a layer of reconstituted extracellular matrix (ECM) of a few microns thick. The spherical capsules, composed of alginate hydrogel, originate from the spontaneous instability of a multi-layered jet formed by co-extrusion using a coaxial flow device. We provide a simple design to manufacture this device using a DLP (digital light processing) 3D printer. Then, we demonstrate how the inner wall of the capsules can be decorated with a continuous ECM layer that is anchored to the alginate gel and mimics the basal membrane of a cellular niche. Finally, we used this approach to encapsulate human Neural Stem Cells (hNSC) derived from human Induced Pluripotent Stem Cells (hIPSC), which were further differentiated into neurons within the capsules with negligible loss of viability. Altogether, we show that these capsules may serve as cell micro-containers compatible with complex cell culture conditions and applications. These developments widen the field of research and biomedical applications of the cell encapsulation technology. PMID:27025278

  9. Incorporation of aggrecan in interpenetrating network hydrogels to improve cellular performance for cartilage tissue engineering.

    PubMed

    Ingavle, Ganesh C; Frei, Anthony W; Gehrke, Stevin H; Detamore, Michael S

    2013-06-01

    Interpenetrating network (IPN) hydrogels were recently introduced to the cartilage tissue engineering literature, with the approach of encapsulating cells in thermally gelling agarose that is then soaked in a poly(ethylene glycol) diacrylate (PEGDA) solution, which is then photopolymerized. These IPNs possess significantly enhanced mechanical performance desirable for cartilage regeneration, potentially allowing patients to return to weight-bearing activities quickly after surgical implantation. In an effort to improve cell viability and performance, inspiration was drawn from previous studies that have elicited positive chondrogenic responses to aggrecan, the proteoglycan largely responsible for the compressive stiffness of cartilage. Aggrecan was incorporated into the IPNs in conservative concentrations (40 μg/mL), and its effect was contrasted with the incorporation of chondroitin sulfate (CS), the primary glycosaminoglycan associated with aggrecan. Aggrecan was incorporated by physical entrapment within agarose and methacrylated CS was incorporated by copolymerization with PEGDA. The IPNs incorporating aggrecan or CS exhibited over 50% viability with encapsulated chondrocytes after 6 weeks. Both aggrecan and CS improved cell viability by 15.6% and 20%, respectively, relative to pure IPNs at 6 weeks culture time. In summary, we have introduced the novel approach of including a raw material from cartilage, namely aggrecan, to serve as a bioactive signal to cells encapsulated in IPN hydrogels for cartilage tissue engineering, which led to improved performance of encapsulated chondrocytes. PMID:23379843

  10. Incorporation of Aggrecan in Interpenetrating Network Hydrogels to Improve Cellular Performance for Cartilage Tissue Engineering

    PubMed Central

    Ingavle, Ganesh C.; Frei, Anthony W.; Gehrke, Stevin H.

    2013-01-01

    Interpenetrating network (IPN) hydrogels were recently introduced to the cartilage tissue engineering literature, with the approach of encapsulating cells in thermally gelling agarose that is then soaked in a poly(ethylene glycol) diacrylate (PEGDA) solution, which is then photopolymerized. These IPNs possess significantly enhanced mechanical performance desirable for cartilage regeneration, potentially allowing patients to return to weight-bearing activities quickly after surgical implantation. In an effort to improve cell viability and performance, inspiration was drawn from previous studies that have elicited positive chondrogenic responses to aggrecan, the proteoglycan largely responsible for the compressive stiffness of cartilage. Aggrecan was incorporated into the IPNs in conservative concentrations (40 μg/mL), and its effect was contrasted with the incorporation of chondroitin sulfate (CS), the primary glycosaminoglycan associated with aggrecan. Aggrecan was incorporated by physical entrapment within agarose and methacrylated CS was incorporated by copolymerization with PEGDA. The IPNs incorporating aggrecan or CS exhibited over 50% viability with encapsulated chondrocytes after 6 weeks. Both aggrecan and CS improved cell viability by 15.6% and 20%, respectively, relative to pure IPNs at 6 weeks culture time. In summary, we have introduced the novel approach of including a raw material from cartilage, namely aggrecan, to serve as a bioactive signal to cells encapsulated in IPN hydrogels for cartilage tissue engineering, which led to improved performance of encapsulated chondrocytes. PMID:23379843

  11. Enzyme actuated bioresponsive hydrogels

    NASA Astrophysics Data System (ADS)

    Wilson, Andrew Nolan

    Bioresponsive hydrogels are emerging with technological significance in targeted drug delivery, biosensors and regenerative medicine. Conferred with the ability to respond to specific biologically derived stimuli, the design challenge is in effectively linking the conferred biospecificity with an engineered response tailored to the needs of a particular application. Moreover, the fundamental phenomena governing the response must support an appropriate dynamic range and limit of detection. The design of these systems is inherently complicated due to the high interdependency of the governing phenomena that guide the sensing, transduction, and the actuation response of hydrogels. To investigate the dynamics of these materials, model systems may be used which seek to interrogate the system dynamics by uni-variable experimentation and limit confounding phenomena such as: polymer-solute interactions, polymer swelling dynamics and biomolecular reaction-diffusion concerns. To this end, a model system, alpha-chymotrypsin (Cht) (a protease) and a cleavable peptide-chromogen (pro-drug) covalently incorporated into a hydrogel, was investigated to understand the mechanisms of covalent loading and release by enzymatic cleavage in bio-responsive delivery systems. Using EDC and Sulfo-NHS, terminal carboxyl groups of N-succinyl-Ala-Ala-Pro-Phe p-nitroanilide, a cleavable chromogen, were conjugated to primary amines of a hydrated poly(HEMA)-based hydrogel. Hydrogel discs were incubated in buffered Cht causing enzyme-mediated cleavage of the peptide and concomitant release of the chromophore for monitoring. To investigate substrate loading and the effects of hydrogel morphology on the system, the concentration of the amino groups (5, 10, 20, and 30 mol%) and the cross-linked density (1, 5, 7, 9 and 12 mol%) were independently varied. Loading-Release Efficiency of the chromogen was shown to exhibit a positive relation to increasing amino groups (AEMA). The release rates demonstrated a

  12. Magnetically aligned supramolecular hydrogels.

    PubMed

    Wallace, Matthew; Cardoso, Andre Zamith; Frith, William J; Iggo, Jonathan A; Adams, Dave J

    2014-12-01

    The magnetic-field-induced alignment of the fibrillar structures present in an aqueous solution of a dipeptide gelator, and the subsequent retention of this alignment upon transformation to a hydrogel upon the addition of CaCl2 or upon a reduction in solution pH is reported. Utilising the switchable nature of the magnetic field coupled with the slow diffusion of CaCl2 , it is possible to precisely control the extent of anisotropy across a hydrogel, something that is generally very difficult to do using alternative methods. The approach is readily extended to other compounds that form viscous solutions at high pH. It is expected that this work will greatly expand the utility of such low-molecular-weight gelators (LMWG) in areas where alignment is key. PMID:25345918

  13. Insitu grafting silica nanoparticles reinforced nanocomposite hydrogels

    NASA Astrophysics Data System (ADS)

    Yang, Jun; Han, Chun-Rui; Duan, Jiu-Fang; Xu, Feng; Sun, Run-Cang

    2013-10-01

    Highly flexible nanocomposite hydrogels were prepared by using silica nanoparticles (SNPs) as fillers and multi-functional cross-links to graft hydrophilic poly(acrylic acid) (PAA) by free radical polymerization from an aqueous solution. The SNPs were collected by neighboring polymer chains and dispersed uniformly within a PAA matrix. The mechanical properties of the nanocomposite hydrogels were tailored by the concentration of SNPs according to the percolation model. It was proposed that covalent bonds of adsorbed chains on the filler surface resulted in the formation of a shell of an immobilized glassy layer and trapped entanglements, where the glassy polymer layer greatly enhanced the elastic modulus and the release of trapped entanglements at deformation contributed to the viscoelastic properties.Highly flexible nanocomposite hydrogels were prepared by using silica nanoparticles (SNPs) as fillers and multi-functional cross-links to graft hydrophilic poly(acrylic acid) (PAA) by free radical polymerization from an aqueous solution. The SNPs were collected by neighboring polymer chains and dispersed uniformly within a PAA matrix. The mechanical properties of the nanocomposite hydrogels were tailored by the concentration of SNPs according to the percolation model. It was proposed that covalent bonds of adsorbed chains on the filler surface resulted in the formation of a shell of an immobilized glassy layer and trapped entanglements, where the glassy polymer layer greatly enhanced the elastic modulus and the release of trapped entanglements at deformation contributed to the viscoelastic properties. Electronic supplementary information (ESI) available: FTIR spectra of SNP after silane treatment, dynamic oscillatory shear measurements as a function of frequency, constrained polymer chain analysis by a change in the peak height in loss factor spectra, molecular weight of grafted chains at different stages of gelation, prediction of the SNP reinforcing mechanism in the

  14. Fabrication of superporous agarose beads for protein adsorption: effect of CaCO3 granules content.

    PubMed

    Du, Kai-Feng; Bai, Shu; Dong, Xiao-Yan; Sun, Yan

    2010-09-10

    Agarose gels were fabricated by water-in-oil emulsification with the addition of CaCO(3) granules at 8-16 wt%. Thus agarose beads of different superporosities were produced after dissolving the solid porogen. The superporous agarose (SA) and homogeneous agarose gels were double cross-linked and modified with diethylaminoethyl chloride to produce anion exchangers. We have proposed to use a superporous replica (porous titania microspheres) to examine the superporous structure and pore size distribution of the soft gel. The replica was prepared with the agarose gel entrapping CaCO(3) granules by a sol-gel-templating method. It was found that the superpores created by CaCO(3) granules were uniformly distributed and ranged from 0.95 microm to 1.33 microm. The physical properties of the gels were significantly affected by the porogen content. Importantly, by increasing the solid porogen to 12 wt%, the bed permeability and effective porosity increased about 48% and 33%, respectively. Further increase in the porogen to 16 wt% led to a decrease of the mechanical strength. With increasing superpores in the beads, the dynamic adsorption capacity of the packed columns increased obviously at 305-916 cm/h. Besides, the column efficiency changed less with increasing flow velocity up to 1200 cm/h. It was concluded that the use of 12 wt% CaCO(3) granules in agarose solution was beneficial for the fabrication of the SA gel with good mechanical stability and promising performance for protein chromatography.

  15. Plaque assay of Heliothis zea baculovirus employing a mixed agarose overlay.

    PubMed

    Yamada, K; Maramorosch, K

    1981-01-01

    The nuclear polyhedrosis virus of Heliothis zea has been titrated in Heliothis zea cells by the plaque method, using 1 percent mixed agarose containing a mixture of Seakem and Ultra pure agarose. Visible plaques, formed 8 days postinfection, ranged in diameter from 0.5 to 2 mm. Dose-response experiments indicated that a single particle initiated the formation of a plaque. The titration of Heliothis zea baculovirus by the newly described plaque method provides an accurate technique for the determination of virus concentration.

  16. Studies of assay conditions for macrophage migration from an agarose droplet.

    PubMed

    Fahlbusch, B; Dornberger, G

    1979-01-01

    The agarose microdroplet method is a relatively simple and economic technique to determine migration inhibition of leukocytes or macrophages in vitro. In the present study, further cultural and technical requirements of this method for the determination of macrophage migration inhibition have been defined: influence of macrophage handling before the assay, kinetics of migration and dependence on the pH of the medium. Considering defined conditions, the agarose microdoplet assay gives highly reliable and reproducible results. In comparative experiments, it proved to be as sensitive and valid as the capillary tube technique.

  17. Continuous Separation of Metallic and Semiconducting Carbon Nanotubes Using Agarose Gel

    NASA Astrophysics Data System (ADS)

    Tanaka, Takeshi; Urabe, Yasuko; Nishide, Daisuke; Kataura, Hiromichi

    2009-12-01

    We have developed a novel method to separate metallic and semiconducting single-wall carbon nanotubes (SWCNTs) with high purities using agarose gel. When an SWCNTs/sodium dodecyl sulfate (SDS) dispersion was applied to a column containing agarose gel beads, semiconducting SWCNTs were trapped by the beads, while metallic SWCNTs passed through the column. After the semiconducting SWCNTs adsorbed to the beads were eluted with sodium deoxycholate solution, the column could be used for repeated separation. Because this continuous, repeatable separation method is applicable to a low-cost, large-scale process, it should enable the industrial production of metallic and semiconducting SWCNTs.

  18. Self-Adjustable Adhesion of Polyampholyte Hydrogels.

    PubMed

    Roy, Chanchal Kumar; Guo, Hong Lei; Sun, Tao Lin; Ihsan, Abu Bin; Kurokawa, Takayuki; Takahata, Masakazu; Nonoyama, Takayuki; Nakajima, Tasuku; Gong, Jian Ping

    2015-12-01

    Developing nonspecific, fast, and strong adhesives that can glue hydrogels and biotissues substantially promotes the application of hydrogels as biomaterials. Inspired by the ubiquitous adhesiveness of bacteria, it is reported that neutral polyampholyte hydrogels, through their self-adjustable surface, can show rapid, strong, and reversible adhesion to charged hydrogels and biological tissues through the Coulombic interaction.

  19. Drying of poloxamer hydrogel films.

    PubMed

    Gu, Zhiyong; Alexandridis, Paschalis

    2004-06-01

    The drying of hydrogel films formed by Poloxamer 407 poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) amphiphilic block copolymer was investigated at various air relative humidity (RH) conditions ranging from 11 to 97%. Initially, the amount of water lost increased linearly with the drying time. After this linear region (stage I), a nonlinear behavior was observed (stage II). The drying rate increased with decreasing RH, thus greatly shortening the drying time. A decrease of the film thickness also shortened the drying time; however, the drying mechanism did not change. Three models for one-dimensional water diffusion were used to fit the experimental results at different RH conditions and film thicknesses. Model 1 assumes semi-infinite medium and constant diffusion coefficient, and fits very well the data in stage I of the drying process. The fitted water diffusion coefficient (D) is 5 x 10(-10) m(2)/s, whereas the effects of the RH are captured by a proportionality constant (alpha) that appears in the boundary condition. Model 2 considers a finite (constant) film thickness and captures the experimental observations over the whole drying period for the same D and alpha as in Model 1. The analytical solutions available for Models 1 and 2, used together with the experimentally derived model parameters D and alpha, allow for easy estimation of drying time and water loss from Poloxamer hydrogel films of various compositions and thicknesses and at different relative humidities. Numerical solutions for water diffusion under conditions of decreasing film thickness and diffusion coefficient being a function of concentration are also presented (Model 3). It becomes apparent from the fit of the data to the different models that the drying rate is more sensitive to the boundary condition at the film-air interface (represented by alpha) than to the diffusion in the film. It is notable that the alpha values obtained from the fits of the Poloxamer hydrogel drying

  20. Reinforcement of Mono- and Bi-layer Poly(Ethylene Glycol) Hydrogels with a Fibrous Collagen Scaffold.

    PubMed

    Kinneberg, K R C; Nelson, A; Stender, M E; Aziz, A H; Mozdzen, L C; Harley, B A C; Bryant, S J; Ferguson, V L

    2015-11-01

    Biomaterial-based tissue engineering strategies hold great promise for osteochondral tissue repair. Yet significant challenges remain in joining highly dissimilar materials to achieve a biomimetic, mechanically robust design for repairing interfaces between soft tissue and bone. This study sought to improve interfacial properties and function in a bi-layer hydrogel interpenetrated with a fibrous collagen scaffold. 'Soft' 10% (w/w) and 'stiff' 30% (w/w) PEGDM was formed into mono- or bi-layer hydrogels possessing a sharp diffusional interface. Hydrogels were evaluated as single-(hydrogel only) or multi-phase (hydrogel + fibrous scaffold penetrating throughout the stiff layer and extending >500 μm into the soft layer). Including a fibrous scaffold into both soft and stiff mono-layer hydrogels significantly increased tangent modulus and toughness and decreased lateral expansion under compressive loading. Finite element simulations predicted substantially reduced stress and strain gradients across the soft-stiff hydrogel interface in multi-phase, bilayer hydrogels. When combining two low moduli constituent materials, composites theory poorly predicts the observed, large modulus increases. These results suggest material structure associated with the fibrous scaffold penetrating within the PEG hydrogel as the major contributor to improved properties and function-the hydrogel bore compressive loads and the 3D fibrous scaffold was loaded in tension thus resisting lateral expansion. PMID:26001970

  1. Reinforcement of Mono- and Bi-layer Poly(Ethylene Glycol) Hydrogels with a Fibrous Collagen Scaffold.

    PubMed

    Kinneberg, K R C; Nelson, A; Stender, M E; Aziz, A H; Mozdzen, L C; Harley, B A C; Bryant, S J; Ferguson, V L

    2015-11-01

    Biomaterial-based tissue engineering strategies hold great promise for osteochondral tissue repair. Yet significant challenges remain in joining highly dissimilar materials to achieve a biomimetic, mechanically robust design for repairing interfaces between soft tissue and bone. This study sought to improve interfacial properties and function in a bi-layer hydrogel interpenetrated with a fibrous collagen scaffold. 'Soft' 10% (w/w) and 'stiff' 30% (w/w) PEGDM was formed into mono- or bi-layer hydrogels possessing a sharp diffusional interface. Hydrogels were evaluated as single-(hydrogel only) or multi-phase (hydrogel + fibrous scaffold penetrating throughout the stiff layer and extending >500 μm into the soft layer). Including a fibrous scaffold into both soft and stiff mono-layer hydrogels significantly increased tangent modulus and toughness and decreased lateral expansion under compressive loading. Finite element simulations predicted substantially reduced stress and strain gradients across the soft-stiff hydrogel interface in multi-phase, bilayer hydrogels. When combining two low moduli constituent materials, composites theory poorly predicts the observed, large modulus increases. These results suggest material structure associated with the fibrous scaffold penetrating within the PEG hydrogel as the major contributor to improved properties and function-the hydrogel bore compressive loads and the 3D fibrous scaffold was loaded in tension thus resisting lateral expansion.

  2. Cavitation, Elasticity and Fracture in Strong Hydrogels

    NASA Astrophysics Data System (ADS)

    Cui, Jun; Madkour, Ahmad; Tew, Gregory; Crosby, Alfred

    2010-03-01

    The interplay between the molecular network and material microstructure of a polymer-based hydrogel is critical for determining both the low strain elastic properties and fracture toughness. We present a novel complex hydrogel network developed by introducing polydimethylsiloxane (PDMS) into a polyethylene glycol (PEG)-based network. Using a combination of conventional characterization techniques, as well as the recently developed technique of cavitation rheology, we investigate the balance of elasticity and fracture in these complex networks. The polymer network maintains elasticity, with negligible hysteresis, at large strains over a wide range of swelling ratios. These properties are investigated across a continuum of length scales ranging from microns to centimeters by taking advantage of cavitation rheology, which uses the onset of an elastic instability to quantify local network mechanics. We compare our results with established scaling theories to describe both the elastic and fracture properties as a function of polymer volume fraction.

  3. Effects of DS-modified agarose gels on neurite extension in 3D scaffold through mechanisms other than changing the pore radius of the gels.

    PubMed

    Peng, Jin; Pan, Qian; Zhang, Wei; Yang, Hao; Zhou, Xue; Jiang, Hua

    2014-07-01

    Dermatan sulfate is widely distributed as glycosaminoglycan side chains of proteoglycans, which are the main components of glial scar and inhibit neurite regeneration after nerve injury. However its role in the inhibiting process is not clear. Understanding neurite extension in three-dimensional scaffolds is critical for neural tissue engineering. This study used agarose gels modified with dermatan sulfate as the three-dimensional culture scaffold. We explored structure-function relationship between the three-dimensional scaffold and neurite extension and examined the role of dermatan sulfate on neurite extension in the three-dimensional scaffold. A range of agarose concentrations was used to generate varied gel physical structures and the corresponding neurite extension of embryonic day (E9) chick dorsal root ganglia was examined. We measured gel stiffness and gel pore size to determine whether dermatan sulfate changed the gels' conformation. As gel concentration increased, neurite length and gel pore size decreased, and gel stiffness increased. At 1.00 and 1.25% (wt/vol) concentrations, dermatan sulfates both immobilized with agarose gels and dissolved in culture medium inhibit neurite extension. While at 1.50 and 1.75% (wt/vol) concentrations, only immobilized dermatan sulfate worked. Immobilized dermatan sulfate could modify molecular shape of agarose gels, decrease gel pore size statistically, but did not influence gel stiffness. We have proved that the decrease of gel pore size is insufficient to inhibit neurite extension. These results indicate that dermatan sulfate inhibits neurite extension not through forming a mechanical barrier. Maybe its interaction with neuron membrane is the key factor in neurite extension.

  4. Small-angle neutron scattering from polymer hydrogels with memory effect for medicine immobilization

    SciTech Connect

    Kulvelis, Yu. V. Lebedev, V. T.; Trunov, V. A.; Pavlyuchenko, V. N.; Ivanchev, S. S.; Primachenko, O. N.; Khaikin, S. Ya.

    2011-12-15

    Hydrogels synthesized based on cross-linked copolymers of 2-hydroxyethyl methacrylate and functional monomers (acrylic acid or dimethylaminoethyl methacrylate), having a memory effect with respect to target medicine (cefazolin), have been investigated by small-angle neutron scattering. The hydrogels are found to have a two-level structural organization: large (up to 100 nm) aggregates filled with network cells (4-7 nm in size). The structural differences in the anionic, cationic, and amphiphilic hydrogels and the relationship between their structure and the ability of hydrogels to absorb moisture are shown. A relationship between the memory effect during cefazolin immobilization and the internal structure of hydrogels, depending on their composition and type of functional groups, is established.

  5. Crosslinkable Hydrogels Derived from Cartilage, Meniscus, and Tendon Tissue

    PubMed Central

    Visser, Jetze; Levett, Peter A.; te Moller, Nikae C.R.; Besems, Jeremy; Boere, Kristel W.M.; van Rijen, Mattie H.P.; de Grauw, Janny C.; Dhert, Wouter J.A.; van Weeren, P. René

    2015-01-01

    Decellularized tissues have proven to be versatile matrices for the engineering of tissues and organs. These matrices usually consist of collagens, matrix-specific proteins, and a set of largely undefined growth factors and signaling molecules. Although several decellularized tissues have found their way to clinical applications, their use in the engineering of cartilage tissue has only been explored to a limited extent. We set out to generate hydrogels from several tissue-derived matrices, as hydrogels are the current preferred cell carriers for cartilage repair. Equine cartilage, meniscus, and tendon tissue was harvested, decellularized, enzymatically digested, and functionalized with methacrylamide groups. After photo-cross-linking, these tissue digests were mechanically characterized. Next, gelatin methacrylamide (GelMA) hydrogel was functionalized with these methacrylated tissue digests. Equine chondrocytes and mesenchymal stromal cells (MSCs) (both from three donors) were encapsulated and cultured in vitro up to 6 weeks. Gene expression (COL1A1, COL2A1, ACAN, MMP-3, MMP-13, and MMP-14), cartilage-specific matrix formation, and hydrogel stiffness were analyzed after culture. The cartilage, meniscus, and tendon digests were successfully photo-cross-linked into hydrogels. The addition of the tissue-derived matrices to GelMA affected chondrogenic differentiation of MSCs, although no consequent improvement was demonstrated. For chondrocytes, the tissue-derived matrix gels performed worse compared to GelMA alone. This work demonstrates for the first time that native tissues can be processed into crosslinkable hydrogels for the engineering of tissues. Moreover, the differentiation of encapsulated cells can be influenced in these stable, decellularized matrix hydrogels. PMID:25557049

  6. Crosslinkable hydrogels derived from cartilage, meniscus, and tendon tissue.

    PubMed

    Visser, Jetze; Levett, Peter A; te Moller, Nikae C R; Besems, Jeremy; Boere, Kristel W M; van Rijen, Mattie H P; de Grauw, Janny C; Dhert, Wouter J A; van Weeren, P René; Malda, Jos

    2015-04-01

    Decellularized tissues have proven to be versatile matrices for the engineering of tissues and organs. These matrices usually consist of collagens, matrix-specific proteins, and a set of largely undefined growth factors and signaling molecules. Although several decellularized tissues have found their way to clinical applications, their use in the engineering of cartilage tissue has only been explored to a limited extent. We set out to generate hydrogels from several tissue-derived matrices, as hydrogels are the current preferred cell carriers for cartilage repair. Equine cartilage, meniscus, and tendon tissue was harvested, decellularized, enzymatically digested, and functionalized with methacrylamide groups. After photo-cross-linking, these tissue digests were mechanically characterized. Next, gelatin methacrylamide (GelMA) hydrogel was functionalized with these methacrylated tissue digests. Equine chondrocytes and mesenchymal stromal cells (MSCs) (both from three donors) were encapsulated and cultured in vitro up to 6 weeks. Gene expression (COL1A1, COL2A1, ACAN, MMP-3, MMP-13, and MMP-14), cartilage-specific matrix formation, and hydrogel stiffness were analyzed after culture. The cartilage, meniscus, and tendon digests were successfully photo-cross-linked into hydrogels. The addition of the tissue-derived matrices to GelMA affected chondrogenic differentiation of MSCs, although no consequent improvement was demonstrated. For chondrocytes, the tissue-derived matrix gels performed worse compared to GelMA alone. This work demonstrates for the first time that native tissues can be processed into crosslinkable hydrogels for the engineering of tissues. Moreover, the differentiation of encapsulated cells can be influenced in these stable, decellularized matrix hydrogels.

  7. Performance of an in situ formed bioactive hydrogel dressing from a PEG-based hyperbranched multifunctional copolymer.

    PubMed

    Dong, Yixiao; Hassan, Waqar U; Kennedy, Robert; Greiser, Udo; Pandit, Abhay; Garcia, Yolanda; Wang, Wenxin

    2014-05-01

    Hydrogel dressings have been widely used for wound management due to their ability to maintain a hydrated wound environment, restore the skin's physical barrier and facilitate regular dressing replacement. However, the therapeutic functions of standard hydrogel dressings are restricted. In this study, an injectable hybrid hydrogel dressing system was prepared from a polyethylene glycol (PEG)-based thermoresponsive hyperbranched multiacrylate functional copolymer and thiol-modified hyaluronic acid in combination with adipose-derived stem cells (ADSCs). The cell viability, proliferation and metabolic activity of the encapsulated ADSCs were studied in vitro, and a rat dorsal full-thickness wound model was used to evaluate this bioactive hydrogel dressing in vivo. It was found that long-term cell viability could be achieved for both in vitro (21days) and in vivo (14days) studies. With ADSCs, this hydrogel system prevented wound contraction and enhanced angiogenesis, showing the potential of this system as a bioactive hydrogel dressing for wound healing.

  8. Performance of an in situ formed bioactive hydrogel dressing from a PEG-based hyperbranched multifunctional copolymer.

    PubMed

    Dong, Yixiao; Hassan, Waqar U; Kennedy, Robert; Greiser, Udo; Pandit, Abhay; Garcia, Yolanda; Wang, Wenxin

    2014-05-01

    Hydrogel dressings have been widely used for wound management due to their ability to maintain a hydrated wound environment, restore the skin's physical barrier and facilitate regular dressing replacement. However, the therapeutic functions of standard hydrogel dressings are restricted. In this study, an injectable hybrid hydrogel dressing system was prepared from a polyethylene glycol (PEG)-based thermoresponsive hyperbranched multiacrylate functional copolymer and thiol-modified hyaluronic acid in combination with adipose-derived stem cells (ADSCs). The cell viability, proliferation and metabolic activity of the encapsulated ADSCs were studied in vitro, and a rat dorsal full-thickness wound model was used to evaluate this bioactive hydrogel dressing in vivo. It was found that long-term cell viability could be achieved for both in vitro (21days) and in vivo (14days) studies. With ADSCs, this hydrogel system prevented wound contraction and enhanced angiogenesis, showing the potential of this system as a bioactive hydrogel dressing for wound healing. PMID:24389319

  9. Peptide-modified zwitterionic porous hydrogels for endothelial cell and vascular engineering.

    PubMed

    Lin, Chih-Yeh; Wang, Yi-Ren; Lin, Che-Wei; Wang, Shih-Wen; Chien, Hsiu-Wen; Cheng, Nai-Chen; Tsai, Wei-Bor; Yu, Jiashing

    2014-12-01

    Hydrogels allow control of gel composition and mechanics, and permit incorporation of cells and a wide variety of molecules from nanoparticles to micromolecules. Peptide-linked hydrogels should tune the basic polymer into a more bioactive template to influence cellular activities. In this study, we first introduced the generation of 2D poly-(sulfobetaine methacrylate [SBMA]) hydrogel surfaces. By incorporating with functional peptide RGD and vascular endothelial growth factor-mimicking peptide KLTWQELYQLKYKG (QK) peptides, endothelial cells attached to the surface well and proliferated in a short-term culturing. However, the mechanical property, which plays a crucial role directing the cellular functions and supporting the structures, decreased when peptides graft onto hydrogels. Manipulating the mechanical property was thus necessary, and the most related factor was the monomer concentration. From our results, the higher amount of SBMA caused greater stiffness in hydrogels. Following the 2D surface studies, we fabricated 3D porous hydrogels for cell scaffolds by several methods. The salt/particle leaching method showed a more reliable way than gas-foaming method to fabricate homogeneous and open-interconnected pores within the hydrogel. Using the salt/particle leaching method, we can control the pore size before leaching. Morphology of endothelial cells within scaffolds was also investigated by scanning electron microscopy, and histological analysis was conducted in vitro and in vivo to test the biocompatibility of SB hydrogel and its potential as a therapeutic reagent for ischemic tissue repair in mice. PMID:25469315

  10. Peptide-Modified Zwitterionic Porous Hydrogels for Endothelial Cell and Vascular Engineering

    PubMed Central

    Lin, Chih-Yeh; Wang, Yi-Ren; Lin, Che-Wei; Wang, Shih-Wen; Chien, Hsiu-Wen; Cheng, Nai-Chen; Tsai, Wei-Bor

    2014-01-01

    Abstract Hydrogels allow control of gel composition and mechanics, and permit incorporation of cells and a wide variety of molecules from nanoparticles to micromolecules. Peptide-linked hydrogels should tune the basic polymer into a more bioactive template to influence cellular activities. In this study, we first introduced the generation of 2D poly-(sulfobetaine methacrylate [SBMA]) hydrogel surfaces. By incorporating with functional peptide RGD and vascular endothelial growth factor-mimicking peptide KLTWQELYQLKYKG (QK) peptides, endothelial cells attached to the surface well and proliferated in a short-term culturing. However, the mechanical property, which plays a crucial role directing the cellular functions and supporting the structures, decreased when peptides graft onto hydrogels. Manipulating the mechanical property was thus necessary, and the most related factor was the monomer concentration. From our results, the higher amount of SBMA caused greater stiffness in hydrogels. Following the 2D surface studies, we fabricated 3D porous hydrogels for cell scaffolds by several methods. The salt/particle leaching method showed a more reliable way than gas-foaming method to fabricate homogeneous and open-interconnected pores within the hydrogel. Using the salt/particle leaching method, we can control the pore size before leaching. Morphology of endothelial cells within scaffolds was also investigated by scanning electron microscopy, and histological analysis was conducted in vitro and in vivo to test the biocompatibility of SB hydrogel and its potential as a therapeutic reagent for ischemic tissue repair in mice. PMID:25469315

  11. Biodegradable DNA-enabled poly(ethylene glycol) hydrogels prepared by copper-free click chemistry.

    PubMed

    Barker, Karolyn; Rastogi, Shiva K; Dominguez, Jose; Cantu, Travis; Brittain, William; Irvin, Jennifer; Betancourt, Tania

    2016-01-01

    Significant research has focused on investigating the potential of hydrogels in various applications and, in particular, in medicine. Specifically, hydrogels that are biodegradable lend promise to many therapeutic and biosensing applications. Endonucleases are critical for mechanisms of DNA repair. However, they are also known to be overexpressed in cancer and to be present in wounds with bacterial contamination. In this work, we set out to demonstrate the preparation of DNA-enabled hydrogels that could be degraded by nucleases. Specifically, hydrogels were prepared through the reaction of dibenzocyclooctyne-functionalized multi-arm poly(ethylene glycol) with azide-functionalized single-stranded DNA in aqueous solutions via copper-free click chemistry. Through the use of this method, biodegradable hydrogels were formed at room temperature in buffered saline solutions that mimic physiological conditions, avoiding possible harmful effects associated with other polymerization techniques that can be detrimental to cells or other bioactive molecules. The degradation of these DNA-cross-linked hydrogels upon exposure to the model endonucleases Benzonase(®) and DNase I was studied. In addition, the ability of the hydrogels to act as depots for encapsulation and nuclease-controlled release of a model protein was demonstrated. This model has the potential to be tailored and expanded upon for use in a variety of applications where mild hydrogel preparation techniques and controlled material degradation are necessary including in drug delivery and wound healing systems. PMID:26541212

  12. Biodegradable DNA-enabled poly(ethylene glycol) hydrogels prepared by copper-free click chemistry.

    PubMed

    Barker, Karolyn; Rastogi, Shiva K; Dominguez, Jose; Cantu, Travis; Brittain, William; Irvin, Jennifer; Betancourt, Tania

    2016-01-01

    Significant research has focused on investigating the potential of hydrogels in various applications and, in particular, in medicine. Specifically, hydrogels that are biodegradable lend promise to many therapeutic and biosensing applications. Endonucleases are critical for mechanisms of DNA repair. However, they are also known to be overexpressed in cancer and to be present in wounds with bacterial contamination. In this work, we set out to demonstrate the preparation of DNA-enabled hydrogels that could be degraded by nucleases. Specifically, hydrogels were prepared through the reaction of dibenzocyclooctyne-functionalized multi-arm poly(ethylene glycol) with azide-functionalized single-stranded DNA in aqueous solutions via copper-free click chemistry. Through the use of this method, biodegradable hydrogels were formed at room temperature in buffered saline solutions that mimic physiological conditions, avoiding possible harmful effects associated with other polymerization techniques that can be detrimental to cells or other bioactive molecules. The degradation of these DNA-cross-linked hydrogels upon exposure to the model endonucleases Benzonase(®) and DNase I was studied. In addition, the ability of the hydrogels to act as depots for encapsulation and nuclease-controlled release of a model protein was demonstrated. This model has the potential to be tailored and expanded upon for use in a variety of applications where mild hydrogel preparation techniques and controlled material degradation are necessary including in drug delivery and wound healing systems.

  13. 3-D Self-Assembling Leucine Zipper Hydrogel With Tunable Properties For Tissue Engineering

    PubMed Central

    Huang, Chun-Chieh; Ravindran, Sriram; Yin, Ziying; George, Anne

    2014-01-01

    Peptide-based engineered hydrogel scaffolds present several advantages over traditional protein or polymeric hydrogels by imparting more robust control over hydrogel properties. In this manuscript, we report the synthesis and characterization of a leucine zipper (LZ) based self assembling hydrogel for use in tissue engineering applications. Although, LZ hydrogels posses several advantages, the stability of these hydrogels has always been elusive. In this study, we have standardized the procedure for creating a stable LZ hydrogel. Pore-size was tunable by altering the peptide concentration from 7% to 12% by weight. In order to create a microenvironment for cell adhesion, the LZ polypeptide was functionalized by the incorporation of the cell attachment RGD domain. In vivo implantation of the LZ scaffolds in a mouse model showed absence of foreign body reaction to the scaffold. In vivo experiments with human marrow stem cells (HMSCs) in immunocompromised mice showed the biological property of the hydrogel to promote cell attachment, proliferation and its ability to support neovascularization. Our results show for the first time, that it is possible to generate a functional and stable LZ scaffold that can be used in vivo for tissue engineering applications. PMID:24713184

  14. Enhancement of mesenchymal stem cell angiogenic capacity and stemness by a biomimetic hydrogel scaffold

    PubMed Central

    Rustad, Kristine C.; Wong, Victor W.; Sorkin, Michael; Glotzbach, Jason P.; Major, Melanie R.; Rajadas, Jayakumar; Longaker, Michael T.; Gurtner, Geoffrey C.

    2014-01-01

    In this study, we examined the capacity of a biomimetic pullulan–collagen hydrogel to create a functional biomaterial-based stem cell niche for the delivery of mesenchymal stem cells (MSCs) into wounds. Murine bone marrow-derived MSCs were seeded into hydrogels and compared to MSCs grown in standard culture conditions. Hydrogels induced MSC secretion of angiogenic cytokines and expression of transcription factors associated with maintenance of pluripotency and self-renewal (Oct4, Sox2, Klf4) when compared to MSCs grown in standard conditions. An excisonal wound healing model was used to compare the ability of MSC-hydrogel constructs versus MSC injection alone to accelerate wound healing. Injection of MSCs did not significantly improve time to wound closure. In contrast, wounds treated with MSC-seeded hydrogels showed significantly accelerated healing and a return of skin appendages. Bioluminescence imaging and FACS analysis of luciferase+/GFP+ MSCs indicated that stem cells delivered within the hydrogel remained viable longer and demonstrated enhanced engraftment efficiency than those delivered via injection. Engrafted MSCs were found to differentiate into fibroblasts, pericytes and endothelial cells but did not contribute to the epidermis. Wounds treated with MSC-seeded hydrogels demonstrated significantly enhanced angiogenesis, which was associated with increased levels of VEGF and other angiogenic cytokines within the wounds. Our data suggest that biomimetic hydrogels provide a functional niche capable of augmenting MSC regenerative potential and enhancing wound healing. PMID:21963148

  15. Organic hydrogels as potential sorbent materials for water purification

    NASA Astrophysics Data System (ADS)

    Linardatos, George; Bekiari, Vlasoula; Bokias, George

    2014-05-01

    Hydrogels are three-dimensional, hydrophilic, polymeric networks capable to adsorb large amounts of water or biological fluids. The networks are composed of homopolymers or copolymers and are insoluble due to the presence of chemical or physical cross-links. Depending on the nature of the structural units, swelling or shrinking of these gels can be activated by several external stimuli, such as solvent, heat, pH, electric stimuli. As a consequence, these materials are attractive for several applications in a variety of fields: drug delivery, muscle mimetic soft linear actuators, hosts of nanoparticles and semiconductors, regenerative medicine etc. Of special interest is the application of hydrogels for water purification, since they can effectively adsorb several water soluble pollutants such as metal ions, inorganic or organic anions, organic dyestaff, etc. In the present work, anionic hydrogels bearing negatively charged -COO- groups were prepared and investigated. These are based on the anionic monomer sodium acrylate (ANa) and the nonionic one N,N-dimethylacrylamide (DMAM). A series of copolymeric hydrogels (P(DMAM-co-ANax) were synthesized. The molar content x of ANa units (expressing the molar charged content of the hydrogel) varies from 0 (nonionic poly(N,N-dimethylacrylamide), PDMAM, hydrogel) up to 1 (fully charged poly(sodium acrylate), PANa, hydrogel). The hydrogels were used to extract organic or inorganic solutes from water. Cationic and anionic model dyes, as well as multivalent inorganic ions, have been studied. It is found that cationic dyes are strongly adsorbed and retained by the hydrogels, while adsorbance of anionic dyes was negligible. Both maximum adsorption and equilibrium binding constant depend on the chemical structure of the dye, the presence of functional chemical groups and the hydrophobic-hydrophilic balance. In the case of metal cations, adsorption depends mostly on the charge of the cation. In addition, crucial factors controlling

  16. Can You Solve the Crime? Using Agarose Electrophoresis To Identify an Unknown Colored Protein.

    ERIC Educational Resources Information Center

    Wiltfong, Cynthia L.; Chester, Emily; Albertin, Faith; Smith, Julia; Hall, Judith C.; Arth, Emily C.; Martin, Stephanie

    2003-01-01

    Describes a lab that introduces agarose electrophoresis techniques and basic information on proteins to middle school and high school students. Insists that, built around a scenario in which students must solve a crime, the lab has real-world applications that should spark student interest. (KHR)

  17. Enhanced Resolution of DNA Separation Using Agarose Gel Electrophoresis Doped with Graphene Oxide.

    PubMed

    Li, Jialiang; Yang, Yushi; Mao, Zhou; Huang, Wenjie; Qiu, Tong; Wu, Qingzhi

    2016-12-01

    In this work, a novel agarose gel electrophoresis strategy has been developed for separation of DNA fragments by doping graphene oxide (GO) into agarose gel. The results show that the addition of GO into agarose gel significantly improved the separation resolution of DNA fragments by increasing the shift distances of both the single DNA fragments and the adjacent DNA fragments and completely eliminating the background noise derived from the diffusion of the excessive ethidium bromide (EB) dye in the gel after electrophoresis. The improved resolution of DNA fragments in GO-doped agarose gel could be attributed to the successive adsorption-desorption processes between DNA fragments and GO sheets, while the elimination of the background noise could be attributed to the adsorption of the excessive EB dye on the surface of GO sheets and high fluorescence quenching efficiency of GO. These results provide promising potential for graphene and its derivate utilized in various electrophoresis techniques for separation and detection of DAN fragments and other biomolecules. PMID:27637896

  18. Enhanced Resolution of DNA Separation Using Agarose Gel Electrophoresis Doped with Graphene Oxide

    NASA Astrophysics Data System (ADS)

    Li, Jialiang; Yang, Yushi; Mao, Zhou; Huang, Wenjie; Qiu, Tong; Wu, Qingzhi

    2016-09-01

    In this work, a novel agarose gel electrophoresis strategy has been developed for separation of DNA fragments by doping graphene oxide (GO) into agarose gel. The results show that the addition of GO into agarose gel significantly improved the separation resolution of DNA fragments by increasing the shift distances of both the single DNA fragments and the adjacent DNA fragments and completely eliminating the background noise derived from the diffusion of the excessive ethidium bromide (EB) dye in the gel after electrophoresis. The improved resolution of DNA fragments in GO-doped agarose gel could be attributed to the successive adsorption-desorption processes between DNA fragments and GO sheets, while the elimination of the background noise could be attributed to the adsorption of the excessive EB dye on the surface of GO sheets and high fluorescence quenching efficiency of GO. These results provide promising potential for graphene and its derivate utilized in various electrophoresis techniques for separation and detection of DAN fragments and other biomolecules.

  19. Agarose/gelatin immobilisation of tissues or embryo segments for orientated paraffin embedding and sectioning.

    PubMed

    McClelland, Kathryn S; Ng, Ee Ting; Bowles, Josephine

    2016-01-01

    The technique described in this protocol allows the user to position small tissues in the optimal orientation for paraffin embedding and sectioning by first immobilising the tissue in an agarose/gelatin cube. This method is an adaptation of methods used for early embryos and can be used for any small tissues or embryo segments. Processing of larger tissue sections using molds to create agarose/gelatin blocks has been described previously; this detailed protocol provides a method for dealing with much smaller tissues or embryos (≤5mm). The tissue is briefly fixed then an agarose/gelatin drop is created to surround the tissue. The tissue can be orientated as per the user's preference in the drop before it sets as is carved into a cube with a domed top. The cube is then dehydrated and goes through the embedding and sectioning process. The domed cube is easy to orientate when embedding the tissue in a wax block giving the user assured orientation of the small tissue for sectioning. Additionally, the agarose/gelatin cube is easy to see in the unmolded wax once embedded, making the region of interest easy to identify. PMID:26742717

  20. Effects of calcium salts of acidic monomers on mineral induction of phosphoprotein immobilized to agarose beads.

    PubMed

    Ito, Shuichi; Iijima, Masahiro; Motai, Fumiko; Mizoguchi, Itaru; Saito, Takashi

    2012-10-01

    The aim of this study is to evaluate the mineralizing potential of acidic monomers and their calcium salts for mineralization, using an in vitro mineral induction model. Phosvitin (PV) was used as a model phosphoprotein in this study. PV was immobilized on agarose beads with divinyl sulfone. Five aliquots of agarose-immobilized PV, acidic monomers, and their calcium salts were incubated in mineralizing solution at various concentrations. The PV beads and acidic monomers were incubated at 37°C. Samples were taken at several time points during the incubation. Then, the agarose beads were analyzed for bound calcium by atomic absorption spectrometry. The mineral formed on the agarose beads was identified as an apatite by microarea X-ray diffraction. Additionally, the specimens were observed using scanning electron microscopy (SEM). Mineral induction time decreased with increasing solution saturation. 4-METCa salt [calcium salt of 4-methacryloxyethyl trimellitate (CMET)] significantly reduced the mineral induction time. Using these data, the interfacial tension for mineral induction of PV and CMET was determined to be 90.1 and 92.7 ergs/cm(2), respectively. The mineral induced in each specimen after incubation for 24 h was identified by its X-ray diffraction pattern as apatite. SEM observation showed that lath-shaped crystals were formed on the surfaces of the CMET. We conclude that CMET could play a role in dentin remineralization.

  1. Mucin Agarose Gel Electrophoresis: Western Blotting for High-molecular-weight Glycoproteins.

    PubMed

    Ramsey, Kathryn A; Rushton, Zachary L; Ehre, Camille

    2016-06-14

    Mucins, the heavily-glycosylated proteins lining mucosal surfaces, have evolved as a key component of innate defense by protecting the epithelium against invading pathogens. The main role of these macromolecules is to facilitate particle trapping and clearance while promoting lubrication of the mucosa. During protein synthesis, mucins undergo intense O-glycosylation and multimerization, which dramatically increase the mass and size of these molecules. These post-translational modifications are critical for the viscoelastic properties of mucus. As a result of the complex biochemical and biophysical nature of these molecules, working with mucins provides many challenges that cannot be overcome by conventional protein analysis methods. For instance, their high-molecular-weight prevents electrophoretic migration via regular polyacrylamide gels and their sticky nature causes adhesion to experimental tubing. However, investigating the role of mucins in health (e.g., maintaining mucosal integrity) and disease (e.g., hyperconcentration, mucostasis, cancer) has recently gained interest and mucins are being investigated as a therapeutic target. A better understanding of the production and function of mucin macromolecules may lead to novel pharmaceutical approaches, e.g., inhibitors of mucin granule exocytosis and/or mucolytic agents. Therefore, consistent and reliable protocols to investigate mucin biology are critical for scientific advancement. Here, we describe conventional methods to separate mucin macromolecules by electrophoresis using an agarose gel, transfer protein into nitrocellulose membrane, and detect signal with mucin-specific antibodies as well as infrared fluorescent gel reader. These techniques are widely applicable to determine mucin quantitation, multimerization and to test the effects of pharmacological compounds on mucins.

  2. Development of an arginine-based cationic hydrogel platform: Synthesis, characterization and biomedical applications.

    PubMed

    Pang, Xuan; Wu, Jun; Chu, Chih-Chang; Chen, Xuesi

    2014-07-01

    A series of biodegradable and biocompatible cationic hybrid hydrogels was developed from water-soluble arginine-based unsaturated polymer (Arg-AG) and poly(ethylene glycol) diacrylate (PEG-DA) by a photocrosslinking method. The physicochemical, mechanical and biological properties of these hydrogels were intensively examined. The hydrogels were characterized in terms of equilibrium swelling ratio (Qeq), compression modulus and interior morphology. The effects of the chemical structure of the two Arg-AG precursors and the feed ratio of these precursors on the properties of resulting hybrid hydrogels were investigated. The crosslinking density and mechanical strength of the hybrid hydrogels increased with an increase in allylglycine (AG) content in the Arg-AG precursor, as the gelation efficiency (Gf) increased from 80% to 90%, but the swelling and pore size of the hybrid hydrogels decreased as the equilibrium swelling weight (Qeq) decreased from 1890% to 1330% and the pore size from 28 to 22 μm. The short-term in vitro biodegradation properties of hydrogels were investigated as a function of Arg-AG chemical structures and enzymes. Hybrid hydrogels showed faster biodegradation in an enzyme solution than in a phosphate-buffered saline solution. Bovine serum albumin and insulin release profiles indicated that this cationic hydrogel system could significantly improve the sustained release of the negatively charged proteins. The cellular response of the hybrid hydrogels was preliminarily evaluated by cell attachment, encapsulation and proliferation tests using live-dead and MTT assay. The results showed that the hybrid hydrogels supported cell attachment well and were nontoxic to the cells.

  3. Connections Matter: Channeled Hydrogels to Improve Vascularization

    PubMed Central

    Muehleder, Severin; Ovsianikov, Aleksandr; Zipperle, Johannes; Redl, Heinz; Holnthoner, Wolfgang

    2014-01-01

    The use of cell-laden hydrogels to engineer soft tissue has been emerging within the past years. Despite, several newly developed and sophisticated techniques to encapsulate different cell types the importance of vascularization of the engineered constructs is often underestimated. As a result, cell death within a construct leads to impaired function and inclusion of the implant. Here, we discuss the fabrication of hollow channels within hydrogels as a promising strategy to facilitate vascularization. Furthermore, we present an overview on the feasible use of removable spacers, 3D laser-, and planar processing strategies to create channels within hydrogels. The implementation of these structures promotes control over cell distribution and increases oxygen transport and nutrient supply in vitro. However, many studies lack the use of endothelial cells in their approaches leaving out an important factor to enhance vessel ingrowth and anastomosis formation upon implantation. In addition, the adequate endothelial cell type needs to be considered to make these approaches bridge the gap to in vivo applications. PMID:25453032

  4. Hyaluronic Acid Hydrogels for Biomedical Applications

    PubMed Central

    Burdick, Jason A.; Prestwich, Glenn D.

    2013-01-01

    Hyaluronic acid (HA), an immunoneutral polysaccharide that is ubiquitous in the human body, is crucial for many cellular and tissue functions and has been in clinical use for over thirty years. When chemically modified, HA can be transformed into many physical forms -- viscoelastic solutions, soft or stiff hydrogels, electrospun fibers, non-woven meshes, macroporous and fibrillar sponges, flexible sheets, and nanoparticulate fluids -- for use in a range of preclinical and clinical settings. Many of these forms are derived from the chemical crosslinking of pendant reactive groups by addition/condensation chemistry or by radical polymerization. Clinical products for cell therapy and regenerative medicine require crosslinking chemistry that is compatible with the encapsulation of cells and injection into tissues. Moreover, an injectable clinical biomaterial must meet marketing, regulatory, and financial constraints to provide affordable products that can be approved, deployed to the clinic, and used by physicians. Many HA-derived hydrogels meet these criteria, and can deliver cells and therapeutic agents for tissue repair and regeneration. This progress report covers both basic concepts and recent advances in the development of HA-based hydrogels for biomedical applications. PMID:21394792

  5. Engineering hydrogels as extracellular matrix mimics

    PubMed Central

    Geckil, Hikmet; Xu, Feng; Zhang, Xiaohui; Moon, SangJun

    2010-01-01

    Extracellular matrix (ECM) is a complex cellular environment consisting of proteins, proteoglycans, and other soluble molecules. ECM provides structural support to mammalian cells and a regulatory milieu with a variety of important cell functions, including assembling cells into various tissues and organs, regulating growth and cell–cell communication. Developing a tailored in vitro cell culture environment that mimics the intricate and organized nanoscale meshwork of native ECM is desirable. Recent studies have shown the potential of hydrogels to mimic native ECM. Such an engineered native-like ECM is more likely to provide cells with rational cues for diagnostic and therapeutic studies. The research for novel biomaterials has led to an extension of the scope and techniques used to fabricate biomimetic hydrogel scaffolds for tissue engineering and regenerative medicine applications. In this article, we detail the progress of the current state-of-the-art engineering methods to create cell-encapsulating hydrogel tissue constructs as well as their applications in in vitro models in biomedicine. PMID:20394538

  6. Protein surface patterning using nanoscale PEG hydrogels.

    PubMed

    Hong, Ye; Krsko, Peter; Libera, Matthew

    2004-12-01

    We have used focused electron-beam cross-linking to create nanosized hydrogels and thus present a new method with which to bring the attractive biocompatibility associated with macroscopic hydrogels into the submicron length-scale regime. Using amine-terminated poly(ethylene glycol) thin films on silicon substrates, we generate nanohydrogels with lateral dimensions of order 200 nm which can swell by a factor of at least five, depending on the radiative dose. With the focused electron beam, high-density arrays of such nanohydrogels can be flexibly patterned onto silicon surfaces. Significantly, the amine groups remain functional after e-beam exposure, and we show that they can be used to covalently bind proteins and other molecules. We use bovine serum albumin to amplify the number of amine groups, and we further demonstrate that different proteins can be covalently bound to different hydrogel pads on the same substrate to create multifunctional surfaces useful in emerging bio/proteomic and sensor technologies.

  7. Stem cells and injectable hydrogels: Synergistic therapeutics in myocardial repair.

    PubMed

    Sepantafar, Mohammadmajid; Maheronnaghsh, Reihan; Mohammadi, Hossein; Rajabi-Zeleti, Sareh; Annabi, Nasim; Aghdami, Nasser; Baharvand, Hossein

    2016-01-01

    One of the major problems in the treatment of cardiovascular diseases is the inability of myocardium to self-regenerate. Current therapies are unable to restore the heart's function after myocardial infarction. Myocardial tissue engineering is potentially a key approach to regenerate damaged heart muscle. Myocardial patches are applied surgically, whereas injectable hydrogels provide effective minimally invasive approaches to recover functional myocardium. These hydrogels are easily administered and can be either cell free or loaded with bioactive agents and/or cardiac stem cells, which may apply paracrine effects. The aim of this review is to investigate the advantages and disadvantages of injectable stem cell-laden hydrogels and highlight their potential applications for myocardium repair.

  8. Poly(2-oxazoline) hydrogels for controlled fibroblast attachment.

    PubMed

    Farrugia, Brooke L; Kempe, Kristian; Schubert, Ulrich S; Hoogenboom, Richard; Dargaville, Tim R

    2013-08-12

    Currently there is a lack of choice when selecting synthetic materials with the cell-instructive properties demanded by modern biomaterials. The purpose of this study was to investigate the attachment of cells onto hydrogels prepared from poly(2-oxazoline)s selectively functionalized with cell adhesion motifs. A water-soluble macromer based on the microwave-assisted cationic ring-opening polymerization of 2-methyl-2-oxazoline and 2-(dec-9-enyl)-2-oxazoline was functionalized with the peptide CRGDSG or controls using thiol-ene photochemistry followed by facile cross-linking in the presence of a dithiol cross-linker. The growth of human fibroblasts on the hydrogel surfaces was dictated by the structure and amount of incorporated peptide. Controls without any peptide showed resistance to cellular attachment. The benignity of the cross-linking conditions was demonstrated by the incorporation of fibroblasts within the hydrogels to produce three-dimensional cell-polymer constructs.

  9. Non-toxic agarose/gelatin-based microencapsulation system containing gallic acid for antifungal application.

    PubMed

    Lam, P-L; Gambari, R; Kok, S H-L; Lam, K-H; Tang, J C-O; Bian, Z-X; Lee, K K-H; Chui, C-H

    2015-02-01

    Aspergillus niger (A. niger) is a common species of Aspergillus molds. Cutaneous aspergillosis usually occurs in skin sites near intravenous injection and approximately 6% of cutaneous aspergillosis cases which do not involve burn or HIV-infected patients are caused by A. niger. Biomaterials and biopharmaceuticals produced from microparticle-based drug delivery systems have received much attention as microencapsulated drugs offer an improvement in therapeutic efficacy due to better human absorption. The frequently used crosslinker, glutaraldehyde, in gelatin-based microencapsulation systems is considered harmful to human beings. In order to tackle the potential risks, agarose has become an alternative polymer to be used with gelatin as wall matrix materials of microcapsules. In the present study, we report the eco-friendly use of an agarose/gelatin-based microencapsulation system to enhance the antifungal activity of gallic acid and reduce its potential cytotoxic effects towards human skin keratinocytes. We used optimal parameter combinations, such as an agarose/gelatin ratio of 1:1, a polymer/oil ratio of 1:60, a surfactant volume of 1% w/w and a stirring speed of 900 rpm. The minimum inhibitory concentration of microencapsulated gallic acid (62.5 µg/ml) was significantly improved when compared with that of the original drug (>750 µg/ml). The anti-A. niger activity of gallic acid -containing microcapsules was much stronger than that of the original drug. Following 48 h of treatment, skin cell survival was approximately 90% with agarose/gelatin microcapsules containing gallic acid, whereas cell viability was only 25-35% with free gallic acid. Our results demonstrate that agarose/gelatin-based microcapsules containing gallic acid may prove to be helpful in the treatment of A. niger-induced skin infections near intravenous injection sites.

  10. Biomimetic fiber assembled gradient hydrogel to engineer glycosaminoglycan enriched and mineralized cartilage: An in vitro study.

    PubMed

    Mohan, Neethu; Wilson, Jijo; Joseph, Dexy; Vaikkath, Dhanesh; Nair, Prabha D

    2015-12-01

    The study investigated the potential of electrospun fiber assembled hydrogel, with physical gradients of chondroitin sulfate (CS) and sol-gel-derived bioactive glass (BG), to engineer hyaline and mineralized cartilage in a single 3D system. Electrospun poly(caprolactone) (PCL) fibers incorporated with 0.1% w/w of CS (CSL) and 0.5% w/w of CS (CSH), 2.4% w/w of BG (BGL) and 12.5% w/w of BG (BGH) were fabricated. The CS showed a sustained release up to 3 days from CSL and 14 days from CSH fibers. Chondrocytes secreted hyaline like matrix with higher sulfated glycosaminoglycans (sGAG), collagen type II and aggrecan on CSL and CSH fibers. Mineralization was observed on BGL and BGH fibers when incubated in simulated body fluid for 14 days. Chondrocytes cultured on these fibers secreted a mineralized matrix that consisted of sGAG, hypertrophic proteins, collagen type X, and osteocalcin. The CS and BG incorporated PCL fiber mats were assembled in an agarose-gelatin hydrogel to generate a 3D hybrid scaffold. The signals in the fibers diffused and generated continuous opposing gradients of CS (chondrogenic signal) and BG (mineralization) in the hydrogel. The chondrocytes were encapsulated in hybrid scaffolds; live dead assay at 48 h showed viable cells. Cells maintained their phenotype and secreted specific extracellular matrix (ECM) in response to signals within the hydrogel. Continuous opposing gradients of sGAG enriched and mineralized ECM were observed surrounding each cell clusters on gradient hydrogel after 14 days of culture in response to the physical gradients of raw materials CS and BG. A construct with gradient mineralization might accelerate integration to subchondral bone during in vivo regeneration. PMID:26014103

  11. Biomimetic fiber assembled gradient hydrogel to engineer glycosaminoglycan enriched and mineralized cartilage: An in vitro study.

    PubMed

    Mohan, Neethu; Wilson, Jijo; Joseph, Dexy; Vaikkath, Dhanesh; Nair, Prabha D

    2015-12-01

    The study investigated the potential of electrospun fiber assembled hydrogel, with physical gradients of chondroitin sulfate (CS) and sol-gel-derived bioactive glass (BG), to engineer hyaline and mineralized cartilage in a single 3D system. Electrospun poly(caprolactone) (PCL) fibers incorporated with 0.1% w/w of CS (CSL) and 0.5% w/w of CS (CSH), 2.4% w/w of BG (BGL) and 12.5% w/w of BG (BGH) were fabricated. The CS showed a sustained release up to 3 days from CSL and 14 days from CSH fibers. Chondrocytes secreted hyaline like matrix with higher sulfated glycosaminoglycans (sGAG), collagen type II and aggrecan on CSL and CSH fibers. Mineralization was observed on BGL and BGH fibers when incubated in simulated body fluid for 14 days. Chondrocytes cultured on these fibers secreted a mineralized matrix that consisted of sGAG, hypertrophic proteins, collagen type X, and osteocalcin. The CS and BG incorporated PCL fiber mats were assembled in an agarose-gelatin hydrogel to generate a 3D hybrid scaffold. The signals in the fibers diffused and generated continuous opposing gradients of CS (chondrogenic signal) and BG (mineralization) in the hydrogel. The chondrocytes were encapsulated in hybrid scaffolds; live dead assay at 48 h showed viable cells. Cells maintained their phenotype and secreted specific extracellular matrix (ECM) in response to signals within the hydrogel. Continuous opposing gradients of sGAG enriched and mineralized ECM were observed surrounding each cell clusters on gradient hydrogel after 14 days of culture in response to the physical gradients of raw materials CS and BG. A construct with gradient mineralization might accelerate integration to subchondral bone during in vivo regeneration.

  12. Thermogelling and Chemoselectively Cross-Linked Hydrogels with Controlled Mechanical Properties and Degradation Behavior.

    PubMed

    Boere, Kristel W M; van den Dikkenberg, Joep; Gao, Yuan; Visser, Jetze; Hennink, Wim E; Vermonden, Tina

    2015-09-14

    Chemoselectively cross-linked hydrogels have recently gained increasing attention for the development of novel, injectable biomaterials given their limited side reactions. In this study, we compared the properties of hydrogels obtained by native chemical ligation (NCL) and its recently described variation termed oxo-ester-mediated native chemical ligation (OMNCL) in combination with temperature-induced physical gelation. Triblock copolymers consisting of cysteine functionalities, thermoresponsive N-isopropylacrylamide (NIPAAm) units and degradable moieties were mixed with functionalized poly(ethylene glycol) (PEG) cross-linkers. Thioester or N-hydroxysuccinimide (NHS) functionalities attached to PEG reacted with cysteine residues of the triblock copolymers via either an NCL or OMNCL pathway. The combined physical and chemical cross-linking resulted in rapid network formation and mechanically strong hydrogels. Stiffness of the hydrogels was highest for thermogels that were covalently linked via OMNCL. Specifically, the storage modulus after 4 h reached a value of 26 kPa, which was over a 100 times higher than hydrogels formed by solely thermal physical interactions. Endothelial cells showed high cell viability of 98 ± 2% in the presence of OMNCL cross-linked hydrogels after 16 h of incubation, in contrast to a low cell viability (13 ± 7%) for hydrogels obtained by NCL cross-linking. Lysozyme was loaded in the gels and after 2 days more than 90% was released, indicating that the cross-linking reaction was indeed chemoselective as the protein was not covalently grafted to the hydrogel network. Moreover, the degradation rates of these hydrogels under physiological conditions could be tailored from 12 days up to 6 months by incorporation of a monomer containing a hydrolyzable lactone ring in the thermosensitive triblock copolymer. These results demonstrate a high tunability of mechanical properties and degradation rates of these in situ forming hydrogels that could be

  13. Syneresis in agar hydrogels.

    PubMed

    Boral, Shilpi; Saxena, Anita; Bohidar, H B

    2010-03-01

    Agar hydrogels exhibit syneresis which creates internal osmotic stress on the physical network. It was observed that such a stress gives rise to characteristic pulsating modes (breathing modes). Experiments carried over a period of 60-day revealed that the network deformations grew monotonously when the solvent released by syneresis was removed periodically from gel surface. However, when the solvent was not withdrawn, the gel exhibited very slowly relaxing breathing modes. The swelling-deswelling dynamics has been discussed in the generalized framework of a dissipative damped oscillator.

  14. Co-delivery of antiviral and antifungal therapeutics for the treatment of sexually transmitted infections using a moldable, supramolecular hydrogel.

    PubMed

    Lee, Ashlynn L Z; Ng, Victor W L; Poon, Ghim Lee; Ke, Xiyu; Hedrick, James L; Yang, Yi Yan

    2015-02-18

    In this investigation, a therapeutic co-delivery hydrogel system is developed to provide effective HIV prophylaxis, alongside the prevention and/or treatment of candidiasis. Two components-a HIV reverse transcriptase inhibitor, tenofovir, and a cationic macromolecular antifungal agent derived from a vitamin D-functionalized polycarbonate (VD/BnCl (1:30))-are formulated into biodegradable vitamin D-functionalized polycarbonate/PEG-based supramolecular hydrogels. The hydrogels exhibit thixotropic properties and can be easily spread across surfaces for efficient drug absorption. Sustained release of tenofovir from the hydrogel is observed, where approximately 85% tenofovir is released within 3 h. VD/BnCl (1:30) does not impede drug diffusion from the hydrogel as the drug release profiles are similar with and without the polycation. Antimicrobial efficacy studies indicate that the hydrogels kill C. albicans efficiently with a minimum bactericidal concentration (MBC) of 0.25-0.5 g L(-1) . These hydrogels also eradicate C. albicans biofilm effectively at 4× MBC. When human dermal fibroblasts (as model mammalian cells) are treated with these hydrogels, cell viability remains high at above 80%, demonstrating excellent biocompatibility. When applied topically, this dual-functional hydrogel can potentially prevent HIV transmission and eliminate microbes that cause infections in the vulvovagina region.

  15. Hydrogel-Based Nanocomposites and Mesenchymal Stem Cells: A Promising Synergistic Strategy for Neurodegenerative Disorders Therapy

    PubMed Central

    Albani, Diego; Gloria, Antonio; Giordano, Carmen; Rodilossi, Serena; Russo, Teresa; D'Amora, Ugo; Tunesi, Marta; Cigada, Alberto; Ambrosio, Luigi; Forloni, Gianluigi

    2013-01-01

    Hydrogel-based materials are widely employed in the biomedical field. With regard to central nervous system (CNS) neurodegenerative disorders, the design of injectable nanocomposite hydrogels for in situ drug or cell release represents an interesting and minimally invasive solution that might play a key role in the development of successful treatments. In particular, biocompatible and biodegradable hydrogels can be designed as specific injectable tools and loaded with nanoparticles (NPs), to improve and to tailor their viscoelastic properties upon injection and release profile. An intriguing application is hydrogel loading with mesenchymal stem cells (MSCs) that are a very promising therapeutic tool for neurodegenerative or traumatic disorders of the CNS. This multidisciplinary review will focus on the basic concepts to design acellular and cell-loaded materials with specific and tunable rheological and functional properties. The use of hydrogel-based nanocomposites and mesenchymal stem cells as a synergistic strategy for nervous tissue applications will be then discussed. PMID:24459423

  16. Enhanced mechanical performance of biocompatible hemicelluloses-based hydrogel via chain extension.

    PubMed

    Qi, Xian-Ming; Chen, Ge-Gu; Gong, Xiao-Dong; Fu, Gen-Que; Niu, Ya-Shuai; Bian, Jing; Peng, Feng; Sun, Run-Cang

    2016-09-16

    Hemicelluloses are widely used to prepare gel materials because of their renewability, biodegradability, and biocompatibility. Here, molecular chain extension of hemicelluloses was obtained in a two-step process. Composite hydrogels were prepared via free radical graft copolymerization of crosslinked quaternized hemicelluloses (CQH) and acrylic acid (AA) in the presence of crosslinking agent N,N'-methylenebisacrylamide (MBA). This chain extension strategy significantly improved the mechanical performance of the resulting hydrogels. The crosslinking density, compression modulus, and swelling capacities of hydrogels were tuned by changing the AA/CQH and MBA/CQH contents. Moreover, the biocompatibility test suggests that the hemicelluloses-based hydrogels exhibited no toxicity to cells and allowed cell growth. Taken together, these properties demonstrated that the composite hydrogels have potential applications in the fields of water absorbents, cell culture, and other functional biomaterials.

  17. Enhanced mechanical performance of biocompatible hemicelluloses-based hydrogel via chain extension

    PubMed Central

    Qi, Xian-Ming; Chen, Ge-Gu; Gong, Xiao-Dong; Fu, Gen-Que; Niu, Ya-Shuai; Bian, Jing; Peng, Feng; Sun, Run-Cang

    2016-01-01

    Hemicelluloses are widely used to prepare gel materials because of their renewability, biodegradability, and biocompatibility. Here, molecular chain extension of hemicelluloses was obtained in a two-step process. Composite hydrogels were prepared via free radical graft copolymerization of crosslinked quaternized hemicelluloses (CQH) and acrylic acid (AA) in the presence of crosslinking agent N,N’-methylenebisacrylamide (MBA). This chain extension strategy significantly improved the mechanical performance of the resulting hydrogels. The crosslinking density, compression modulus, and swelling capacities of hydrogels were tuned by changing the AA/CQH and MBA/CQH contents. Moreover, the biocompatibility test suggests that the hemicelluloses-based hydrogels exhibited no toxicity to cells and allowed cell growth. Taken together, these properties demonstrated that the composite hydrogels have potential applications in the fields of water absorbents, cell culture, and other functional biomaterials. PMID:27634095

  18. Hydrogel-based nanocomposites and mesenchymal stem cells: a promising synergistic strategy for neurodegenerative disorders therapy.

    PubMed

    Albani, Diego; Gloria, Antonio; Giordano, Carmen; Rodilossi, Serena; Russo, Teresa; D'Amora, Ugo; Tunesi, Marta; Cigada, Alberto; Ambrosio, Luigi; Forloni, Gianluigi

    2013-01-01

    Hydrogel-based materials are widely employed in the biomedical field. With regard to central nervous system (CNS) neurodegenerative disorders, the design of injectable nanocomposite hydrogels for in situ drug or cell release represents an interesting and minimally invasive solution that might play a key role in the development of successful treatments. In particular, biocompatible and biodegradable hydrogels can be designed as specific injectable tools and loaded with nanoparticles (NPs), to improve and to tailor their viscoelastic properties upon injection and release profile. An intriguing application is hydrogel loading with mesenchymal stem cells (MSCs) that are a very promising therapeutic tool for neurodegenerative or traumatic disorders of the CNS. This multidisciplinary review will focus on the basic concepts to design acellular and cell-loaded materials with specific and tunable rheological and functional properties. The use of hydrogel-based nanocomposites and mesenchymal stem cells as a synergistic strategy for nervous tissue applications will be then discussed.

  19. Enhanced mechanical performance of biocompatible hemicelluloses-based hydrogel via chain extension.

    PubMed

    Qi, Xian-Ming; Chen, Ge-Gu; Gong, Xiao-Dong; Fu, Gen-Que; Niu, Ya-Shuai; Bian, Jing; Peng, Feng; Sun, Run-Cang

    2016-01-01

    Hemicelluloses are widely used to prepare gel materials because of their renewability, biodegradability, and biocompatibility. Here, molecular chain extension of hemicelluloses was obtained in a two-step process. Composite hydrogels were prepared via free radical graft copolymerization of crosslinked quaternized hemicelluloses (CQH) and acrylic acid (AA) in the presence of crosslinking agent N,N'-methylenebisacrylamide (MBA). This chain extension strategy significantly improved the mechanical performance of the resulting hydrogels. The crosslinking density, compression modulus, and swelling capacities of hydrogels were tuned by changing the AA/CQH and MBA/CQH contents. Moreover, the biocompatibility test suggests that the hemicelluloses-based hydrogels exhibited no toxicity to cells and allowed cell growth. Taken together, these properties demonstrated that the composite hydrogels have potential applications in the fields of water absorbents, cell culture, and other functional biomaterials. PMID:27634095

  20. Self-Healing Supramolecular Self-Assembled Hydrogels Based on Poly(L-glutamic acid).

    PubMed

    Li, Guifei; Wu, Jie; Wang, Bo; Yan, Shifeng; Zhang, Kunxi; Ding, Jianxun; Yin, Jingbo

    2015-11-01

    Self-healing polymeric hydrogels have the capability to recover their structures and functionalities upon injury, which are extremely attractive in emerging biomedical applications. This research reports a new kind of self-healing polypeptide hydrogels based on self-assembly between cholesterol (Chol)-modified triblock poly(L-glutamic acid)-block-poly(ethylene glycol)-block-poly(L-glutamic acid) ((PLGA-b-PEG-b-PLGA)-g-Chol) and β-cyclodextrin (β-CD)-modified poly(L-glutamic acid) (PLGA-g-β-CD). The hydrogel formation relied on the host and guest linkage between β-CD and Chol. This study demonstrates the influences of polymer concentration and β-CD/Chol molar ratio on viscoelastic behavior of the hydrogels. The results showed that storage modulus was highest at polymer concentration of 15% w/v and β-CD/Chol molar ratio of 1:1. The effect of the PLGA molecular weight in (PLGA-b-PEG-b-PLGA)-g-Chol on viscoelastic behavior, mechanical properties and in vitro degradation of the supramolecular hydrogels was also studied. The hydrogels showed outstanding self-healing capability and good cytocompatibility. The multilayer structure was constructed using hydrogels with self-healing ability. The developed hydrogels provide a fascinating glimpse for the applications in tissue engineering. PMID:26414083

  1. Cells Behave Distinctly Within Sponges and Hydrogels Due to Differences of Internal Structure

    PubMed Central

    Zhang, Jingjing; Yang, Zheng; Li, Chao; Dou, Yana; Li, Yijiang; Thote, Tanushree; Wang, Dong-an

    2013-01-01

    Different forms of biomaterials, including microspheres, sponges, hydrogels, and nanofibers, have been broadly used in cartilage regeneration; however, effects of internal structures of the biomaterials on cells and chondrogenesis remain largely unexplored. We hypothesized that different internal structures of sponges and hydrogels led to phenotypic disparity of the cells and may lead to disparate chondrogenesis. In the current study, the chondrocytes in sponges and hydrogels of chitosan were compared with regard to cell distribution, morphology, gene expression, and production of extracellular matrix. The chondrocytes clustered or attached to the materials with spindle morphologies in the sponges, while they distributed evenly with spherical morphologies in the hydrogels. The chondrocytes proliferated faster with elevated gene expression of collagen type I and down-regulated gene expression of aggracan in sponges, when compared with those in the hydrogels. However, there was no significant difference of the expression of collagen type II between these two scaffolds. Excretion of both glycosaminoglycan (GAG) and collagen type II increased with time in vitro, but there was no significant difference between the sponges and the hydrogels. There was no significant difference in secretion of GAG and collagen type II in the two scaffolds, while the levels of collagen type I and collagen type X were much higher in sponges compared with those in hydrogels during an in vivo study. Though the chondrocytes displayed different phenotypes in the sponges and hydrogels, they led to comparable chondrogenesis. An optimized design of the biomaterials could further improve chondrogenesis through enhancing functionalities of the chondrocytes. PMID:23614637

  2. Self-Healing Supramolecular Self-Assembled Hydrogels Based on Poly(L-glutamic acid).

    PubMed

    Li, Guifei; Wu, Jie; Wang, Bo; Yan, Shifeng; Zhang, Kunxi; Ding, Jianxun; Yin, Jingbo

    2015-11-01

    Self-healing polymeric hydrogels have the capability to recover their structures and functionalities upon injury, which are extremely attractive in emerging biomedical applications. This research reports a new kind of self-healing polypeptide hydrogels based on self-assembly between cholesterol (Chol)-modified triblock poly(L-glutamic acid)-block-poly(ethylene glycol)-block-poly(L-glutamic acid) ((PLGA-b-PEG-b-PLGA)-g-Chol) and β-cyclodextrin (β-CD)-modified poly(L-glutamic acid) (PLGA-g-β-CD). The hydrogel formation relied on the host and guest linkage between β-CD and Chol. This study demonstrates the influences of polymer concentration and β-CD/Chol molar ratio on viscoelastic behavior of the hydrogels. The results showed that storage modulus was highest at polymer concentration of 15% w/v and β-CD/Chol molar ratio of 1:1. The effect of the PLGA molecular weight in (PLGA-b-PEG-b-PLGA)-g-Chol on viscoelastic behavior, mechanical properties and in vitro degradation of the supramolecular hydrogels was also studied. The hydrogels showed outstanding self-healing capability and good cytocompatibility. The multilayer structure was constructed using hydrogels with self-healing ability. The developed hydrogels provide a fascinating glimpse for the applications in tissue engineering.

  3. Cells behave distinctly within sponges and hydrogels due to differences of internal structure.

    PubMed

    Zhang, Jingjing; Yang, Zheng; Li, Chao; Dou, Yana; Li, Yijiang; Thote, Tanushree; Wang, Dong-an; Ge, Zigang

    2013-10-01

    Different forms of biomaterials, including microspheres, sponges, hydrogels, and nanofibers, have been broadly used in cartilage regeneration; however, effects of internal structures of the biomaterials on cells and chondrogenesis remain largely unexplored. We hypothesized that different internal structures of sponges and hydrogels led to phenotypic disparity of the cells and may lead to disparate chondrogenesis. In the current study, the chondrocytes in sponges and hydrogels of chitosan were compared with regard to cell distribution, morphology, gene expression, and production of extracellular matrix. The chondrocytes clustered or attached to the materials with spindle morphologies in the sponges, while they distributed evenly with spherical morphologies in the hydrogels. The chondrocytes proliferated faster with elevated gene expression of collagen type I and down-regulated gene expression of aggracan in sponges, when compared with those in the hydrogels. However, there was no significant difference of the expression of collagen type II between these two scaffolds. Excretion of both glycosaminoglycan (GAG) and collagen type II increased with time in vitro, but there was no significant difference between the sponges and the hydrogels. There was no significant difference in secretion of GAG and collagen type II in the two scaffolds, while the levels of collagen type I and collagen type X were much higher in sponges compared with those in hydrogels during an in vivo study. Though the chondrocytes displayed different phenotypes in the sponges and hydrogels, they led to comparable chondrogenesis. An optimized design of the biomaterials could further improve chondrogenesis through enhancing functionalities of the chondrocytes.

  4. IGF-1 C Domain-Modified Hydrogel Enhances Cell Therapy for AKI.

    PubMed

    Feng, Guowei; Zhang, Jimin; Li, Yang; Nie, Yan; Zhu, Dashuai; Wang, Ran; Liu, Jianfeng; Gao, Jie; Liu, Na; He, Ningning; Du, Wei; Tao, Hongyan; Che, Yongzhe; Xu, Yong; Kong, Deling; Zhao, Qiang; Li, Zongjin

    2016-08-01

    Low cell retention and engraftment after transplantation limit the successful application of stem cell therapy for AKI. Engineered microenvironments consisting of a hydrogel matrix and growth factors have been increasingly successful in controlling stem cell fate by mimicking native stem cell niche components. Here, we synthesized a bioactive hydrogel by immobilizing the C domain peptide of IGF-1 (IGF-1C) on chitosan, and we hypothesized that this hydrogel could provide a favorable niche for adipose-derived mesenchymal stem cells (ADSCs) and thereby enhance cell survival in an AKI model. In vitro studies demonstrated that compared with no hydrogel or chitosan hydrogel only, the chitosan-IGF-1C hydrogel increased cell viability through paracrine effects. In vivo, cotransplantation of the chitosan-IGF-1C hydrogel and ADSCs in ischemic kidneys ameliorated renal function, likely by the observed promotion of stem cell survival and angiogenesis, as visualized by bioluminescence imaging and attenuation of fibrosis. In conclusion, IGF-1C immobilized on a chitosan hydrogel provides an artificial microenvironment for ADSCs and may be a promising therapeutic approach for AKI. PMID:26869006

  5. Mechanical and viscoelastic properties of cellulose nanocrystals reinforced poly(ethylene glycol) nanocomposite hydrogels.

    PubMed

    Yang, Jun; Han, Chun-Rui; Duan, Jiu-Fang; Xu, Feng; Sun, Run-Cang

    2013-04-24

    The preparation and mechanical properties of elastomeric nanocomposite hydrogels consisting of cellulose nanocrystals (CNCs) and poly(ethylene glycol) (PEG) are reported. The aqueous nanocomposite CNC/PEG precursor solutions covalently cross-linked through a one-stage photocross-linking process. The mechanical properties of nanocomposite hydrogels, including Young's modulus (E), fracture stress (σ), and fracture strain (ε), were measured as a function of CNC volume fraction (φCNC, 0.2-1.8%, v/v) within polymeric matrix. It was found that the homogeneously dispersed nanocomposite hydrogels can be prepared with φCNC being less than 1.5%, whereas the heterogeneous nanocomposite hydrogels were obtained with φCNC being higher than 1.5%. The nanocomposite hydrogels exhibited higher strengths and flexibilities when compared with neat PEG hydrogels, where the modulus, fracture stress, and fracture strain enhanced by a factor of 3.48, 5, and 3.28, respectively, over the matrix material alone at 1.2% v/v CNC loading. Oscillatory shear data indicated the CNC-PEG nanocomposite hydrogels were more viscous than the neat PEG hydrogels and were efficient at energy dissipation due to the reversible interactions between CNC and PEG polymer chains. It was proposed that the strong gel viscoelastic behavior and the mechanical reinforcement were related to "filler network", where the temporary interactions between CNC and PEG interfered with the covalent cross-links of PEG. PMID:23534336

  6. 25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine

    PubMed Central

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

    2014-01-01

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

  7. Towards temperature driven forward osmosis desalination using Semi-IPN hydrogels as reversible draw agents.

    PubMed

    Cai, Yufeng; Shen, Wenming; Loo, Siew Leng; Krantz, William B; Wang, Rong; Fane, Anthony G; Hu, Xiao

    2013-07-01

    We report a study to explore new materials and a new concept for temperature driven quasi-continuous desalination using hydrogels as draw agents in forward osmosis (FO). This concept is enabled by the design and preparation of thermally responsive hydrogels having a semi-interpenetrating network (semi-IPN) structure. Thermally responsive semi-IPN hydrogels were synthesized by polymerization of N-isopropylacrylamide (NIPAm) in the presence of polysodium acrylate (PSA) or polyvinyl alcohol (PVA). Their functions as draw agents in FO were systematically studied and compared with hydrogels prepared from the PNIPAm homopolymer or the NIPAM-SA copolymer. While the semi-IPN hydrogels displayed the desirable balanced thermally responsive swelling and dewatering behavior, the NIPAm-SA copolymer hydrogels were found to have poor dewatering behavior, making them unsuitable for a continuous temperature driven desalination process. At 40 °C, the semi-IPN hydrogels rapidly release nearly 100% of the water absorbed during the FO drawing process carried out at room temperature. Results clearly indicate the potential of semi-IPN hydrogels as semi-solid draw agents in the FO process, in which quasi-continuous desalination could be achieved by cyclic heating and cooling within a moderate temperature change. PMID:23726714

  8. Towards temperature driven forward osmosis desalination using Semi-IPN hydrogels as reversible draw agents.

    PubMed

    Cai, Yufeng; Shen, Wenming; Loo, Siew Leng; Krantz, William B; Wang, Rong; Fane, Anthony G; Hu, Xiao

    2013-07-01

    We report a study to explore new materials and a new concept for temperature driven quasi-continuous desalination using hydrogels as draw agents in forward osmosis (FO). This concept is enabled by the design and preparation of thermally responsive hydrogels having a semi-interpenetrating network (semi-IPN) structure. Thermally responsive semi-IPN hydrogels were synthesized by polymerization of N-isopropylacrylamide (NIPAm) in the presence of polysodium acrylate (PSA) or polyvinyl alcohol (PVA). Their functions as draw agents in FO were systematically studied and compared with hydrogels prepared from the PNIPAm homopolymer or the NIPAM-SA copolymer. While the semi-IPN hydrogels displayed the desirable balanced thermally responsive swelling and dewatering behavior, the NIPAm-SA copolymer hydrogels were found to have poor dewatering behavior, making them unsuitable for a continuous temperature driven desalination process. At 40 °C, the semi-IPN hydrogels rapidly release nearly 100% of the water absorbed during the FO drawing process carried out at room temperature. Results clearly indicate the potential of semi-IPN hydrogels as semi-solid draw agents in the FO process, in which quasi-continuous desalination could be achieved by cyclic heating and cooling within a moderate temperature change.

  9. Stiffness and Adhesivity Control Aortic Valve Interstitial Cell Behavior within Hyaluronic Acid Based Hydrogels

    PubMed Central

    Duan, Bin; Hockaday, Laura A.; Kapetanovic, Edi; Kang, Kevin H.; Butcher, Jonathan T.

    2013-01-01

    Bioactive and biodegradable hydrogels that mimic the extracellular matrix and regulate valve interstitial cells (VIC) behavior are of great interest as three dimensional (3D) model systems for understanding mechanisms of valvular heart disease pathogenesis in vitro and the basis for regenerative templates for tissue engineering. However, the role of stiffness and adhesivity of hydrogels in VIC behavior remains poorly understood. This study reports synthesis of oxidized and methacrylated hyaluronic acid (Me-HA and MOHA) and subsequent development of hybrid hydrogels based on modified HA and methacrylated gelatin (Me-Gel) for VIC encapsulation. The mechanical stiffness and swelling ratio of the hydrogels were tunable with molecular weight of HA and concentration/composition of precursor solution. The encapsulated VIC in pure HA hydrogels with lower mechanical stiffness showed more spreading morphology comparing to stiffer counterparts and dramatically upregulated alpha smooth muscle actin expression indicating more activated myofibroblast properties. The addition of Me-Gel in Me-HA facilitated cell spreading, proliferation and VIC migration from encapsulated spheroids and better maintained VIC fibroblastic phenotype. The VIC phenotype transition during migration from encapsulated spheroids in both Me-HA and Me-HA/Me-Gel hydrogel matrix was also observed. These findings are important for the rational design of hydrogels for controlling VIC morphology, and for regulating VIC phenotype and function. The Me-HA/Me-Gel hybrid hydrogels accommodated with VIC are promising as valve tissue engineering scaffolds and 3D model for understanding valvular pathobiology. PMID:23648571

  10. [Modern dressings. Hydrogels].

    PubMed

    Sedlarik, K M; Vacik, J; Wichterle, O; Hájek, M

    1995-02-01

    Hydrogels are occlusive types of dressings. They are three-dimensional nets made up of hydrophil polymers. They can be produced from synthetic or semisynthetic materials or a combination of the two. Hydrogels retain different percentages of water but are themselves insoluble in water. This is why they maintain on the wound surface their structure and do not dissolve. They are suited for the dressing of wounds with low secretion such as grade I and II burns, grade I and II bedsores and above all epithelial defects, major skin abrasions and areas after collection of epithelial grafts. Their use is contraindicated in infected wounds, in wounds with a massive secretion and ulcers of arterial origin. Although the domain of their clinical use are clean granulating or already epithelizing wounds, they are very well suited also for rehydration of dry and black skin necroses. Their advantages include minimal pain in the wound as well as the fact that they can be left on the wound without redressing till complete healing. This is made possible also by the fact that they are translucent. PMID:7777948

  11. Autonomously-triggered microfluidic cooling using thermo-responsive hydrogels.

    PubMed

    Agarwal, Abhishek K; Dong, Liang; Beebe, David J; Jiang, Hongrui

    2007-03-01

    We present autonomously-triggered on-chip microfluidic cooling devices that utilize thermo-responsive hydrogels to adapt to local environmental temperatures. An external rotating magnetic stirrer couples with an in situ fabricated nickel impeller in these centrifugal-based microfluidic cooling devices to recirculate cooler water. Temperature-responsive hydrogels, which exhibit volumetric expansion and contraction, are integrated at the axle of the impeller. In this design, the hydrogels behave similar to an automotive clutch, to autonomously control the impeller's rotation as a function of the local environmental temperature. Therefore, the hydrogels act as both sensors and actuators and help take away the necessity for additional temperature sensing, feedback, and/or control units here. Cooling devices capable of on-chip thermal management at multiple predetermined onset operation points are realized by changes to the composition of hydrogel to alter its lowest critical solution temperature (LCST). Furthermore, the effect of magnetic stirrer frequency on the fluid cooling and flowrates for different two-blade nickel impeller designs are presented. PMID:17330161

  12. Drug-sensing hydrogels for the inducible release of biopharmaceuticals

    NASA Astrophysics Data System (ADS)

    Ehrbar, Martin; Schoenmakers, Ronald; Christen, Erik H.; Fussenegger, Martin; Weber, Wilfried

    2008-10-01

    Drug-dependent dissociation or association of cellular receptors represents a potent pharmacologic mode of action for regulating cell fate and function. Transferring the knowledge of pharmacologically triggered protein-protein interactions to materials science will enable novel design concepts for stimuli-sensing smart hydrogels. Here, we show the design and validation of an antibiotic-sensing hydrogel for the trigger-inducible release of human vascular endothelial growth factor. Genetically engineered bacterial gyrase subunit B (GyrB) (ref. 4) coupled to polyacrylamide was dimerized by the addition of the aminocoumarin antibiotic coumermycin, resulting in hydrogel formation. Addition of increasing concentrations of clinically validated novobiocin (Albamycin) dissociated the GyrB subunits, thereby resulting in dissociation of the hydrogel and dose- and time-dependent liberation of the entrapped protein pharmaceutical VEGF121 for triggering proliferation of human umbilical vein endothelial cells. Pharmacologically controlled hydrogels have the potential to fulfil the promises of stimuli-sensing materials as smart devices for spatiotemporally controlled delivery of drugs within the patient.

  13. Cationic amphiphilic dextran hydrogels with potential biomedical applications.

    PubMed

    Mocanu, Georgeta; Nichifor, Marieta

    2014-01-01

    Dextran microparticles were chemically modified for the attachment of quaternary ammonium groups carrying substituents with different hydrophobicity, in order to obtain amphiphilic cationic hydrogels with different hydrophilic/lipophilic balance. These hydrogels retain various amounts of dyes: Rose Bengal, Brilliant Blue and Vitamin B12, used as models for hydrophobic, amphiphilic and hydrophilic drugs, as a function of their hydrophilic/hydrophobic properties. Bovine serum albumin (BSA) retention by hydrogels occurs in higher amounts at pH 6.9, and is influenced by electrostatic, hydrophobic forces and the swelling of the supports. Tetanus anatoxin is retained by the supports through electrostatic and/or hydrophobic forces, in amounts varying between 110 and 200 mg/g. Both proteins are gradually released, through increasing of the eluent ionic strengths. Alpha-tocopherol is retained by the hydrogels preponderantly through hydrophobic forces, in amounts varying between 130 and 300 mg/g. Measurement of the scavenging effect proved the antioxidant properties of the included drug. Based on the obtained results, one can appreciate the potential of the synthesized cationic hydrogels as supports for biomolecules or as vaccine adjuvants.

  14. Nano-Fibrous Biopolymer Hydrogels via Biological Conjugation for Osteogenesis.

    PubMed

    Chen, Huinan; Xing, Xiaodong; Jia, Yang; Mao, Jiahui; Zhang, Ziwei; Tan, Huaping

    2016-06-01

    Nanostructured biopolymer hydrogels have great potential in the field of drug delivery and regenerative medicine. In this work, a nano-fibrous (NF) biopolymer hydrogel was developed for cell growth factors (GFs) delivery and in vitro osteogenesis. The nano-fibrous hydrogel was produced via biological conjugation of streptavidin functionalized hyaluronic acid (HA-Streptavidin) and biotin terminated star-shaped poly(ethylene glycol) (PEG-Biotin). In the present work, in vitro gelation, mechanical properties, degradation and equilibrium swelling of the NF hydrogel were examined. The potential application of this NF gel scaffold in bone tissue engineering was confirmed by encapsulation behavior of osteoblasts. Osteoblasts seeded directly in NF gel scaffold containing cell growth factor, e.g. bone morphogenetic protein 2 (BMP-2), was to mimic the in vivo microenvironment in which cells interface biomaterials and interact with BMP-2. In combination with BMP-2, the NF hydrogel exhibited beneficial effects on osteoblast activity and differentiation, which suggested a promising future for local treatment of pathologies involving bone loss. PMID:27427597

  15. Chemomechanical properties and the applications of semi-confined hydrogel microstructures

    NASA Astrophysics Data System (ADS)

    Ding, Zhenwen

    Environmentally sensitive hydrogels are three-dimensional crosslinked polymer networks capable of undergoing reversible volume change in response to different stimuli such as temperature, pH, ionic strength, electric field, etc. The integration of these soft polymeric materials with conventional micromachined hard materials (such as silicon and glass) offers unique opportunities to enhance their applications and functionalities. Many such applications require the hydrogel to be trapped in a semi-confined structure. This calls for a careful study of hydrogel thermodynamics, kinetics, and chemomechanical properties associated with such a confinement. This physiochemical understanding is essential in order to design hydrogel-based smart sensing and actuating microdevices. This Ph.D. thesis consists of two parts. The first part will be focused on the physical concepts and measurements of the physical parameters of hydrogels. We will discuss the hydrogel network structure, kinetics of hydrogel volume phase transition (VPT), biomolecule diffusion in hydrogel network, and characterizations of hydrogel properties. In the second part, we will discuss the applications of semi-confined hydrogel structures in microsystems. A high-resolution technique for fabricating hydrogel microstructures will be presented. In this method, squeeze-film is used to generate hydrogel thin film on a smooth substrate. Parylene passivation and dry etching are utilized for micropatterning. This method allows for the integration of hydrogel with MEMS and NEMS microstructures in order to fabricate miniaturized devices for sensing and actuating. Subsequently, two applications will be discussed using the patterning technique: a hydrogel diffraction grating and a hydrogel-based integrated-antenna pH sensor. Microscale patterning of biomolecules (DNA, antibody, enzyme, etc.) on solid surfaces is necessary for the successful development of many biotechnological microdevices. We developed a hydrogel

  16. Hydrogel-derived non-precious electrocatalysts for efficient oxygen reduction

    PubMed Central

    You, Bo; Yin, Peiqun; Zhang, Junli; He, Daping; Chen, Gaoli; Kang, Fei; Wang, Huiqiao; Deng, Zhaoxiang; Li, Yadong

    2015-01-01

    The development of highly active, cheap and robust oxygen reduction reaction (ORR) electrocatalysts to replace precious metal platinum is extremely urgent and challenging for renewable energy devices. Herein we report a novel, green and especially facile hydrogel strategy to construct N and B co-doped nanocarbon embedded with Co-based nanoparticles as an efficient non-precious ORR catalyst. The agarose hydrogel provides a general host matrix to achieve a homogeneous distribution of key precursory components including cobalt (II) acetate and buffer salts, which, upon freeze-drying and carbonization, produces the highly active ORR catalyst. The gel buffer containing Tris base, boric acid and ethylenediaminetetraacetic acid, commonly adopted for pH and ionic strength control, plays distinctively different roles here. These include a green precursor for N- and B-doping, a salt porogen and a Co2+ chelating agent, all contributing to the excellent ORR activity. This hydrogel-based process is potentially generalizable for many other catalytic materials. PMID:26130371

  17. Hydrogel-derived non-precious electrocatalysts for efficient oxygen reduction

    NASA Astrophysics Data System (ADS)

    You, Bo; Yin, Peiqun; Zhang, Junli; He, Daping; Chen, Gaoli; Kang, Fei; Wang, Huiqiao; Deng, Zhaoxiang; Li, Yadong

    2015-07-01

    The development of highly active, cheap and robust oxygen reduction reaction (ORR) electrocatalysts to replace precious metal platinum is extremely urgent and challenging for renewable energy devices. Herein we report a novel, green and especially facile hydrogel strategy to construct N and B co-doped nanocarbon embedded with Co-based nanoparticles as an efficient non-precious ORR catalyst. The agarose hydrogel provides a general host matrix to achieve a homogeneous distribution of key precursory components including cobalt (II) acetate and buffer salts, which, upon freeze-drying and carbonization, produces the highly active ORR catalyst. The gel buffer containing Tris base, boric acid and ethylenediaminetetraacetic acid, commonly adopted for pH and ionic strength control, plays distinctively different roles here. These include a green precursor for N- and B-doping, a salt porogen and a Co2+ chelating agent, all contributing to the excellent ORR activity. This hydrogel-based process is potentially generalizable for many other catalytic materials.

  18. Structure of Block Copolymer Hydrogel Formed by Complex Coacervate Process

    NASA Astrophysics Data System (ADS)

    Choi, Soohyung; Ortony, Julia; Krogstad, Daniel; Spruell, Jason; Lynd, Nathaniel; Han, Songi; Kramer, Edward

    2012-02-01

    Complex coacervation occurs when oppositely charged polyelectrolytes associate in solution, forming dense micron-sized droplets. Hydrogels with coacervate block domains were formed by mixing two ABA and A'BA' triblock copolymer solutions in water where the A and A' blocks are oppositely charged. Small-angle neutron scattering (SANS) was used to investigate the structure of hydrogels formed by ABA triblock copolymers (A block: poly(allyl glycidyl ether) functionalized with guanidinium (A) or sulfonate (A'), B block: poly(ethylene oxide)). By using an appropriate fitting model, structural information such as coacervate core block radius and water volume fraction w can be extracted from SANS data. The results reveal that w in the coacervate core block was significantly higher than in conventional triblock copolymer hydrogels where microphase separation is driven by the hydrophobicity of the core-forming blocks.

  19. Gelatin-Methacryloyl Hydrogels: Towards Biofabrication-Based Tissue Repair.

    PubMed

    Klotz, Barbara J; Gawlitta, Debby; Rosenberg, Antoine J W P; Malda, Jos; Melchels, Ferry P W

    2016-05-01

    Research over the past decade on the cell-biomaterial interface has shifted to the third dimension. Besides mimicking the native extracellular environment by 3D cell culture, hydrogels offer the possibility to generate well-defined 3D biofabricated tissue analogs. In this context, gelatin-methacryloyl (gelMA) hydrogels have recently gained increased attention. This interest is sparked by the combination of the inherent bioactivity of gelatin and the physicochemical tailorability of photo-crosslinkable hydrogels. GelMA is a versatile matrix that can be used to engineer tissue analogs ranging from vasculature to cartilage and bone. Convergence of biological and biofabrication approaches is necessary to progress from merely proving cell functionality or construct shape fidelity towards regenerating tissues. GelMA has a critical pioneering role in this process and could be used to accelerate the development of clinically relevant applications. PMID:26867787

  20. Biocompatible hydrogel nanocomposite with covalently embedded silver nanoparticles.

    PubMed

    García-Astrain, Clara; Chen, Cheng; Burón, María; Palomares, Teodoro; Eceiza, Arantxa; Fruk, Ljiljana; Corcuera, M Ángeles; Gabilondo, Nagore

    2015-04-13

    Bionanocomposite materials, combining the properties of biopolymers and nanostructured materials, are attracting interest of the wider scientific community due to their potential application in design of implants, drug delivery systems, and tissue design platforms. Herein, we report on the use of maleimide-coated silver nanoparticles (Ag NPs) as cocross-linkers for the preparation of a bionanocomposite gelatin based hydrogel. Diels-Alder cycloaddition of benzotriazole maleimide (BTM) functionalized Ag NPs and furan containing gelatin in combination with additional amide coupling resulted in stable and biocompatible hybrid nanocomposite. The storage moduli values for the hydrogel are nearly three times higher than that of control hydrogel without NPs indicating a stabilizing role of the covalently bound NPs. Finally, the swelling and drug release properties of the materials as well as the biocompatibility and toxicity tests indicate the biomedical potential of this type of material.

  1. Gelatin-Methacryloyl Hydrogels: Towards Biofabrication-Based Tissue Repair.

    PubMed

    Klotz, Barbara J; Gawlitta, Debby; Rosenberg, Antoine J W P; Malda, Jos; Melchels, Ferry P W

    2016-05-01

    Research over the past decade on the cell-biomaterial interface has shifted to the third dimension. Besides mimicking the native extracellular environment by 3D cell culture, hydrogels offer the possibility to generate well-defined 3D biofabricated tissue analogs. In this context, gelatin-methacryloyl (gelMA) hydrogels have recently gained increased attention. This interest is sparked by the combination of the inherent bioactivity of gelatin and the physicochemical tailorability of photo-crosslinkable hydrogels. GelMA is a versatile matrix that can be used to engineer tissue analogs ranging from vasculature to cartilage and bone. Convergence of biological and biofabrication approaches is necessary to progress from merely proving cell functionality or construct shape fidelity towards regenerating tissues. GelMA has a critical pioneering role in this process and could be used to accelerate the development of clinically relevant applications.

  2. Rationally designing the mechanical properties of protein hydrogels

    NASA Astrophysics Data System (ADS)

    Cao, Yi

    Naturally occurring biomaterials possess diverse mechanical properties, which are critical to their unique biological functions. However, it remains challenging to rationally control the mechanical properties of synthetic biomaterials. Here we provide a bottom-up approach to rationally design the mechanical properties of protein-based hydrogels. We first use atomic fore microscope (AFM) based single-molecule force spectroscopy to characterize the mechanical stability of individual protein building blocks. We then rationally design the mechanical properties of hydrogels by selecting different combination of protein building blocks of known mechanical properties. As a proof-of-principle, we demonstrate the engineering of hydrogels of distinct extensibility and toughness. This simple combinatorial approach allows direct translation of the mechanical properties of proteins from the single molecule level to the macroscopic level and represents an important step towards rationally designing the mechanical properties of biomaterials.

  3. Mechanical properties of alginate hydrogels manufactured using external gelation.

    PubMed

    Kaklamani, Georgia; Cheneler, David; Grover, Liam M; Adams, Michael J; Bowen, James

    2014-08-01

    Alginate hydrogels are commonly used in biomedical applications such as scaffolds for tissue engineering, drug delivery, and as a medium for cell immobilisation. Multivalent cations are often employed to create physical crosslinks between carboxyl and hydroxyl moieties on neighbouring polysaccharide chains, creating hydrogels with a range of mechanical properties. This work describes the manufacture and characterisation of sodium alginate hydrogels using the divalent cations Mg(2+), Ca(2+) and Sr(2+) to promote gelation via non-covalent crosslinks. Gelation time and Young׳s modulus are characterised as a function of cation and alginate concentrations. The implications of this work towards the use of environmental elasticity to control stem cell differentiation are discussed.

  4. Block copolymer mixtures as antimicrobial hydrogels for biofilm eradication.

    PubMed

    Lee, Ashlynn L Z; Ng, Victor W L; Wang, Weixin; Hedrick, James L; Yang, Yi Yan

    2013-12-01

    Current antimicrobial strategies have mostly been developed to manage infections due to planktonic cells. However, microbes in their nature state will tend to exist by attaching to and growing on living and inanimate surfaces that result in the formation of biofilms. Conventional therapies for treating biofilm-related infections are likely to be insufficient due to the lower susceptibility of microbes that are embedded in the biofilm matrix. In this study, we report the development of biodegradable hydrogels from vitamin E-functionalized polycarbonates for antimicrobial applications. These hydrogels were formed by incorporating positively-charged polycarbonates containing propyl and benzyl side chains with vitamin E moiety into physically cross-linked networks of "ABA"-type polycarbonate and poly(ethylene glycol) triblock copolymers. Investigations of the mechanical properties of the hydrogels showed that the G' values ranged from 1400 to 1600 Pa and the presence of cationic polycarbonate did not affect the stiffness of the hydrogels. Shear-thinning behavior was observed as the hydrogels displayed high viscosity at low shear rates that dramatically decreased as the shear rate increased. In vitro antimicrobial studies revealed that the more hydrophobic VE/BnCl(1:30)-loaded hydrogels generally exhibited better antimicrobial/antifungal effects compared to the VE/PrBr(1:30) counterpart as lower minimum biocidal concentrations (MBC) were observed in Staphylococcus aureus (Gram-positive), Escherichia coli (Gram-negative) and Candida albicans (fungus) (156.2, 312.5, 312.5 mg/L for VE/BnCl(1:30) and 312.5, 2500 and 625 mg/L for VE/PrBr(1:30) respectively). Similar trends were observed for the treatment of biofilms where VE/BnCl(1:30)-loaded hydrogels displayed better efficiency with regards to eradication of biomass and reduction of microbe viability of the biofilms. Furthermore, a high degree of synergistic antimicrobial effects was also observed through the co

  5. Massively parallel single-molecule and single-cell emulsion reverse transcription polymerase chain reaction using agarose droplet microfluidics.

    PubMed

    Zhang, Huifa; Jenkins, Gareth; Zou, Yuan; Zhu, Zhi; Yang, Chaoyong James

    2012-04-17

    A microfluidic device for performing single copy, emulsion Reverse Transcription Polymerase Chain Reaction (RT-PCR) within agarose droplets is presented. A two-aqueous-inlet emulsion droplet generator was designed and fabricated to produce highly uniform monodisperse picoliter agarose emulsion droplets with RT-PCR reagents in carrier oil. Template RNA or cells were delivered from one inlet with RT-PCR reagents/cell lysis buffer delivered separately from the other. Efficient RNA/cell encapsulation and RT-PCR at the single copy level was achieved in agarose-in-oil droplets, which, after amplification, can be solidified into agarose beads for further analysis. A simple and efficient method to graft primer to the polymer matrix using 5'-acrydite primer was developed to ensure highly efficient trapping of RT-PCR products in agarose. High-throughput single RNA molecule/cell RT-PCR was demonstrated in stochastically diluted solutions. Our results indicate that single-molecule RT-PCR can be efficiently carried out in agarose matrix. Single-cell RT-PCR was successfully performed which showed a clear difference in gene expression level of EpCAM, a cancer biomarker gene, at the single-cell level between different types of cancer cells. This work clearly demonstrates for the first time, single-copy RT-PCR in agarose droplets. We believe this will open up new possibilities for viral RNA detection and single-cell transcription analysis.

  6. Computerized methods for analyzing two-dimensional agarose gel electropherograms.

    PubMed

    Aldroubi, A; Unser, M; Tietz, D; Trus, B

    1991-01-01

    Previous methods interpret zonal or polydisperse gel patterns of two-dimensional Serwer-type gels in terms of size and free mobility (surface net charge density). These two parameters have been determined for each component without quantitatively measuring the abundance of the components. The present study advances these previous methods by determining the relative concentration of each component by computer evaluation of densitometrically analyzed gel patterns. Suitable procedures and their underlying algorithms are presented. The mathematical routines are implemented in a user-friendly software package, called GelFit and designed for a Macintosh personal computer. The program input consists of digitized images of gel staining patterns exemplified by those obtained from electrophoresis of native subcellular-sized particles. The data are processed through the following steps: (i) Noise reduction and calibration. (ii) Geometrical transformation of the pattern onto a rectangular size/free mobility coordinate system using rationales of the extended Ogston model. (iii) Analysis of the transformed image to determine density maxima, density profiles along iso-free-mobility or iso-size lines, curve fitting of one-dimensional profiles or two-dimensional surfaces using Gaussian functions and curve stripping of surfaces to determine the possible number of particle populations.

  7. Zwitterionic hydrogels: an in vivo implantation study.

    PubMed

    Zhang, Zheng; Chao, Timothy; Liu, Lingyun; Cheng, Gang; Ratner, Buddy D; Jiang, Shaoyi

    2009-01-01

    Zwitterionic hydrogels, including poly(sulfobetaine methacrylate) (polySBMA) and poly(carboxybetaine methacrylate) (polyCBMA), and co-polymeric hydrogels of CBMA and 2-hydroxyethyl methacrylate (HEMA) (poly(CBMA-co-HEMA)) were prepared. Their in vitro and in vivo properties were evaluated and compared with those of polyHEMA hydrogels. Bovine aortic endothelial cells (BAECs) were incubated with zwitterionic and polyHEMA hydrogels to evaluate their bioadhesion properties. Both polySBMA and polyCBMA hydrogels were found to be non-cytotoxic and their endotoxin levels were found to be acceptable for in vivo implantation. Results from in vivo subcutaneous implantation showed reduced cell attachment to the surfaces of polySBMA and poly(CBMA-co-HEMA) hydrogels after one-week implantation as compared with polyHEMA hydrogels. After a 4-week implantation, capsules with higher vascularities surrounding the two zwitterionic hydrogels were found. However, polyHEMA, polySBMA and poly(CBMA-co-HEMA) hydrogels showed similar capsule thicknesses and similar numbers of attached foreign body giant cells (FBGCs). In this work, zwitterionic hydrogels demonstrate healing and integration comparable to polyHEMA hydrogels, but with improved vascularity. These zwitterionic hydrogels are promising alternatives to polyHEMA hydrogels as implantable materials. PMID:19793443

  8. Energy conversion in polyelectrolyte hydrogels

    NASA Astrophysics Data System (ADS)

    Olvera de La Cruz, Monica; Erbas, Aykut; Olvera de la Cruz Team

    Energy conversion and storage have been an active field of research in nanotechnology parallel to recent interests towards renewable energy. Polyelectrolyte (PE) hydrogels have attracted considerable attention in this field due to their mechanical flexibility and stimuli-responsive properties. Ideally, when a hydrogel is deformed, applied mechanical work can be converted into electrostatic, elastic and steric-interaction energies. In this talk, we discuss the results of our extensive molecular dynamics simulations of PE hydrogels. We demonstrate that, on deformation, hydrogels adjust their deformed state predominantly by altering electrostatic interactions between their charged groups rather than excluded-volume and bond energies. This is due to the hydrogel's inherent tendency to preserve electro-neutrality in its interior, in combination with correlations imposed by backbone charges. Our findings are valid for a wide range of compression ratios and ionic strengths. The electrostatic-energy alterations that we observe in our MD simulations may induce pH or redox-potential changes inside the hydrogels. The resulting energetic difference can be harvested, for instance, analogously to a Carnot engine, or facilitated for sensor applications. Center for Bio-inspired Energy Science (CBES).

  9. Thiol-norbornene photo-click hydrogels for tissue engineering applications

    PubMed Central

    Lin, Chien-Chi; Ki, Chang Seok; Shih, Han

    2014-01-01

    Thiol-norbornene (thiol-ene) photo-click hydrogels have emerged as a diverse material system for tissue engineering applications. These hydrogels are cross-linked through light mediated orthogonal reactions between multi-functional norbornene-modified macromers (e.g., poly(ethylene glycol), hyaluronic acid, gelatin) and sulfhydryl-containing linkers (e.g., dithiothreitol, PEG-dithiol, bis-cysteine peptides) using low concentration of photoinitiator. The gelation of thiol-norbornene hydrogels can be initiated by long-wave UV light or visible light without additional co-initiator or co-monomer. The cross-linking and degradation behaviors of thiol-norbornene hydrogels are controlled through material selections, whereas the biophysical and biochemical properties of the gels are easily and independently tuned owing to the orthogonal reactivity between norbornene and thiol moieties. Uniquely, the cross-linking of step-growth thiol-norbornene hydrogels is not oxygen-inhibited, therefore the gelation is much faster and highly cytocompatible compared with chain-growth polymerized hydrogels using similar gelation conditions. These hydrogels have been prepared as tunable substrates for 2D cell culture, as microgels or bulk gels for affinity-based or protease-sensitive drug delivery, and as scaffolds for 3D cell culture. Reports from different laboratories have demonstrated the broad utility of thiol-norbornene hydrogels in tissue engineering and regenerative medicine applications, including valvular and vascular tissue engineering, liver and pancreas-related tissue engineering, neural regeneration, musculoskeletal (bone and cartilage) tissue regeneration, stem cell culture and differentiation, as well as cancer cell biology. This article provides an up-to-date overview on thiol-norbornene hydrogel cross-linking and degradation mechanisms, tunable material properties, as well as the use of thiol-norbornene hydrogels in drug delivery and tissue engineering applications. PMID

  10. Isolation of DNA from agarose gels using DEAE-paper. Application to restriction site mapping of adenovirus type 16 DNA.

    PubMed Central

    Winberg, G; Hammarskjöld, M L

    1980-01-01

    A new method for isolating DNA from agarose gels is described. The method involves the simultaneous transfer of all DNA-fragments from an agarose slab gel onto DEAE-cellulose paper and the elution of the individual fragments from the paper with 1 M NaCl. DNA isolated from agarose gels in this way is susceptible to cleavage with several restriction endonucleases, and can be labeled in vitro with E coli DNA-polymerase I, T4 DNA-polymerase and T4 polynucleotide kinase. We have used the method to construct restriction endonuclease maps of adenovirus type 16 DNA. Images PMID:6252542

  11. Multifunctional 3D printing of heterogeneous hydrogel structures

    PubMed Central

    Nadernezhad, Ali; Khani, Navid; Skvortsov, Gözde Akdeniz; Toprakhisar, Burak; Bakirci, Ezgi; Menceloglu, Yusuf; Unal, Serkan; Koc, Bahattin

    2016-01-01

    Multimaterial additive manufacturing or three-dimensional (3D) printing of hydrogel structures provides the opportunity to engineer geometrically dependent functionalities. However, current fabrication methods are mostly limited to one type of material or only provide one type of functionality. In this paper, we report a novel method of multimaterial deposition of hydrogel structures based on an aspiration-on-demand protocol, in which the constitutive multimaterial segments of extruded filaments were first assembled in liquid state by sequential aspiration of inks into a glass capillary, followed by in situ gel formation. We printed different patterned objects with varying chemical, electrical, mechanical, and biological properties by tuning process and material related parameters, to demonstrate the abilities of this method in producing heterogeneous and multi-functional hydrogel structures. Our results show the potential of proposed method in producing heterogeneous objects with spatially controlled functionalities while preserving structural integrity at the switching interface between different segments. We anticipate that this method would introduce new opportunities in multimaterial additive manufacturing of hydrogels for diverse applications such as biosensors, flexible electronics, tissue engineering and organ printing. PMID:27630079

  12. Multifunctional 3D printing of heterogeneous hydrogel structures

    NASA Astrophysics Data System (ADS)

    Nadernezhad, Ali; Khani, Navid; Skvortsov, Gözde Akdeniz; Toprakhisar, Burak; Bakirci, Ezgi; Menceloglu, Yusuf; Unal, Serkan; Koc, Bahattin

    2016-09-01

    Multimaterial additive manufacturing or three-dimensional (3D) printing of hydrogel structures provides the opportunity to engineer geometrically dependent functionalities. However, current fabrication methods are mostly limited to one type of material or only provide one type of functionality. In this paper, we report a novel method of multimaterial deposition of hydrogel structures based on an aspiration-on-demand protocol, in which the constitutive multimaterial segments of extruded filaments were first assembled in liquid state by sequential aspiration of inks into a glass capillary, followed by in situ gel formation. We printed different patterned objects with varying chemical, electrical, mechanical, and biological properties by tuning process and material related parameters, to demonstrate the abilities of this method in producing heterogeneous and multi-functional hydrogel structures. Our results show the potential of proposed method in producing heterogeneous objects with spatially controlled functionalities while preserving structural integrity at the switching interface between different segments. We anticipate that this method would introduce new opportunities in multimaterial additive manufacturing of hydrogels for diverse applications such as biosensors, flexible electronics, tissue engineering and organ printing.

  13. Multifunctional 3D printing of heterogeneous hydrogel structures.

    PubMed

    Nadernezhad, Ali; Khani, Navid; Skvortsov, Gözde Akdeniz; Toprakhisar, Burak; Bakirci, Ezgi; Menceloglu, Yusuf; Unal, Serkan; Koc, Bahattin

    2016-01-01

    Multimaterial additive manufacturing or three-dimensional (3D) printing of hydrogel structures provides the opportunity to engineer geometrically dependent functionalities. However, current fabrication methods are mostly limited to one type of material or only provide one type of functionality. In this paper, we report a novel method of multimaterial deposition of hydrogel structures based on an aspiration-on-demand protocol, in which the constitutive multimaterial segments of extruded filaments were first assembled in liquid state by sequential aspiration of inks into a glass capillary, followed by in situ gel formation. We printed different patterned objects with varying chemical, electrical, mechanical, and biological properties by tuning process and material related parameters, to demonstrate the abilities of this method in producing heterogeneous and multi-functional hydrogel structures. Our results show the potential of proposed method in producing heterogeneous objects with spatially controlled functionalities while preserving structural integrity at the switching interface between different segments. We anticipate that this method would introduce new opportunities in multimaterial additive manufacturing of hydrogels for diverse applications such as biosensors, flexible electronics, tissue engineering and organ printing. PMID:27630079

  14. Multifunctional 3D printing of heterogeneous hydrogel structures.

    PubMed

    Nadernezhad, Ali; Khani, Navid; Skvortsov, Gözde Akdeniz; Toprakhisar, Burak; Bakirci, Ezgi; Menceloglu, Yusuf; Unal, Serkan; Koc, Bahattin

    2016-09-15

    Multimaterial additive manufacturing or three-dimensional (3D) printing of hydrogel structures provides the opportunity to engineer geometrically dependent functionalities. However, current fabrication methods are mostly limited to one type of material or only provide one type of functionality. In this paper, we report a novel method of multimaterial deposition of hydrogel structures based on an aspiration-on-demand protocol, in which the constitutive multimaterial segments of extruded filaments were first assembled in liquid state by sequential aspiration of inks into a glass capillary, followed by in situ gel formation. We printed different patterned objects with varying chemical, electrical, mechanical, and biological properties by tuning process and material related parameters, to demonstrate the abilities of this method in producing heterogeneous and multi-functional hydrogel structures. Our results show the potential of proposed method in producing heterogeneous objects with spatially controlled functionalities while preserving structural integrity at the switching interface between different segments. We anticipate that this method would introduce new opportunities in multimaterial additive manufacturing of hydrogels for diverse applications such as biosensors, flexible electronics, tissue engineering and organ printing.

  15. Self-formation of bilayer lipid membranes on agarose-coated silicon surfaces studied by simultaneous electrophysiological and surface infrared spectroscopic measurements

    NASA Astrophysics Data System (ADS)

    Hirano-Iwata, Ayumi; Oshima, Azusa; Onodera, Kota; Aoto, Kouji; Taira, Tasuku; Yamaguchi, Ryo-taro; Kimura, Yasuo; Niwano, Michio

    2009-06-01

    Self-formation process of bilayer lipid membranes (BLMs) cushioned on agarose-coated Si surfaces was in situ monitored by simultaneous electrophysiological and infrared absorption spectroscopic (IRAS) measurements using IRAS with the multiple internal reflection geometry. IRAS signals corresponding to self-thinning of lipid solution to form BLMs were demonstrated. It was found that the appearance of IRAS bands due to C=O modes of phosphstidylcholine is related to formation of BLMs with a gigaohm seal. The functionality of the present BLM system was also demonstrated by incorporating gramicidin into the BLMs and recording its channel activities.

  16. Minimizing inhibition of PCR-STR typing using digital agarose droplet microfluidics.

    PubMed

    Geng, Tao; Mathies, Richard A

    2015-01-01

    The presence of PCR inhibitors in forensic and other biological samples reduces the amplification efficiency, sometimes resulting in complete PCR failure. Here we demonstrate a high-performance digital agarose droplet microfluidics technique for single-cell and single-molecule forensic short tandem repeat (STR) typing of samples contaminated with high concentrations of PCR inhibitors. In our multifaceted strategy, the mitigation of inhibitory effects is achieved by the efficient removal of inhibitors from the porous agarose microgel droplets carrying the DNA template through washing and by the significant dilution of targets and remaining inhibitors to the stochastic limit within the ultralow nL volume droplet reactors. Compared to conventional tube-based bulk PCR, our technique shows enhanced (20 ×, 10 ×, and 16 ×) tolerance of urea, tannic acid, and humic acid, respectively, in STR typing of GM09948 human lymphoid cells. STR profiling of single cells is not affected by small soluble molecules like urea and tannic acid because of their effective elimination from the agarose droplets; however, higher molecular weight humic acid still partially inhibits single-cell PCR when the concentration is higher than 200 ng/μL. Nevertheless, the full STR profile of 9948 male genomic DNA contaminated with 500 ng/μL humic acid was generated by pooling and amplifying beads carrying single-molecule 9948 DNA PCR products in a single secondary reaction. This superior performance suggests that our digital agarose droplet microfluidics technology is a promising approach for analyzing low-abundance DNA targets in the presence of inhibitors.

  17. Confined Flocculation of Ionic Pollutants by Poly(L-dopa)-Based Polyelectrolyte Complexes in Hydrogel Beads for Three-Dimensional, Quantitative, Efficient Water Decontamination.

    PubMed

    Yu, Li; Liu, Xiaokong; Yuan, Weichang; Brown, Lauren Joan; Wang, Dayang

    2015-06-16

    The development of simple and recyclable adsorbents with high adsorption capacity is a technical imperative for water treatment. In this work, we have successfully developed new adsorbents for the removal of ionic pollutants from water via encapsulation of polyelectrolyte complexes (PECs) made from positively charged poly(allylamine hydrochloride) (PAH) and negatively charged poly(l-3,4-dihydroxyphenylalanine) (PDopa), obtained via the self-polymerization of l-3,4-dihydroxyphenylalanine (l-Dopa). Given the outstanding mass transport through the hydrogel host matrixes, the PDopa-PAH PEC guests loaded inside can effectively and efficiently remove various ionic pollutants, including heavy metal ions and ionic organic dyes, from water. The adsorption efficiency of the PDopa-PAH PECs can be quantitatively correlated to and tailored by the PDopa-to-PAH molar ratio. Because PDopa embodies one catechol group, one carboxyl group, and one amino group in each repeating unit, the resulting PDopa-PAH PECs exhibit the largest capacity of adsorption of heavy metal ions compared to available adsorbents. Because both PDopa and PAH are pH-sensitive, the PDopa-PAH PEC-loaded agarose hydrogel beads can be easily and completely recovered after the adsorption of ionic pollutants by adjusting the pH of the surrounding media. The present strategy is similar to the conventional process of using PECs to flocculate ionic pollutants from water, while in our system flocculation is confined to the agarose hydrogel beads, thus allowing easy separation of the resulting adsorbents from water.

  18. Rapid monoclonal antibody adsorption on dextran-grafted agarose media for ion-exchange chromatography.

    PubMed

    Tao, Yinying; Carta, Giorgio

    2008-11-21

    The binding capacity and adsorption kinetics of a monoclonal antibody (mAb) are measured for experimental cation exchangers obtained by grafting dextran polymers to agarose beads and compared with measurements for two commercial agarose-based cation exchangers with and without dextran grafts. Introduction of charged dextran polymers results in enhanced adsorption kinetics despite a dramatic reduction of the accessible pore size as determined by inverse size-exclusion chromatography. Incorporation of neutral dextran polymers in a charged agarose bead results instead in substantially lower binding capacities. The effective pore diffusivities obtained from batch uptake curves increase substantially as the protein concentration is reduced for the resins containing charged dextran grafts, but are much less dependent on protein concentration for the resins with no dextran or uncharged dextran grafts. The batch uptake results are corroborated by microscopic observations of transient adsorption in individual particles. In all cases studied, the adsorption kinetics is characterized by a sharp adsorption front consistent with a shell-progressive, diffusion limited mechanism. Greatly enhanced transport rates are obtained with an experimental resin containing charged dextran grafts with effective pore diffusivities that are 1-9 times larger than the free solution diffusivity and adsorption capacity approaching 300 mg/cm3 of particle volume.

  19. Methods for determining agent concentration profiles in agarose gel during convection-enhanced delivery.

    PubMed

    Sindhwani, Nikhil; Ivanchenko, Oleksandr; Lueshen, Eric; Prem, Komal; Linninger, Andreas A

    2011-03-01

    Convection-enhanced delivery (CED) is a promising technique to deliver large molecular weight drugs to the human brain for treatment of Parkinson's, Alzheimer's, or brain tumors. Researchers have used agarose gels to study mechanisms of agent transport in soft tissues like brain due to its similar mechanical and transport properties. However, inexpensive quantitative techniques to precisely measure achieved agent distribution in agarose gel phantoms during CED are missing. Such precise measurements of concentration distribution are needed to optimize drug delivery. An optical experimental method to accurately quantify agent concentration in agarose is presented. A novel geometry correction algorithm is used to determine real concentrations from observable light intensities captured by a digital camera. We demonstrate the technique in dye infusion experiments that provide cylindrical and spherical distributions when infusing with porous membrane and conventional single-port catheters, respectively. This optical method incorporates important parameters, such as optimum camera exposure, captured camera intensity calibration, and use of collimated light source for maximum precision. We compare experimental results with numerical solutions to the convection diffusion equation. The solutions of convection-diffusion equations in the cylindrical and spherical domains were found to match the experimental data obtained by geometry correction algorithm.

  20. A disposable bio-nano-chip using agarose beads for high performance immunoassays.

    PubMed

    Du, Nan; Chou, Jie; Kulla, Eliona; Floriano, Pierre N; Christodoulides, Nicolaos; McDevitt, John T

    2011-10-15

    This article reports on the fabrication of a disposable bio-nano-chip (BNC), a microfluidic device composed of polydimethylsiloxane (PDMS) and thiolene-based optical epoxy which is both cost-effective and suitable for high performance immunoassays. A novel room temperature (RT) bonding technique was utilized so as to achieve irreversible covalent bonding between PDMS and thiolene-based epoxy layers, while at the same time being compatible with the insertion of agarose bead sensors, selectively arranged in an array of pyramidal microcavities replicated in the thiolene thin film layer. In the sealed device, the bead-supporting epoxy film is sandwiched between two PDMS layers comprising of fluidic injection and drain channels. The agarose bead sensors used in the device are sensitized with anti-C-reactive protein (CRP) antibody, and a fluorescent sandwich-type immunoassay was run to characterize the performance of this device. Computational fluid dynamics (CFD) was used based on the device specifications to model the bead penetration. Experimental data revealed analyte penetration of the immunocomplex to 100 μm into the 280 μm diameter agarose beads, which correlated well with the simulation. A dose-response curve was obtained and the linear dynamic range of the assay was established over 1 ng/mL to 50 ng/mL with a limit of detection less than 1 ng/mL.

  1. Aqueous phase catalytic conversion of agarose to 5-hydroxymethylfurfural by metal chlorides

    SciTech Connect

    Yan, Lishi; Laskar, Dhrubojyoti D.; Lee, Suh-Jane; Yang, Bin

    2013-12-14

    Abstract: 5-HMF is a key intermediate for producing chemicals and fuels that can substitute for today’s petroleum-derived feedstocks. A series of metal chlorides, including NaCl, CaCl2, MgCl2, ZnCl2, CuCl2, FeCl3, and CrCl3, were comparatively investigated to catalyze agarose degradation for production of 5-HMF at temperature 180 oC, 200 oC, and 220 oC for 30 min, with catalyst concentration of 0.5% (w/w), 1% (w/w) and 5% (w/w), and substrate concentration of 2% (w/w). Our results revealed that alkali metal chlorides and alkali earth metal chlorides such as NaCl, CaCl2 and MgCl2 gave better 5-HMF yield compared with transition metal chlorides including ZnCl2, CrCl3, CuCl2 and FeCl3. 1% (w/w) MgCl2 was the more favorable catalyst for 5-HMF production from agarose, and resulted in 40.7% 5-HMF yield but no levulinic acid or lactic acid at 200 oC, 35 min. The reaction pathways of agarose degradation catalyzed by MgCl2 were also discussed.

  2. Chondroitin sulfate-derivatized agarose beads: a new system for studying cation binding to glycosaminoglycans

    SciTech Connect

    Hunter, G.K.

    1987-09-01

    Chondroitin sulfate (CS) has been covalently attached to aminoethyl-agarose beads in a carbodiimide-catalyzed reaction. In this process, an amide bond is formed between carboxylate groups on the glycosaminoglycan (GAG) and the primary amine groups of the beads. Under optimal conditions, up to 160 micrograms of CS is attached per milligram of beads. CS-agarose beads have been used to study Ca binding to GAGs. The beads are mixed with a solution containing CaCl/sub 2/ and /sup 45/Ca and allowed to sediment under unit gravity. An aliquot of supernatant is then removed and /sup 45/Ca activity is determined to quantitate remaining (free) Ca. Using this system, it was shown that CS binds approximately 0.7 Ca/disaccharide unit at saturation. Under the conditions used, the apparent association constant (KA) is approximately 14 mM. In principle, this derivatization protocol may be used to attach any proteoglycan or GAG (except keratan sulfate) to an insoluble support. CS-agarose beads provide a rapid, simple, and relatively artifact-free system for studying cation-GAG interactions.

  3. Preparation of uniform-sized agarose beads by microporous membrane emulsification technique.

    PubMed

    Zhou, Qing-Zhu; Wang, Lian-Yan; Ma, Guang-Hui; Su, Zhi-Guo

    2007-07-01

    Uniform-sized agarose beads were prepared by membrane emulsification technique in this study. Agarose was dissolved in boiling water (containing 0.9% sodium chloride) and used as water phase. A mixture of liquid paraffin and petroleum ether containing 4 wt% of hexaglycerin penta ester (PO-500) emulsifier was used as oil phase. At 55 degrees C, the water phase permeated through uniform pores of microporous membrane into the oil phase by a pressure of nitrogen gas to form uniform W/O emulsion. Then the emulsion was cooled down to room temperature under gentle agitation to form gel beads. The effect of oil phase, emulsifier, especially temperature on the uniformity of the beads were investigated and interpreted from interfacial tension between water phase and oil phase. Under optimized condition, the coefficient variation (C.V.) showing the size distribution of the beads was under 15%. This was the first report to prepare uniform agarose beads by membrane emulsification, and to investigate the effect of temperature on the size distribution of the droplets and beads. The beads with different size can be prepared by using membranes with different pore size, and the result showed that there was a linear relationship between the average diameter of beads and pore size of the membranes; beads with diameter from 15 to 60 microm were able to obtain in this study.

  4. Radiation synthesis of temperature-responsive hydrogels by copolymerization of [2-(methacryloyloxy)ethyl]trimethylammonium chloride with /N-isopropylacrylamide

    NASA Astrophysics Data System (ADS)

    Mun, Grigoriy A.; Nurkeeva, Zauresh S.; Khutoryanskiy, Vitaliy V.; Sergaziyev, Aibek D.; Rosiak, Janusz M.

    2002-08-01

    Novel cationic hydrogels were synthesized by γ-irradiation copolymerization of [2-(methacryloyloxy)ethyl]trimethylammonium chloride with N-isopropylacrylamide in the presence of cross-linking agent. The synthesis regularities have been studied. The swelling behavior of hydrogels as a function of copolymers composition and temperature was evaluated.

  5. Hybrid hydrogels containing vertically aligned carbon nanotubes with anisotropic electrical conductivity for muscle myofiber fabrication

    PubMed Central

    Ahadian, Samad; Ramón-Azcón, Javier; Estili, Mehdi; Liang, Xiaobin; Ostrovidov, Serge; Shiku, Hitoshi; Ramalingam, Murugan; Nakajima, Ken; Sakka, Yoshio; Bae, Hojae; Matsue, Tomokazu; Khademhosseini, Ali

    2014-01-01

    Biological scaffolds with tunable electrical and mechanical properties are of great interest in many different fields, such as regenerative medicine, biorobotics, and biosensing. In this study, dielectrophoresis (DEP) was used to vertically align carbon nanotubes (CNTs) within methacrylated gelatin (GelMA) hydrogels in a robust, simple, and rapid manner. GelMA-aligned CNT hydrogels showed anisotropic electrical conductivity and superior mechanical properties compared with pristine GelMA hydrogels and GelMA hydrogels containing randomly distributed CNTs. Skeletal muscle cells grown on vertically aligned CNTs in GelMA hydrogels yielded a higher number of functional myofibers than cells that were cultured on hydrogels with randomly distributed CNTs and horizontally aligned CNTs, as confirmed by the expression of myogenic genes and proteins. In addition, the myogenic gene and protein expression increased more profoundly after applying electrical stimulation along the direction of the aligned CNTs due to the anisotropic conductivity of the hybrid GelMA-vertically aligned CNT hydrogels. We believe that platform could attract great attention in other biomedical applications, such as biosensing, bioelectronics, and creating functional biomedical devices. PMID:24642903

  6. A drug delivery hydrogel system based on activin B for Parkinson's disease.

    PubMed

    Li, Juan; Darabi, Mohammadali; Gu, Jingjing; Shi, Junbin; Xue, Jinhua; Huang, Lu; Liu, Yutong; Zhang, Lei; Liu, N; Zhong, Wen; Zhang, Lin; Xing, Malcolm; Zhang, Lu

    2016-09-01

    Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Activins are members of the superfamily of transforming growth factors and have many potential neuroprotective effects. Herein, at the first place, we verified activin B's neuroprotective role in a PD model, and revealed that activin B's fast release has limited function in the PD therapy. To this end, we developed a multi-functional crosslinker based thermosensitive injectable hydrogels to deliver activin B, and stereotactically injected the activin B-loaded hydrogel into the striatum of a mouse model of PD. The histological evaluation showed that activin B can be detected even 5 weeks post-surgery in PD mice implanted with activin B-loaded hydrogels, and activin B-loaded hydrogels can significantly increase the density of tyrosine hydroxylase positive (TH(+)) nerve fibers and reduce inflammatory responses. The behavioral evaluation demonstrated that activin B-loaded hydrogels significantly improved the performance of the mice in the PD model. Meanwhile, we found that hydrogels can slightly induce the activation of microglia cells and astrocytes, while cannot induce apoptosis in the striatum. Overall, our data demonstrated that the developed activin B-loaded hydrogels provide sustained release of activin B for over 5 weeks and contribute to substantial cellular protection and behavioral improvement, suggesting their potential as a therapeutic strategy for PD.

  7. Design of Hyaluronic Acid Hydrogels to Promote Neurite Outgrowth in Three Dimensions.

    PubMed

    Tarus, Dominte; Hamard, Lauriane; Caraguel, Flavien; Wion, Didier; Szarpak-Jankowska, Anna; van der Sanden, Boudewijn; Auzély-Velty, Rachel

    2016-09-28

    A hyaluronic acid (HA)-based extracellular matrix (ECM) platform with independently tunable stiffness and density of cell-adhesive peptide (RGD, arginine-glycine-aspartic acid) that mimics key biochemical and mechanical features of brain matrix has been designed. We demonstrated here its utility in elucidating ECM regulation of neural progenitor cell behavior and neurite outgrowth. The analysis of neurite outgrowth in 3-D by two-photon microscopy showed several important results in the development of these hydrogels. First, the ability of neurites to extend deeply into these soft HA-based matrices even in the absence of cell-adhesive ligand further confirms the potential of HA hydrogels for central nervous system (CNS) regeneration. Second, the behavior of hippocampal neural progenitor cells differed markedly between the hydrogels with a storage modulus of 400 Pa and those with a modulus of 800 Pa. We observed an increased outgrowth and density of neurites in the softest hydrogels (G' = 400 Pa). Interestingly, cells seeded on the surface of the hydrogels functionalized with the RGD ligand experienced an optimum in neurite outgrowth as a function of ligand density. Surprinsingly, neurites preferentially progressed inside the gels in a vertical direction, suggesting that outgrowth is directed by the hydrogel structure. This work may provide design principles for the development of hydrogels to facilitate neuronal regeneration in the adult brain.

  8. Hybrid hydrogels containing vertically aligned carbon nanotubes with anisotropic electrical conductivity for muscle myofiber fabrication.

    PubMed

    Ahadian, Samad; Ramón-Azcón, Javier; Estili, Mehdi; Liang, Xiaobin; Ostrovidov, Serge; Shiku, Hitoshi; Ramalingam, Murugan; Nakajima, Ken; Sakka, Yoshio; Bae, Hojae; Matsue, Tomokazu; Khademhosseini, Ali

    2014-01-01

    Biological scaffolds with tunable electrical and mechanical properties are of great interest in many different fields, such as regenerative medicine, biorobotics, and biosensing. In this study, dielectrophoresis (DEP) was used to vertically align carbon nanotubes (CNTs) within methacrylated gelatin (GelMA) hydrogels in a robust, simple, and rapid manner. GelMA-aligned CNT hydrogels showed anisotropic electrical conductivity and superior mechanical properties compared with pristine GelMA hydrogels and GelMA hydrogels containing randomly distributed CNTs. Skeletal muscle cells grown on vertically aligned CNTs in GelMA hydrogels yielded a higher number of functional myofibers than cells that were cultured on hydrogels with randomly distributed CNTs and horizontally aligned CNTs, as confirmed by the expression of myogenic genes and proteins. In addition, the myogenic gene and protein expression increased more profoundly after applying electrical stimulation along the direction of the aligned CNTs due to the anisotropic conductivity of the hybrid GelMA-vertically aligned CNT hydrogels. We believe that platform could attract great attention in other biomedical applications, such as biosensing, bioelectronics, and creating functional biomedical devices.

  9. Hybrid hydrogels containing vertically aligned carbon nanotubes with anisotropic electrical conductivity for muscle myofiber fabrication.

    PubMed

    Ahadian, Samad; Ramón-Azcón, Javier; Estili, Mehdi; Liang, Xiaobin; Ostrovidov, Serge; Shiku, Hitoshi; Ramalingam, Murugan; Nakajima, Ken; Sakka, Yoshio; Bae, Hojae; Matsue, Tomokazu; Khademhosseini, Ali

    2014-01-01

    Biological scaffolds with tunable electrical and mechanical properties are of great interest in many different fields, such as regenerative medicine, biorobotics, and biosensing. In this study, dielectrophoresis (DEP) was used to vertically align carbon nanotubes (CNTs) within methacrylated gelatin (GelMA) hydrogels in a robust, simple, and rapid manner. GelMA-aligned CNT hydrogels showed anisotropic electrical conductivity and superior mechanical properties compared with pristine GelMA hydrogels and GelMA hydrogels containing randomly distributed CNTs. Skeletal muscle cells grown on vertically aligned CNTs in GelMA hydrogels yielded a higher number of functional myofibers than cells that were cultured on hydrogels with randomly distributed CNTs and horizontally aligned CNTs, as confirmed by the expression of myogenic genes and proteins. In addition, the myogenic gene and protein expression increased more profoundly after applying electrical stimulation along the direction of the aligned CNTs due to the anisotropic conductivity of the hybrid GelMA-vertically aligned CNT hydrogels. We believe that platform could attract great attention in other biomedical applications, such as biosensing, bioelectronics, and creating functional biomedical devices. PMID:24642903

  10. Drying and Storage Effects on Poly(ethylene glycol) Hydrogel Mechanical Properties and Bioactivity

    PubMed Central

    Luong, P.T.; Browning, M.B.; Bixler, R.S.; Cosgriff-Hernandez, E.

    2014-01-01

    Hydrogels based on poly(ethylene glycol) (PEG) are increasingly used in biomedical applications due to the ability to control cell-material interactions by tuning hydrogel physical and biological properties. Evaluation of stability after drying and storage are critical in creating an off-the-shelf biomaterial that functions in vivo according to original specifications. However, there has not been a study that systematically investigates the effects of different drying conditions and hydrogel compositional variables. In the first part of this study, PEG-diacrylate hydrogels underwent common processing procedures (vacuum-drying, lyophilizing, hydrating then vacuum-drying) and the effect of this processing on the mechanical properties and swelling ratios was measured. Significant changes in compressive modulus, tensile modulus, and swelling ratio only occurred for select processed hydrogels. No consistent trends were observed after processing for any of the formulations tested. The effect of storage conditions on cell adhesion and spreading on collagen- and streptococcal collagen-like protein (Scl2-2)-PEG-diacrylamide hydrogels was then evaluated to characterize bioactivity retention after storage. Dry storage conditions preserved bioactivity after 6 weeks of storage; whereas, storage in PBS significantly reduced bioactivity. This loss of bioactivity was attributed to ester hydrolysis of the protein linker, acrylate-PEG-N-hydroxysuccinimide. These studies demonstrate that these processing methods and dry storage conditions may be used to prepare bioactive PEG hydrogel scaffolds with recoverable functionality after storage. PMID:24123725

  11. Design of Hyaluronic Acid Hydrogels to Promote Neurite Outgrowth in Three Dimensions.

    PubMed

    Tarus, Dominte; Hamard, Lauriane; Caraguel, Flavien; Wion, Didier; Szarpak-Jankowska, Anna; van der Sanden, Boudewijn; Auzély-Velty, Rachel

    2016-09-28

    A hyaluronic acid (HA)-based extracellular matrix (ECM) platform with independently tunable stiffness and density of cell-adhesive peptide (RGD, arginine-glycine-aspartic acid) that mimics key biochemical and mechanical features of brain matrix has been designed. We demonstrated here its utility in elucidating ECM regulation of neural progenitor cell behavior and neurite outgrowth. The analysis of neurite outgrowth in 3-D by two-photon microscopy showed several important results in the development of these hydrogels. First, the ability of neurites to extend deeply into these soft HA-based matrices even in the absence of cell-adhesive ligand further confirms the potential of HA hydrogels for central nervous system (CNS) regeneration. Second, the behavior of hippocampal neural progenitor cells differed markedly between the hydrogels with a storage modulus of 400 Pa and those with a modulus of 800 Pa. We observed an increased outgrowth and density of neurites in the softest hydrogels (G' = 400 Pa). Interestingly, cells seeded on the surface of the hydrogels functionalized with the RGD ligand experienced an optimum in neurite outgrowth as a function of ligand density. Surprinsingly, neurites preferentially progressed inside the gels in a vertical direction, suggesting that outgrowth is directed by the hydrogel structure. This work may provide design principles for the development of hydrogels to facilitate neuronal regeneration in the adult brain. PMID:27598554

  12. Hybrid hydrogels containing vertically aligned carbon nanotubes with anisotropic electrical conductivity for muscle myofiber fabrication

    NASA Astrophysics Data System (ADS)

    Ahadian, Samad; Ramón-Azcón, Javier; Estili, Mehdi; Liang, Xiaobin; Ostrovidov, Serge; Shiku, Hitoshi; Ramalingam, Murugan; Nakajima, Ken; Sakka, Yoshio; Bae, Hojae; Matsue, Tomokazu; Khademhosseini, Ali

    2014-03-01

    Biological scaffolds with tunable electrical and mechanical properties are of great interest in many different fields, such as regenerative medicine, biorobotics, and biosensing. In this study, dielectrophoresis (DEP) was used to vertically align carbon nanotubes (CNTs) within methacrylated gelatin (GelMA) hydrogels in a robust, simple, and rapid manner. GelMA-aligned CNT hydrogels showed anisotropic electrical conductivity and superior mechanical properties compared with pristine GelMA hydrogels and GelMA hydrogels containing randomly distributed CNTs. Skeletal muscle cells grown on vertically aligned CNTs in GelMA hydrogels yielded a higher number of functional myofibers than cells that were cultured on hydrogels with randomly distributed CNTs and horizontally aligned CNTs, as confirmed by the expression of myogenic genes and proteins. In addition, the myogenic gene and protein expression increased more profoundly after applying electrical stimulation along the direction of the aligned CNTs due to the anisotropic conductivity of the hybrid GelMA-vertically aligned CNT hydrogels. We believe that platform could attract great attention in other biomedical applications, such as biosensing, bioelectronics, and creating functional biomedical devices.

  13. A novel in situ-formed hydrogel wound dressing by the photocross-linking of a chitosan derivative.

    PubMed

    Lu, Guozhong; Ling, Kai; Zhao, Peng; Xu, Zhenghong; Deng, Cao; Zheng, Hua; Huang, Jin; Chen, Jinghua

    2010-01-01

    In situ photopolymerized hydrogel dressings create minimally invasive methods that offer advantages over the use of preformed dressings such as conformability in any wound bed, convenience of application, and improved patient compliance and comfort. Here, we report an in situ-formed hydrogel membrane through ultraviolet cross-linking of a photocross-linkable azidobenzoic hydroxypropyl chitosan aqueous solution. The hydrogel membrane is stable, flexible, and transparent, with a bulk network structure of smoothness, integrity, and density. Fluid uptake ability, water vapor transmission rate, water retention, and bioadhesion of the thus resulted hydrogel membranes (0.1 mm thick) were determined to range from 97.0-96.3%, 2,934-2,561 g/m(2)/day, 36.69-22.94% (after 6 days), and 4.8-12.3 N/cm(2), respectively. These data indicate that the hydrogel membrane can maintain a long period of moist environment over the wound bed for enhancing reepithelialization. Specifically, these properties of the hydrogel membrane were controllable to some extent, by adjusting the substitution degree of the photoreactive azide groups. The hydrogel membrane also exhibited barrier function, as it was impermeable to bacteria but permeable to oxygen. In vitro experiments using two major skin cell types (dermal fibroblast and epidermal keratinocyte) revealed the hydrogel membrane have neither cytotoxicity nor an effect on cell proliferation. Taken together, the in situ photocross-linked azidobenzoic hydroxypropyl chitosan hydrogel membrane has a great potential in the management of wound healing and skin burn.

  14. Hyperbranched poly(glycidol)/poly(ethylene oxide) crosslinked hydrogel for tissue engineering scaffold using e-beams.

    PubMed

    Haryanto; Singh, Deepti; Huh, Pil Ho; Kim, Seong Cheol

    2016-01-01

    A microporous hydrogel scaffold was developed from hyperbranched poly(glycidol) (HPG) and poly(ethylene oxide) (PEO) using electron beam (e-beam) induced cross-linking for tissue engineering applications. In this study, HPG was synthesized from glycidol using trimethylol propane as a core initiator and cross-linked hydrogels were made using 0, 10, 20, and 30% HPG with respect to PEO. The effects of %-HPG on the swelling ratio, cross-linking density, mechanical properties, morphology, degradation, and cytotoxicity of the hydrogel scaffolds were then investigated. Increasing the HPG content increased the pore size of the hydrogel scaffold, as well as the porosity, elongation at break, degree of degradation and swelling ratio. In contrast, the presence of HPG decreased the cross-linking density of the hydrogel. There was no significant difference in compressive modulus and tensile strength of all compositions. The pore size of hydrogel scaffolds could be easily tailored by controlling the content of HPG in the polymer blend. Evaluation of the cytotoxicity demonstrated that HPG/PEO hydrogel scaffold has potential for use as a matrix for cellular attachment and proliferation. These results indicate that cross-linked HPG/PEO hydrogel can function as a potential material for tissue engineering scaffolds. Moreover, a facile method to prepare hydrogel microporous scaffolds for tissue engineering by e-beam irradiation was developed.

  15. Investigation of citric acid-glycerol based pH-sensitive biopolymeric hydrogels for dye removal applications: A green approach.

    PubMed

    Franklin, D S; Guhanathan, S

    2015-11-01

    Hydrogels are three dimensional polymeric structure with segments of hydrophilic groups. The special structure of hydrogels facilitates the diffusion of solutes into the interior network and possess numerous ionic and non-ionic functional groups, which can absorb or trap ionic dyes from waste water. The present investigation was devoted to the synthesis of a series of citric acid and glycerol based pH sensitive biopolymeric hydrogels using a solventless green approach via condensation polymerization in the presence of acidic medium. The formations of hydrogels were confirmed using various spectral investigations viz., FT-IR, (1)H and (13)C NMR. The thermal properties of various hydrogels have been studied using TGA, DTA and DSC analysis. The rationalized relationship was noticed with increasing of pH from 4.0 to 10.0. The surface morphologies of hydrogels were analyzed using SEM technique which was well supported from the results of swelling studies. Methylene blue has been selected as a cationic dye for its removal from various environmental sources using pH-sensitive biopolymeric hydrogels. The results of dye removal revealed that glycerol based biopolymeric hydrogels have shown an excellent dye removal capacity. Hence, the synthesized pH sensitive biopolymeric hydrogels have an adaptability with pH tuned properties might have greater potential opening in various environmental applications viz., metal ion removal, agrochemical release, purification of water, dye removal etc.

  16. A novel in situ-formed hydrogel wound dressing by the photocross-linking of a chitosan derivative.

    PubMed

    Lu, Guozhong; Ling, Kai; Zhao, Peng; Xu, Zhenghong; Deng, Cao; Zheng, Hua; Huang, Jin; Chen, Jinghua

    2010-01-01

    In situ photopolymerized hydrogel dressings create minimally invasive methods that offer advantages over the use of preformed dressings such as conformability in any wound bed, convenience of application, and improved patient compliance and comfort. Here, we report an in situ-formed hydrogel membrane through ultraviolet cross-linking of a photocross-linkable azidobenzoic hydroxypropyl chitosan aqueous solution. The hydrogel membrane is stable, flexible, and transparent, with a bulk network structure of smoothness, integrity, and density. Fluid uptake ability, water vapor transmission rate, water retention, and bioadhesion of the thus resulted hydrogel membranes (0.1 mm thick) were determined to range from 97.0-96.3%, 2,934-2,561 g/m(2)/day, 36.69-22.94% (after 6 days), and 4.8-12.3 N/cm(2), respectively. These data indicate that the hydrogel membrane can maintain a long period of moist environment over the wound bed for enhancing reepithelialization. Specifically, these properties of the hydrogel membrane were controllable to some extent, by adjusting the substitution degree of the photoreactive azide groups. The hydrogel membrane also exhibited barrier function, as it was impermeable to bacteria but permeable to oxygen. In vitro experiments using two major skin cell types (dermal fibroblast and epidermal keratinocyte) revealed the hydrogel membrane have neither cytotoxicity nor an effect on cell proliferation. Taken together, the in situ photocross-linked azidobenzoic hydroxypropyl chitosan hydrogel membrane has a great potential in the management of wound healing and skin burn. PMID:20082682

  17. Development of thermo-responsive hydrogels with immobilized metal affinity groups

    NASA Astrophysics Data System (ADS)

    Yoon, Young-Seo

    A Hydrogel is defined as a polymeric material which possesses the ability to swell in water and retain a significant fraction of water within its structure, but which will not dissolve in water. Hydrogels have been studied by many researchers because they have many useful applications in bio related fields such as drug delivery, bioseparation, and etc. In this thesis, a new hydrogel system that possesses the characteristics of thermo-responsive swelling property and immobilized metal affinity was developed. This affinity material consists of a hydrogel with stimuli responsive swelling characteristics to provide modulated diffusivity and si